Polyendocrine metabolic ovarian syndrome (PMOS), historically described as polycystic ovary syndrome, is a heterogeneous endocrine-metabolic disorder characterized by ovulatory dysfunction, hyperandrogenism, and polycystic ovarian morphology. Beyond reproductive manifestations, affected women have increased risks of obesity, dyslipidaemia, impaired glucose regulation, and type 2 diabetes, warranting systematic metabolic assessment [1,2].

Insulin resistance is central to the pathophysiology of PMOS and may occur independently of obesity. Compensatory hyperinsulinaemia promotes ovarian androgen production and reduces hepatic sex-hormone-binding globulin, thereby aggravating hyperandrogenism and ovulatory dysfunction [3]. Although reference methods for measuring insulin sensitivity are resource intensive, the homeostatic model assessment of insulin resistance (HOMA-IR) provides a practical estimate based on fasting glucose and insulin concentrations [4].

Thyroid dysfunction may further compound the reproductive and metabolic abnormalities of PMOS. Women with the syndrome have been reported to show a higher prevalence of autoimmune thyroiditis, elevated thyroid-stimulating hormone and subclinical hypothyroidism than women without PMOS [5,6].

Subclinical hypothyroidism, defined by persistently elevated thyroid-stimulating hormone with normal free thyroxine, may contribute to weight gain, dyslipidaemia and impaired insulin action. However, its metabolic importance in PMOS remains uncertain. Some studies have found no independent association with insulin resistance despite higher triglyceride concentrations [7], whereas others have reported greater adiposity and adverse metabolic profiles among women with coexisting subclinical hypothyroidism [8]. A systematic review similarly found that the most consistent effects involved lipid abnormalities, while associations with glucose metabolism and insulin resistance varied across studies [9].

Differences in thyroid-stimulating-hormone thresholds, failure to confirm persistent elevation, variation in adiposity and ethnicity, and heterogeneous definitions of insulin resistance may explain these conflicting findings. The present study therefore assessed the prevalence of persistent subclinical hypothyroidism and insulin resistance among women with PMOS and examined their relationship with anthropometric, reproductive, biochemical and ultrasonographic characteristics. Persistent thyroid dysfunction was confirmed by repeat testing, and its independent association with insulin resistance was evaluated after accounting for relevant clinical factors.

