Thyroid-stimulating Hormone Levels in Women with Uterine Fibroids: A Healthcare Setting Perspective from Coastal Karnataka.

In recent years, uterine fibroids (UFs), a prevalent benign disease, have become a public health concern. Globally, it has an annual incidence of 20%–40% with a morbidity rate of 30%.[ 1 2 ] About 30%–40% of UF patients report symptoms such as heavy and prolonged menstrual bleeding, pelvic pain, and anemia on the other hand, which restricts their social participation and negatively impacts their mental health.[ 3 4 5 ] Thyroid disorders, especially goiter and thyroid nodules, have recently been identified among women with UF.[ 6 7 8 ] The changes in thyroid hormones, even without symptoms, can interfere with ovulation and endocrine receptivity, causing menstrual irregularities and infertility.[ 9 10 11 ] The very first screening test to assess thyroid function is thyroid-stimulating hormone (TSH). It changes earlier in hypo/hyperthyroidism and does not fluctuate much as T 3 /T 4 levels.[ 12 ] Previous studies demonstrated the influence of estrogen on thyroid function by interfering with TSH production.[ 11 13 14 ] Most gynecology clinics routinely test serum TSH to evaluate thyroid function. However, many women overlook the signs and symptoms of thyroid disease and refuse to consent to a TSH test. There are limited data reporting thyroid function among women with UF.[ 15 16 17 ] Previous studies mainly captured the incidence of thyroid nodules among UF patients,[ 6 7 15 16 ] or it was among women who underwent hysterectomy.[ 17 ] To the best of our knowledge, few reports are available to reach a definitive conclusion about TSH levels among UF patients. Correcting thyroid dysfunction may help reduce symptom severity and disease management in UF patients. Collecting and comparing TSH levels in women with and without UF is necessary to establish a baseline.

The primary objective of the study was to compare the TSH levels among women with and without UF.

Table 1 presents the sociodemographic characteristics of the women with and without UF in the study. The average BMI values are similar among the two groups, whereas there was a statistically significant difference in the average age between the two groups as observed from two-sample independent t-tests at 5% level of significance. Demographic characteristics of participants in groups 1 and 2 Based on independent sample t -test. *Significant at α=5%. BMI: Body mass index The majority of the participants from group 1 (95%) and group 2 (96%) were married. In group 1, 23 (35.9%) were multiparous, 10 (15.6%) were primiparous, and one (1.6%) nulligravida, while in group 2, 12 (18.8%) were multiparous, 8 (12.5%) were primiparous, and 3 (4.7%) were nulligravid. Nulliparity was reported in 4 (6.3%) of group 1 and 3 (4.7%) in group 2. Table 2 presents the categorical characteristics observed among the two groups regarding symptoms, comorbidities, and family history. Chi-square test or Fisher’s exact test (used when the cell frequencies were less than 5) was used to explore associations between the categorical variables. Apart from other comorbidities, including poly cystic ovarian syndrome (PCOS), endometriosis, and adenomyosis, there was no association between the comorbidities, symptoms, and family history among the two groups. Association between health-related characteristics across groups 1 and 2 Based on Chi-square test c ; based on Fisher’s exact test f ; *Significant at α=5%. Group 1: Women with uterine fibroids; Group 2: Women without uterine fibroids The majority of the participants in group 1 (n = 26, 68.4%) had multiple fibroids, which are of intramural type (n = 28, 73.7%) and with a size of 3 to 7 cm (n = 19, 50%). High TSH levels (>4.2 µIU/mL) were reported among 40% (15/38) of women in group 1 and 31% (8/26)) of women in group 2. Normal TSH levels (0.27–4.2 µIU/mL) were reported among 60% (23/38) in group 1 and 69% (18/26) in group 2 [ Figure 1 ]. No patients from either of the groups were reported to have lower TSH levels (<0.27 µIU/mL). To summarize, the distribution of high TSH levels between the two groups was not statistically significant. Distribution of Thyroid Stimulating Hormone (TSH) levels among the two groups Table 3 compares the average TSH levels across symptoms, comorbidities, and family history of the study participants. At 5% level of significance, based on the Mann–Whitney U test, it is observed that there is a statistically significant difference in the average TSH values across levels of irregular cycles ( P = 0.032) and pain abdomen/back pain ( P = 0.007). There was no statistically significant difference between TSH levels and other aspects of symptoms, comorbidities, and family history. TSH levels observed across symptoms, comorbidities, and family history of the participants Based on the Mann–Whitney U test. *Significant at α=5%. TSH: Thyroid-stimulating hormone

