Effect of time-restricted feeding combined with oral contraceptives on polycystic ovary syndrome: An open-label, randomized trial

Effect of time-restricted feeding combined with oral contraceptives on polycystic ovary syndrome: An open-label, randomized trial | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Effect of time-restricted feeding combined with oral contraceptives on polycystic ovary syndrome: An open-label, randomized trial Minshan Zhu, Dong Liang, Yuan Li, Peiwen Zhong, Weiru Li, Liyun Kuang, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4738766/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract BACKGROUND: Oral contraceptives have limitations in managing polycystic ovary syndrome. We explored time-restricted feeding combined with oral contraceptive use as a novel strategy for the management of polycystic ovary syndrome. STUDY DESIGN: A total of 126 female patients with polycystic ovary syndrome aged 18–40 years were selected for this study. They were randomly assigned to oral contraceptive therapy with an 8-hour time-restricted feeding (eating freely between 8:00 a.m. and 4:00 p.m.) or oral contraceptive therapy alone for 12 weeks. The primary outcome was the difference in spontaneous ovulation rate between the two groups after the intervention, and the secondary outcomes included changes in weight, body mass index, waist circumference, fertility endocrine indices, and glucose and lipid metabolism factors. RESULTS: Of 126 participants who underwent randomization, 116 (92.1%) completed a 12-week follow-up visit. The rates of spontaneous ovulation were 69.4% in the oral contraceptive + time-restricted feeding group and 50% in the oral contraceptive group (odds ratio=2.263; 95% confidence interval, 1.092–4.692; P =0.028). Time-restricted feeding is an independent factor that promotes ovulation recovery in patients with polycystic ovary syndrome, especially in those with insulin resistance. After the intervention, the oral contraceptive + time-restricted feeding group had a significantly lower body weight (-3.6 vs -0.9 kg , P <0.001), body mass index (-1.4 vs -0.4 kg/m 2 , P <0.001), body fat percentage (-1.4% vs 0.01%, P =0.047), waist circumference (-2.9 vs -0.6 cm , P <0.001), and fasting insulin (-2.4 vs -0.1 mIU/L, P =0.032) than the oral contraceptive alone group. CONCLUSIONS: Among patients with polycystic ovary syndrome, a time-restricted feeding regimen combined with oral contraceptive therapy was more beneficial than oral contraceptive use alone in promoting ovulation and reducing body weight, body fat, waist circumference, and fasting insulin. Time-restricted feeding polycystic ovary syndrome short-acting oral contraceptives weight loss ovulation Figures Figure 1 Figure 2 Figure 3 Highlights Time-restricted feeding promotes ovulation recovery in polycystic ovary syndrome. Insulin resistance improved with time-restricted feeding in polycystic ovary syndrome. Time-restricted feeding reduces weight and waist circumference in polycystic ovary syndrome. Novel strategy for polycystic ovary syndrome management: diet and medication synergy. INTRODUCTION Polycystic ovary syndrome (PCOS) is a common gynecological endocrine disorder that affects women of reproductive age and is characterized by hyperandrogenism and menstrual irregularities (anovulation or infrequent ovulation). Treatment with oral contraceptives (OC) is preferred owing to their efficacy in treating hirsutism and creating predictable menstrual cycles. 1 However, pretreatment with OC has poor effects on promoting ovulation, weight loss, and improving glucose and lipid metabolism, with post-withdrawal symptom recurrence. Thus, effective long-term lifestyle interventions are especially important for the treatment of PCOS. Time-restricted feeding (TRF) is a type of intermittent fasting that has garnered increasing public and medical interest owing to its efficacy and ease of adherence. TRF has shown positive effects on obesity and type 2 diabetes mellitus. Long-term weight management in obesity involves increasing ghrelin levels to control appetite. 2 TRF can also improve metabolism and activity, thereby boosting energy expenditure. 3 Moreover, dietary changes can enhance the feelings of hunger and satiety. 4,5 TRF reduces fasting blood glucose and glycosylated hemoglobin in type 2 diabetics. 6 Furthermore, TRF decreases fasting insulin (FINS) and homeostatic model assessment for insulin resistance (HOMA-IR) in non-diabetic obese/overweight patients. 7 However, studies on TRF in patients with PCOS and metabolic disorders are limited. We conducted a randomized trial comparing combined TRF with short-acting OC use versus OC use alone on the ovulation rate, weight, and glucose and lipid metabolism in women with PCOS. METHODS Study design This was a single-center, open-label, prospective, randomized controlled clinical trial. No protocol modifications or interim analyses were conducted following trial initiation. Ethics The trial was approved by the Ethics Committee of the First People's Hospital of Foshan, Guangdong, China (Lunshenyan [2022] No. 17) and registered with Chictr.org.cn (ChiCTR2300078263). All patients received the full study information and were given opportunities to ask questions before providing written consent. Participants The study population comprised female patients with PCOS who sought medical treatment at the First People's Hospital of Foshan from January 2022 to August 2023. Eligible outpatients were recruited by the same team of endocrinologists in the gynecology department. The inclusion criteria were: age 18–40 years and a PCOS diagnosis based on the Rotterdam criteria (oligomenorrhea or amenorrhea, along with clinical or biochemical hyperandrogenism and/or polycystic ovaries). 1 The exclusion criteria included other diseases (e.g., congenital adrenal hyperplasia, Cushing syndrome, androgen-secreting tumors, diabetes, thyroid, and gastrointestinal diseases), use of medication impacting carbohydrate or lipid metabolism (insulin, oral hypoglycemic agents, indomethacin, furosemide, glucocorticoids, OC pills) within 3 months, pregnancy preparation, pregnancy or lactation, uncontrolled mental disorder (including history of hospitalization for mental illness), and currently attending weight loss or weight management classes. Randomization and masking A statistician not involved in the research or data analysis used Microsoft Excel (Microsoft, Redmond, WA, USA) to generate a random number table. A two-zone randomization technique was employed for electronic treatment allocation spreadsheets. Patients meeting the inclusion criteria and willing to participate were randomly assigned 1:1 to the OC (control) or OC + TRF (trial) groups by another investigator not involved in recruitment, based on the patients' consecutive randomization numbers. Owing to the nature of the intervention, an open-label approach was used, wherein detailed dietary intervention instructions and regular supervision were provided to the trial group, whereas the other group had no strict dietary requirements. Procedures Including patients lost to follow-up and those not completing the intervention measures, a total of 126 were enrolled, of which 64 were in the OC group and 62 were in the OC + TRF group. For each participant, body weight and height were measured to calculate the body mass index (BMI; weight [kg] divided by height squared [m 2 ]; kg/m 2 ). Height was measured to the nearest 1 cm using a wall-mounted stadiometer (Seca 711; Hamburg, Germany). A BMI of 25 ≤ and < 30 kg/m 2 was defined as overweight, and BMI ≥ 30 kg/m 2 was defined as obesity. Waist circumference (WC) (cm) and Hip circumference (HC) (cm) were measured by the same nurse. The waist-to-hip ratio (WHR) was calculated using these measurements. Body fat percentage (BF%) = (WC (cm)* 0.74-weight (kg) * 0.082–34.89)/weight (kg) × 100. Hyperandrogenic manifestations included the Pillsbury acne score, modified Ferriman–Gallwey (mFG) hirsutism score, and Ludwig alopecia grade; a hyperandrogenism diagnosis was established if two or more were present. The Pillsbury acne score 8 was categorized as mild (grade I), mainly comedones, non-inflammatory, fewer than 30; moderate (grade II), inflammatory papules, 30–50; moderate (grade Ⅲ), 50–100 pustules; and severe (grade IV), nodules, and cysts, more than 100. The mFG hirsutism score assesses 9 body areas. 9 Chinese women with a score of ≥ 8 points were diagnosed with hirsutism. The Ludwig classification of alopecia 10 is as follows: grade I (mild alopecia), primarily affecting the parietal and coronal regions, with the forehead hairline remaining 1–3 cm wide; grade II (moderate alopecia), the hair in the head and crown area was thinner than in grade I; grade III (severe alopecia), complete hair loss in the crown area. Fasting blood samples were collected on the 3rd to 5th day of menstruation before and after the intervention. Luteinizing hormone (LH) (IU/L), total testosterone (TT) (nmol/L) and follicle-stimulating hormone (FSH) (IU/L) were measured by chemiluminescent immunoassay, fasting plasma glucose (FPG) (mmol/L) by the hexokinase method, FINS (mIU/L) by radioimmunological assay, uric acid (UA) (umol/L) by the uricase-PAP method, total cholesterol (TC) (mmol/L) by the cholesterol oxidase method, triglycerides (TG) (mmol/L) by the deionization & enzyme method, creatinine (CRE) (µmol/L) by the creatinase method, high-density lipoprotein cholesterol (HDL-C) (mmol/L) and low-density lipoprotein cholesterol (LDL-C) (mmol/L) by the direct one-step method, and glutamic oxaloacetic transaminase (AST) (IU/L) and glutamic pyruvic transaminase (ALT) (IU/L) by the rate method. HOMA-IR was calculated according to the formula: FINS (mIU/L)× FPG (mmol/L)/22.5. Patients in the OC group received drospirenone and ethinylestradiol II (Bayer Weimar GmbH und Co.KG, Leverkusen, Germany; 0.02 mg ethinylestradiol and 3.00 mg drospirenone) starting on the first day of menses, 1 pill/day, continuously for 12 weeks (3 boxes total). The patients were informed orally about their regular diet and weight control (excluding weight-loss drugs). Amenorrheic patients were treated with oral dydrogesterone tablets (Abbott Biologicals B.V., Veenendaal, The Netherlands; 10 mg dydrogesterone), one tablet twice daily, followed by drospirenone and ethinylestradiol II on the first day of menses. Patients in the OC + TRF group took drospirenone and ethinylestradiol II regularly and adhered to a strict 8-hour time-restricted dietary pattern for 12 weeks. They were instructed not to change the composition of their daily diet but to eat freely for only 8 hours a day (8 am to 4 pm) and fast for the remaining time (4 pm to 8 am). Only water or non-caloric beverages were allowed during the 16-hour fast; adequate water intake (2,000 mL/day) was encouraged throughout the intervention. The exercise routine of the patients was not defined, and a WeChat group was established for each group. During the experiment, gynecologists supervised the patients' diet implementation every 1–2 weeks, monitored adverse events, and provided professional support and guidance to promote compliance with the intervention measures. Outcomes The primary outcome was the restoration of spontaneous ovulation following cessation of the intervention. Both groups discontinued treatment after 12 weeks and were monitored for post-cessation ovulation. Two methods were used to determine spontaneous ovulation. ( 1 ) Blood samples were collected on days 21, 28, and 35 post-cessation to measure progesterone and estradiol levels. Estradiol levels above 200 ng/L indicated follicular development, while progesterone levels above 3 ug/L indicated spontaneous ovulation. 11 If a patient exhibited spontaneous ovulation on the first blood draw (i.e., day 21 post-cessation), subsequent draws were omitted. If a patient showed no increase in estradiol or progesterone levels across all three blood draws, progestin (e.g., oral dydrogesterone) was administered to induce menstruation. ( 2 ) Ultrasound monitoring of ovulation began on day 10 post-cessation of menstruation, with follow-up ultrasounds every 1–2 days based on follicle size until follicular development and ovulation were observed, confirming the diagnosis of spontaneous ovulation. Secondary outcomes included body composition-related indicators (body weight, BMI, BF%, WC, and WHR), blood pressure, fertility endocrine indices (hirsutism, acne, alopecia, LH, and TT), and glucose and lipid metabolism indicators (FPG, FINS, HOMA-IR, TC, TG, HDL-C, LDL-C, and UA) before and after the intervention. Statistical analysis Based on the literature, the ovulation restoration rate after a 3-month OC intervention for patients with PCOS is 32.8–54.7%. 