Polyendocrine metabolic ovarian syndrome (PMOS) is a prevalent, complicated endocrinologic and metabolic disorder in women of reproductive potential.[1] An international consensus process officially adopted the new name for the condition, PMOS, in 2026, to acknowledge the condition's wider endocrine, metabolic, and ovarian features.[2] It is one of the most common endocrine diseases in women of reproductive age, occurring in about one out of eight women in the world.[3] It is not only associated with ovarian dysfunction, but also with hyperandrogenism, insulin resistance, obesity, dyslipidaemia, and reproductive abnormalities.[4] The

new terminology reflects the multisystemic nature of the condition, and the need for a multi-systemic approach to diagnosis and treatment.[5]

Insulin resistance is a significant metabolic imbalance underlying PMOS and plays an important role in the endocrine and reproductive endophenotypes of PMOS.[6] Decreased insulin sensitivity leads to a compensatory increase in insulin levels (hyperinsulinemia), which in turn drives up the production of androgens by the ovary while also decreasing the levels of sex hormone-binding globulin produced by the liver, thereby raising free androgen levels.[7] These hormonal disturbances affect normal follicular development and ovulatory function, leading to menstrual irregularities, oligomenorrhea, amenorrhea, and anovulation.[8] Insulin resistance can also be present in women with PMOS without obesity, suggesting that metabolic dysfunction can be detected not only through body weight, but also through BMI.[9] Insulin resistance is highlighted as a crucial pathophysiological aspect of insulin resistance in the 2023 international evidence-based guideline, with a focus on the evaluation of related metabolic disorders.[10]

The endometrial thickness is one of the most important ultrasonographic parameters that are indicative of the endometrium's response to hormonal stimulation.[11] A persistent anovulation in women with PMOS can lead to excessive exposure to estrogen and lack of adequate opposition from progesterone, which can stimulate excessive proliferation of the endometrium and contribute to endometrial hyperplasia.[12] In addition, hyperinsulinemic women could affect the activity of endometrial cells via insulin and insulin-like growth factor pathways, indicating a potential link between metabolic disturbances and endometrial changes.[13] However, there are several factors that affect the thickness of the endometrium, such as its menstrual cycle phase, its status, and body mass index. Thus, its assessment together with metabolic parameters could yield helpful details on PMOS reproductive and endometrial effects. Another clinical presentation of PMOS is menstrual irregularity, which could be a reflection of the underlying interaction of insulin resistance, hyperandrogenism, and impaired ovulation.[14] Oligomenorrhea, irregular periods, and amenorrhea are common in women with PMOS, which can lead to increased exposure to unopposed estrogen.[15]

The association between metabolic dysfunction and reproductive abnormalities is becoming well established; however, there is limited research investigating the specific relationship between degree of insulin resistance, endometrial thickness, and patterns of menstrual dysfunction. The assessment of these parameters together is especially important since menstrual disturbances and metabolic abnormalities can occur simultaneously and may even contribute to poor endometrial outcome. These relationships could be helpful in identifying women who need earlier metabolic evaluation and suitable gynecological assessment. Hence, the present study aimed to assess the correlation of insulin resistance and endometrial thickness along with menstrual dysfunction in women with PMOS. It will specifically assess the link between insulin resistance and endometrial thickness, the link between insulin resistance and menstrual irregularities, and whether higher insulin resistance is correlated with greater endometrial and menstrual abnormalities. This study aims to combine metabolic, ultrasonographic, and menstrual evaluations in a single approach to generate clinically relevant data on the metabolic and reproductive aspects of PMOS and to possibly aid in earlier identification of women who are at risk of developing endometrial complications.

An analytical cross-sectional study was conducted at the Department of Obstetrics and Gynecology, Ali Fatima Hospital, Bhobatian, Raiwind Road, Lahore, Pakistan. The study was carried out over a period of six months, from November 1, 2025, to April 30, 2026. The study investigated the association of insulin resistance with endometrial thickness and menstrual dysfunction in women diagnosed with polyendocrine metabolic ovarian syndrome (PMOS).