Study design and participants This hospital-based prospective observational study was conducted at Basaveshwara Medical College and Hospital, Chitradurga, from November 2025 to April 2026. Consecutive women aged 18-40 years with polyendocrine metabolic ovarian syndrome (PMOS) were enrolled after written informed consent. PMOS was defined by the presence of at least two of the following predefined features: ovulatory dysfunction, clinical hyperandrogenism, and polycystic ovarian morphology on ultrasonography. Women who were pregnant; had overt thyroid disease, chronic liver disease, stage 4 or 5 chronic kidney disease, or another relevant confounding endocrine/systemic disorder; or were receiving current metabolic or hormonal treatment were excluded. Prior treatment was permitted only when it had been discontinued for at least 3 months. A total of 200 eligible women were included. Clinical and anthropometric assessment Demographic and clinical information included age, residence, marital status, family history of diabetes or thyroid disease, duration of PMOS-related symptoms, menstrual pattern, infertility status, gravidity, parity, previous treatment history, smoking and alcohol use, and relevant medical history. Hyperandrogenism was assessed using the modified Ferriman-Gallwey (mFG) score; a score of 8 or more was classified as clinical hirsutism. Height, weight, waist circumference, and resting blood pressure were measured using standardized procedures. Body mass index (BMI) was calculated as weight in kilograms divided by height in metres squared. Laboratory and thyroid assessment Venous blood was collected after an 8–12-hour overnight fast for fasting plasma glucose, fasting serum insulin, thyroid-stimulating hormone (TSH), free thyroxine (FT4), total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides. Glycated haemoglobin was recorded where available. The laboratory upper reference limit for TSH was 4.2 mIU/L and the FT4 reference interval was 0.8-1.8 ng/dL. Women with an initial TSH above 4.2 mIU/L and normal FT4 underwent repeat TSH testing after approximately 6 weeks. Persistent subclinical hypothyroidism was defined as a repeat TSH above 4.2 mIU/L with FT4 remaining normal; normalization of repeat TSH was classified as transient TSH elevation. Insulin resistance and ultrasonography Insulin resistance was estimated using the homeostatic model assessment: HOMA-IR = [fasting serum insulin (µIU/mL) × fasting plasma glucose (mg/dL)] / 405. HOMA-IR was analyzed as a continuous variable and a value of 2.5 or greater was classified as insulin resistance. Pelvic ultrasonography documented the presence of polycystic ovarian morphology, right and left ovarian volumes, and follicle counts; the maximum ovarian volume and follicle count from either ovary were used for summary analyses. Outcome measures The principal outcomes were the prevalence of persistent subclinical hypothyroidism and insulin resistance. Secondary analyses compared demographic, anthropometric, reproductive, biochemical, and ultrasonographic characteristics according to persistent subclinical hypothyroidism status and examined associations of thyroid parameters with HOMA-IR and related metabolic measures. For the primary comparison, euthyroid women and those with transient TSH elevation were combined as the no-persistent-subclinical-hypothyroidism group. Statistical analysis Continuous variables were summarized as mean ± standard deviation or median (interquartile range), according to distribution, and categorical variables as n (%). Prevalence estimates were reported with Wilson 95% confidence intervals. Between-group comparisons used Welch's independent t test for approximately normally distributed continuous variables and the Mann-Whitney U test for non-normally distributed variables. Categorical variables were compared using the chi-square test or Fisher's exact test, as appropriate. Spearman rank correlation assessed associations between thyroid, insulin-resistance, anthropometric, and lipid variables. A multivariable binary logistic regression model evaluated independent predictors of insulin resistance, with persistent subclinical hypothyroidism, age, BMI, and family history of diabetes entered simultaneously. Adjusted odds ratios with 95% confidence intervals were reported. All tests were two-sided, and p<0.05 was considered statistically significant. Analyses were performed using SPSS version 24. Ethical considerations The study was conducted after approval by the Institutional Ethics Committee. Written informed consent was obtained from all participants, and confidentiality of study information was maintained.

Study population and clinical profile

All 200 enrolled women met the study eligibility criteria. The mean age was 28.10 ± 4.75 years. Menstrual irregularity was present in 151 (75.5%), clinical hirsutism in 137 (68.5%), and polycystic ovarian morphology in 179 (89.5%). The demographic, reproductive, and anthropometric profile is summarized in Table 1.

Table 1. Baseline demographic and clinical characteristics of the study population

Values are mean ± standard deviation, median (interquartile range), or n (%), as applicable. BMI, body mass index; DBP, diastolic blood pressure; mFG, modified Ferriman–Gallwey; PMOS, polyendocrine metabolic ovarian syndrome; SBP, systolic blood pressure.

Thyroid status, insulin resistance, and ovarian morphology

Initial TSH elevation with normal FT4 was identified in 44 (22.0%) women. Repeat testing confirmed persistent subclinical hypothyroidism in 34 (17.0%), whereas 10 (5.0%) had transient TSH elevation. Insulin resistance was present in 101 (50.5%) women. The thyroid, metabolic, and ultrasonographic findings are presented in Table 2.

Table 2. Thyroid status, insulin resistance, and ultrasonographic findings

Prevalence estimates are shown with Wilson 95% confidence intervals. Continuous values are mean ± standard deviation, except initial TSH, which is median (interquartile range). FT4, free thyroxine; HOMA-IR, homeostatic model assessment of insulin resistance; PCOM, polycystic ovarian morphology; TSH, thyroid-stimulating hormone.

Characteristics according to persistent subclinical hypothyroidism

Women with persistent subclinical hypothyroidism had greater adiposity and a less favorable metabolic profile than those without persistent disease. Fasting insulin and HOMA-IR were higher, while HDL cholesterol was lower. Detailed between-group comparisons are shown in Table 3.