12 The ovulation rate in the group that received OC and lifestyle guidance was 64.3%. The ovulation rate in the trial group was expected to be 70%. Using PASS (NCSS, Kaysville, UT, USA) software to estimate sample size, with a normal approximation, with parameters including two-tailed test (α = 0.05, power = 90%). The control and experimental groups each required 56 patients, and taking into consideration a 20% dropout rate, each group had 70 patients, for a total of 140 patients. Data were analyzed according to the intention-to-treat principle. Statistical analyses were conducted using SPSS (version 20.0; IBM Corp., Armonk, NY, USA). Missing data were analyzed using multiple imputation methods. The Kolmogorov–Smirnov test was used to evaluate whether continuous data followed a normal distribution. Data following a normal distribution is represented by mean ± standard deviation, and comparisons within and between groups were conducted using a t-test. Data that did not follow a normal distribution are represented as the median (interquartile range) using the Mann–Whitney U test. Categorical variables are presented as counts or percentages, and the chi-square test or Fisher's exact test was used for categorical data. Differences among groups were compared using covariance analysis, and the values for the average difference and 95% confidence intervals were estimated using the least-squares method. Variables were screened for inclusion in multivariate logistic regression using single-factor logistic regression analysis. Factors affecting patient intervention termination and subsequent resumption of ovulation were analyzed using multivariate logistic regression. The results were considered statistically significant at P < 0.05 for both sides. RESULTS Trial participants Screening appointments ran from January 30, 2022, to August 31, 2023, with randomizations continuing until September 2023 and a final follow-up in December 2023. A total of 126 patients were randomly assigned to either the OC + TRF (n = 62) or OC (n = 64) groups. Figure 1 shows the flow of study participants. In the OC + TRF group, 56 participants (90.3%) completed the 70-day intervention and 52 (83.9%) completed the 80-day intervention (Table 1 ). There were no significant differences in age, body type, metabolic disorder characteristics, and PCOS characteristics between the two groups. Table 1 Characteristics of the Participants at Baseline OC (n=64) OC+TRF (n=62) P Age (years) 26.3±4.4 26.2±4.8 0.915 Body size [N(%)] BMI≥30 kg/m 2 7 (10.9) 10 (16.1) 0.394 25≤BMI＜30 kg/m 2 19 (29.7) 17 (27.4) 0.423 BMI＜25 kg/m 2 38 (59.4) 35 (56.5) 0.740 WC≥80 cm 25 (39.1) 24 (38.7) 0.968 Metabolic Risk Factors [N(%)] BP≥130/85 mmHg a 11 (17.2) 14 (22.6) 0.448 UA≥360 μmol/L b 37 (57.8) 35 (56.5) 0.877 TG>1.7 mmol/L a 14 (21.9) 14 (22.6) 0.924 HDL-C2.69 25 (39.1) 27 (43.5) 0.609 Fatty liver 23 (35.9) 23 (37.1) 0.893 Symptoms of PCOS [N(%)] Oligomenorrhea 61 (95.3) 60 (96.8) 0.647 Hyperandrogenism 45 (84.4) 54 (87.1) 0.502 PCOM 42 (65.6) 50 (80.7) 0.058 a: IDF metabolic syndrome worldwide definition 13 b: European League Against Rheumatism evidence-based recommendation 14 To convert glucose values to milligrams per deciliter, multiply by 18; To convert cholesterol values to milligrams per deciliter, multiply by 38.65 OC: oral contraceptives; OC+TRF: oral contraceptives + time-restricted feeding; BMI: body mass index; WC: waist circumference; BP: blood pressure; UA: uric acid; TG: triglycerides; HDL-C: high-density lipoprotein cholesterol; FPG: fasting plasma glucose; PCOM: polycystic ovarian morphology. Ovulation The primary endpoint (restoration of spontaneous ovulation) occurred significantly more often in the OC + TRF group than in the OC group (69.4% vs. 50% of patients at 3 months; odds ratio [OR] = 2.263; 95% confidence interval [CI]: 1.092–4.692; P = 0.028). The results regarding the primary endpoint did not show significant heterogeneity in the subgroup analyses, with one exception (Fig. 2). The benefits of TRF appeared to be enhanced in patients with insulin resistance (HOMA-IR > 2.69) ( P = 0.015). Factors potentially affecting ovulation recovery in patients with PCOS were identified using univariate logistic regression analysis (Table 2 ). Variables with P < 0.1 (group, FINS, WHR) after collinearity consideration, along with age, were selected for subsequent logistic regression analysis. Binary logistic regression was used to analyze the effects on the ability of patients with PCOS to recover spontaneous ovulation. The results showed that the logistic regression model, adjusted for age, FINS, WHR factors, and TRF, remained independent factors promoting ovulation recovery in women with PCOS ( P = 0.047). This implies that compared to simple OC treatment, the TRF combination significantly increased the probability of ovulation recovery in patients with PCOS (OR = 2.192, 95% CI: 1.011–4.753) (Table 2 ). Table 2 Factors for Ovulation in Study Participants Variables Univariate analysis Multivariate analysis OR (95%CI) P OR (95%CI) P Age 1.011 (0.934–1.094) 0.786 1.064 (0.972–1.165) 0.180 FINS (mIU/L) 0.924 (0.877–0.973) 0.003 0.930 (0.881–0.983) 0.010 Weight(kg) 0.952 (0.921–0.984) 0.003 - - LH(IU/L) 0.990 (0.883–1.109) 0.857 - - Group OC 1.000 1.000 OC + TRF 2.263 (1.092–4.692) 0.028 2.192 (1.011–4.753) 0.047 Fatty Liver YES 1.000 - - NO 0.404 (0.192–0.852) 0.017 - - TG (mmol/L) ≥ 1.7 1.000 - - < 1.7 0.936 (0.460–1.907) 0.856 - - HDL-C (mmol/L) ≥ 1.29 1.000 - - < 1.29 1.487 (0.710–3.115) 0.292 - - FPG (mmol/L) ≥ 5.6 1.000 - - < 5.6 0.800 (0.231–2.776) 0.725 - - HOMA-IR ≥ 1.29 1.000 - - < 1.29 0.462 (0.224–0.955) 0.037 - - TT (mmol/L) ≥ 1.66 1.000 - - < 1.66 0.647 (0.212–1.972) 0.444 - - WC (cm) ≥ 80 1.000 - - < 80 0.304 (0.138–0.671) 0.003 - - BMI (kg/m 2 ) ≥ 25 1.000 - - < 25 0.419 (0.193–0.910) 0.028 - - Body Fat (%) ≥ 28 1.000 - - < 28 0.357 (0.171–0.746) 0.006 - - WHR ≥ 0.85 1.000 1.000 < 0.85 0.353 (0.155–0.805) 0.013 0.372 (0.144–0.957) 0.040 Hirsutism ≥ 8 1.000 - - < 8 0.518 (0.223–1.206) 0.127 - - OC: oral contraceptives; OC + TRF: oral contraceptives + time-restricted feeding; ALT: glutamic pyruvic transaminase; AST: glutamic oxaloacetic transaminase; CRE: creatinine; UA: uric acid; TC: total cholesterol; TG: triglycerides; HDL-C: high-density lipoprotein cholesterol; LDL-C: low-density lipoprotein cholesterol; FPG: fasting plasma glucose; FINS: fasting insulin; HOMA-IR: homeostasis model assessment-insulin resistance; LH: luteinizing hormone; FSH: follicle-stimulating hormone; TT: total testosterone; WC: waist circumference; HC: hip circumference; BMI: body mass index; BF: body fat; WHR: waist-to-hip ratio; Acne: based on the Pillsbury acne score; Alopecia: based on the Ludwig alopecia grade; Hirsutism: base on the mFG hirsutism score. OR: Odds Ratio; CI: Confidence Interval. Weight loss Both the OC and OC + TRF groups exhibited decreased body weight and BMI after 12 weeks, with statistically significant differences observed. Regarding WC and BF% reduction, the OC + TRF group showed significantly better outcomes than the OC group (Fig. 3a). Thirty-seven participants (60%) in the OC + TRF group achieved a weight loss of ≥ 5%, compared to only 9 (14%) in the OC group (Fig. 3g). Using covariance analysis, we compared the differences in body weight-related indicators between the two groups using the baseline value as a covariate. The OC + TRF group significantly outperformed the OC group in weight reduction, BMI, BF%, and WC (Table 3 ). Table 3 Inter-group comparison of Anthropometric and Metabolic Factors Variables OC组(N = 64) OC + TRF组(N = 62) P x̄ ±s/M (Q1 – Q3) x̄ ±s/M (Q1 – Q3) Baseline Weight (kg) 59.4 (49.6–69.8) 58.6 (53.2–67.7) 0.967 BMI 24.1 (19.8–27.6) 24.5 (21.8 ~ 27.3) 0.388 BF (%) 27.33 ± 7.73 27.91 ± 6.75 0.654 WC (cm) 77.2 (66.7–85.8) 75.3 (70.7–85.1) 0.716 SBP 115.5 ± 13.5 118.0 ± 13.5 0.290 DBP 70.1 ± 9.4 72.3 ± 9.5 0.191 Hirsutism 12.0 (8.0–18.8) 13.0 (8.0–16.3) 0.499 LH(IU/L) 10.1 (7.1–14.8) 9.5 (5.3–15.3) 0.431 TT (nmol/L) 1.1 (1–1.4) 1.2 (0.9–1.6) 0.399 FPG (mmol/L) 5.0 (4.8–5.2) 5.0 (4.7–5.4) 0.911 FINS (mIU/L) 10.9 (6.2–18.1) 10.7 (7.5–17.8) 0.439 HOMA-IR 2.4 (1.4–4.4) 2.4 (1.7–4.2) 0.466 TG (mmol/L) 1.1 (0.7–1.6) 1.2 (0.8–1.7) 0.470 HDL-C (mmol/L) 1.3 (1.0–1.5) 1.3 (1.1–1.5) 0.539 12 weeks Weight (kg) 58.1 (50.6–68.9) 55.8 (50.7–62.5) 0.242 BMI 23.6 (20.5–26.2) 23.2 (20.6–25.4) 0.874 BF (%) 27.4 ± 7.1 26.4 ± 7.2 0.453 WC (cm) 75.2 (68.0–87.0) 74.2 (67.7–80.6) 0.321 SBP 116.0 (107.5–124.8) 113.5 (107.0–122.3) 0.438 DBP 71.0 (65.0–79.8) 74.0 (67.8–79.0) 0.216 Hirsutism 10.0 (8.0–15.8) 11.0 (6.0–14.3) 0.471 LH(IU/L) 5.5 (3.6–7.4) 5.9 (4.2–8.0) 0.957 TT (nmol/L) 1.0 (0.7–1.2) 1.1 (0.8–1.3) 0.466 FPG (mmol/L) 5.0 ± 0.4 5.0 ± 0.4 0.572 FINS (mIU/L) 2.4 (1.7–3.5) 2.4 (1.7–3.5) 0.315 HOMA-IR 2.4 (1.7–3.5) 2.4 (1.7–3.5) 0.668 TG (mmol/L) 1.8 (1.1–2.2) 1.5 (1.0–2.4) 0.638 HDL-C (mmol/L) 1.4 (1.2–1.7) 1.4 (1.2–1.6) 0.660 LS Mean(95%CI) LS Mean(95%CI) P Changes a Weight (kg) -0.9 (-1.4 to -0.3) -3.6 (-4.2 to -3.0) < 0.001 BMI (kg/m 2 ) -0.4 (-0.6 to -0.2) -1.4 (-1.7 to -1.2) < 0.001 BF (%) 0.01 (-1.0 to 1.0) -1.4 (-2.4 to -0.4) 0.047 WC (cm) -0.6 (-1.5 to 0.3) -2.9 (-3.9 to -2.0) < 0.001 SBP -1.0 (-4.4 to 2.4) -2.2 (-5.6 to 1.3) 0.637 DBP 1.0 (-1.5 to 3.4) 2.8 (0.3–5.3) 0.310 Hirsutism -1.9 (-2.8 to -1.1) -2.4 (-3.3 to -1.5) 0.453 LH (IU/L) -5.2 (-5.9 to -4.4) -5.3 (-6.1 to -4.5) 0.762 TT (nmol/L) -0.2 (-0.2 to -0.1) -0.2 (-0.3 to -0.1) 0.957 FPG (mmol/L) -0.1 (-0.2 to -0.1) -0.1 (-0.2 to -0.01) 0.430 FINS (mIU/L) -0.1 (-1.5 to 1.4) -2.4 (-3.9 to -0.9) 0.032 HOMA-IR -0.2 (-0.5 to 0.2) -0.6 (-1.0 to -0.2) 0.137 TG (mmol/L) 1.0 (0.5–1.5) 0.6 (0.1–1.2) 0.375 HDL-C (mmol/L) 0.2 (0.0–0.2) 0.1 (0.0–0.1) 0.102 LS: The least squares method; a: The covariance analysis based on the least squares method estimates the mean and 95% CI, The baseline value serves as the covariate. BMI: body mass index; WC: waist circumference; BF: body fat; BP: blood pressure; SBP: systolic blood; DBP: diastolic pressure; LH: luteinizing hormone; TT: total testosterone; FPG: fasting plasma glucose; FINS: fasting insulin; HOMA-IR: Homeostasis model assessment-insulin resistance; TG: triglycerides; HDL-C: high-density lipoprotein cholesterol; Hirsutism: base on the mFG hirsutism score; OC: oral contraceptives; OC + TRF: oral contraceptives + time-restricted feeding. Endocrine fertility indices, glucose, lipid, and blood pressure LH, TT, LH/FSH ratio, and hirsutism in both groups showed a decreasing trend after the intervention; OC + TRF was better for acne than OC alone, but OC was superior for alopecia, with no substantial between-group differences for all the endocrine fertility indexes. (Fig. 3b and Table 3 ). FPG showed a decreasing trend after OC intervention, however, there were no significant differences in FPG and insulin resistance between the two groups. After the OC + TRF intervention, FINS significantly decreased, with inter-group differences ( P = 0.032; Fig. 3c and Table 3 ). Both OC + TRF and OC were associated with increased TC, TG, and HDL-C levels over 3 months, with no significant difference in lipid metabolism between the groups (Fig. 3e and Table 3 ). The systolic and diastolic blood pressures were similar between the two groups during the 3 months of the trial (Fig. 3f and Table 3 ). Safety evaluation After 12 weeks of intervention, ALT decreased significantly in both groups compared to baseline, whereas AST and CRE showed no significant changes. Neither method resulted in obvious liver or kidney damage (Fig. 3d). Adverse events No deaths or serious adverse events occurred during the study period. The incidence of mild adverse events (vaginal spotting, dizziness, indigestion, and constipation) was similar between the two groups (Table 4 ). Table 4. Comparison of adverse events between the two groups AEs N (%) of participants P OC(N = 64) OC + TRF(N = 62) Vaginal spotting 11 (17.2) 13 (16.1) 0.589 Dizziness 9 (14.1) 12 (19.4) 0.425 Indigestion 5 (7.8) 8 (12.9) 0.348 Constipation 6 (9.4) 7 (11.3) 0.677 Shown are the number of patients with at least one serious adverse event that occurred during the 12-week intervention. AEs: adverse events; OC: oral contraceptives; OC + TRF: oral contraceptives + time-restricted feeding. COMMENT Principal findings This is one of the few studies focusing on the rate of ovulation recovery in patients with PCOS. Compared with short-acting OC alone, patients with PCOS had a significantly higher spontaneous ovulation rate when combined with 8-hour time-restricted eating. This effect was more pronounced in the insulin-resistant groups. After adjusting for interference from HOMA-IR, WHR, and age by logistic regression, TRF remained an independent promoter of PCOS ovulation recovery; TRF combined with OC increased the odds of spontaneous ovulation recovery by 2.192 times compared to OC alone. Results in the context of what is known The mechanism by which TRF might promote the ovulation rate in patients with PCOS is analyzed; steroid hormone secretion is regulated by the biological clock. It is well known that abnormal LH pulse rate and an androgen hypersecretion state are key factors in reduced ovulation and infertility in patients with PCOS. 15,16 From this study's results, compared to OC treatment alone, OC + TRF has more advantages in reducing TT and acne. TRF may improve PCOS symptoms by regulating melatonin levels via the circadian clock. Melatonin plays an important role in circadian rhythms, with receptors present in several female reproductive organs. 17 The loss of melatonin receptors and disruption of circadian clock genes lead to metabolic syndrome, obesity, and diabetes. 18 A retrospective clinical trial showed that menstrual cycles and androgen levels improved in 95% of women with PCOS after 6 months of melatonin treatment. 19 In summary, we believe that TRF regulates the circadian rhythm of patients with PCOS, thereby affecting steroid hormone secretion and ultimately improving anovulation and signs of hyperandrogenism. Obesity is a key contributor toward metabolic comorbidities in women with PCOS. Weight loss is purported to benefit the female reproductive system by reducing androgen levels, regulating menstruation, and promoting ovulation. 20 Hu and Ma retrospectively analyzed the differences in efficacy between bariatric surgery and medication in patients with obesity PCOS. 21 The results showed that 95% of patients with a BMI below the critical value achieved complete remission of hyperandrogenism, polycystic ovarian changes, irregular menstruation, and other symptoms. Hu and Ma concluded that complete symptom remission in patients with obesity and PCOS depends on the final BMI after weight loss. In this study, patients with PCOS who were overweight or obese (BMI ≥ 25 kg/m 2 ) were divided into subgroups by the World Health Organization BMI classification criteria. TRF intervention results in an increased rate of ovulation recovery in patients with PCOS (especially those who are overweight or obese). This may be because overweight or obese individuals were more likely to normalize their BMI after the TRF intervention, whereas the cause of ovulation disorders in normal or lean patients with PCOS may not be related to body weight or BMI; therefore, TRF showed no obvious effect. Another cross-sectional study involving over 250 women with infertility who were overweight or obese showed that WC was the strongest predictor of infrequent ovulation in reproductive-aged women, independent of other parameters, such as hyperinsulinemia and insulin resistance. 20 Thus, the reduction of abdominal fat is particularly important for ovulation recovery. Single-factor regression analysis showed that increased BF% and WC reduced the probability of ovulation recovery, which is consistent with previous studies. 