Prospective, Randomized, Double-blind, Placebo Controlled Study on Safety and Efficacy of Ashwagandha Root Extract (Withania Somnifera) on Menopause Symptoms

Prospective, Randomized, Double-blind, Placebo Controlled Study on Safety and Efficacy of Ashwagandha Root Extract (Withania Somnifera) on Menopause Symptoms | 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 Prospective, Randomized, Double-blind, Placebo Controlled Study on Safety and Efficacy of Ashwagandha Root Extract (Withania Somnifera) on Menopause Symptoms Isukapalli Vani, Gudla Muralidhar, Bade Srinivas Rao This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6409321/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 Hormone replacement therapy (HRT) is of the most recent therapeutic option available for management of menopausal syndrome. But the amalgamation of HRT and pharmaceutical antidepressants are linked to an elevated risk of serious adverse events. In addition, lifestyle changes are somehow ineffective in addressing the psychological signs. Hence, the present study was conducted to assess the safety and efficacy of high concentrated Ashwagandha root extract (ARE) formulation in age group experiencing menopausal syndrome with emphasis on Menopause Rating Scale (MRS). Methodology: A randomized, double-blind, placebo-controlled study was conducted for duration of eight weeks. Total 60 women with clinically diagnosed menopause were enrolled and prescribed either 300 mg of an Ashwagandha root extract capsules or placebo capsule twice daily. Results It was observed that total MRS score reduced significantly (p < 0.0001) with ARE supplementation, especially in psychological (p < 0.0001), somatic (p < 0.0001), and urogenital (p < 0.0001) domains as compared to the placebo group. Group receiving ARE capsules showed improved serum estradiol (p < 0.001), progesterone (p < 0.001) and Short Form survey (SF-12) scores (p < 0.001), while reduction in serum FSH (p < 0.001) and LH (p < 0.001), hot flashes events (p < 0.001) and Perceived Stress Scale (PSS-10) scores (p < 0.001). Conclusion To conclude, inclusion of ashwagandha for management of menopausal syndrome is a promising therapeutic option. The safety and efficacy of different concentrations of Ashwagandha could be studied further. Trial registration: The study was registered with Clinical Trial Registry of India (CTRI/2022/02/040551 dt: 23/02/2022) Ashwagandha root extract menopause safety efficacy Randomized control trial Figures Figure 1 1. Background Menopause is defined as absence of menstrual periods for 12 consecutive months or equivalent to three previous cycles, indicating the end of ovarian function and permanent amenorrhea. There is a gradual transition observed from active to inactive ovarian function, spanning over several years. Besides its association with aging, menopause involves noticeable biological and psychological changes in women. [ 1 , 2 ] The downsize in production of estrogen and progesterone during menopause makes women more vulnerable to psychosomatic issues. Most common symptoms observed are hot flashes, sweating, mood changes, and libido alterations. However, other specific complaints associated with menopause are vasomotor symptoms, sleep disturbances, urogenital problems, breast and joint pain, cognitive changes and mood disorders such as depression and anxiety. [ 3 , 4 ] Currently, a combination of hormone replacement therapy (HRT), pharmaceutical antidepressants, and lifestyle changes are used as therapeutic option. But HRT is associated with an increased risk of venous thromboembolism, stroke, cardiovascular disease, gallstones, and breast cancer. Furthermore, the tendency of women to discontinue antidepressant due to adverse events is high. It was also reported that HRT is not effective in addressing psychological manifestations. [ 1 , 5 – 7 ] Ashwagandha, scientifically known as Withania somnifera (WS) has been a significant herb in Ayurveda. As a potent adaptogen, it boosts the body's resilience to stress, improves cell-mediated immunity, and possesses powerful antioxidant properties. Ashwagandha is revered for its ability to balance, energize, rejuvenate, and revitalize the body system. [ 8 , 9 ] The chemical composition and prophylactic effect of WS in maintaining immune homeostasis is well studied and documented. [ 10 , 11 ] The effects of Ashwagandha on central nervous system and the immune system might be useful in reducing hot flashes. [ 12 , 13 ] Using therapeutic properties of Ashwagandha along with HRT could give broader coverage of menopausal symptoms. Hence, the present study was conducted to assess the safety and efficacy of the KSM-66 Ashwagandha® root extract capsule (300 mg) in patients experiencing menopausal symptoms with emphasis on Menopause Rating Scale (MRS). 2. Methods 2.1 Study Design This was a randomized, prospective, double-blind, placebo-controlled study. The approval of the institutional ethics committee was obtained for this study. It was performed in accordance with Good Clinical Practice guidelines and the ethical principles outlined in the Declaration of Helsinki. The Consolidated Standards of Reporting Trials (CONSORT) guidelines for designing and reporting controlled trials were followed. The study was registered with the Clinical Trial Registry of India (CTRI/2022/02/040551). 2.2 Study Population An adult female subjects aged 45 to 55 years with a clinical diagnosis of menopause with no history of hormone therapy or antidepressant treatment in the past 3 months were included in the study. Demographic parameters included a body mass index (BMI) within the range of 20 to 30 Kg/m² and history of 10 or more hot flashes events per week. Prior to enrollment, each participant was explained in detail about the study and written informed consent was obtained from all participants. 2.3 Study Procedure Randomization was conducted in a 1:1 ratio, with patients being randomly assigned to receive either KSM-66 Ashwagandha® capsule 300 mg (Shri Kartikeya Pharma, India) (Ashwagandha group, AG, n = 30) or an Identical Placebo (Placebo group, PL, n = 30) twice daily after meals (breakfast and dinner) in a double-blinded setting. The study consisted of two site visits (baseline visit - day 1, end of study - day 56), and one telephonic follow-up visit (day 28). All assessments were carried out at the study center during visit 1 (Day 1) and visit 3 (Day 56) while telephonic follow-up visit was conducted to verify drug, protocol compliance and collect details on any adverse events (AEs) without any formal assessment. 2.4 Efficacy Assessments 2.4.1 Primary Outcome Measures The Menopause Rating Scale (MRS) is a standardized Health-Related Quality of Life Scale (HRQoL) with good psychometric characteristics. [ 14 ] The MRS and the mean change in the MRS from baseline were descriptively summarized for each visit and by treatment. 2.4.2 Secondary Outcome Measures The secondary outcomes of the study were mean change in summary scores Mental Component Score (MCS-12) and a Physical Component Score (PCS-12) from Short Form survey (SF-12) [ 15 ] , Perceived Stress Scale-10 (PSS-10) [ 16 ] , serum hormones (Estradiol, Progesterone, FSH, LH), and hot flashes events. 2.5 Safety Assessment and Treatment Compliance Patient's Global Assessment of Tolerability to Therapy (PGATT) [ 17 ] was assessed based on a four-point rating scale as follows: 1 = excellent tolerability, 2 = good tolerability, 3 = average tolerability, and 4 = poor tolerability. This scoring was done by the patients. The adherence to the assigned regimen was assessed and verified by study personnel through recording the dosing of the investigational products. 2.6 Statistical Methods The sample size calculation was done based on the primary endpoint. With two-sided level of significance as 5%, randomization ratio as 1:1 and power as 90%, the study required in all 54 evaluable subjects (27 subjects in each arm). However, total 60 women (30 in each group) were enrolled in the study. All relevant statistical calculations were completed using Stata 13.0 IC (Stata Corp. USA). Since all women completed the study as per the study protocol, both efficacy and safety analysis were performed on all patient’s dataset data (n = 60). All analyses were done using two-sided tests and a p-value of less than 0.05 was considered the threshold to claim statistical significance. For categorical variables, the number and percentage of subjects within each category (with category for missing data as needed) of the parameter were presented and P-values were determined by Chi-square test between the groups (AG vs. PL). For continuous variables, the number of subjects, mean, median, standard deviation (SD), minimum and maximum values were presented. Paired t-test was used for the within group (Baseline-Day 56) comparison, Two-independent samples t-test was used for the between group (AG vs. PL) comparison at Baseline and Day 56 and Analysis of Covariance (ANCOVA) was used for the comparison of between group (AG vs. PL) after controlling baseline. 3. Results A total of 73 participants underwent initial screening and eligibility assessment. Among them, 13 did not meet the eligibility criteria (Fig. 1 ). Subsequently, the remaining 60 participants were enrolled and randomized. No participants from either group were excluded due to follow-up loss or failure of medication adherence. 3.1 Demographics and Baseline Data The demographics data and medical history of patients enrolled and randomized in two groups (Intent to treat (ITT) dataset) were compared using two-independent sample t-tests and chi-square tests. The mean age for AG was 49.8 ± 2.4 years and for PL was 50.0 ± 2.3 years (p = 0.700), indicating no significant difference. The mean BMI for AG was 24.9 ± 2.4 and for PL was 25.0 ± 2.5 (p = 0.955), also showing no significant difference. The prevalence of co-morbidities such as anxiety (AG: 6.7%, PL: 3.3%, p = 0.549), constipation (AG: 3.3%, PL: 0%, p = 0.319), diabetes (AG: 6.7%, PL: 3.3%, p = 0.549), hypertension (AG: 26.7%, PL: 16.7%, p = 0.351), and obesity (AG: 50%, PL: 43.3%, p = 0.605) were also not significantly different between the two groups. 