This retrospective study was conducted for 3 months in a Secondary Care Hospital in Coastal Karnataka. The outpatient (OPD) register from the Department of Obstetrics and Gynecology was screened to select 50 women with UF and 50 women without UF who attended the OBG OPD from October to December 2019. The sample size for the pilot study was decided based on evidence from the literature,[ 18 19 20 ] which was found to be a minimum of 20 or more participants. Institutional Ethics Committee clearance was obtained prior to the study. Premenopausal women with UF aged 15 to 55 years were considered in group 1, and premenopausal women of the same age group without fibroids were considered in group 2. Women with pregnancy and/or malignancy were excluded from both groups. The availability of TSH reports was not considered while selecting eligible participants. A total of 100 women who satisfied the age group (50 women with and 50 women without UF) were selected from the Outpatient Register. Participants’ medical records were retrieved from the Medical Records Department of the secondary healthcare setting and were screened for the eligibility criteria. Since this was a retrospective study, informed consent was not applicable. In group 1, 38 women met the inclusion criteria, while six women were excluded due to malignancy, pregnancy, or menopause and six women due to missing or unavailability of TSH reports. In group 2, only 26 women met all the inclusion criteria; about 13 of them had seedling fibroids, which we missed when screening the outpatient register, and TSH reports were not available for nine women. Two patients were excluded due to malignancy and or menopause. Available clinical history, sociodemographic data, menstrual history, family history, and significant past medical history were collected from their medical and laboratory records and documented. Ultrasound reports of abdomen and/or pelvis were retrieved from their medical records and analyzed. Fibroid symptoms, type, number, location, and size were noted for group 1. TSH levels were collected from the laboratory report and the patient files. The normal serum level was defined as TSH 0.27–4.20 µIU/mL (electrochemiluminescence immunoassay). TSH > 4.2 µIU/mL was considered as high TSH, whereas TSH < 0.27 µIU/mL was considered as low TSH. The study did not exclude women who already had thyroid disorders and were receiving medication. Data were entered in Microsoft Excel version 2016 and analyzed using R programming language.[ 21 ] Subsequently, frequencies and percentages were calculated for all the categorical variables. The Chi-square test and Fisher’s exact test of significance were carried out for exploratory data analysis on categorical variables: symptoms, comorbidities, and family history. For the quantitative variables, namely, TSH, age, and body mass index (BMI), descriptive statistics using mean and standard deviation (SD) and median along with first (Q 1 ) and third quartiles (Q 3 ) were used. The BMI was calculated according to the formula provided by the World Health Organization using the height and weight noted in the medical records following physical examination. The study used the Mann–Whitney U, Chi-square, and two-sample independent t-tests to compare participant characteristics across women with and without UF and observe differences in mean TSH levels across groups. The level of significance was set at 5% throughout the study.

This study concludes that there is an increased frequency of high TSH levels among women with UFs (40%) compared to women without UFs (31%). The difference in TSH levels between women with and without UF observed in this study could be a source of motivation to explore a larger-scale prospective observational study to draw a definitive conclusion. The study protocol was approved by the Institutional Ethics Committee (Ref No: KMC and KH IEC: 275/2020). I) Conception and design: Vineetha K K, Rajeshwari G Bhat, Archana P R and Bhamini Krishna Rao; II) Administrative support: Shashikala K Bhat, Rajeshwari G Bhat; III) Provision of study materials or patients: Shashikala K Bhat and Rajeshwari G Bhat (IV) Collection and assembly of data: Vineetha K K;(V) Data analysis and interpretation: Vineetha K K, Vani Lakshmi R;(VI) Manuscript writing: All authors (VII) Final approval of manuscript: All authors There are no conflicts of interest.