22 We also found that the OC + TRF intervention significantly increased ovulation rates in patients with a WC of ≥ 80 cm, compared to the OC group (70.8% vs. 36%, P = 0.017). This could be related to the significant reduction in WC after intervention in the OC + TRF group. When comparing the changes in glucose metabolism indicators between the two groups through covariance analysis, the results showed that the OC + TRF group had an advantage in reducing FINS compared to the OC group, but there was no difference in FPG, which was similar to the results of previous studies. Two randomized control trials 7,23 demonstrated that 4, 6, and 8 h of time-restricted eating over 8 weeks significantly reduced FINS. In another randomized control trial of patients who were overweight or obese, Lowe 24 found that a 16:8 TRF (self-selected eating time) did not significantly change fasting glucose levels. In our subgroup analysis, 4 out of 5 subgroups showed an advantage in ovulation rate for the OC + TRF group compared to the OC group. The remaining subgroup (insulin resistant or not) showed significant differences ( P = 0.001 for heterogeneity). These findings may have been due to chance or influenced by the sample size. Multiple studies have found that an imbalanced diet with nighttime eating promotes body weight gain and metabolic dysfunction. 25,26 Lipid metabolism also follows a circadian rhythm. 27 According to this study's results, all participants showed an upward trend in HDL-C, TC, and TG levels after 12 weeks of treatment. OC + TRF slightly decreased the LDL-C levels in patients with PCOS, but the difference was not statistically significant. This is inconsistent with related literature reporting that TRF may promote fat reduction and decrease TC, TG, and LDL-C levels in long-term studies. 28,29 Based on this study, it may be because all patients underwent OC treatment simultaneously. It may be concluded that long-term use of OCs can elevate TG and HDL-C levels in patients with PCOS but with no significant change in TC and LDL-C. 30 Our results indicate a combined time-restricted diet may help improve the decrease in LDL-C, but this was not statistically significant, and further research is needed. Strengths and limitations The strengths of this trial include being the first randomized controlled trial of OC treatment combined with TRF for improving the ovulation rate in patients with PCOS, confirming the importance of TRF for ovulation. High adherence to assignments also strengthened the study. The limitations of this study include a lack of detailed records and classification of individual eating times, and no comparative analysis of participants' dietary structure and total intake before and after. Potential bias from participants' compliance in implementing TRF cannot be ruled out, thereby affecting the study results. The study only measured common laboratory indicators and lacked an in-depth analysis of molecular biology and cytology. Conclusions Our study showed that TRF has a good weight loss effect in patients who are overweight or obese with PCOS, and when combined with OC treatment, can significantly increase the ovulation rate and improve fertility. This dietary pattern is simple, safe, and economical, and does not require deliberate changes to inherent dietary habits. The long-term adherence and acceptance of TRF make it worthy of use in patients with PCOS. Abbreviations PCOS polycystic ovary syndrome PCOM polycystic ovarian morphology TRF time-restricted feeding FSH follicle-stimulating hormone LH luteotropic hormone TT total testosterone BMI body mass index BF body fat IR insulin resistance WC waist circumference HC hip circumference WHR waist-to-hip ratio FPG fasting plasma glucose FINS fasting insulin HOMA-IR homeostasis model assessment insulinresistance TG triglyceride TC total cholesterol HDL-C high density lipoprotein cholesterol LDL-C low density lipoprotein cholesterol UA uric acid CRE creatinine AST aspartate transaminase ALT alanine aminotransferase OR odds ratio CI confidence interval. Declarations Sources of funding: This study was supported by the Foshan science and Technology Bureau (Grant No. 222000100381), the Natural science Foundation of Guangdong Province (Grant No. 2024A1515013145), the Foshan Engineering Technology Research center (Grant No. 2420001000333), the Basic and Applied Basic Research Foundation of Guangdong Province (Grant No. 2023A1515140165) and the Basic and Applied Basic Research Foundation of Guangdong Province (Grant No. 2021A1515111176). Conflicts of interest There are no competing interests of declare. Author contributions MZ: Data curation, Visualization, Writing-original draft. DL: Software, Supervision, Writing - original draft.YL: Conceptualization, Methodology, Writing - original draft. PZ: Funding acquisition, Investigation, Writing - original draft. WL: Project administration, Resources. LK: Data curation, Formal analysis, Project administration, Software. YL: Data curation, Investigation, Methodology. SW: Supervision, Visualization. SZ: Project administration, Supervision, Writing - review & editing. LL: onceptualization, Supervision, Writing - original draft, Writing - review & editing. Acknowledgments We gratefully acknowledge the financial support provided by the Natural science Foundation of Guangdong Province (Grant No. 2024A1515013145). We are also indebted to the experts who generously shared their insights and expertise ring the online survey. References Teede HJ, Misso ML, Costello MF, et al. Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome. Fertil Steril. 2018;110(3):364–79. 10.1016/j.fertnstert.2018.05.004 . Ravussin E, Beyl RA, Poggiogalle E, Hsia DS, Peterson CM. Early time-restricted feeding reduces appetite and increases fat oxidation but does not affect energy expenditure in humans. Obesity. 2019;27(8):1244–54. 10.1002/oby.22518 . Xie Z, Sun Y, Ye Y, et al. Randomized controlled trial for time-restricted eating in healthy volunteers without obesity. Nat Commun. 2022;13(1):1003. 10.1038/s41467-022-28662-5 . Parr EB, Devlin BL, Radford BE, Hawley JA. A delayed morning and earlier evening time-restricted feeding protocol for improving glycemic control and dietary adherence in men with overweight/obesity: A randomized controlled trial. Nutrients. 2020;12(2):505. 10.3390/nu12020505 . Sutton EF, Beyl R, Early KS, Cefalu WT, Ravussin E, Peterson CM. Early time-restricted feeding improves insulin sensitivity, blood pressure, and oxidative stress even without weight loss in men with prediabetes. Cell Metab. 2018;27(6):1212–e12213. 10.1016/j.cmet.2018.04.010 . Obermayer A, Tripolt NJ, Pferschy PN, et al. Efficacy and safety of intermittent fasting in people with insulin-treated type 2 diabetes (INTERFAST-2)—a randomized controlled trial. Diabetes Care. 2023;46(2):463–8. 10.2337/dc22-1622 . Cienfuegos S, Gabel K, Kalam F, et al. Effects of 4- and 6-h time-restricted feeding on weight and cardiometabolic health: A randomized controlled trial in adults with obesity. Cell Metab. 2020;32(3):366–e3783. 10.1016/j.cmet.2020.06.018 . Colonna L, Pacifico V, Lello S, Sorge R, Raskovic D, Primavera G. Skin improvement with two different oestroprogestins in patients affected by acne and polycystic ovary syndrome: Clinical and instrumental evaluation. J Eur Acad Dermatol Venereol. 2012;26(11):1364–71. 10.1111/j.1468-3083.2011.04292.x . Li R, Qiao J, Yang D, et al. Epidemiology of hirsutism among women of reproductive age in the community: A simplified scoring system. Eur J Obstet Gyn R B. 2012;163(2):165–9. 10.1016/j.ejogrb.2012.03.023 . Kanti V, Messenger A, Dobos G, et al. Evidence-based (S3) guideline for the treatment of androgenetic alopecia in women and in men – short version. J Eur Acad Dermatol Venereol. 2018;32(1):11–22. 10.1111/jdv.14624 . Aydin T, Koroglu N, Albayrak N, Insel MA. 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Wang D, Weng Y, Zhang Y, et al. Exposure to hyperandrogen drives ovarian dysfunction and fibrosis by activating the NLRP3 inflammasome in mice. Sci Total Environ. 2020;745:141049. 10.1016/j.scitotenv.2020.141049 . Reiter R, Tan D, Rosales-Corral S, Galano A, Zhou X, Xu B. Mitochondria: Central organelles for melatonin′s antioxidant and anti-aging actions. Molecules. 2018;23(2):509. 10.3390/molecules23020509 . Depner CM, Melanson EL, McHill AW, Wright KP. Mistimed food intake and sleep alters 24-hour time-of-day patterns of the human plasma proteome. Proc Natl Acad Sci. 2018;115(23). 10.1073/pnas.1714813115 . Tagliaferri V, Romualdi D, Scarinci E, et al. Melatonin treatment may be able to restore menstrual cyclicity in women with PCOS: A pilot study. Reprod Sci. 2018;25(2):269–75. 10.1177/1933719117711262 . Silvestris E, De Pergola G, Rosania R, Loverro G. Obesity as disruptor of the female fertility. Reprod Biol Endocrinol. 2018;16(1):22. 10.1186/s12958-018-0336-z . Hu L, Ma L, Xia X, et al. Efficacy of bariatric surgery in the treatment of women with obesity and polycystic ovary syndrome. J Clin Endocrinol Metab. 2022;107(8):e3217–29. 10.1210/clinem/dgac294 . Feyzioglu BS, Güven CM, Avul Z. Eight-hour time-restricted feeding: A strong candidate diet protocol for first-line therapy in polycystic ovary syndrome. Nutrients. 2023;15(10):2260. 10.3390/nu15102260 . Jamshed H, Steger FL, Bryan DR, et al. Effectiveness of early time-restricted eating for weight loss, fat loss, and cardiometabolic health in adults with obesity: A randomized clinical trial. JAMA Intern Med. 2022;182(9):953. 10.1001/jamainternmed.2022.3050 . Lowe DA, Wu N, Rohdin-Bibby L, et al. Effects of time-restricted eating on weight loss and other metabolic parameters in women and men with overweight and obesity: The TREAT randomized clinical trial. JAMA Intern Med. 2020;180(11):1491. 10.1001/jamainternmed.2020.4153 . Hibi M, Masumoto A, Naito Y, et al. Nighttime snacking reduces whole body fat oxidation and increases LDL cholesterol in healthy young women. Am J Physiol Regul Integr Comp Physiol. 2013;304(2):R94–101. 10.1152/ajpregu.00115.2012 . Ruan W, Yuan X, Eltzschig HK. Circadian rhythm as a therapeutic target. Nat Rev Drug Discovery. 2021;20(4):287–307. 10.1038/s41573-020-00109-w . Poggiogalle E, Jamshed H, Peterson CM. Circadian regulation of glucose, lipid, and energy metabolism in humans. Metabolis. 2018;84:11–27. 10.1016/j.metabol.2017.11.017 . Moro T, Tinsley G, Bianco A, et al. Effects of eight weeks of time-restricted feeding (16/8) on basal metabolism, maximal strength, body composition, inflammation, and cardiovascular risk factors in resistance-trained males. J Transl Med. 2016;14(1):290. 10.1186/s12967-016-1044-0 . Liu D, Huang Y, Huang C, et al. Calorie restriction with or without time-restricted eating in weight loss. N Engl J Med. 2022;386(16):1495–504. 10.1056/NEJMoa2114833 . Halperin IJ, Sujana Kumar S, Stroup DF, Laredo SE. The association between the combined oral contraceptive pill and insulin resistance, dysglycemia and dyslipidemia in women with polycystic ovary syndrome: A systematic review and meta-analysis of observational studies. Hum Reprod. 2011;26(1):191–201. 10.1093/humrep/deq301 . Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4738766","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":330920495,"identity":"3a4d67bc-1001-43e1-a01d-7da0055b0882","order_by":0,"name":"Minshan Zhu","email":"","orcid":"","institution":"First People's Hospital of Foshan","correspondingAuthor":false,"prefix":"","firstName":"Minshan","middleName":"","lastName":"Zhu","suffix":""},{"id":330920496,"identity":"c081ac01-eb59-4576-a954-854c5646a971","order_by":1,"name":"Dong Liang","email":"","orcid":"","institution":"First People's Hospital of Foshan","correspondingAuthor":false,"prefix":"","firstName":"Dong","middleName":"","lastName":"Liang","suffix":""},{"id":330920497,"identity":"71a1ffed-cb19-4561-aa35-12437f1774c2","order_by":2,"name":"Yuan Li","email":"","orcid":"","institution":"First People's Hospital of Foshan","correspondingAuthor":false,"prefix":"","firstName":"Yuan","middleName":"","lastName":"Li","suffix":""},{"id":330920498,"identity":"7f58e05a-e91a-4d45-ad61-38f96b9c6f0e","order_by":3,"name":"Peiwen Zhong","email":"","orcid":"","institution":"First People's Hospital of Foshan","correspondingAuthor":false,"prefix":"","firstName":"Peiwen","middleName":"","lastName":"Zhong","suffix":""},{"id":330920499,"identity":"3ff36764-c46a-4040-8baa-b0da5423cec1","order_by":4,"name":"Weiru Li","email":"","orcid":"","institution":"First People's Hospital of Foshan","correspondingAuthor":false,"prefix":"","firstName":"Weiru","middleName":"","lastName":"Li","suffix":""},{"id":330920500,"identity":"74f3cf6d-5283-499a-9ce8-199f26ecbc53","order_by":5,"name":"Liyun Kuang","email":"","orcid":"","institution":"First People's Hospital of Foshan","correspondingAuthor":false,"prefix":"","firstName":"Liyun","middleName":"","lastName":"Kuang","suffix":""},{"id":330920501,"identity":"94893907-158a-46c8-bd5e-0da2e0a84df6","order_by":6,"name":"Yanting Lin","email":"","orcid":"","institution":"First People's Hospital of Foshan","correspondingAuthor":false,"prefix":"","firstName":"Yanting","middleName":"","lastName":"Lin","suffix":""},{"id":330920502,"identity":"6dfba0f9-a594-47c1-8ba4-6df1b6458ca3","order_by":7,"name":"Shengfu Wang","email":"","orcid":"","institution":"First People's Hospital of Foshan","correspondingAuthor":false,"prefix":"","firstName":"Shengfu","middleName":"","lastName":"Wang","suffix":""},{"id":330920503,"identity":"780cfd19-9556-49d3-895e-f86ece9ecf0b","order_by":8,"name":"Siyou Zhang","email":"","orcid":"","institution":"First People's Hospital of Foshan","correspondingAuthor":false,"prefix":"","firstName":"Siyou","middleName":"","lastName":"Zhang","suffix":""},{"id":330920504,"identity":"45d884ae-af56-4c16-854a-1a3e8d5e91dd","order_by":9,"name":"Li Li","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAu0lEQVRIiWNgGAWjYBACPmbmhgMMBmw8/OyNjQ8/EKOFjZkRqKWAT06y53CzsQRRWhgYGxgYPsgZG8xIbxPgIUoLO2Mj0GFmiRskH7YxSDDYyek2EOUwg7TE7dKJbQ8KGJKNzQ4QoeXwH4NjiTtnJ7YbSDAcSNxGjBagLf8TN9w82CbBQ4IWNmODG4wkagEGciIwkA2I8As//+HDHxj+gKLy+MOHHyrs5AhqQQMGpCkfBaNgFIyCUYADAACzHD3o2wi4PAAAAABJRU5ErkJggg==","orcid":"","institution":"Guangdong Women and Children Hospital","correspondingAuthor":true,"prefix":"","firstName":"Li","middleName":"","lastName":"Li","suffix":""}],"badges":[],"createdAt":"2024-07-14 14:13:45","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4738766/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4738766/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":63285311,"identity":"0e853b0c-ae7c-46c7-bc4a-5310f29130a1","added_by":"auto","created_at":"2024-08-26 