3.2 Vital parameters Table 1 presents the vital parameters at baseline (day 1) and end of study period (day 56) without any significant changes in the two groups (p > 0.05). The physical examination of patients in either group was found to be within normal parameters. Table 1 Vital parameters and laboratory values at baseline and end of study. AG (n = 30) PL (n = 30) Day 1 Day 56 P Day 1 Day 56 P Mean (SD) Mean (SD) Mean (SD) Mean (SD) SBP (mmHg) 142.50 (20.5) 140.8 (19.6) 0.748 129.8 (16.8) 130.0 (16.4) 0.969 DBP (mmHg) 90.0 (10.7) 88.8 (9.3) 0.653 84.5 (7.8) 84.3 (7.2) 0.932 Pulse Rate (/min) 95.3 (15.4) 94.1 (15.4) 0.770 84.7 (7.0) 84.9 (7.0) 0.927 Respiration Rate (/min) 20.5 (2.8) 20.4 (2.9) 0.858 19.4 (2.7) 19.4 (2.7) > 0.999 Temperature (˚C) 36.5 (0.4) 36.5 (0.4) > 0.999 36.6 (0.4) 36.6 (0.4) 0.812 Haemoglobin (g/dL) 12.2 (0.8) 12.6 (1.0) 0.177 11.7 (0.9) 11.7 (0.9) 0.753 RBC count (x10^6/µL) 4.7 (0.5) 4.8 (0.5) 0.336 4.7 (0.6) 4.6 (0.5) 0.823 Haematocrit (PCV) (%) 42.9 (3.5) 43.2 (3.2) 0.79 43.0 (3.4) 41.1 (4.7) 0.084 TLC (cells/µL) 4740.0 (447.7) 4736.7 (426.3) 0.997 4846.7 (337.1) 4693.3 (865.4) 0.37 Lymphocytes (%) 29.2 (5.7) 29.1 (5.4) 0.926 32.3 (6.6) 32.9 (6.4) 0.752 Monocytes (%) 4.7 (1.7) 4.7 (1.7) 0.958 5.5 (1.3) 5.4 (1.3) 0.775 Eosinophils (%) 3.3 (1.3) 3.4 (1.2) 0.757 3.1 (1.0) 3.2 (1.0) 0.518 Basophils (%) 0.5 (0.4) 0.5 (0.3) 0.848 0.5 (0.2) 0.5 (0.2) 0.533 Absolute Neutrophils (%) 3930.0 (490.0) 3933.3 (488.0) 0.979 3916.7 (472.2) 3893.3 (441.1) 0.844 Platelet Count (cells/µL) 159833.3 (10627.2) 160350.0 (9150.2) 0.841 159566.7 (12475.3) 160100.0 (0.5) 0.861 Total bilirubin (mg/dL) 0.5 (0.3) 0.5 (0.3) 0.897 0.6 (0.2) 0.6 (0.2) 0.46 AST/SGOT (U/L) 12.2 (3.9) 11.7 (3.5) 0.553 12.3 (3.4) 13.0 (3.2) 0.44 ALT/SGPT (U/L) 10.3 (3.5) 10 (3.2) 0.7 12.4 (3.2) 13.1 (3.4) 0.393 ALP (U/L) 101.4 (13.6) 103.9 (15.5) 0.51 101.5 (17.3) 103.5 (20.1) 0.681 BUN (mg/dL) 9.5 (2.0) 9.5 (2.0) > 0.999 9.4 (1.5) 9.4 (1.5) > 0.999 Creatinine (mg/dL) 0.8 (0.2) 0.8 (0.2) 0.803 0.7 (0.2) 0.7 (0.2) 0.702 Total Cholesterol (mg/dL) 192.0 (30.3) 192.0 (30.3) > 0.999 190.8 (16.2) 191.8 (16.3) 0.824 AG: Ashwagandha; PL: Placebo; SD: Standard Deviation; PCV: Packed Cell Volume; TLC: Total Leukocyte Count; AST/SGOP: Aspartate aminotransferase; ALT/SGPT: Alanine aminotransferase; ALP: Alkaline phosphatase; BUN: Blood Urea Nitrogen (Added at end due to larger length than A4 size) 3.3 Efficacy Assessment 3.3.1 Menopause Rating Scale Table 2 shows the Menopause Rating Scale (MRS) and its sub-domain scores at baseline (day 1) and end of study period (day 56). Greater reduction in scores was seen in AG group as compared to PL group (p < 0.0001). There was greater reduction in mean (SD) total MRS scores with AG (from 31.37 (1.45) at baseline to 18.53 (2.29) at day 56) as compared to placebo (p < 0.0001). This reduction was observed in all sub-scales (psychological, somatic, and urogenital) of the MRS scale. Table 2 Menopause Rating Scale scores in two groups. MRS and sub-domain scores AG (N = 30) PL (N = 30) P-value Mean (SD) Mean (SD) Psychological score • Baseline 12.77 (1.41) 12.58 (1.42) 0.605 • Day 56 7.07 (1.05) 12.33 (1.52) < 0.0001* • Change from baseline -5.7 (0.36) -0.25 (-0.10) < 0.0001* Somatic score • Baseline 12.03 (1.25) 11.87 (1.45) 0.6488 • Day 56 6.97 (1.07) 11.77 (0.90) < 0.0001* • Change from baseline -5.06 (0.18) -0.1 (0.55) < 0.0001* Urogenital score • Baseline 6.57 (0.82) 6.28 (1.13) 0.2599 • Day 56 4.5 (1.01) 5.93 (1.26) < 0.0001* • Change from baseline -2.07 (0.19) -0.35 (-0.13) < 0.0001* MRS total score • Baseline 31.37 (1.45) 30.73 (2.50) 0.235 • Day 56 18.53 (2.29) 30.03 (2.55) < 0.0001* • Change from baseline -12.84 (0.40) -0.7 (0.20) < 0.0001* AG: Ashwagandha; PL: Placebo; SD: Standard Deviation; MRS: Menstrual Rating Scale * Statistically significant at < 0.0001 3.3.2 Hormone Levels and Hot Flashes Tables 3 shows the serum hormone levels and occurrence of hot flashes respectively. There were statistically significant changes observed in all parameters between the two groups (p < 0.001). Serum estradiol and serum progesterone levels increased in AG group while luteinizing hormone (LH), follicle stimulating hormone (FSH) increased in PL group. There was non-significant decrease in hot flashes score (number of events) in both the groups at day 56 compared to baseline (p > 0.05) however this reduction was statistically significant when compared between the groups (p < 0.05). Table 3 Hormone levels and scores for hot flashes in the two groups. AG (N = 30) PL (N = 30) ‘p’ value between group Mean (SD) Mean (SD) Serum Estradiol (pg/dL) Baseline – Mean (SD) 22.2 (3.8) 22.2 (3.8) > 0.999 Day 56 – Mean (SD) 23.2 (3.5) 21.6 (3.3) 0.068 Change – Mean change ± SE (‘p’ value Within group) 1.0 ± 0.2 (< 0.001) * -0.6 ± 0.2 (0.012) * < 0.001* Serum Progesterone (ng/dL) Baseline – Mean (SD) 0.283 (0.079) 0.307 (0.069) 0.229 Day 56 – Mean (SD) 0.433 (0.190) 0.300 (0.083) 0.001* Change – Mean change ± SE (‘p’ value Within group) 0.150 ± 0.032 (< 0.001) * -0.0067 ± 0.013 (0.601) < 0.001* Serum LH (IU/L) Baseline – Mean (SD) 36.8 (8.6) 34.8 (7.7) 0.328 Day 56 – Mean (SD) 35.5 (8.6) 35.6 (7.7) 0.948 Change – Mean change ± SE (‘p’ value Within group) -1.3 ± 0.2 (< 0.0001) * 0.8 ± 0.2 (0.001) * < 0.001* Serum FSH (IU/L) Baseline – Mean (SD) 61.9 (16.1) 58.2 (15.3) 0.362 Day 56 – Mean (SD) 60.9 (15.9) 58.6 (15.4) 0.574 Change – Mean change ± SE (‘p’ value Within group) -1.0 ± 0.2 (< 0.001) * 0.4 ± 0.2 (0.034) * < 0.001* No. of Hot Flashes events Baseline – Mean (SD) 14.5 (2.0) 14.6 (2.2) 0.855 Day 56 – Mean (SD) 10.6 (2.4) 14.0 (2.3) 0.078 Change – Mean change ± SE (‘p’ value Within group) -3.9 ± 0.5 (< 0.001) * -0.6 ± 0.2 (0.001) * < 0.001* AG: Ashwagandha; PL: Placebo; SD: Standard Deviation; FSH: Follicle stimulating hormone; LH: Luteinizing hormone; IU: International units; dL: Deciliter * Statistically significant (Added at end due to larger length than A4 size) 3.3.3 Short Form Survey (SF-12) Table 4 shows the SF-12 (PCS-12, MCS-12) and PSS-10 scores at baseline (day 1) and end of study period (day 56). There was marked improvement in all SF-12 scores in both the groups and between the groups (p < 0.001). 3.3.4 Perceived Stress Scale (PSS-10) Table 4 shows the PSS-10 scores at baseline (day 1) and end of study period (day 56). There was a marked improvement in all PSS-10 score in the AG group and the changes were statistically significant between the groups (p < 0.001). There was reduction (improvement) in mean (SD) PSS-10 score from baseline to day 56 in AG group (p 0.05). Table 4 SF-12 (PCS-12, MCS-12) and PSS scores in two groups. AG (N = 30) PL (N = 30) ‘p’ value between group Mean (SD) Mean (SD) PCS-12 (SF-12) Baseline – Mean (SD) 23.2 (1.5) 22.7 (1.1) 0.193 Day 56 – Mean (SD) 49.9 (2.0) 34.2 (3.9) < 0.001* Change – Mean change ± SE (‘p’ value Within group) 26.7 ± 0.5 (< 0.001*) 11.5 ± 0.7 (< 0.001*) < 0.001* MCS-12 (SF-12) Baseline – Mean (SD) 28.2 (7.9) 30.8 (6.6) 0.175 Day 56 – Mean (SD) 53.6 (2.5) 36.4 (6.5) < 0.001* Change – Mean change ± SE (‘p’ value Within group) 25.5 ± 1.5 (< 0.001*) 5.6 ± 1.2 (< 0.001*) < 0.001* PSS Baseline – Mean (SD) 28.5 (3.1) 27.7 (3.1) 0.281 Day 56 – Mean (SD) 15.1 (3.0) 27.4 (3.0) < 0.001* Change – Mean change ± SE (‘p’ value Within group) -13.4 ± 0.7 (< 0.001*) -0.2 ± 0.2 (0.326) < 0.001* AG: Ashwagandha; PL: Placebo; SD: Standard Deviation; PCS-12; Physical component score; MCS-12; Mental component score; PSS: Perceived stress scale * Statistically significant 3.4 Safety Assessment and Treatment Compliance Total 3 women (1 in AG group and 2 in PL group) reported adverse events. One woman in AG group reported cough and cold while two women in PL group reported stomachache and indigestion respectively. All events were of mild severity, were not associated with the study treatments, and completely resolved with or without symptomatic treatment. None of the women stopped treatment due to adverse event and treatment compliance was 100% in both the groups. Table 5 shows the Patient’s Global Assessment of Tolerability to Therapy (PGATT) parameters. The tolerability of Ashwagandha was reported between good to excellent by most of the patients in AG group compared to placebo in the PL group (p < 0.001). Twenty-eight patients (93.3%) in AG group rated the tolerability of Ashwagandha as ‘good’ to ‘excellent’. Table 5 PGATT parameters at Baseline and End of Study Period AG (N = 30) PL (N = 30) Chi-square Test No. (%) No. (%) χ2 ‘p’ Excellent Tolerability 13 (43.3%) 0 (-) 22.941 < 0.001* Good Tolerability 15 (50.0%) 15 (50.0%) Average Tolerability 0 (-) 0 (-) Poor Tolerability 2 (6.7%) 15 (50.0%) AG: Ashwagandha; PL: Placebo * Statistically significant 4. Discussion Menopause, occurring typically between ages 45–52, entails hormonal changes leading to the cessation of menstrual cycles. [ 18 , 19 ] By 2030, an estimated 1.2 billion women globally will be menopausal or postmenopausal, with 47 million new entrants annually. [ 20 ] Menopause encompasses roughly one-third of a woman's lifespan. It is marked by irregular menstrual cycles and hot flashes due to hormonal changes and aging. Postmenopausal symptoms feature genitourinary concerns such as vulvovaginal atrophy and urinary symptoms. [ 21 ] Over 85% of women experience challenging symptoms such as hot flashes, night sweats, sleep disturbances, sexual dysfunction, mood disorders, weight gain, and cognitive decline. [ 18 , 22 , 23 ] Vasomotor symptoms, experienced by over 80% of women, can last from 5 to 15 years, significantly impacting sleep, mood, cognition, and quality of life. [ 24 – 26 ] HRT has historically been the primary treatment, showing benefits with estrogen, gabapentin, paroxetine, and clonidine for vasomotor dysfunction, but health risk concerns lead many women to seek alternative options. [ 27 ] Gopal S et al examined the effects of 300 mg of ashwagandha root extract twice daily on climacteric symptoms in perimenopausal women over eight weeks in a randomized, double-blind, placebo-controlled study. Out of 91 participants, 46 women received ashwagandha and experienced significant improvements in symptoms within four weeks, including hot flashes. At the end of the study, the Ashwagandha group showed a decrease in overall MRS scores, accompanied by a statistically significant rise in serum estradiol and a notable decrease in serum FSH and LH levels compared to the placebo group. [ 13 ] Another study by Modi MB et al evaluated Ashokarishta , Ashwagandha Churna and Praval Pishti in the management of menopausal syndrome. Similar reductions in MRS scores and Menopause Specific Quality of Life (MENQoL) questionnaires score were found in 51 women who completed the study. [ 28 ] We observed similar findings in our study where statistically significant reduction in mean MRS score from 31.37 to 18.53 was noted (p < 0.001). This was associated with a statistically significant increase in serum estradiol (p < 0.001), serum progesterone (p < 0.001) and a significant reduction in serum FSH (p < 0.001) and serum LH (p < 0.001) compared with the placebo. There was also a statistically significant reduction in hot flashes events (p < 0.05) in the Ashwagandha group while increased events were noted in placebo group. While previous studies used MENQoL for quality-of-life assessment, we used SF-12 and PSS-10 scales to focus on physical, mental, and psychological wellbeing. Our result showed improvement in quality-of-life of menopausal women in Ashwagandha group reflected in statistically significant improvements in PCS-12, MCS-12, and PSS-10 scores (p < 0.001). Ashwagandha root extract is reported to be safe for human use with a daily dosage of up to 1,000 mg. [ 29 ] This finding is substantiated with our results as we did not observe any serious adverse events related to Ashwagandha and more than 90% of the participants reported tolerability of Ashwagandha as good to excellent. Moreover, treatment compliance was 100% in our study. Our findings add crucial evidence to the ashwagandha efficacy and safety assessment in addressing menopause symptoms. The primary strength of our study lies in its robust randomized, double-blind, and placebo-controlled design, which enhances the reliability of the findings. However, a notable limitation is the well-defined and homogeneous cohort, drawn from a specific cross-section of society. Future research conducted in a real-world setting with participants representing a wider range of demographics, occupations, and socio-economic statuses is necessary to validate and extend the applicability of the findings. Additionally, the study's shorter duration of eight weeks may limit the ability to draw conclusions about long-term benefits, warranting consideration in future investigations. 