This retrospective study in a modest sample aimed to determine the TSH levels in women with and without UF. The main findings were that 40% of participants in group 1 and 31% participants in group 2 had high TSH levels. For the past few years, the increasing incidence of abnormal TSH levels among UF patients has been of great concern in the gynecology clinics. However, not much data are available, particularly from an Indian perspective.[ 22 23 ] To the best of our knowledge, this study carried out during the COVID-19 phase in the country is the first such attempt to assess the TSH levels in women with and without UF. The challenges associated with data collection are reflected in the relatively small sample size. The association of overt hypothyroidism[ 17 ] and incidence of thyroid nodules were identified in women with UF in studies.[ 15 16 ] The 9% increase in high TSH levels between the groups in this study with this modest sample size may not be sufficient to make a definitive conclusion. However, according to Kieser and Wassmer,[ 20 ] for pilot studies incorporating group comparisons to establish relevant group differences, a smaller sample of 10–20 individuals per group might be sufficient to implement the method of acquiring information for a power analysis. We considered TSH in this study as it was part of routine blood investigations. Moreover, TSH is regarded as a first-line test to evaluate thyroid function.[ 12 ] This difference in thyroid dysfunction among women with and without UF might be due to the hormone’s estrogen and progesterone.[ 13 ] Most of the women in group 1 were in the age group of 35–55 years, and those in group 2 were in the age group of 25–45 years in this study. Srilatha et al .[ 24 ] reported the predominant age group with UF as 40–59 years (57.3%), followed by 37.2% of women in the age group of 20–39 years. In both groups, the majority of women had a slightly higher BMI, even though the difference was not statistically significant. This was distinct from the results of Sun et al .,[ 25 ] who reported that women with a lower BMI were less likely to develop fibroids. This observation is inconclusive due to the limited sample size and the prevalence of several comorbid conditions that may lead to overweight and obesity, which we could not rule out in this retrospective analysis. The majority of the women (78.95%) in group 1 in our study were symptomatic, with a combination of symptoms like heavy menstrual bleeding (HMB), dysmenorrhea, irregular menstruation, and pain in the abdomen. This was in concordance with the previous study findings.[ 26 27 ] Most of the women in the present study were presented with multiple fibroids (68.4%), predominantly of intramural type (73.7%). Sheelaa et al .[ 28 ] observed intramural single fibroid as the most common type, followed by submucosal multiple fibroids in South Indian women. In the women without UF group, approximately 15.4% had HMB and 15.4% had irregular menstruation, which may have contributed to thyroid dysfunction. Substantial differences in TSH were reported among women with abnormal uterine bleeding (AUB) as well as other menstrual problems in a few studies.[ 11 29 30 ] Fluctuations in thyroid hormones may contribute to changes in ovulatory hormones, predisposing to abnormal bleeding.[ 31 ] This could contribute to the 30% thyroid dysfunction reported among the women without UF group in our study. There is a dearth of studies on impaired TSH levels in women with UF. This strengthens the validity of our results, which revealed an increased frequency of high TSH levels among fibroid patients, even though it was from a small sample population. It adds to the imperative scarce literature. However, the small sample size limits the consistency of the findings in this study as the power is restricted to 23%. We are confident that our findings could serve as a foundation for researchers planning large-scale studies in the future. The lack of TSH reports for Six women with UF and nine women without UF limits our study. This was because these participants’ TSH reports were missing from their medical records. Individuals who had complained of burning micturition, white discharge per vagina, or other symptoms would not have been requested to conduct the test because it was not indicated. On the other hand, thyroid dysfunction in women without UF could have been caused by AUB and menstrual abnormalities, which we could not rule out. Other factors such as age and BMI should be considered in the case of thyroid dysfunction in UF patients. We were unable to classify the type of thyroid dysfunction in this study due to the lack of complete thyroid function parameters such as T3 and T4, which were not documented in the records. These limitations could be surpassed with future prospective studies.