13:38:27","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":185045,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFlowchart of the study design\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-4738766/v1/2ebc1ac6a1ccad910e9ad305.png"},{"id":63286583,"identity":"fa036b92-8e8a-4d2d-b625-a757f1f8cc73","added_by":"auto","created_at":"2024-08-26 13:46:27","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":257018,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eOdds Ratio and Rates of Ovulation by Subgroups in Study Participants\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOC: oral contraceptives; OC+TRF: oral contraceptives + time-restricted feeding; BMI: body mass index; WC: waist circumference; HOMA-IR: hHomeostasis model assessment-insulin resistance; a: IDF metabolic syndrome world-wide definition\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-4738766/v1/f762ed5d2232a299d95b55e6.png"},{"id":63285313,"identity":"b49efe85-ff3a-41e2-90c6-4e2ec46cce1c","added_by":"auto","created_at":"2024-08-26 13:38:27","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":769150,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eIntra-group comparison \u0026nbsp;\u0026nbsp;of Anthropometric and Metabolic Factors\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e(a) \u0026nbsp;\u0026nbsp;Change in weight, body mass index (BMI), body fat (BF), waist circumference \u0026nbsp;\u0026nbsp;(WC), hip circumference (HC), and waist-to-hip ratio (WHR) over 12 weeks;\u003c/p\u003e\n\u003cp\u003e(b) \u0026nbsp;\u0026nbsp;Change in luteinizing hormone (LH), LH/FSH, total testosterone (TT), Acnnce \u0026nbsp;\u0026nbsp;score, Alopecia score, and Hirsutism score over 12 weeks12weeks;\u003c/p\u003e\n\u003cp\u003e(c) \u0026nbsp;\u0026nbsp;Change in fasting plasma glucose (FPG), fasting insulin (FINS), Homeostasis \u0026nbsp;\u0026nbsp;model assessment-insulin resistance (HOMA-IR) over 12 weeks;\u003c/p\u003e\n\u003cp\u003e(d) \u0026nbsp;\u0026nbsp;Change in glutamic pyruvic transaminase (ALT), glutamic oxaloacetic \u0026nbsp;\u0026nbsp;transaminase (AST), creatinine (CRE) over 12 weeks;\u003c/p\u003e\n\u003cp\u003e(e) \u0026nbsp;\u0026nbsp;Change in total cholesterol (TC), triglycerides (TG), high-density \u0026nbsp;\u0026nbsp;lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol \u0026nbsp;\u0026nbsp;(LDL-C) over 12 weeks;\u003c/p\u003e\n\u003cp\u003e(f) \u0026nbsp;\u0026nbsp;Change in systolic and diastole blood pressure (SBP, DBP) over 12 weeks;\u003c/p\u003e\n\u003cp\u003e(g) \u0026nbsp;\u0026nbsp;Change in body weight percentage over 12 weeks;\u003c/p\u003e\n\u003cp\u003eOC: \u0026nbsp;\u0026nbsp;oral contraceptives; OC+TRF: oral contraceptives + time-restricted feeding; \u0026nbsp;\u0026nbsp;FSH: follicle-stimulating hormone; Acnnce: based on the Pillsbury acne score; \u0026nbsp;\u0026nbsp;Alopecia: based on the Ludwig alopecia grade; Hirsutism: based on the mF-G \u0026nbsp;\u0026nbsp;hirsutism score.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-4738766/v1/e014768e3a7b8587d87f2a36.png"},{"id":63289162,"identity":"b8cb0575-7f76-49a8-94d1-45c12c4fcb35","added_by":"auto","created_at":"2024-08-26 14:02:37","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3766268,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4738766/v1/9f077ee5-cfb7-4fef-b4fa-3e0aa0713540.pdf"}],"financialInterests":"","formattedTitle":"Effect of time-restricted feeding combined with oral contraceptives on polycystic ovary syndrome: An open-label, randomized trial","fulltext":[{"header":"Highlights","content":"\u003cul\u003e\n\u003cli\u003eTime-restricted feeding promotes ovulation recovery in polycystic ovary syndrome.\u003c/li\u003e\n\u003cli\u003eInsulin resistance improved with time-restricted feeding in polycystic ovary syndrome.\u003c/li\u003e\n\u003cli\u003eTime-restricted feeding reduces weight and waist circumference in polycystic ovary syndrome.\u003c/li\u003e\n\u003cli\u003eNovel strategy for polycystic ovary syndrome management: diet and medication synergy.\u003c/li\u003e\n\u003c/ul\u003e"},{"header":"INTRODUCTION","content":"\u003cp\u003ePolycystic ovary syndrome (PCOS) is a common gynecological endocrine disorder that affects women of reproductive age and is characterized by hyperandrogenism and menstrual irregularities (anovulation or infrequent ovulation). Treatment with oral contraceptives (OC) is preferred owing to their efficacy in treating hirsutism and creating predictable menstrual cycles.\u003csup\u003e1\u003c/sup\u003e However, pretreatment with OC has poor effects on promoting ovulation, weight loss, and improving glucose and lipid metabolism, with post-withdrawal symptom recurrence. Thus, effective long-term lifestyle interventions are especially important for the treatment of PCOS.\u003c/p\u003e \u003cp\u003eTime-restricted feeding (TRF) is a type of intermittent fasting that has garnered increasing public and medical interest owing to its efficacy and ease of adherence. TRF has shown positive effects on obesity and type 2 diabetes mellitus. Long-term weight management in obesity involves increasing ghrelin levels to control appetite.\u003csup\u003e2\u003c/sup\u003e TRF can also improve metabolism and activity, thereby boosting energy expenditure.\u003csup\u003e3\u003c/sup\u003e Moreover, dietary changes can enhance the feelings of hunger and satiety.\u003csup\u003e4,5\u003c/sup\u003e TRF reduces fasting blood glucose and glycosylated hemoglobin in type 2 diabetics.\u003csup\u003e6\u003c/sup\u003e Furthermore, TRF decreases fasting insulin (FINS) and homeostatic model assessment for insulin resistance (HOMA-IR) in non-diabetic obese/overweight patients.\u003csup\u003e7\u003c/sup\u003e However, studies on TRF in patients with PCOS and metabolic disorders are limited.\u003c/p\u003e \u003cp\u003eWe conducted a randomized trial comparing combined TRF with short-acting OC use versus OC use alone on the ovulation rate, weight, and glucose and lipid metabolism in women with PCOS.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design\u003c/h2\u003e \u003cp\u003eThis was a single-center, open-label, prospective, randomized controlled clinical trial. No protocol modifications or interim analyses were conducted following trial initiation.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eEthics\u003c/h2\u003e \u003cp\u003eThe trial was approved by the Ethics Committee of the First People's Hospital of Foshan, Guangdong, China (Lunshenyan [2022] No. 17) and registered with Chictr.org.cn (ChiCTR2300078263). All patients received the full study information and were given opportunities to ask questions before providing written consent.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eParticipants\u003c/h2\u003e \u003cp\u003eThe study population comprised female patients with PCOS who sought medical treatment at the First People's Hospital of Foshan from January 2022 to August 2023. Eligible outpatients were recruited by the same team of endocrinologists in the gynecology department.\u003c/p\u003e \u003cp\u003eThe inclusion criteria were: age 18\u0026ndash;40 years and a PCOS diagnosis based on the Rotterdam criteria (oligomenorrhea or amenorrhea, along with clinical or biochemical hyperandrogenism and/or polycystic ovaries).\u003csup\u003e1\u003c/sup\u003e The exclusion criteria included other diseases (e.g., congenital adrenal hyperplasia, Cushing syndrome, androgen-secreting tumors, diabetes, thyroid, and gastrointestinal diseases), use of medication impacting carbohydrate or lipid metabolism (insulin, oral hypoglycemic agents, indomethacin, furosemide, glucocorticoids, OC pills) within 3 months, pregnancy preparation, pregnancy or lactation, uncontrolled mental disorder (including history of hospitalization for mental illness), and currently attending weight loss or weight management classes.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eRandomization and masking\u003c/h2\u003e \u003cp\u003eA statistician not involved in the research or data analysis used Microsoft Excel (Microsoft, Redmond, WA, USA) to generate a random number table. A two-zone randomization technique was employed for electronic treatment allocation spreadsheets. Patients meeting the inclusion criteria and willing to participate were randomly assigned 1:1 to the OC (control) or OC\u0026thinsp;+\u0026thinsp;TRF (trial) groups by another investigator not involved in recruitment, based on the patients' consecutive randomization numbers. Owing to the nature of the intervention, an open-label approach was used, wherein detailed dietary intervention instructions and regular supervision were provided to the trial group, whereas the other group had no strict dietary requirements.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eProcedures\u003c/h2\u003e \u003cp\u003eIncluding patients lost to follow-up and those not completing the intervention measures, a total of 126 were enrolled, of which 64 were in the OC group and 62 were in the OC\u0026thinsp;+\u0026thinsp;TRF group.\u003c/p\u003e \u003cp\u003eFor each participant, body weight and height were measured to calculate the body mass index (BMI; weight [kg] divided by height squared [m\u003csup\u003e2\u003c/sup\u003e]; kg/m\u003csup\u003e2\u003c/sup\u003e). Height was measured to the nearest 1 cm using a wall-mounted stadiometer (Seca 711; Hamburg, Germany). A BMI of 25\u0026thinsp;\u0026le;\u0026thinsp;and \u0026lt;\u0026thinsp;30 kg/m\u003csup\u003e2\u003c/sup\u003e was defined as overweight, and BMI\u0026thinsp;\u0026ge;\u0026thinsp;30 kg/m\u003csup\u003e2\u003c/sup\u003e was defined as obesity. Waist circumference (WC) (cm) and Hip circumference (HC) (cm) were measured by the same nurse. The waist-to-hip ratio (WHR) was calculated using these measurements. Body fat percentage (BF%) = (WC (cm)* 0.74-weight (kg) * 0.082\u0026ndash;34.89)/weight (kg) \u0026times; 100.\u003c/p\u003e \u003cp\u003eHyperandrogenic manifestations included the Pillsbury acne score, modified Ferriman\u0026ndash;Gallwey (mFG) hirsutism score, and Ludwig alopecia grade; a hyperandrogenism diagnosis was established if two or more were present. The Pillsbury acne score\u003csup\u003e8\u003c/sup\u003e was categorized as mild (grade I), mainly comedones, non-inflammatory, fewer than 30; moderate (grade II), inflammatory papules, 30\u0026ndash;50; moderate (grade Ⅲ), 50\u0026ndash;100 pustules; and severe (grade IV), nodules, and cysts, more than 100. The mFG hirsutism score assesses 9 body areas.\u003csup\u003e9\u003c/sup\u003e Chinese women with a score of \u0026ge;\u0026thinsp;8 points were diagnosed with hirsutism. The Ludwig classification of alopecia\u003csup\u003e10\u003c/sup\u003e is as follows: grade I (mild alopecia), primarily affecting the parietal and coronal regions, with the forehead hairline remaining 1\u0026ndash;3 cm wide; grade II (moderate alopecia), the hair in the head and crown area was thinner than in grade I; grade III (severe alopecia), complete hair loss in the crown area.\u003c/p\u003e \u003cp\u003eFasting blood samples were collected on the 3rd to 5th day of menstruation before and after the intervention. Luteinizing hormone (LH) (IU/L), total testosterone (TT) (nmol/L) and follicle-stimulating hormone (FSH) (IU/L) were measured by chemiluminescent immunoassay, fasting plasma glucose (FPG) (mmol/L) by the hexokinase method, FINS (mIU/L) by radioimmunological assay, uric acid (UA) (umol/L) by the uricase-PAP method, total cholesterol (TC) (mmol/L) by the cholesterol oxidase method, triglycerides (TG) (mmol/L) by the deionization \u0026amp; enzyme method, creatinine (CRE) (\u0026micro;mol/L) by the creatinase method, high-density lipoprotein cholesterol (HDL-C) (mmol/L) and low-density lipoprotein cholesterol (LDL-C) (mmol/L) by the direct one-step method, and glutamic oxaloacetic transaminase (AST) (IU/L) and glutamic pyruvic transaminase (ALT) (IU/L) by the rate method. HOMA-IR was calculated according to the formula: FINS (mIU/L)\u0026times; FPG (mmol/L)/22.5.\u003c/p\u003e \u003cp\u003ePatients in the OC group received drospirenone and ethinylestradiol II (Bayer Weimar GmbH und Co.KG, Leverkusen, Germany; 0.02 mg ethinylestradiol and 3.00 mg drospirenone) starting on the first day of menses, 1 pill/day, continuously for 12 weeks (3 boxes total). The patients were informed orally about their regular diet and weight control (excluding weight-loss drugs). Amenorrheic patients were treated with oral dydrogesterone tablets (Abbott Biologicals B.V., Veenendaal, The Netherlands; 10 mg dydrogesterone), one tablet twice daily, followed by drospirenone and ethinylestradiol II on the first day of menses. Patients in the OC\u0026thinsp;+\u0026thinsp;TRF group took drospirenone and ethinylestradiol II regularly and adhered to a strict 8-hour time-restricted dietary pattern for 12 weeks. They were instructed not to change the composition of their daily diet but to eat freely for only 8 hours a day (8 am to 4 pm) and fast for the remaining time (4 pm to 8 am). Only water or non-caloric beverages were allowed during the 16-hour fast; adequate water intake (2,000 mL/day) was encouraged throughout the intervention. The exercise routine of the patients was not defined, and a WeChat group was established for each group. During the experiment, gynecologists supervised the patients' diet implementation every 1\u0026ndash;2 weeks, monitored adverse events, and provided professional support and guidance to promote compliance with the intervention measures.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eOutcomes\u003c/h2\u003e \u003cp\u003eThe primary outcome was the restoration of spontaneous ovulation following cessation of the intervention. Both groups discontinued treatment after 12 weeks and were monitored for post-cessation ovulation. Two methods were used to determine spontaneous ovulation. (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) Blood samples were collected on days 21, 28, and 35 post-cessation to measure progesterone and estradiol levels. Estradiol levels above 200 ng/L indicated follicular development, while progesterone levels above 3 ug/L indicated spontaneous ovulation.