5. Conclusions This study evaluated the efficacy and safety of KSM-66 Ashwagandha® capsule (300 mg) in improving menopausal symptoms in women aged 45 to 55 years clinically diagnosed with menopause. Significant improvements in the MRS scores were reflected in psychological, somatic, and urogenital domains were observed with Ashwagandha. Oral administration of standardized Ashwagandha root extract for eight weeks improved outcomes in menopausal women covering multiple variables of menopausal symptoms. Abbreviations AG Ashwagandha PL Placebo HRT Hormone Replacement Therapy MRS Menopause Rating Scale HRQoL Health-Related Quality of Life MCS-12 Mental Component Score (from SF-12) PCS-12 Physical Component Score (from SF-12) SF-12 Short Form Survey-12 PSS-10 Perceived Stress Scale-10 FSH Follicle-Stimulating Hormone LH Luteinizing Hormone Declarations 7.1 Ethics approval and consent to participate Not applicable 7.2 Consent for publication Not applicable 7.3 Availability of data and materials The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. 7.4 Competing interests The authors declare no conflicts of interest with the publication of this study. 7.5 Funding This research did not receive financial grant from funding agencies in the public, commercial, or not-for-profit organization 7.6 Authors' contributions VI contributed to c onceptualization, methodology, investigation, resources, data collection and formal analysis, data curation, writing - original draft, writing - review & editing. BS and GM contributed towards project administration, resources, data collection and formal analysis, data curation, writing - review & editing. 7.7 Acknowledgements The authors thank Ixoreal BioMed Inc., Los Angeles, California, USA, for supplying the KSM-66 high concentration root extract used in this study. References Howkins B. Shaw’s A Textbook of Gynecology. Reprinted ed. Elsevier; 2005. pp. 56–67. Mashiloane CD, Bagratee J, Moodley J. Awareness of and attitude toward menopause and hormone replacement therapy in an African community. Int J Gynaecol Obstet. 2002;76:913. Cobin RH, Futterweit W, Ginzburg SB, et al. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the diagnosis and treatment of menopause. Endocr Pract. 2006;12(3):317. Davis SR, Lambrinoudaki I, Lumsden M, et al. Menopause Nat Rev Dis Primers. 2015;1:15004. Martin KA, Manson JE. Approach to the patient with menopausal symptoms. J Clin Endocrinol Metab. 2008;93(12):4567–75. Fait T. Menopause hormone therapy: latest developments and clinical practice. Drugs Context. 2019;8:212551. Wu CK, Tseng PT, Wu MK, et al. Antidepressants during and after Menopausal Transition: A Systematic Review and Meta-Analysis. Sci Rep. 2020;10(1):8026. Sharma CG. Ashwagandharishta – Rastantra Sar Evam Sidhyaprayog Sangrah. Nagpur, India. Krishna–Gopal Ayurveda Bhawan (Dharmarth Trust); 1938; 743–4. Vetvicka V, Vetvickova J. Immune enhancing effects of WB365, a novel combination of Ashwagandha (Withania somnifera) and Maitake (Grifola frondosa) extracts. N Am J Med Sci. 2011;3(7):320–4. Mishra LC, Singh BB, Dagenais S. Scientific basis for the therapeutic use of Withania somnifera (ashwagandha): a review. Altern Med Rev. 2000;5(4):334–46. Minhas U, Minz R, Bhatnagar A. Prophylactic effect of Withania somnifera on inflammation in a non-autoimmune prone murine model of lupus. Drug Discov Ther. 2011;5(4):195–201. Millar S. Ashwagandha and Hot Flashes. [Article available on internet] Available from: http://www.livestrong.com/article/187966 ashwagandha hotflashes. [Last updated 2012 Jul 28]. Gopal S, Ajgaonkar A, Kanchi P, Kaundinya A, Thakare V, Chauhan S, Langade D. Effect of an ashwagandha (Withania Somnifera) root extract on climacteric symptoms in women during perimenopause: A randomized, double-blind, placebo-controlled study. J Obstet Gynaecol Res. 2021;47(12):4414–25. 10.1111/jog.15030 . Heinemann K, Ruebig A, Potthoff P, et al. The Menopause Rating Scale (MRS) scale: a methodological review. Health Qual Life Outcomes. 2004;2:45. 12 – Item short form survey (SF-12). Physio-pedia. https://www.physio-pedia.com/12-Item_Short_Form_Survey_(SF-12 ). Updated 2021. Accessed 17 November 2021. Cohen S. Perceived stress scale. J Health Soc Behav. 1994;24:386–96. Dash A, Ravat S, Srinivasan A. Evaluation of safety and efficacy of zonisamide in adult patients with partial, generalized, and combined seizures: an open labeled, noncomparative, observational Indian study. Ther Clin Risk Manag. 2016;12:327–34. Sussman M, Trocio J, Best C, Mirkin S, Bushmakin AG, Yood R, Friedman M, Menzin J, Louie M. Prevalence of menopausal symptoms among mid-life women: findings from electronic medical records. BMC Womens Health. 2015;15:58. 10.1186/s12905-015-0217-y . PMID: 26271251; PMCID: PMC4542113. Treloar AE. Menstrual cyclicity and the pre-menopause. Maturitas. 1981;3(3–4):249 – 64. 10.1016/0378-5122(81)90032-3 . PMID: 7334935. Hill K. The demography of menopause. Maturitas. 1996;23(2):113 – 27. 10.1016/0378-5122(95)00968-x . PMID: 8735350. Takahashi TA, Johnson KM, Menopause. Med Clin North Am. 2015;99(3):521 – 34. 10.1016/j.mcna.2015.01.006 . PMID: 25841598. Woods NF, Mitchell ES. Symptoms during the perimenopause: prevalence, severity, trajectory, and significance in women's lives. Am J Med. 2005;118 Suppl 12B:14–24. 10.1016/j.amjmed.2005.09.031 . PMID: 16414323. Thurston RC, Joffe H. Vasomotor symptoms and menopause: findings from the Study of Women's Health across the Nation. Obstet Gynecol Clin North Am. 2011;38(3):489–501. 10.1016/j.ogc.2011.05.006 . PMID: 21961716; PMCID: PMC3185243. Dennerstein L, Lehert P, Burger HG, Guthrie JR. New findings from non-linear longitudinal modelling of menopausal hormone changes. Hum Reprod Update. 2007 Nov-Dec;13(6):551–7. 10.1093/humupd/dmm022 . Epub 2007 Jul 6. PMID: 17616552. Shapiro M. Menopause practice: A clinician’s guide. Can Fam Physician. 2012;58(9):989. Utian WH. Psychosocial and socioeconomic burden of vasomotor symptoms in menopause: a comprehensive review. Health Qual Life Outcomes. 2005;3:47. 10.1186/1477-7525-3-47 . PMID: 16083502; PMCID: PMC1190205. Nelson HD, Menopause. Lancet. 2008;371(9614):760 – 70. 10.1016/S0140-6736(08)60346-3 . PMID: 18313505. Modi MB, Donga SB, Dei L. Clinical evaluation of Ashokarishta, Ashwagandha Churna and Praval Pishti in the management of menopausal syndrome. Ayu. 2012;33(4):511–6. 10.4103/0974-8520.110529 . Kelgane SB, Salve J, Sampara P et al. February 23,. (2020) Efficacy and Tolerability of Ashwagandha Root Extract in the Elderly for Improvement of General Well-being and Sleep: A Prospective, Randomized, Double-blind, Placebo-controlled Study. Cureus 12(2): e7083. 10.7759/cureus.7083 Additional Declarations No competing interests reported. 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. 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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-6409321","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":440845354,"identity":"be84a340-67f5-4e26-b791-98eda95d07b6","order_by":0,"name":"Isukapalli Vani","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABB0lEQVRIiWNgGAWjYJCCAwkMDAZAmvHAAwMbObDIAyK1ABkGacYwEYIAqoXhUGIDiIVPi8HxswcPPPhz2Jh/dvODAwkFB9Lnhx1+CNRrJ6fbgEPLmbyEA4lth80k7hwzADrsTu7G22lABkOysdkB7FokG3IMDiQ2HLZhuJEA0vIsd+NsEIPhQOI2XFr63wAV/DlsI38j/QNQy+F0w9kgBh4t/BJAWxLYDpsZ3AAxDA4nyEvn4LeFXwJoS2JburHhnTMFoEA23CCdA2Lg9gsbf47xxx9/rA3n3W7f+ODDHxt5+dnpmz98qLCTw6UFASSgtAFYpQEh5cha5BuIUT0KRsEoGAUjCQAA/rJwG25dotQAAAAASUVORK5CYII=","orcid":"","institution":"Govt. Medical College \u0026 Govt. General Hospital (Old RIMSGGH)","correspondingAuthor":true,"prefix":"","firstName":"Isukapalli","middleName":"","lastName":"Vani","suffix":""},{"id":440845355,"identity":"7c09bb3e-b0ce-4370-8d8f-e711186872aa","order_by":1,"name":"Gudla Muralidhar","email":"","orcid":"","institution":"Govt. Medical College \u0026 Govt. General Hospital (Old RIMSGGH)","correspondingAuthor":false,"prefix":"","firstName":"Gudla","middleName":"","lastName":"Muralidhar","suffix":""},{"id":440845356,"identity":"dcf73c30-40eb-4e88-8d85-ea7e7f120540","order_by":2,"name":"Bade Srinivas Rao","email":"","orcid":"","institution":"Govt. Medical College \u0026 Govt. General Hospital (Old RIMSGGH)","correspondingAuthor":false,"prefix":"","firstName":"Bade","middleName":"Srinivas","lastName":"Rao","suffix":""}],"badges":[],"createdAt":"2025-04-09 07:53:17","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6409321/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6409321/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":80304935,"identity":"0bc2b8cf-2d21-4525-b638-c04884db0548","added_by":"auto","created_at":"2025-04-10 10:06:29","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":157965,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eCONSORT flow representation of the patient enrollment, allocation, follow-up and analysis\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-6409321/v1/aa9d2cabf0302515b77276af.png"},{"id":80307313,"identity":"78e9b3c8-4248-4b2d-9d6b-944f7d7c9538","added_by":"auto","created_at":"2025-04-10 10:30:31","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1384260,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6409321/v1/e4d95e4d-6fce-4dac-99a8-b25ee68a1de6.