Table 3. Continuous characteristics according to persistent subclinical hypothyroidism status

Values are mean ± standard deviation except TSH, shown as median (interquartile range). The group without persistent SCH includes euthyroid women and women with transient TSH elevation. HbA1c was available for 170 women. SCH, subclinical hypothyroidism; TSH, thyroid-stimulating hormone; FT4, free thyroxine.

Insulin resistance was substantially more frequent among women with persistent subclinical hypothyroidism, occurring in 30 (88.2%) compared with 71 (42.8%) women without persistent disease (χ²=23.335, p<0.001). Menstrual irregularity and a family history of thyroid disease were also more frequent in the persistent subclinical hypothyroidism group, whereas infertility, clinical hirsutism, and polycystic ovarian morphology did not differ significantly (Table 4).

Table 4. Clinical, reproductive, and ultrasonographic comparison by persistent subclinical hypothyroidism status

Categorical data are n/N (%). Infertility was analyzed only among women whose fertility status was assessed. The group without persistent SCH includes euthyroid women and women with transient TSH elevation. PCOM, polycystic ovarian morphology; SCH, subclinical hypothyroidism.

Figure 1. Prevalence of insulin resistance according to persistent subclinical hypothyroidism status. Error bars represent 95% confidence intervals.

Correlation between thyroid and metabolic parameters

Initial TSH showed a moderate positive correlation with HOMA-IR and fasting insulin, and weaker associations with adiposity and lipid parameters. HOMA-IR was strongly related to BMI and waist circumference and was also associated with triglyceride and HDL cholesterol levels (Table 5).

Table 5. Correlation of thyroid and insulin resistance measures with selected metabolic variables

Spearman rank correlation was used. BMI, body mass index; HDL, high-density lipoprotein; HOMA-IR, homeostatic model assessment of insulin resistance; TSH, thyroid-stimulating hormone.

Figure 2. Association between initial TSH and HOMA-IR in women with PMOS. A positive correlation was observed (Spearman ρ=0.449, p<0.001).

Independent predictors of insulin resistance

In multivariable analysis, persistent subclinical hypothyroidism and higher BMI were independently associated with insulin resistance. Age and family history of diabetes were not independently associated with the outcome (Table 6).

Table 6. Multivariable logistic regression for insulin resistance

Outcome: HOMA-IR ≥2.5. All listed predictors were entered simultaneously. CI, confidence interval; OR, odds ratio; SCH, subclinical hypothyroidism.