\u003csup\u003e11\u003c/sup\u003e If a patient exhibited spontaneous ovulation on the first blood draw (i.e., day 21 post-cessation), subsequent draws were omitted. If a patient showed no increase in estradiol or progesterone levels across all three blood draws, progestin (e.g., oral dydrogesterone) was administered to induce menstruation. (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) Ultrasound monitoring of ovulation began on day 10 post-cessation of menstruation, with follow-up ultrasounds every 1\u0026ndash;2 days based on follicle size until follicular development and ovulation were observed, confirming the diagnosis of spontaneous ovulation.\u003c/p\u003e \u003cp\u003eSecondary outcomes included body composition-related indicators (body weight, BMI, BF%, WC, and WHR), blood pressure, fertility endocrine indices (hirsutism, acne, alopecia, LH, and TT), and glucose and lipid metabolism indicators (FPG, FINS, HOMA-IR, TC, TG, HDL-C, LDL-C, and UA) before and after the intervention.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eBased on the literature, the ovulation restoration rate after a 3-month OC intervention for patients with PCOS is 32.8\u0026ndash;54.7%.\u003csup\u003e12\u003c/sup\u003e The ovulation rate in the group that received OC and lifestyle guidance was 64.3%. The ovulation rate in the trial group was expected to be 70%. Using PASS (NCSS, Kaysville, UT, USA) software to estimate sample size, with a normal approximation, with parameters including two-tailed test (α\u0026thinsp;=\u0026thinsp;0.05, power\u0026thinsp;=\u0026thinsp;90%). The control and experimental groups each required 56 patients, and taking into consideration a 20% dropout rate, each group had 70 patients, for a total of 140 patients.\u003c/p\u003e \u003cp\u003eData were analyzed according to the intention-to-treat principle. Statistical analyses were conducted using SPSS (version 20.0; IBM Corp., Armonk, NY, USA). Missing data were analyzed using multiple imputation methods. The Kolmogorov\u0026ndash;Smirnov test was used to evaluate whether continuous data followed a normal distribution. Data following a normal distribution is represented by mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation, and comparisons within and between groups were conducted using a t-test. Data that did not follow a normal distribution are represented as the median (interquartile range) using the Mann\u0026ndash;Whitney U test. Categorical variables are presented as counts or percentages, and the chi-square test or Fisher's exact test was used for categorical data. Differences among groups were compared using covariance analysis, and the values for the average difference and 95% confidence intervals were estimated using the least-squares method. Variables were screened for inclusion in multivariate logistic regression using single-factor logistic regression analysis. Factors affecting patient intervention termination and subsequent resumption of ovulation were analyzed using multivariate logistic regression. The results were considered statistically significant at \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05 for both sides.\u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\n\u003ch2\u003eTrial participants\u003c/h2\u003e\n\u003cp\u003eScreening appointments ran from January 30, 2022, to August 31, 2023, with randomizations continuing until September 2023 and a final follow-up in December 2023. A total of 126 patients were randomly assigned to either the OC\u0026thinsp;+\u0026thinsp;TRF (n\u0026thinsp;=\u0026thinsp;62) or OC (n\u0026thinsp;=\u0026thinsp;64) groups. Figure\u0026nbsp;1 shows the flow of study participants. In the OC\u0026thinsp;+\u0026thinsp;TRF group, 56 participants (90.3%) completed the 70-day intervention and 52 (83.9%) completed the 80-day intervention (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). There were no significant differences in age, body type, metabolic disorder characteristics, and PCOS characteristics between the two groups.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u0026nbsp;\u003cstrong\u003e\u003cbr /\u003e \u003c/strong\u003e\n\u003ctable id=\"Tab1\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eCharacteristics of the Participants at Baseline\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd width=\"41%\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"20%\"\u003e\n\u003cp\u003e\u003cstrong\u003eOC (n=64)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"28%\"\u003e\n\u003cp\u003e\u003cstrong\u003eOC+TRF (n=62)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"9%\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eP\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"41%\"\u003e\n\u003cp\u003eAge (years)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"20%\"\u003e\n\u003cp\u003e26.3\u0026plusmn;4.4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"28%\"\u003e\n\u003cp\u003e26.2\u0026plusmn;4.8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"9%\"\u003e\n\u003cp\u003e0.915\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"41%\"\u003e\n\u003cp\u003eBody size [N(%)]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"20%\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"28%\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"9%\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"41%\"\u003e\n\u003cp\u003eBMI\u0026ge;30 kg/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"20%\"\u003e\n\u003cp\u003e7 (10.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"28%\"\u003e\n\u003cp\u003e10 (16.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"9%\"\u003e\n\u003cp\u003e0.394\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"41%\"\u003e\n\u003cp\u003e25\u0026le;BMI＜30 kg/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"20%\"\u003e\n\u003cp\u003e19 (29.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"28%\"\u003e\n\u003cp\u003e17 (27.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"9%\"\u003e\n\u003cp\u003e0.423\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"41%\"\u003e\n\u003cp\u003eBMI＜25 kg/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"20%\"\u003e\n\u003cp\u003e38 (59.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"28%\"\u003e\n\u003cp\u003e35 (56.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"9%\"\u003e\n\u003cp\u003e0.740\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"41%\"\u003e\n\u003cp\u003eWC\u0026ge;80 cm\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"20%\"\u003e\n\u003cp\u003e25 (39.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"28%\"\u003e\n\u003cp\u003e24 (38.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"9%\"\u003e\n\u003cp\u003e0.968\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"41%\"\u003e\n\u003cp\u003eMetabolic Risk Factors [N(%)]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"20%\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"28%\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"9%\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"41%\"\u003e\n\u003cp\u003eBP\u0026ge;130/85 mmHg \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"20%\"\u003e\n\u003cp\u003e11 (17.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"28%\"\u003e\n\u003cp\u003e14 (22.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"9%\"\u003e\n\u003cp\u003e0.448\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"41%\"\u003e\n\u003cp\u003eUA\u0026ge;360 \u0026mu;mol/L \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"20%\"\u003e\n\u003cp\u003e37 (57.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"28%\"\u003e\n\u003cp\u003e35 (56.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"9%\"\u003e\n\u003cp\u003e0.877\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"41%\"\u003e\n\u003cp\u003eTG\u0026gt;1.7 mmol/L \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"20%\"\u003e\n\u003cp\u003e14 (21.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"28%\"\u003e\n\u003cp\u003e14 (22.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"9%\"\u003e\n\u003cp\u003e0.924\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"41%\"\u003e\n\u003cp\u003eHDL-C\u0026lt;1.29 mmol/L \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"20%\"\u003e\n\u003cp\u003e35 (54.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"28%\"\u003e\n\u003cp\u003e35 (56.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"9%\"\u003e\n\u003cp\u003e0.842\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"41%\"\u003e\n\u003cp\u003eFPG\u0026ge;5.6 mmol/L \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"20%\"\u003e\n\u003cp\u003e10 (15.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"28%\"\u003e\n\u003cp\u003e9 (14.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"9%\"\u003e\n\u003cp\u003e0.862\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"41%\"\u003e\n\u003cp\u003eHOMA-IR\u0026gt;2.69\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"20%\"\u003e\n\u003cp\u003e25 (39.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"28%\"\u003e\n\u003cp\u003e27 (43.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"9%\"\u003e\n\u003cp\u003e0.609\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"41%\"\u003e\n\u003cp\u003eFatty liver\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"20%\"\u003e\n\u003cp\u003e23 (35.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"28%\"\u003e\n\u003cp\u003e23 (37.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"9%\"\u003e\n\u003cp\u003e0.893\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"41%\"\u003e\n\u003cp\u003eSymptoms of PCOS [N(%)]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"20%\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"28%\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"9%\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"41%\"\u003e\n\u003cp\u003eOligomenorrhea\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"20%\"\u003e\n\u003cp\u003e61 (95.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"28%\"\u003e\n\u003cp\u003e60 (96.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"9%\"\u003e\n\u003cp\u003e0.647\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"41%\"\u003e\n\u003cp\u003eHyperandrogenism\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"20%\"\u003e\n\u003cp\u003e45 (84.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"28%\"\u003e\n\u003cp\u003e54 (87.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"9%\"\u003e\n\u003cp\u003e0.502\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"41%\"\u003e\n\u003cp\u003ePCOM\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"20%\"\u003e\n\u003cp\u003e42 (65.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"28%\"\u003e\n\u003cp\u003e50 (80.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"9%\"\u003e\n\u003cp\u003e0.058\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"4\" width=\"100%\"\u003e\n\u003cp\u003ea: IDF metabolic syndrome worldwide definition\u003csup\u003e13\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eb: European League Against Rheumatism evidence-based recommendation\u003csup\u003e14\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eTo convert glucose values to milligrams per deciliter, multiply by 18; To convert cholesterol values to milligrams per deciliter, multiply by 38.65\u003c/p\u003e\n\u003cp\u003eOC: oral contraceptives; OC+TRF: oral contraceptives + time-restricted feeding; BMI: body mass index; WC: waist circumference; BP: blood pressure; UA: uric acid; TG: triglycerides; HDL-C: high-density lipoprotein cholesterol; FPG: fasting plasma glucose; PCOM: polycystic ovarian morphology.\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\n\u003ch2\u003eOvulation\u003c/h2\u003e\n\u003cp\u003eThe primary endpoint (restoration of spontaneous ovulation) occurred significantly more often in the OC\u0026thinsp;+\u0026thinsp;TRF group than in the OC group (69.4% vs. 50% of patients at 3 months; odds ratio [OR]\u0026thinsp;=\u0026thinsp;2.263; 95% confidence interval [CI]: 1.092\u0026ndash;4.692; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.028). The results regarding the primary endpoint did not show significant heterogeneity in the subgroup analyses, with one exception (Fig.\u0026nbsp;2). The benefits of TRF appeared to be enhanced in patients with insulin resistance (HOMA-IR\u0026thinsp;\u0026gt;\u0026thinsp;2.69) (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.015).