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Prospective, Randomized, Double-blind, Placebo Controlled Study on Safety and Efficacy of Ashwagandha Root Extract (Withania Somnifera) on Menopause Symptoms","fulltext":[{"header":"1. Background","content":"\u003cp\u003eMenopause is defined as absence of menstrual periods for 12 consecutive months or equivalent to three previous cycles, indicating the end of ovarian function and permanent amenorrhea. There is a gradual transition observed from active to inactive ovarian function, spanning over several years. Besides its association with aging, menopause involves noticeable biological and psychological changes in women. \u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eThe downsize in production of estrogen and progesterone during menopause makes women more vulnerable to psychosomatic issues. Most common symptoms observed are hot flashes, sweating, mood changes, and libido alterations. However, other specific complaints associated with menopause are vasomotor symptoms, sleep disturbances, urogenital problems, breast and joint pain, cognitive changes and mood disorders such as depression and anxiety. \u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eCurrently, a combination of hormone replacement therapy (HRT), pharmaceutical antidepressants, and lifestyle changes are used as therapeutic option. But HRT is associated with an increased risk of venous thromboembolism, stroke, cardiovascular disease, gallstones, and breast cancer. Furthermore, the tendency of women to discontinue antidepressant due to adverse events is high. It was also reported that HRT is not effective in addressing psychological manifestations. \u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan additionalcitationids=\"CR6\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eAshwagandha, scientifically known as \u003cem\u003eWithania somnifera\u003c/em\u003e (WS) has been a significant herb in Ayurveda. As a potent adaptogen, it boosts the body's resilience to stress, improves cell-mediated immunity, and possesses powerful antioxidant properties. Ashwagandha is revered for its ability to balance, energize, rejuvenate, and revitalize the body system. \u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eThe chemical composition and prophylactic effect of WS in maintaining immune homeostasis is well studied and documented. \u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e The effects of Ashwagandha on central nervous system and the immune system might be useful in reducing hot flashes. \u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e Using therapeutic properties of Ashwagandha along with HRT could give broader coverage of menopausal symptoms.\u003c/p\u003e \u003cp\u003eHence, the present study was conducted to assess the safety and efficacy of the KSM-66 Ashwagandha\u0026reg; root extract capsule (300 mg) in patients experiencing menopausal symptoms with emphasis on Menopause Rating Scale (MRS).\u003c/p\u003e"},{"header":"2. Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Study Design\u003c/h2\u003e \u003cp\u003eThis was a randomized, prospective, double-blind, placebo-controlled study. The approval of the institutional ethics committee was obtained for this study. It was performed in accordance with Good Clinical Practice guidelines and the ethical principles outlined in the Declaration of Helsinki. The Consolidated Standards of Reporting Trials (CONSORT) guidelines for designing and reporting controlled trials were followed. The study was registered with the Clinical Trial Registry of India (CTRI/2022/02/040551).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Study Population\u003c/h2\u003e \u003cp\u003eAn adult female subjects aged 45 to 55 years with a clinical diagnosis of menopause with no history of hormone therapy or antidepressant treatment in the past 3 months were included in the study. Demographic parameters included a body mass index (BMI) within the range of 20 to 30 Kg/m\u0026sup2; and history of 10 or more hot flashes events per week. Prior to enrollment, each participant was explained in detail about the study and written informed consent was obtained from all participants.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3 Study Procedure\u003c/h2\u003e \u003cp\u003eRandomization was conducted in a 1:1 ratio, with patients being randomly assigned to receive either KSM-66 Ashwagandha\u0026reg; capsule 300 mg (Shri Kartikeya Pharma, India) (Ashwagandha group, AG, n\u0026thinsp;=\u0026thinsp;30) or an Identical Placebo (Placebo group, PL, n\u0026thinsp;=\u0026thinsp;30) twice daily after meals (breakfast and dinner) in a double-blinded setting. The study consisted of two site visits (baseline visit - day 1, end of study - day 56), and one telephonic follow-up visit (day 28). All assessments were carried out at the study center during visit 1 (Day 1) and visit 3 (Day 56) while telephonic follow-up visit was conducted to verify drug, protocol compliance and collect details on any adverse events (AEs) without any formal assessment.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4 Efficacy Assessments\u003c/h2\u003e \u003cdiv id=\"Sec7\" class=\"Section3\"\u003e \u003ch2\u003e2.4.1 Primary Outcome Measures\u003c/h2\u003e \u003cp\u003eThe Menopause Rating Scale (MRS) is a standardized Health-Related Quality of Life Scale (HRQoL) with good psychometric characteristics.\u003csup\u003e[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e The MRS and the mean change in the MRS from baseline were descriptively summarized for each visit and by treatment.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section3\"\u003e \u003ch2\u003e2.4.2 Secondary Outcome Measures\u003c/h2\u003e \u003cp\u003eThe secondary outcomes of the study were mean change in summary scores Mental Component Score (MCS-12) and a Physical Component Score (PCS-12) from Short Form survey (SF-12) \u003csup\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e, Perceived Stress Scale-10 (PSS-10) \u003csup\u003e[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/sup\u003e, serum hormones (Estradiol, Progesterone, FSH, LH), and hot flashes events.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e2.5 \u003cem\u003eSafety Assessment and Treatment Compliance\u003c/em\u003e\u003c/h2\u003e \u003cp\u003ePatient's Global Assessment of Tolerability to Therapy (PGATT) \u003csup\u003e[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/sup\u003e was assessed based on a four-point rating scale as follows: 1\u0026thinsp;=\u0026thinsp;excellent tolerability, 2\u0026thinsp;=\u0026thinsp;good tolerability, 3\u0026thinsp;=\u0026thinsp;average tolerability, and 4\u0026thinsp;=\u0026thinsp;poor tolerability. This scoring was done by the patients. The adherence to the assigned regimen was assessed and verified by study personnel through recording the dosing of the investigational products.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003e2.6 \u003cem\u003eStatistical Methods\u003c/em\u003e\u003c/h2\u003e \u003cp\u003eThe sample size calculation was done based on the primary endpoint. With two-sided level of significance as 5%, randomization ratio as 1:1 and power as 90%, the study required in all 54 evaluable subjects (27 subjects in each arm). However, total 60 women (30 in each group) were enrolled in the study. All relevant statistical calculations were completed using Stata 13.0 IC (Stata Corp. USA). Since all women completed the study as per the study protocol, both efficacy and safety analysis were performed on all patient\u0026rsquo;s dataset data (n\u0026thinsp;=\u0026thinsp;60). All analyses were done using two-sided tests and a p-value of less than 0.05 was considered the threshold to claim statistical significance. For categorical variables, the number and percentage of subjects within each category (with category for missing data as needed) of the parameter were presented and P-values were determined by Chi-square test between the groups (AG vs. PL). For continuous variables, the number of subjects, mean, median, standard deviation (SD), minimum and maximum values were presented. Paired t-test was used for the within group (Baseline-Day 56) comparison, Two-independent samples t-test was used for the between group (AG vs. PL) comparison at Baseline and Day 56 and Analysis of Covariance (ANCOVA) was used for the comparison of between group (AG vs. PL) after controlling baseline.\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results","content":"\u003cp\u003eA total of 73 participants underwent initial screening and eligibility assessment. Among them, 13 did not meet the eligibility criteria (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Subsequently, the remaining 60 participants were enrolled and randomized. No participants from either group were excluded due to follow-up loss or failure of medication adherence.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003e3.1 \u003cem\u003eDemographics and Baseline Data\u003c/em\u003e\u003c/h2\u003e \u003cp\u003eThe demographics data and medical history of patients enrolled and randomized in two groups (Intent to treat (ITT) dataset) were compared using two-independent sample t-tests and chi-square tests. The mean age for AG was 49.8\u0026thinsp;\u0026plusmn;\u0026thinsp;2.4 years and for PL was 50.0\u0026thinsp;\u0026plusmn;\u0026thinsp;2.3 years (p\u0026thinsp;=\u0026thinsp;0.700), indicating no significant difference. The mean BMI for AG was 24.9\u0026thinsp;\u0026plusmn;\u0026thinsp;2.4 and for PL was 25.0\u0026thinsp;\u0026plusmn;\u0026thinsp;2.5 (p\u0026thinsp;=\u0026thinsp;0.955), also showing no significant difference. The prevalence of co-morbidities such as anxiety (AG: 6.7%, PL: 3.3%, p\u0026thinsp;=\u0026thinsp;0.549), constipation (AG: 3.3%, PL: 0%, p\u0026thinsp;=\u0026thinsp;0.319), diabetes (AG: 6.7%, PL: 3.3%, p\u0026thinsp;=\u0026thinsp;0.549), hypertension (AG: 26.7%, PL: 16.7%, p\u0026thinsp;=\u0026thinsp;0.351), and obesity (AG: 50%, PL: 43.3%, p\u0026thinsp;=\u0026thinsp;0.605) were also not significantly different between the two groups.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003e3.2 Vital parameters\u003c/h2\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e presents the vital parameters at baseline (day 1) and end of study period (day 56) without any significant changes in the two groups (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). The physical examination of patients in either group was found to be within normal parameters.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eVital parameters and laboratory values at baseline and end of study.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eAG (n\u0026thinsp;=\u0026thinsp;30)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e \u003cp\u003ePL (n\u0026thinsp;=\u0026thinsp;30)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDay 1\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDay 56\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eDay 1\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eDay 56\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMean (SD)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMean (SD)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eMean (SD)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMean (SD)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSBP (mmHg)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e142.50 (20.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e140.8 (19.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.748\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e129.8 (16.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e130.0 (16.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.969\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDBP (mmHg)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e90.0 (10.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e88.8 (9.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.653\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e84.5 (7.