The sample size was calculated using the OpenEpi online sample size calculator based on an expected prevalence of insulin resistance of 60.5%, a 95% confidence level, 8% margin of error, and a design effect of 1. The minimum calculated sample size was 144 participants.[16] After adding 10% to account for potential non-response and incomplete data, the final target sample size was increased to 160 participants.

Eligible participants were selected using a non-probability consecutive sampling technique.  Women aged 18-40 years with PMOS diagnosed by the Rotterdam criteria were recruited. The diagnosis was confirmed by the presence of at least two of the following three characteristics: oligo-ovulation or anovulation, clinical or biochemical hyperandrogenism, and polycystic ovarian morphology on ultrasonography, in addition to the exclusion of other causes of these characteristics. Women who consented to clinical, biochemical, and ultrasonographic evaluation were included.

The exclusion criteria included women with a prior diagnosis of type 1 or 2 diabetes mellitus, thyroid disorders, hyperprolactinemia, Cushing syndrome, congenital adrenal hyperplasia, or any other condition that would affect hormonal and metabolic status. Pregnant and lactating women, women who have had a hysterectomy, and women with a known endometrial malignancy were also excluded to limit the possible confounding effects on insulin resistance and endometrial measurements.

Demographic and clinical data were collected from each participant with a structured data collection proforma after obtaining written informed consent. Data on age, marital status, body weight, height, body mass index (BMI), waist circumference, period irregularity duration, and related medical and medication history were collected. Menstrual patterns were determined by the participants' menstrual history in the last six months and classified into regular menstruation, oligomenorrhea, or amenorrhea. Oligomenorrhea was described as having a menstrual cycle of 35 days or more, while amenorrhea was defined as having no menstruation at all for three months or more in women who have experienced menstruation.

Venous blood samples were obtained after an overnight fast (8-12 hours). Fasting blood glucose and fasting serum insulin levels were determined by conventional laboratory methods. The Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) was used for estimating insulin resistance.

Pelvic ultrasonography was used by a qualified radiologist to measure the thickness of the endometrium. Transvaginal ultrasonography was performed when appropriate, while transabdominal ultrasonography was used when transvaginal examination was unsuitable. Endometrial thickness was measured in millimeters as the maximum double-layer thickness in the mid-sagittal plane. Documentation of the phase of the menstrual cycle and date of last menstrual period was obtained for the purpose of interpreting the measurements of the endometrium. The study proforma recorded all biochemical, clinical, menstrual, and ultrasonographic data.

IBM SPSS Statistics, version 26.0, was the software used to analyze the data collected. All quantitative variables were presented as means± SD. The qualitative variables such as menstrual pattern, presence and absence of insulin resistance were shown in frequencies and percentages. The normality of continuous variables was tested with the Shapiro–Wilk test. The independent-samples t-test was used to compare continuous variables between insulin-resistant and non-insulin-resistant groups. The chi-square test was used to determine associations between categorical variables. The correlations of HOMA-IR were examined. Multivariable linear regression was used to evaluate independent relationships between insulin resistance and endometrial thickness after adjusting for potential confounders such as age and BMI. The association of insulin resistance with menstrual dysfunction was evaluated using logistic regression after adjusting for the confounding factors. A p-value of ≤0.05 was considered statistically significant.

A total of 160 women diagnosed with polyendocrine metabolic ovarian syndrome (PMOS) were included in the study. Demographic and clinical evaluation showed that the study population consisted mainly of women of reproductive age. The anthropometric profile showed that there was a high prevalence of overweight, excess body weight, and central adiposity among most participants, who were married. In metabolic assessment, variations in fasting glucose, serum insulin, and HOMA-IR were found, and in ultrasonographic assessment, variations in endometrial thickness were found among the participants (Table 1).

A comparison of insulin-resistant and non-insulin-resistant subjects showed that there are significant differences between the two in several metabolic and anthropometric parameters. BMI, WC, FBG, and FSI were significantly elevated in women with insulin resistance. They also had a significantly thicker endometrium than women without insulin resistance. In addition, the length of time with irregular periods was significantly greater for the insulin-resistant group. But the age of both groups was not significantly different (Table 2).