\u003c/p\u003e\n\u003cp\u003eFactors potentially affecting ovulation recovery in patients with PCOS were identified using univariate logistic regression analysis (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). Variables with \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.1 (group, FINS, WHR) after collinearity consideration, along with age, were selected for subsequent logistic regression analysis. Binary logistic regression was used to analyze the effects on the ability of patients with PCOS to recover spontaneous ovulation. The results showed that the logistic regression model, adjusted for age, FINS, WHR factors, and TRF, remained independent factors promoting ovulation recovery in women with PCOS (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.047). This implies that compared to simple OC treatment, the TRF combination significantly increased the probability of ovulation recovery in patients with PCOS (OR\u0026thinsp;=\u0026thinsp;2.192, 95% CI: 1.011\u0026ndash;4.753) (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003ctable id=\"Tab3\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable\u0026nbsp;2\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eFactors for Ovulation in Study Participants\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eVariables\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eUnivariate analysis\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eMultivariate analysis\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eOR (95%CI)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eOR (95%CI)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAge\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.011 (0.934\u0026ndash;1.094)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.786\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.064 (0.972\u0026ndash;1.165)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.180\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eFINS (mIU/L)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.924 (0.877\u0026ndash;0.973)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.003\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.930 (0.881\u0026ndash;0.983)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.010\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eWeight(kg)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.952 (0.921\u0026ndash;0.984)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.003\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLH(IU/L)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.990 (0.883\u0026ndash;1.109)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.857\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e-\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eGroup\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eOC\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.000\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.000\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eOC\u0026thinsp;+\u0026thinsp;TRF\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.263 (1.092\u0026ndash;4.692)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.028\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.192 (1.011\u0026ndash;4.753)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.047\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eFatty Liver\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eYES\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.000\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNO\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.404 (0.192\u0026ndash;0.852)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.017\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTG (mmol/L)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ge;\u0026thinsp;1.7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.000\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt;\u0026thinsp;1.7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.936 (0.460\u0026ndash;1.907)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.856\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHDL-C (mmol/L)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ge;\u0026thinsp;1.29\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.000\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt;\u0026thinsp;1.29\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.487 (0.710\u0026ndash;3.115)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.292\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e-\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eFPG (mmol/L)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ge;\u0026thinsp;5.6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.000\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt;\u0026thinsp;5.6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.800 (0.231\u0026ndash;2.776)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.725\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHOMA-IR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ge;\u0026thinsp;1.29\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.000\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt;\u0026thinsp;1.29\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.462 (0.224\u0026ndash;0.955)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.037\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTT (mmol/L)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ge;\u0026thinsp;1.66\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.000\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt;\u0026thinsp;1.66\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.647 (0.212\u0026ndash;1.972)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.444\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eWC (cm)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ge;\u0026thinsp;80\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.000\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt;\u0026thinsp;80\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.304 (0.138\u0026ndash;0.671)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.003\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e-\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBMI (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ge;\u0026thinsp;25\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.000\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt;\u0026thinsp;25\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.419 (0.193\u0026ndash;0.910)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.028\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBody Fat (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ge;\u0026thinsp;28\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.000\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt;\u0026thinsp;28\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.357 (0.171\u0026ndash;0.746)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.006\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eWHR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ge;\u0026thinsp;0.85\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.000\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.000\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt;\u0026thinsp;0.85\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.353 (0.155\u0026ndash;0.805)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.013\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.372 (0.144\u0026ndash;0.957)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.040\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHirsutism\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ge;\u0026thinsp;8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.000\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt;\u0026thinsp;8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.518 (0.223\u0026ndash;1.206)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.127\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"5\" align=\"left\"\u003e\n\u003cp\u003eOC: oral contraceptives; OC\u0026thinsp;+\u0026thinsp;TRF: oral contraceptives\u0026thinsp;+\u0026thinsp;time-restricted feeding; ALT: glutamic pyruvic transaminase; AST: glutamic oxaloacetic transaminase; CRE: creatinine; UA: uric acid; TC: total cholesterol; TG: triglycerides; HDL-C: high-density lipoprotein cholesterol; LDL-C: low-density lipoprotein cholesterol; FPG: fasting plasma glucose; FINS: fasting insulin; HOMA-IR: homeostasis model assessment-insulin resistance; LH: luteinizing hormone; FSH: follicle-stimulating hormone; TT: total testosterone; WC: waist circumference; HC: hip circumference; BMI: body mass index; BF: body fat; WHR: waist-to-hip ratio; Acne: based on the Pillsbury acne score; Alopecia: based on the Ludwig alopecia grade; Hirsutism: base on the mFG hirsutism score. OR: Odds Ratio; CI: Confidence Interval.\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e\n\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\n\u003ch2\u003eWeight loss\u003c/h2\u003e\n\u003cp\u003eBoth the OC and OC\u0026thinsp;+\u0026thinsp;TRF groups exhibited decreased body weight and BMI after 12 weeks, with statistically significant differences observed. Regarding WC and BF% reduction, the OC\u0026thinsp;+\u0026thinsp;TRF group showed significantly better outcomes than the OC group (Fig.\u0026nbsp;3a). Thirty-seven participants (60%) in the OC\u0026thinsp;+\u0026thinsp;TRF group achieved a weight loss of \u0026ge;\u0026thinsp;5%, compared to only 9 (14%) in the OC group (Fig.\u0026nbsp;3g). Using covariance analysis, we compared the differences in body weight-related indicators between the two groups using the baseline value as a covariate. The OC\u0026thinsp;+\u0026thinsp;TRF group significantly outperformed the OC group in weight reduction, BMI, BF%, and WC (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab4\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable\u0026nbsp;3\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eInter-group comparison of Anthropometric and Metabolic Factors\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eVariables\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eOC组(N\u0026thinsp;=\u0026thinsp;64)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eOC\u0026thinsp;+\u0026thinsp;TRF组(N\u0026thinsp;=\u0026thinsp;62)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003ex̄\u0026nbsp;\u0026plusmn;s/M (Q1\u003c/strong\u003e\u0026ndash;\u003cstrong\u003eQ3)\u003c/strong\u003e\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003ex̄ \u0026plusmn;s/M (Q1\u003c/strong\u003e\u0026ndash;\u003cstrong\u003eQ3)\u003c/strong\u003e\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"14\" align=\"left\"\u003e\n\u003cp\u003eBaseline\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eWeight (kg)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e59.4 (49.6\u0026ndash;69.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e58.6 (53.2\u0026ndash;67.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.967\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBMI\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e24.1 (19.8\u0026ndash;27.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e24.5 (21.8\u0026thinsp;~\u0026thinsp;27.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.388\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBF (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e27.33\u0026thinsp;\u0026plusmn;\u0026thinsp;7.73\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e27.91\u0026thinsp;\u0026plusmn;\u0026thinsp;6.75\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.654\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eWC (cm)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e77.2 (66.7\u0026ndash;85.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e75.3 (70.7\u0026ndash;85.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.716\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSBP\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e115.5\u0026thinsp;\u0026plusmn;\u0026thinsp;13.5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e118.0\u0026thinsp;\u0026plusmn;\u0026thinsp;13.5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.290\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDBP\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e70.1\u0026thinsp;\u0026plusmn;\u0026thinsp;9.4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e72.3\u0026thinsp;\u0026plusmn;\u0026thinsp;9.5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.191\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHirsutism\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e12.0 (8.0\u0026ndash;18.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e13.0 (8.0\u0026ndash;16.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.499\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLH(IU/L)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e10.1 (7.1\u0026ndash;14.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e9.5 (5.3\u0026ndash;15.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.431\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTT (nmol/L)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.1 (1\u0026ndash;1.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.2 (0.9\u0026ndash;1.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.399\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eFPG (mmol/L)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5.0 (4.8\u0026ndash;5.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5.0 (4.7\u0026ndash;5.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.911\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eFINS (mIU/L)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e10.9 (6.2\u0026ndash;18.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e10.7 (7.5\u0026ndash;17.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.439\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHOMA-IR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.4 (1.4\u0026ndash;4.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.4 (1.7\u0026ndash;4.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.466\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTG (mmol/L)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.1 (0.7\u0026ndash;1.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.2 (0.8\u0026ndash;1.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.470\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHDL-C (mmol/L)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.3 (1.0\u0026ndash;1.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.3 (1.1\u0026ndash;1.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.539\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"14\" align=\"left\"\u003e\n\u003cp\u003e12 weeks\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eWeight (kg)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e58.1 (50.6\u0026ndash;68.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e55.8 (50.7\u0026ndash;62.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.242\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBMI\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e23.6 (20.5\u0026ndash;26.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e23.2 (20.6\u0026ndash;25.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.874\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBF (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e27.4\u0026thinsp;\u0026plusmn;\u0026thinsp;7.1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e26.4\u0026thinsp;\u0026plusmn;\u0026thinsp;7.2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.453\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eWC (cm)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e75.2 (68.0\u0026ndash;87.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e74.2 (67.7\u0026ndash;80.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.321\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSBP\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e116.0 (107.5\u0026ndash;124.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e113.5 (107.0\u0026ndash;122.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.438\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDBP\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e71.0 (65.0\u0026ndash;79.