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e84.3 (7.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.932\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePulse Rate (/min)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e95.3 (15.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e94.1 (15.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.770\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e84.7 (7.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e84.9 (7.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.927\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRespiration Rate (/min)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20.5 (2.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20.4 (2.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.858\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e19.4 (2.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e19.4 (2.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.999\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTemperature (˚C)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36.5 (0.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36.5 (0.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.999\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e36.6 (0.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e36.6 (0.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.812\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHaemoglobin (g/dL)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12.2 (0.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12.6 (1.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.177\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e11.7 (0.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e11.7 (0.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.753\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRBC count (x10^6/\u0026micro;L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.7 (0.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.8 (0.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.336\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.7 (0.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4.6 (0.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.823\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHaematocrit (PCV) (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e42.9 (3.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e43.2 (3.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e43.0 (3.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e41.1 (4.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.084\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTLC (cells/\u0026micro;L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4740.0 (447.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4736.7 (426.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.997\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4846.7 (337.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4693.3 (865.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.37\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLymphocytes (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29.2 (5.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29.1 (5.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.926\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e32.3 (6.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e32.9 (6.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.752\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMonocytes (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.7 (1.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.7 (1.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.958\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.5 (1.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5.4 (1.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.775\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eEosinophils (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.3 (1.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.4 (1.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.757\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.1 (1.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.2 (1.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.518\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBasophils (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.5 (0.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.5 (0.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.848\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.5 (0.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.5 (0.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.533\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAbsolute Neutrophils (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3930.0 (490.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3933.3 (488.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.979\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3916.7 (472.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3893.3 (441.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.844\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePlatelet Count (cells/\u0026micro;L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e159833.3 (10627.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e160350.0 (9150.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.841\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e159566.7 (12475.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e160100.0 (0.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.861\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTotal bilirubin (mg/dL)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.5 (0.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.5 (0.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.897\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.6 (0.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.6 (0.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.46\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAST/SGOT (U/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12.2 (3.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11.7 (3.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.553\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e12.3 (3.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e13.0 (3.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.44\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eALT/SGPT (U/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10.3 (3.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (3.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e12.4 (3.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e13.1 (3.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.393\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eALP (U/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e101.4 (13.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e103.9 (15.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e101.5 (17.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e103.5 (20.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.681\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBUN (mg/dL)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9.5 (2.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.5 (2.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.999\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9.4 (1.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e9.4 (1.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.999\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCreatinine (mg/dL)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.8 (0.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.8 (0.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.803\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.7 (0.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.7 (0.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.702\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTotal Cholesterol (mg/dL)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e192.0 (30.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e192.0 (30.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.999\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e190.8 (16.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e191.8 (16.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.824\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e \u003cp\u003e\u003cem\u003eAG: Ashwagandha; PL: Placebo; SD: Standard Deviation; PCV: Packed Cell Volume; TLC: Total Leukocyte Count; AST/SGOP: Aspartate aminotransferase; ALT/SGPT: Alanine aminotransferase; ALP: Alkaline phosphatase; BUN: Blood Urea Nitrogen\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e(Added at end due to larger length than A4 size)\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003e3.3 Efficacy Assessment\u003c/h2\u003e \u003cdiv id=\"Sec15\" class=\"Section3\"\u003e \u003ch2\u003e3.3.1 Menopause Rating Scale\u003c/h2\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e shows the Menopause Rating Scale (MRS) and its sub-domain scores at baseline (day 1) and end of study period (day 56). Greater reduction in scores was seen in AG group as compared to PL group (p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001). There was greater reduction in mean (SD) total MRS scores with AG (from 31.37 (1.45) at baseline to 18.53 (2.29) at day 56) as compared to placebo (p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001). This reduction was observed in all sub-scales (psychological, somatic, and urogenital) of the MRS scale.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMenopause Rating Scale scores in two groups.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eMRS and sub-domain scores\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAG (N\u0026thinsp;=\u0026thinsp;30)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePL (N\u0026thinsp;=\u0026thinsp;30)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eP-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eMean (SD)\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eMean (SD)\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePsychological score\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026bull; Baseline\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e12.77 (1.41)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e12.58 (1.42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.605\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026bull; Day 56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7.07 (1.05)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e12.33 (1.52)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026bull; Change from baseline\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-5.7 (0.36)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e-0.25 (-0.10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSomatic score\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026bull; Baseline\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e12.03 (1.