Menstrual dysfunction was associated with insulin resistance as revealed by analysis of menstrual patterns. Menstrual irregularities were more common in women with insulin resistance, and the most common menstrual irregularity in both groups was oligomenorrhea. Additionally, the insulin-resistant group had a higher relative prevalence of amenorrhea, while the women without insulin resistance had a higher prevalence of regular menstrual cycles. Overall, the findings indicated a significant relationship between insulin resistance and menstrual patterns (Table 3).

The endometrial thickness was compared between different menstrual patterns, and the group difference was found to be statistically significant. Women with amenorrhea showed the thickest endometria compared to women with oligomenorrhea, and women with regular menstruation showed relatively thin endometria. This progressive increase in endometrial thickness in association with the worsening of menstrual irregularity indicated that there might be a correlation between the disruption of menstrual activity and endometrial proliferation (Table 4).

The correlation analysis revealed a positive correlation between the insulin resistance index (HOMA-IR) and endometrial thickness, suggesting that the thicker the endometrial thickness, the higher the insulin resistance would be. HOMA-IR was also positively correlated with anthropometric and metabolic parameters such as BMI, WC, FBG, and FSI. In addition, there was a significant positive correlation between the duration of menstrual irregularities and HOMA-IR, which indicated that higher insulin resistance was related to the longer duration of menstrual irregularities (Table 5).

Multivariate linear regression analysis showed that insulin resistance continued to be a significant predictor of increased endometrial thickness after controlling for potential confounding factors. BMI and menstrual irregularity period were also positively associated with endometrial thickness in a manner independent of each other. The independent association of age, however, was not statistically significant. The results indicated that the metabolic status and the length of the reproductive disturbance were independent factors affecting the differences in endometrial thickness, as well as age (Table 6).

In the same way, multivariable logistic regression analysis showed that insulin resistance, independent of other relevant demographic and anthropometric parameters, was associated with higher odds of menstrual dysfunction. BMI was also found to have a significant association with menstrual dysfunction, while age and waist circumference did not have statistically significant independent associations. These results indicated that insulin resistance and general adiposity could play a role in the development of menstrual disturbances in women with PMOS (Table 7).

Table 1. Demographic, anthropometric and clinical characteristics of the study participants (n = 160)

Table 2. Comparison of demographic, metabolic, and ultrasonographic characteristics between

insulin-resistant and non-insulin-resistant participants (n = 160)

Table 3. Association between insulin resistance and menstrual patterns among study participants (n = 160)

Table 4. Comparison of endometrial thickness according to menstrual patterns (n = 160)

Table 5. Correlation of HOMA-IR with endometrial thickness and other metabolic parameters (n = 160)

Table 6. Multivariable regression analysis of factors associated with endometrial thickness and

menstrual dysfunction

Table 7. Logistic regression analysis with menstrual dysfunction as the dependent variable

The present study examined the association of insulin resistance with endometrial thickness and menstrual dysfunction among women with polyendocrine metabolic ovarian syndrome (PMOS). The findings suggested that insulin resistance was associated with greater endometrial thickness, more frequent menstrual disturbances, and a longer duration of menstrual irregularities. Furthermore, insulin resistance remained significantly associated with endometrial thickness and menstrual dysfunction after adjustment for selected confounding variables. These findings support the importance of considering metabolic and reproductive characteristics together when evaluating women with PMOS.

In the present study, insulin-resistant women demonstrated significantly higher BMI, waist circumference, fasting glucose, and fasting insulin levels than their non-insulin-resistant counterparts. This finding was consistent with Khan et al. (2024), who reported higher insulin resistance among women with PCOS compared with women without the condition, although the difference in HOMA-IR was not statistically significant in their study.[17] Similarly, Razzaq et al. (2024) reported insulin resistance in 67.8% of adolescent participants with PCOS and identified significant associations with BMI and menstrual irregularities.[18] Hussein and Karami (2023) also reported higher BMI and HOMA-IR among women with PCOS than controls.[19] These findings collectively support the coexistence of metabolic abnormalities and reproductive disturbances in this population.