In this prospective observational study of 200 women with PMOS, persistent subclinical hypothyroidism (SCH) was present in 17.0%, while insulin resistance occurred in 50.5%. Women with persistent SCH had substantially higher fasting insulin, HOMA-IR, BMI, waist circumference, triglycerides and LDL cholesterol, together with lower HDL cholesterol. Insulin resistance was present in 88.2% of women with persistent SCH versus 42.8% without persistent SCH. TSH correlated positively with HOMA-IR, and persistent SCH remained independently associated with insulin resistance after adjustment for age, BMI and family history of diabetes (adjusted OR 11.23). These findings agree with Mueller et al., who evaluated 337 women with PCOS and found greater insulin resistance among those with TSH ≥2.0 mIU/L. The relationship persisted after adjustment for age and BMI, suggesting that thyroid status may influence insulin sensitivity beyond adiposity alone [10]. This parallels our multivariable findings, although our stricter definition required persistent TSH elevation above 4.2 mIU/L with normal FT4, which may have identified a metabolically higher-risk subgroup. Dittrich et al. studied 103 women with PCOS using a TSH threshold of 2.5 mIU/L. Women above this threshold had higher BMI, insulin-resistance indices and total and free testosterone concentrations than those with lower TSH levels [11]. Their findings support a thyroid–metabolic association at TSH concentrations below the conventional SCH range. In contrast, ovarian morphology, follicle count and hirsutism did not differ by persistent SCH status in our cohort, suggesting that thyroid dysfunction was more closely related to metabolic than structural ovarian features. Celik et al. compared 20 women with PCOS and SCH, 39 euthyroid women with PCOS and 53 euthyroid controls. The PCOS–SCH group showed adverse lipid and glucose-insulin characteristics, and the authors recommended evaluation for both dyslipidaemia and insulin resistance; however, the insulin-resistance difference was attenuated after accounting for BMI [12]. Our study similarly found higher BMI in persistent SCH, but SCH remained independently associated with insulin resistance, indicating that adiposity alone did not explain the observed relationship. In a larger cohort of 583 women with PCOS, Trummer et al. reported that elevated TSH and hypothyroid disturbances were common and associated with higher BMI, systolic blood pressure and an adverse HDL profile [13]. Their metabolic pattern resembles our findings of greater central adiposity, higher systolic pressure, lower HDL and higher triglycerides among women with persistent SCH. Unlike that study, our protocol repeated TSH testing after approximately six weeks and showed that 5.0% of participants had transient rather than persistent elevation, underscoring the value of biochemical confirmation before assigning SCH status. Gawron et al. evaluated 367 women with PCOS, of whom 114 had TSH >2.5 mIU/L and 16 had autoimmune thyroiditis. Women with higher TSH had greater insulin concentrations throughout oral glucose-tolerance testing, higher HOMA-IR, higher total cholesterol, LDL cholesterol and triglycerides, and less favourable cholesterol ratios. Anti-thyroid antibody positivity did not materially worsen these metabolic abnormalities [14]. Their findings closely match our observed associations between TSH, fasting insulin, HOMA-IR and lipid variables, although thyroid autoantibodies were not measured in our study. Not all studies have demonstrated clinically useful discrimination. Benetti-Pinto et al. identified 2.77 mIU/L as the TSH threshold most closely associated with insulin resistance in women with PCOS, but its sensitivity was only 47.9% and specificity 65.3%. Clinical, hormonal and metabolic characteristics did not differ meaningfully above and below that threshold, leading the authors to recommend assessment of insulin resistance irrespective of TSH [15]. This contrasts with the marked HOMA-IR difference in our cohort, possibly because we examined confirmed SCH rather than a single low-normal TSH cut-off. Nevertheless, our findings do not support using TSH as a substitute for direct metabolic screening. Yu and Wang compared women with PCOS and SCH with euthyroid PCOS and non-PCOS groups. Hypertension, dyslipidaemia and HOMA-IR differed significantly across groups, with HOMA-IR and dyslipidaemia particularly pronounced when PCOS and SCH coexisted [16]. These results reinforce the possibility of additive metabolic effects from ovarian and thyroid dysfunction. Our accompanying findings of higher triglycerides, lower HDL and greater waist circumference suggest that persistent SCH may identify a subgroup requiring more intensive cardiometabolic evaluation. The present study also showed that menstrual irregularity was more frequent with persistent SCH, whereas infertility, hirsutism and polycystic ovarian morphology were similar between groups. This pattern suggests that mild thyroid dysfunction may aggravate cycle disturbance without materially altering androgenic or sonographic expression. The absence of an HbA1c difference despite higher fasting insulin and HOMA-IR may indicate compensated insulin resistance preceding sustained hyperglycaemia. Important strengths include consecutive recruitment, confirmation of persistent TSH elevation, standardized fasting biochemical assessment and multivariable adjustment for major confounders. However, the single-centre design and hospital-based sample limit generalisability. HOMA-IR is a surrogate rather than a clamp-derived measure of insulin sensitivity, the cut-off of 2.5 may not be optimal for every population, and thyroid autoantibodies were not assessed. Residual confounding from diet, physical activity and body-fat distribution also remains possible, while the observational design precludes causal inference. Overall, persistent SCH was associated with a distinctly adverse metabolic phenotype and substantially greater insulin resistance in women with PMOS, independent of BMI. Repeat thyroid testing may help distinguish transient TSH elevation from a clinically relevant persistent abnormality, while women with confirmed SCH may warrant particularly careful assessment of insulin resistance, central adiposity and dyslipidaemia.

Persistent subclinical hypothyroidism was common among women with PMOS and was independently associated with greater insulin resistance and an adverse metabolic profile. Repeat thyroid testing may help identify women requiring closer metabolic surveillance.

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