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e11.87 (1.45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.6488\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026bull; Day 56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6.97 (1.07)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e11.77 (0.90)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026bull; Change from baseline\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-5.06 (0.18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e-0.1 (0.55)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eUrogenital score\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026bull; Baseline\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6.57 (0.82)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6.28 (1.13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.2599\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026bull; Day 56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4.5 (1.01)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5.93 (1.26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026bull; Change from baseline\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-2.07 (0.19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e-0.35 (-0.13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMRS total score\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026bull; Baseline\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e31.37 (1.45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e30.73 (2.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.235\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026bull; Day 56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e18.53 (2.29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e30.03 (2.55)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026bull; Change from baseline\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-12.84 (0.40)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e-0.7 (0.20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003cem\u003eAG: Ashwagandha; PL: Placebo; SD: Standard Deviation; MRS: Menstrual Rating Scale\u003c/em\u003e\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003cem\u003e* Statistically significant at \u0026lt;\u0026thinsp;0.0001\u003c/em\u003e\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section3\"\u003e \u003ch2\u003e3.3.2 Hormone Levels and Hot Flashes\u003c/h2\u003e \u003cp\u003eTables\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e shows the serum hormone levels and occurrence of hot flashes respectively. There were statistically significant changes observed in all parameters between the two groups (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Serum estradiol and serum progesterone levels increased in AG group while luteinizing hormone (LH), follicle stimulating hormone (FSH) increased in PL group. There was non-significant decrease in hot flashes score (number of events) in both the groups at day 56 compared to baseline (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05) however this reduction was statistically significant when compared between the groups (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eHormone levels and scores for hot flashes in the two groups.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" morerows=\"1\" nameend=\"c2\" namest=\"c1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAG (N\u0026thinsp;=\u0026thinsp;30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePL (N\u0026thinsp;=\u0026thinsp;30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cem\u003e\u0026lsquo;p\u0026rsquo; value\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003ebetween group\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMean (SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMean (SD)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e\u003cb\u003eSerum\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003eEstradiol (pg/dL)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBaseline \u0026ndash; \u003cem\u003eMean (SD)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22.2 (3.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e22.2 (3.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.999\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDay 56 \u0026ndash; \u003cem\u003eMean (SD)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23.2 (3.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21.6 (3.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.068\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eChange \u0026ndash; \u003cem\u003eMean change\u003c/em\u003e\u0026thinsp;\u0026plusmn;\u0026thinsp;\u003cem\u003eSE\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e(\u0026lsquo;p\u0026rsquo; value Within group)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.0 \u0026plusmn;\u0026thinsp;0.2\u003c/p\u003e \u003cp\u003e(\u0026lt;\u0026thinsp;0.001) *\u003c/p\u003e\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.6\u0026thinsp;\u0026plusmn;\u0026thinsp;0.2\u003c/p\u003e \u003cp\u003e(0.012) *\u003c/p\u003e\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e\u003cb\u003eSerum\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003eProgesterone (ng/dL)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBaseline \u0026ndash; \u003cem\u003eMean (SD)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.283 (0.079)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.307 (0.069)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.229\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDay 56 \u0026ndash; \u003cem\u003eMean (SD)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.433 (0.190)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.300 (0.083)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.001*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eChange \u0026ndash; \u003cem\u003eMean change\u003c/em\u003e\u0026thinsp;\u0026plusmn;\u0026thinsp;\u003cem\u003eSE\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e(\u0026lsquo;p\u0026rsquo; value Within group)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.150\u0026thinsp;\u0026plusmn;\u0026thinsp;0.032\u003c/p\u003e \u003cp\u003e(\u0026lt;\u0026thinsp;0.001) *\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.0067\u0026thinsp;\u0026plusmn;\u0026thinsp;0.013 (0.601)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e\u003cb\u003eSerum LH (IU/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBaseline \u0026ndash; \u003cem\u003eMean (SD)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36.8 (8.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e34.8 (7.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.328\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDay 56 \u0026ndash; \u003cem\u003eMean (SD)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35.5 (8.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e35.6 (7.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.948\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eChange \u0026ndash; \u003cem\u003eMean change\u003c/em\u003e\u0026thinsp;\u0026plusmn;\u0026thinsp;\u003cem\u003eSE\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e(\u0026lsquo;p\u0026rsquo; value Within group)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-1.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.2\u003c/p\u003e \u003cp\u003e(\u0026lt;\u0026thinsp;0.0001) *\u003c/p\u003e\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.8\u0026thinsp;\u0026plusmn;\u0026thinsp;0.2\u003c/p\u003e \u003cp\u003e(0.001) *\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e\u003cb\u003eSerum FSH (IU/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBaseline \u0026ndash; \u003cem\u003eMean (SD)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e61.9 (16.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e58.2 (15.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.362\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDay 56 \u0026ndash; \u003cem\u003eMean (SD)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e60.9 (15.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e58.6 (15.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.574\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eChange \u0026ndash; \u003cem\u003eMean change\u003c/em\u003e\u0026thinsp;\u0026plusmn;\u0026thinsp;\u003cem\u003eSE\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e(\u0026lsquo;p\u0026rsquo; value Within group)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-1.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.2\u003c/p\u003e \u003cp\u003e(\u0026lt;\u0026thinsp;0.001) *\u003c/p\u003e\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.2\u003c/p\u003e \u003cp\u003e(0.034) *\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e\u003cb\u003eNo. of Hot Flashes events\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBaseline \u0026ndash; \u003cem\u003eMean (SD)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14.5 (2.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14.6 (2.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.855\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDay 56 \u0026ndash; \u003cem\u003eMean (SD)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10.6 (2.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14.0 (2.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.078\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eChange \u0026ndash; \u003cem\u003eMean change\u003c/em\u003e\u0026thinsp;\u0026plusmn;\u0026thinsp;\u003cem\u003eSE\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e(\u0026lsquo;p\u0026rsquo; value Within group)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-3.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5\u003c/p\u003e \u003cp\u003e(\u0026lt;\u0026thinsp;0.001) *\u003c/p\u003e\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.6\u0026thinsp;\u0026plusmn;\u0026thinsp;0.2\u003c/p\u003e \u003cp\u003e(0.001) *\u003c/p\u003e\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003cem\u003eAG: Ashwagandha; PL: Placebo; SD: Standard Deviation; FSH: Follicle stimulating hormone; LH: Luteinizing hormone; IU: International units; dL: Deciliter\u003c/em\u003e\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003cem\u003e* Statistically significant\u003c/em\u003e\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e(Added at end due to larger length than A4 size)\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section3\"\u003e \u003ch2\u003e3.3.3 Short Form Survey (SF-12)\u003c/h2\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e shows the SF-12 (PCS-12, MCS-12) and PSS-10 scores at baseline (day 1) and end of study period (day 56). There was marked improvement in all SF-12 scores in both the groups and between the groups (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec18\" class=\"Section3\"\u003e \u003ch2\u003e3.3.4 Perceived Stress Scale (PSS-10)\u003c/h2\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e shows the PSS-10 scores at baseline (day 1) and end of study period (day 56). There was a marked improvement in all PSS-10 score in the AG group and the changes were statistically significant between the groups (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). There was reduction (improvement) in mean (SD) PSS-10 score from baseline to day 56 in AG group (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) with statistically non-significant negligible change from baseline to day 56 in PL group scores (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSF-12 (PCS-12, MCS-12) and PSS scores in two groups.