The present study also demonstrated a significant association between insulin resistance and menstrual dysfunction, with oligomenorrhea and amenorrhea being more frequent among insulin-resistant women. This observation was comparable to the findings of Niu et al. (2023), who investigated 140 women with PCOS and reported a progressive increase in HOMA-IR across normal menstruation, oligomenorrhea, and amenorrhea groups.[20] Similarly, Hussein and Karami (2023) observed higher HOMA-IR levels among women with longer intervals between menstrual periods.[19] Li et al. (2022) also demonstrated that greater menstrual dysfunction was associated with more pronounced insulin resistance and hyperinsulinemia in women with PCOS.[21] In addition, a prospective study by the same research group involving 333 women with hyperandrogenic PCOS identified a relationship between menstrual dysfunction, hyperinsulinemia, and dysglycemia.[22] These studies support the association observed in the present analysis, although differences in study populations and methods should be considered.

Regarding endometrial thickness, the present study demonstrated significantly greater endometrial thickness among insulin-resistant women, with a positive correlation between HOMA-IR and endometrial measurements. These findings are particularly relevant to the study by Lynn et al. (2023), who specifically investigated the relationship between endometrial thickness, insulin resistance, and menstrual patterns in adolescent females with PCOS. Their work provides a close comparison with the present research because it evaluated the same three principal variables.[23] However, differences in age groups and clinical characteristics should be considered when interpreting the findings. Furthermore, Li et al. (2024) examined metabolic differences between obese and non-obese women with PCOS in relation to endometrial receptivity indicators, highlighting the relevance of metabolic status when assessing endometrial characteristics.[24]

The observed increase in endometrial thickness across different menstrual patterns, particularly among women with amenorrhea, may be related to prolonged anovulation and inadequate progesterone exposure. This interpretation is supported by Palomba et al. (2021), who reviewed endometrial dysfunction in women with PCOS and discussed the effects of altered hormonal and metabolic environments on endometrial function.[25] Similarly, Pathare et al. (2022) highlighted abnormalities in endometrial receptivity and the molecular mechanisms affecting the endometrium in PCOS.[26] More recently, Ijaz et al. (2025), in a systematic review and meta-analysis involving 20,914 participants, reported that menstrual irregularities were associated with a higher risk of endometrial hyperplasia or abnormal histology.[27] However, their pooled analysis did not demonstrate a statistically significant overall difference in endometrial thickness between the compared populations. This distinction is important because increased endometrial thickness does not necessarily establish endometrial hyperplasia.

Overall, the findings suggest that insulin resistance may be an important metabolic correlate of menstrual dysfunction and increased endometrial thickness in women with PMOS. The combined assessment of HOMA-IR, menstrual history, and ultrasonographic endometrial measurements may provide additional clinical information during the evaluation of these women. However, the findings should be interpreted cautiously because endometrial thickness is influenced by menstrual cycle phase, age, BMI, and hormonal status. Further prospective studies involving larger populations and standardized ultrasonographic assessments are warranted to clarify these relationships and determine their clinical significance.

LIMITATIONS

The present study had certain limitations. Its cross-sectional design restricted the ability to establish causal relationships between insulin resistance, endometrial thickness, and menstrual dysfunction. The study was conducted at a single tertiary care hospital, which may limit the generalizability of the findings to other populations. Furthermore, endometrial thickness may have been influenced by menstrual cycle phase, age, BMI, and hormonal variations. The use of HOMA-IR as an indirect measure of insulin resistance, rather than a direct assessment of insulin sensitivity, was another limitation. Additionally, residual confounding from unmeasured metabolic and hormonal factors could not be excluded. Further multicentre prospective studies are recommended to validate these findings.

The study demonstrated significant associations between insulin resistance, increased endometrial thickness, and menstrual dysfunction among women with PMOS. Insulin-resistant women exhibited greater endometrial thickness and more frequent menstrual irregularities than those without insulin resistance. Furthermore, HOMA-IR showed a positive correlation with endometrial thickness and other metabolic parameters. These findings highlight the importance of considering metabolic and reproductive characteristics together during the clinical assessment of women with PMOS. Routine evaluation of metabolic status alongside menstrual history and appropriate ultrasonographic assessment may help identify women requiring closer clinical follow-up.

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