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e74.0 (67.8\u0026ndash;79.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.216\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHirsutism\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e10.0 (8.0\u0026ndash;15.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e11.0 (6.0\u0026ndash;14.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.471\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLH(IU/L)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5.5 (3.6\u0026ndash;7.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5.9 (4.2\u0026ndash;8.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.957\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTT (nmol/L)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.0 (0.7\u0026ndash;1.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.1 (0.8\u0026ndash;1.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.466\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eFPG (mmol/L)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.572\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eFINS (mIU/L)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.4 (1.7\u0026ndash;3.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.4 (1.7\u0026ndash;3.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.315\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHOMA-IR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.4 (1.7\u0026ndash;3.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.4 (1.7\u0026ndash;3.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.668\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTG (mmol/L)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.8 (1.1\u0026ndash;2.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.5 (1.0\u0026ndash;2.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.638\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHDL-C (mmol/L)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.4 (1.2\u0026ndash;1.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.4 (1.2\u0026ndash;1.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.660\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eLS Mean(95%CI)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eLS Mean(95%CI)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eP\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"14\" align=\"left\"\u003e\n\u003cp\u003eChanges\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eWeight (kg)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-0.9 (-1.4 to -0.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-3.6 (-4.2 to -3.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026lt;\u0026thinsp;0.001\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBMI (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-0.4 (-0.6 to -0.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-1.4 (-1.7 to -1.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026lt;\u0026thinsp;0.001\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBF (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.01 (-1.0 to 1.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-1.4 (-2.4 to -0.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.047\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eWC (cm)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-0.6 (-1.5 to 0.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-2.9 (-3.9 to -2.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026lt;\u0026thinsp;0.001\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSBP\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-1.0 (-4.4 to 2.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-2.2 (-5.6 to 1.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.637\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDBP\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.0 (-1.5 to 3.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.8 (0.3\u0026ndash;5.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.310\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHirsutism\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-1.9 (-2.8 to -1.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-2.4 (-3.3 to -1.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.453\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLH (IU/L)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-5.2 (-5.9 to -4.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-5.3 (-6.1 to -4.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.762\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTT (nmol/L)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-0.2 (-0.2 to -0.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-0.2 (-0.3 to -0.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.957\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eFPG (mmol/L)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-0.1 (-0.2 to -0.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-0.1 (-0.2 to -0.01)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.430\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eFINS (mIU/L)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-0.1 (-1.5 to 1.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-2.4 (-3.9 to -0.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.032\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHOMA-IR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-0.2 (-0.5 to 0.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-0.6 (-1.0 to -0.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.137\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTG (mmol/L)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.0 (0.5\u0026ndash;1.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.6 (0.1\u0026ndash;1.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.375\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHDL-C (mmol/L)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.2 (0.0\u0026ndash;0.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.1 (0.0\u0026ndash;0.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.102\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"5\" align=\"left\"\u003e\n\u003cp\u003eLS: The least squares method; a: The covariance analysis based on the least squares method estimates the mean and 95% CI, The baseline value serves as the covariate.\u003c/p\u003e\n\u003cp\u003eBMI: body mass index; WC: waist circumference; BF: body fat; BP: blood pressure; SBP: systolic blood; DBP: diastolic pressure; LH: luteinizing hormone; TT: total testosterone; FPG: fasting plasma glucose; FINS: fasting insulin; HOMA-IR: Homeostasis model assessment-insulin resistance; TG: triglycerides; HDL-C: high-density lipoprotein cholesterol; Hirsutism: base on the mFG hirsutism score; OC: oral contraceptives; OC\u0026thinsp;+\u0026thinsp;TRF: oral contraceptives\u0026thinsp;+\u0026thinsp;time-restricted feeding.\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003c/div\u003e\n\u003c/div\u003e\n\u003ch2\u003eEndocrine fertility indices, glucose, lipid, and blood pressure\u003c/h2\u003e\n\u003cp\u003eLH, TT, LH/FSH ratio, and hirsutism in both groups showed a decreasing trend after the intervention; OC\u0026thinsp;+\u0026thinsp;TRF was better for acne than OC alone, but OC was superior for alopecia, with no substantial between-group differences for all the endocrine fertility indexes. (Fig.\u0026nbsp;3b and Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e). FPG showed a decreasing trend after OC intervention, however, there were no significant differences in FPG and insulin resistance between the two groups. After the OC\u0026thinsp;+\u0026thinsp;TRF intervention, FINS significantly decreased, with inter-group differences (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.032; Fig.\u0026nbsp;3c and Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e). Both OC\u0026thinsp;+\u0026thinsp;TRF and OC were associated with increased TC, TG, and HDL-C levels over 3 months, with no significant difference in lipid metabolism between the groups (Fig.\u0026nbsp;3e and Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e). The systolic and diastolic blood pressures were similar between the two groups during the 3 months of the trial (Fig.\u0026nbsp;3f and Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec15\" class=\"Section2\"\u003e\n\u003ch2\u003eSafety evaluation\u003c/h2\u003e\n\u003cp\u003eAfter 12 weeks of intervention, ALT decreased significantly in both groups compared to baseline, whereas AST and CRE showed no significant changes. Neither method resulted in obvious liver or kidney damage (Fig.\u0026nbsp;3d).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec16\" class=\"Section2\"\u003e\n\u003ch2\u003eAdverse events\u003c/h2\u003e\n\u003cp\u003eNo deaths or serious adverse events occurred during the study period. The incidence of mild adverse events (vaginal spotting, dizziness, indigestion, and constipation) was similar between the two groups (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003cstrong\u003eTable 4. Comparison of adverse events between the two groups\u003c/strong\u003e\u003c/div\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003ctable id=\"Taba\" border=\"1\"\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eAEs\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eN (%) of participants\u003c/p\u003e\n\u003c/th\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eOC(N\u0026thinsp;=\u0026thinsp;64)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eOC\u0026thinsp;+\u0026thinsp;TRF(N\u0026thinsp;=\u0026thinsp;62)\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eVaginal spotting\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e11 (17.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e13 (16.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.589\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDizziness\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e9 (14.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e12 (19.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.425\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eIndigestion\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5 (7.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e8 (12.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.348\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eConstipation\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6 (9.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7 (11.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.677\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"4\" align=\"left\"\u003e\n\u003cp\u003eShown are the number of patients with at least one serious adverse event that occurred during the 12-week intervention.\u003c/p\u003e\n\u003cp\u003eAEs: adverse events; OC: oral contraceptives; OC\u0026thinsp;+\u0026thinsp;TRF: oral contraceptives\u0026thinsp;+\u0026thinsp;time-restricted feeding.\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec17\" class=\"Section2\"\u003e\u0026nbsp;\u003c/div\u003e"},{"header":"COMMENT","content":"\u003cdiv id=\"Sec17\" class=\"Section2\"\u003e\n\u003ch2\u003ePrincipal findings\u003c/h2\u003e\n\u003cdiv id=\"Sec18\" class=\"Section3\"\u003e\n\u003cp\u003eThis is one of the few studies focusing on the rate of ovulation recovery in patients with PCOS. Compared with short-acting OC alone, patients with PCOS had a significantly higher spontaneous ovulation rate when combined with 8-hour time-restricted eating. This effect was more pronounced in the insulin-resistant groups. After adjusting for interference from HOMA-IR, WHR, and age by logistic regression, TRF remained an independent promoter of PCOS ovulation recovery; TRF combined with OC increased the odds of spontaneous ovulation recovery by 2.192 times compared to OC alone.\u003c/p\u003e\n\u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec19\" class=\"Section2\"\u003e\n\u003ch2\u003eResults in the context of what is known\u003c/h2\u003e\n\u003cp\u003eThe mechanism by which TRF might promote the ovulation rate in patients with PCOS is analyzed; steroid hormone secretion is regulated by the biological clock. It is well known that abnormal LH pulse rate and an androgen hypersecretion state are key factors in reduced ovulation and infertility in patients with PCOS.\u003csup\u003e15,16\u003c/sup\u003e From this study's results, compared to OC treatment alone, OC\u0026thinsp;+\u0026thinsp;TRF has more advantages in reducing TT and acne. TRF may improve PCOS symptoms by regulating melatonin levels via the circadian clock. Melatonin plays an important role in circadian rhythms, with receptors present in several female reproductive organs.\u003csup\u003e17\u003c/sup\u003e The loss of melatonin receptors and disruption of circadian clock genes lead to metabolic syndrome, obesity, and diabetes.\u003csup\u003e18\u003c/sup\u003e A retrospective clinical trial showed that menstrual cycles and androgen levels improved in 95% of women with PCOS after 6 months of melatonin treatment.\u003csup\u003e19\u003c/sup\u003e In summary, we believe that TRF regulates the circadian rhythm of patients with PCOS, thereby affecting steroid hormone secretion and ultimately improving anovulation and signs of hyperandrogenism.\u003c/p\u003e\n\u003cp\u003eObesity is a key contributor toward metabolic comorbidities in women with PCOS. Weight loss is purported to benefit the female reproductive system by reducing androgen levels, regulating menstruation, and promoting ovulation.\u003csup\u003e20\u003c/sup\u003e Hu and Ma retrospectively analyzed the differences in efficacy between bariatric surgery and medication in patients with obesity PCOS.