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" morerows=\"1\" nameend=\"c2\" namest=\"c1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAG (N\u0026thinsp;=\u0026thinsp;30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePL (N\u0026thinsp;=\u0026thinsp;30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cem\u003e\u0026lsquo;p\u0026rsquo; value\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003ebetween group\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMean (SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMean (SD)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003ePCS-12 (SF-12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBaseline \u0026ndash; \u003cem\u003eMean (SD)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23.2 (1.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e22.7 (1.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.193\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDay 56 \u0026ndash; \u003cem\u003eMean (SD)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e49.9 (2.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e34.2 (3.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eChange \u0026ndash; \u003cem\u003eMean change\u003c/em\u003e\u0026thinsp;\u0026plusmn;\u0026thinsp;\u003cem\u003eSE\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e(\u0026lsquo;p\u0026rsquo; value Within group)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5 (\u0026lt;\u0026thinsp;0.001*)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11.5\u0026thinsp;\u0026plusmn;\u0026thinsp;0.7 (\u0026lt;\u0026thinsp;0.001*)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eMCS-12 (SF-12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBaseline \u0026ndash; \u003cem\u003eMean (SD)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28.2 (7.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e30.8 (6.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.175\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDay 56 \u0026ndash; \u003cem\u003eMean (SD)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e53.6 (2.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e36.4 (6.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eChange \u0026ndash; \u003cem\u003eMean change\u003c/em\u003e\u0026thinsp;\u0026plusmn;\u0026thinsp;\u003cem\u003eSE\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e(\u0026lsquo;p\u0026rsquo; value Within group)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25.5\u0026thinsp;\u0026plusmn;\u0026thinsp;1.5 (\u0026lt;\u0026thinsp;0.001*)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.2 (\u0026lt;\u0026thinsp;0.001*)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003ePSS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBaseline \u0026ndash; \u003cem\u003eMean (SD)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28.5 (3.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e27.7 (3.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.281\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDay 56 \u0026ndash; \u003cem\u003eMean (SD)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15.1 (3.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e27.4 (3.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eChange \u0026ndash; \u003cem\u003eMean change\u003c/em\u003e\u0026thinsp;\u0026plusmn;\u0026thinsp;\u003cem\u003eSE\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e(\u0026lsquo;p\u0026rsquo; value Within group)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-13.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.7 (\u0026lt;\u0026thinsp;0.001*)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.2\u003c/p\u003e \u003cp\u003e(0.326)\u003c/p\u003e\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003cem\u003eAG: Ashwagandha; PL: Placebo; SD: Standard Deviation; PCS-12; Physical component score; MCS-12; Mental component score; PSS: Perceived stress scale\u003c/em\u003e\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003cem\u003e* Statistically significant\u003c/em\u003e\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec19\" class=\"Section2\"\u003e \u003ch2\u003e3.4 Safety Assessment and Treatment Compliance\u003c/h2\u003e \u003cp\u003eTotal 3 women (1 in AG group and 2 in PL group) reported adverse events. One woman in AG group reported cough and cold while two women in PL group reported stomachache and indigestion respectively. All events were of mild severity, were not associated with the study treatments, and completely resolved with or without symptomatic treatment. None of the women stopped treatment due to adverse event and treatment compliance was 100% in both the groups.\u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e shows the Patient\u0026rsquo;s Global Assessment of Tolerability to Therapy (PGATT) parameters. The tolerability of Ashwagandha was reported between good to excellent by most of the patients in AG group compared to placebo in the PL group (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Twenty-eight patients (93.3%) in AG group rated the tolerability of Ashwagandha as \u0026lsquo;good\u0026rsquo; to \u0026lsquo;excellent\u0026rsquo;.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePGATT parameters at Baseline and End of Study Period\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAG (N\u0026thinsp;=\u0026thinsp;30)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePL (N\u0026thinsp;=\u0026thinsp;30)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eChi-square Test\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eNo. (%)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eNo. (%)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eχ2\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003e\u0026lsquo;p\u0026rsquo;\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eExcellent Tolerability\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (43.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (-)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003e22.941\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGood Tolerability\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15 (50.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (50.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAverage Tolerability\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (-)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (-)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePoor Tolerability\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (6.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (50.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003cem\u003eAG: Ashwagandha; PL: Placebo\u003c/em\u003e\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003cem\u003e* Statistically significant\u003c/em\u003e\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eMenopause, occurring typically between ages 45\u0026ndash;52, entails hormonal changes leading to the cessation of menstrual cycles. \u003csup\u003e[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/sup\u003e By 2030, an estimated 1.2\u0026nbsp;billion women globally will be menopausal or postmenopausal, with 47\u0026nbsp;million new entrants annually.\u003csup\u003e[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e Menopause encompasses roughly one-third of a woman's lifespan. It is marked by irregular menstrual cycles and hot flashes due to hormonal changes and aging. Postmenopausal symptoms feature genitourinary concerns such as vulvovaginal atrophy and urinary symptoms.\u003csup\u003e[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/sup\u003e Over 85% of women experience challenging symptoms such as hot flashes, night sweats, sleep disturbances, sexual dysfunction, mood disorders, weight gain, and cognitive decline.\u003csup\u003e[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/sup\u003e Vasomotor symptoms, experienced by over 80% of women, can last from 5 to 15 years, significantly impacting sleep, mood, cognition, and quality of life.\u003csup\u003e[\u003cspan additionalcitationids=\"CR25\" citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]\u003c/sup\u003e HRT has historically been the primary treatment, showing benefits with estrogen, gabapentin, paroxetine, and clonidine for vasomotor dysfunction, but health risk concerns lead many women to seek alternative options.\u003csup\u003e[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eGopal S \u003cem\u003eet al\u003c/em\u003e examined the effects of 300 mg of ashwagandha root extract twice daily on climacteric symptoms in perimenopausal women over eight weeks in a randomized, double-blind, placebo-controlled study. Out of 91 participants, 46 women received ashwagandha and experienced significant improvements in symptoms within four weeks, including hot flashes. At the end of the study, the Ashwagandha group showed a decrease in overall MRS scores, accompanied by a statistically significant rise in serum estradiol and a notable decrease in serum FSH and LH levels compared to the placebo group.\u003csup\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e Another study by Modi MB \u003cem\u003eet al\u003c/em\u003e evaluated \u003cem\u003eAshokarishta\u003c/em\u003e, \u003cem\u003eAshwagandha Churna\u003c/em\u003e and \u003cem\u003ePraval Pishti\u003c/em\u003e in the management of menopausal syndrome. Similar reductions in MRS scores and Menopause Specific Quality of Life (MENQoL) questionnaires score were found in 51 women who completed the study.\u003csup\u003e[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]\u003c/sup\u003e We observed similar findings in our study where statistically significant reduction in mean MRS score from 31.37 to 18.53 was noted (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). This was associated with a statistically significant increase in serum estradiol (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), serum progesterone (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and a significant reduction in serum FSH (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and serum LH (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) compared with the placebo. There was also a statistically significant reduction in hot flashes events (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) in the Ashwagandha group while increased events were noted in placebo group. While previous studies used MENQoL for quality-of-life assessment, we used SF-12 and PSS-10 scales to focus on physical, mental, and psychological wellbeing. Our result showed improvement in quality-of-life of menopausal women in Ashwagandha group reflected in statistically significant improvements in PCS-12, MCS-12, and PSS-10 scores (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003eAshwagandha root extract is reported to be safe for human use with a daily dosage of up to 1,000 mg. \u003csup\u003e[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]\u003c/sup\u003e This finding is substantiated with our results as we did not observe any serious adverse events related to Ashwagandha and more than 90% of the participants reported tolerability of Ashwagandha as good to excellent. Moreover, treatment compliance was 100% in our study. Our findings add crucial evidence to the ashwagandha efficacy and safety assessment in addressing menopause symptoms.\u003c/p\u003e \u003cp\u003eThe primary strength of our study lies in its robust randomized, double-blind, and placebo-controlled design, which enhances the reliability of the findings. However, a notable limitation is the well-defined and homogeneous cohort, drawn from a specific cross-section of society. Future research conducted in a real-world setting with participants representing a wider range of demographics, occupations, and socio-economic statuses is necessary to validate and extend the applicability of the findings. Additionally, the study's shorter duration of eight weeks may limit the ability to draw conclusions about long-term benefits, warranting consideration in future investigations.\u003c/p\u003e"},{"header":"5. Conclusions","content":"\u003cp\u003eThis study evaluated the efficacy and safety of KSM-66 Ashwagandha\u0026reg; capsule (300 mg) in improving menopausal symptoms in women aged 45 to 55 years clinically diagnosed with menopause. Significant improvements in the MRS scores were reflected in psychological, somatic, and urogenital domains were observed with Ashwagandha. Oral administration of standardized Ashwagandha root extract for eight weeks improved outcomes in menopausal women covering multiple variables of menopausal symptoms.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 312px;\"\u003e\n \u003cp\u003eAG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 312px;\"\u003e\n \u003cp\u003eAshwagandha\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 312px;\"\u003e\n \u003cp\u003ePL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 312px;\"\u003e\n \u003cp\u003ePlacebo\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 312px;\"\u003e\n \u003cp\u003eHRT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 312px;\"\u003e\n \u003cp\u003eHormone Replacement Therapy\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 312px;\"\u003e\n \u003cp\u003eMRS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 312px;\"\u003e\n \u003cp\u003eMenopause Rating Scale\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 312px;\"\u003e\n \u003cp\u003eHRQoL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 312px;\"\u003e\n \u003cp\u003eHealth-Related Quality of Life\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 312px;\"\u003e\n \u003cp\u003eMCS-12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 312px;\"\u003e\n \u003cp\u003eMental Component Score (from SF-12)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 312px;\"\u003e\n \u003cp\u003ePCS-12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 312px;\"\u003e\n \u003cp\u003ePhysical Component Score (from SF-12)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 312px;\"\u003e\n \u003cp\u003eSF-12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 312px;\"\u003e\n \u003cp\u003eShort Form Survey-12\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 312px;\"\u003e\n \u003cp\u003ePSS-10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 312px;\"\u003e\n \u003cp\u003ePerceived Stress Scale-10\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 312px;\"\u003e\n \u003cp\u003eFSH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 312px;\"\u003e\n \u003cp\u003eFollicle-Stimulating Hormone\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 312px;\"\u003e\n \u003cp\u003eLH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 312px;\"\u003e\n \u003cp\u003eLuteinizing Hormone\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cem\u003e7.1 Ethics approval and consent to participate\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e7.2 Consent for publication\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e7.3 Availability of data and materials\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e7.4 Competing interests\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no conflicts of interest with the publication of this study.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e7.5 Funding\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThis research did not receive financial grant from funding agencies in the public, commercial, or not-for-profit organization\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e7.6 Authors' contributions\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eVI\u0026nbsp;\u003c/strong\u003econtributed to\u003cstrong\u003e\u0026nbsp;c\u003c/strong\u003eonceptualization, methodology, investigation, resources, data collection and formal analysis, data curation, writing - original draft, writing - review \u0026amp; editing. \u003cstrong\u003eBS and\u003c/strong\u003e \u003cstrong\u003eGM\u0026nbsp;\u003c/strong\u003econtributed towards project administration, resources, data collection and formal analysis, data curation, writing - review \u0026amp; editing.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e7.7 Acknowledgements\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe authors thank Ixoreal BioMed Inc., Los Angeles, California, USA, for supplying the KSM-66 high concentration root extract used in this study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eHowkins B. Shaw\u0026rsquo;s A Textbook of Gynecology. Reprinted ed. Elsevier; 2005. pp. 56\u0026ndash;67.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMashiloane CD, Bagratee J, Moodley J. Awareness of and attitude toward menopause and hormone replacement therapy in an African community. Int J Gynaecol Obstet. 2002;76:913.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCobin RH, Futterweit W, Ginzburg SB, et al. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the diagnosis and treatment of menopause. Endocr Pract. 2006;12(3):317.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDavis SR, Lambrinoudaki I, Lumsden M, et al. Menopause Nat Rev Dis Primers. 2015;1:15004.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMartin KA, Manson JE. Approach to the patient with menopausal symptoms. 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Ayu. 2012;33(4):511\u0026ndash;6. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.4103/0974-8520.110529\u003c/span\u003e\u003cspan address=\"10.4103/0974-8520.110529\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKelgane SB, Salve J, Sampara P et al. February 23,. (2020) Efficacy and Tolerability of Ashwagandha Root Extract in the Elderly for Improvement of General Well-being and Sleep: A Prospective, Randomized, Double-blind, Placebo-controlled Study. Cureus 12(2): e7083. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.7759/cureus.7083\u003c/span\u003e\u003cspan address=\"10.7759/cureus.7083\" 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":true,"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":"Ashwagandha root extract, menopause, safety, efficacy, Randomized control trial","lastPublishedDoi":"10.21203/rs.3.rs-6409321/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6409321/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eHormone replacement therapy (HRT) is of the most recent therapeutic option available for management of menopausal syndrome. But the amalgamation of HRT and pharmaceutical antidepressants are linked to an elevated risk of serious adverse events. In addition, lifestyle changes are somehow ineffective in addressing the psychological signs. Hence, the present study was conducted to assess the safety and efficacy of high concentrated Ashwagandha root extract (ARE) formulation in age group experiencing menopausal syndrome with emphasis on Menopause Rating Scale (MRS).\u003c/p\u003e\u003ch2\u003eMethodology:\u003c/h2\u003e \u003cp\u003eA randomized, double-blind, placebo-controlled study was conducted for duration of eight weeks. Total 60 women with clinically diagnosed menopause were enrolled and prescribed either 300 mg of an Ashwagandha root extract capsules or placebo capsule twice daily.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eIt was observed that total MRS score reduced significantly (p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001) with ARE supplementation, especially in psychological (p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001), somatic (p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001), and urogenital (p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001) domains as compared to the placebo group. Group receiving ARE capsules showed improved serum estradiol (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), progesterone (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and Short Form survey (SF-12) scores (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), while reduction in serum FSH (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and LH (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), hot flashes events (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and Perceived Stress Scale (PSS-10) scores (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eTo conclude, inclusion of ashwagandha for management of menopausal syndrome is a promising therapeutic option. The safety and efficacy of different concentrations of Ashwagandha could be studied further.\u003c/p\u003e\u003ch2\u003eTrial registration:\u003c/h2\u003e \u003cp\u003eThe study was registered with Clinical Trial Registry of India (CTRI/2022/02/040551 dt: 23/02/2022)\u003c/p\u003e","manuscriptTitle":"Prospective, Randomized, Double-blind, Placebo Controlled Study on Safety and Efficacy of Ashwagandha Root Extract (Withania Somnifera) on Menopause Symptoms","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-04-10 09:58:24","doi":"10.21203/rs.3.rs-6409321/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":"78dd73dc-f3fa-4098-999a-e6d3b6d96026","owner":[],"postedDate":"April 10th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-04-10T09:58:27+00:00","versionOfRecord":[],"versionCreatedAt":"2025-04-10 09:58:24","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6409321","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6409321","identity":"rs-6409321","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}