\u003csup\u003e21\u003c/sup\u003e The results showed that 95% of patients with a BMI below the critical value achieved complete remission of hyperandrogenism, polycystic ovarian changes, irregular menstruation, and other symptoms. Hu and Ma concluded that complete symptom remission in patients with obesity and PCOS depends on the final BMI after weight loss. In this study, patients with PCOS who were overweight or obese (BMI\u0026thinsp;\u0026ge;\u0026thinsp;25 kg/m\u003csup\u003e2\u003c/sup\u003e) were divided into subgroups by the World Health Organization BMI classification criteria. TRF intervention results in an increased rate of ovulation recovery in patients with PCOS (especially those who are overweight or obese). This may be because overweight or obese individuals were more likely to normalize their BMI after the TRF intervention, whereas the cause of ovulation disorders in normal or lean patients with PCOS may not be related to body weight or BMI; therefore, TRF showed no obvious effect. Another cross-sectional study involving over 250 women with infertility who were overweight or obese showed that WC was the strongest predictor of infrequent ovulation in reproductive-aged women, independent of other parameters, such as hyperinsulinemia and insulin resistance.\u003csup\u003e20\u003c/sup\u003e Thus, the reduction of abdominal fat is particularly important for ovulation recovery. Single-factor regression analysis showed that increased BF% and WC reduced the probability of ovulation recovery, which is consistent with previous studies.\u003csup\u003e22\u003c/sup\u003e We also found that the OC\u0026thinsp;+\u0026thinsp;TRF intervention significantly increased ovulation rates in patients with a WC of \u0026ge;\u0026thinsp;80 cm, compared to the OC group (70.8% vs. 36%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.017). This could be related to the significant reduction in WC after intervention in the OC\u0026thinsp;+\u0026thinsp;TRF group.\u003c/p\u003e\n\u003cp\u003eWhen comparing the changes in glucose metabolism indicators between the two groups through covariance analysis, the results showed that the OC\u0026thinsp;+\u0026thinsp;TRF group had an advantage in reducing FINS compared to the OC group, but there was no difference in FPG, which was similar to the results of previous studies. Two randomized control trials\u003csup\u003e7,23\u003c/sup\u003e demonstrated that 4, 6, and 8 h of time-restricted eating over 8 weeks significantly reduced FINS. In another randomized control trial of patients who were overweight or obese, Lowe\u003csup\u003e24\u003c/sup\u003e found that a 16:8 TRF (self-selected eating time) did not significantly change fasting glucose levels. In our subgroup analysis, 4 out of 5 subgroups showed an advantage in ovulation rate for the OC\u0026thinsp;+\u0026thinsp;TRF group compared to the OC group. The remaining subgroup (insulin resistant or not) showed significant differences (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001 for heterogeneity). These findings may have been due to chance or influenced by the sample size.\u003c/p\u003e\n\u003cp\u003eMultiple studies have found that an imbalanced diet with nighttime eating promotes body weight gain and metabolic dysfunction.\u003csup\u003e25,26\u003c/sup\u003e Lipid metabolism also follows a circadian rhythm.\u003csup\u003e27\u003c/sup\u003e According to this study's results, all participants showed an upward trend in HDL-C, TC, and TG levels after 12 weeks of treatment. OC\u0026thinsp;+\u0026thinsp;TRF slightly decreased the LDL-C levels in patients with PCOS, but the difference was not statistically significant. This is inconsistent with related literature reporting that TRF may promote fat reduction and decrease TC, TG, and LDL-C levels in long-term studies.\u003csup\u003e28,29\u003c/sup\u003e Based on this study, it may be because all patients underwent OC treatment simultaneously. It may be concluded that long-term use of OCs can elevate TG and HDL-C levels in patients with PCOS but with no significant change in TC and LDL-C.\u003csup\u003e30\u003c/sup\u003e Our results indicate a combined time-restricted diet may help improve the decrease in LDL-C, but this was not statistically significant, and further research is needed.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec20\" class=\"Section2\"\u003e\n\u003ch2\u003eStrengths and limitations\u003c/h2\u003e\n\u003cp\u003eThe strengths of this trial include being the first randomized controlled trial of OC treatment combined with TRF for improving the ovulation rate in patients with PCOS, confirming the importance of TRF for ovulation. High adherence to assignments also strengthened the study. The limitations of this study include a lack of detailed records and classification of individual eating times, and no comparative analysis of participants' dietary structure and total intake before and after. Potential bias from participants' compliance in implementing TRF cannot be ruled out, thereby affecting the study results. The study only measured common laboratory indicators and lacked an in-depth analysis of molecular biology and cytology.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Conclusions","content":"\u003cp\u003eOur study showed that TRF has a good weight loss effect in patients who are overweight or obese with PCOS, and when combined with OC treatment, can significantly increase the ovulation rate and improve fertility. This dietary pattern is simple, safe, and economical, and does not require deliberate changes to inherent dietary habits. The long-term adherence and acceptance of TRF make it worthy of use in patients with PCOS.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePCOS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003epolycystic ovary syndrome\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePCOM\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003epolycystic ovarian morphology\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eTRF\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003etime-restricted feeding\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eFSH\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003efollicle-stimulating hormone\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eLH\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eluteotropic hormone\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eTT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003etotal testosterone\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eBMI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ebody mass index\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eBF\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ebody fat\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003einsulin resistance\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eWC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ewaist circumference\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eHC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ehip circumference\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eWHR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ewaist-to-hip ratio\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eFPG\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003efasting plasma glucose\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eFINS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003efasting insulin\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eHOMA-IR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ehomeostasis model assessment insulinresistance\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eTG\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003etriglyceride\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eTC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003etotal cholesterol\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eHDL-C\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ehigh density lipoprotein cholesterol\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eLDL-C\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003elow density lipoprotein cholesterol\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eUA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003euric acid\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCRE\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ecreatinine\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eAST\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003easpartate transaminase\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eALT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ealanine aminotransferase\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eOR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eodds ratio\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003econfidence interval.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eSources of funding:\u0026nbsp;\u003c/strong\u003eThis study was supported by the Foshan science and Technology Bureau (Grant No. 222000100381), the Natural science Foundation of Guangdong Province (Grant No. 2024A1515013145), the Foshan Engineering Technology Research center (Grant No. 2420001000333), the Basic and Applied Basic Research Foundation of Guangdong Province (Grant No. 2023A1515140165) and the Basic and Applied Basic Research Foundation of Guangdong Province (Grant No. 2021A1515111176).\u003cstrong\u003e\u003c/p\u003e\n\u003cp\u003e \u003ch2\u003eConflicts of interest\u003c/h2\u003e \u003cp\u003eThere are no competing interests of declare.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eAuthor contributions\u003c/h2\u003e \u003cp\u003eMZ: Data curation, Visualization, Writing-original draft. DL: Software, Supervision, Writing - original draft.YL: Conceptualization, Methodology, Writing - original draft. PZ: Funding acquisition, Investigation, Writing - original draft. WL: Project administration, Resources. LK: Data curation, Formal analysis, Project administration, Software. YL: Data curation, Investigation, Methodology. SW: Supervision, Visualization. SZ: Project administration, Supervision, Writing - review \u0026amp; editing. LL: onceptualization, Supervision, Writing - original draft, Writing - review \u0026amp; editing.\u003c/p\u003e\u003ch2\u003eAcknowledgments\u003c/h2\u003e \u003cp\u003eWe gratefully acknowledge the financial support provided by the Natural science Foundation of Guangdong Province (Grant No. 2024A1515013145). We are also indebted to the experts who generously shared their insights and expertise ring the online survey.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eTeede HJ, Misso ML, Costello MF, et al. Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome. Fertil Steril. 2018;110(3):364\u0026ndash;79. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.fertnstert.2018.05.004\u003c/span\u003e\u003cspan address=\"10.1016/j.fertnstert.2018.05.004\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRavussin E, Beyl RA, Poggiogalle E, Hsia DS, Peterson CM. Early time-restricted feeding reduces appetite and increases fat oxidation but does not affect energy expenditure in humans. 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Hum Reprod. 2011;26(1):191\u0026ndash;201. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/humrep/deq301\u003c/span\u003e\u003cspan address=\"10.1093/humrep/deq301\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Time-restricted feeding, polycystic ovary syndrome, short-acting oral contraceptives, weight loss, ovulation","lastPublishedDoi":"10.21203/rs.3.rs-4738766/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4738766/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBACKGROUND: \u003c/strong\u003eOral contraceptives have limitations in managing polycystic ovary syndrome. We explored time-restricted feeding combined with oral contraceptive use as a novel strategy for the management of polycystic ovary syndrome.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSTUDY DESIGN: \u003c/strong\u003eA total of 126 female patients with polycystic ovary syndrome aged 18–40 years were selected for this study. They were randomly assigned to oral contraceptive therapy with an 8-hour time-restricted feeding (eating freely between 8:00 a.m. and 4:00 p.m.) or oral contraceptive therapy alone for 12 weeks. The primary outcome was the difference in spontaneous ovulation rate between the two groups after the intervention, and the secondary outcomes included changes in weight, body mass index, waist circumference, fertility endocrine indices, and glucose and lipid metabolism factors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRESULTS: \u003c/strong\u003eOf 126 participants who underwent randomization, 116 (92.1%) completed a 12-week follow-up visit. The rates of spontaneous ovulation were 69.4% in the oral contraceptive + time-restricted feeding group and 50% in the oral contraceptive group (odds ratio=2.263; 95% confidence interval, 1.092–4.692; \u003cem\u003eP\u003c/em\u003e=0.028). Time-restricted feeding is an independent factor that promotes ovulation recovery in patients with polycystic ovary syndrome, especially in those with insulin resistance. After the intervention, the oral contraceptive + time-restricted feeding group had a significantly lower body weight (-3.6 vs -0.9 kg\u003cem\u003e,\u003c/em\u003e \u003cem\u003eP\u003c/em\u003e \u0026lt;0.001), body mass index (-1.4 vs -0.4 kg/m\u003csup\u003e2\u003c/sup\u003e, \u003cem\u003eP\u003c/em\u003e\u0026lt;0.001), body fat percentage (-1.4% vs 0.01%, \u003cem\u003eP\u003c/em\u003e=0.047), waist circumference (-2.9 vs -0.6 cm\u003cem\u003e,\u003c/em\u003e \u003cem\u003eP\u003c/em\u003e \u0026lt;0.001), and fasting insulin (-2.4 vs -0.1 mIU/L, \u003cem\u003eP\u003c/em\u003e=0.032) than the oral contraceptive alone group.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCONCLUSIONS:\u003c/strong\u003e Among patients with polycystic ovary syndrome, a time-restricted feeding regimen combined with oral contraceptive therapy was more beneficial than oral contraceptive use alone in promoting ovulation and reducing body weight, body fat, waist circumference, and fasting insulin.\u003c/p\u003e","manuscriptTitle":"Effect of time-restricted feeding combined with oral contraceptives on polycystic ovary syndrome: An open-label, randomized trial","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-08-26 13:38:22","doi":"10.21203/rs.3.rs-4738766/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"bfe06d4d-3a10-4a0a-ae97-429920bc115d","owner":[],"postedDate":"August 26th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-08-26T13:38:25+00:00","versionOfRecord":[],"versionCreatedAt":"2024-08-26 13:38:22","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4738766","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4738766","identity":"rs-4738766","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}