Leptin and LH/FSH Ratio as Independent Predictors of Polycystic Ovary Syndrome in Normoglycemic Women: A Case-Control Study

2025 · doi:10.1101/2025.09.11.25335551
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This case-control study found that leptin and the LH/FSH ratio were independent predictors of polycystic ovary syndrome in normoglycemic women.

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This case-control study compared 30 newly diagnosed normoglycemic women with PCOS (using Rotterdam 2003 criteria) to 30 age-matched healthy controls, assessing anthropometrics, a broad panel of reproductive hormones (including LH, FSH, and the LH/FSH ratio), metabolic markers (fasting insulin, HOMA-IR), lipid parameters, hematology, and the adipokine leptin. PCOS participants had higher BMI, WHR, LH, LH/FSH ratio, estrogen, testosterone, fasting insulin, HOMA-IR, and leptin, and lower FSH and HDL, with correlations showing inter-relationships among adiposity, insulin resistance, gonadotropin imbalance, and estrogen and leptin. Multivariate logistic regression identified leptin and the LH/FSH ratio as independent predictors of PCOS. A key limitation is the small sample size (30 per group) inherent to the case-control design, which can affect precision of effect estimates. The paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.

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Abstract

ABSTRACT BACKGROUND Polycystic ovary syndrome (PCOS) is a multifaceted disorder characterized by reproductive, metabolic, and endocrine disturbances. While insulin resistance (IR) is recognized as a central feature, the interplay of adipokines, lipid metabolism, gonadotropin imbalance, and inflammation in normoglycemic PCOS women remains underexplored. METHODS A case-control study was conducted on 30 newly diagnosed normoglycemic women with PCOS (Rotterdam criteria, 2003) and 30 age-matched healthy controls. Anthropometric, hormonal (LH, FSH, LH/FSH ratio, prolactin, estrogen, progesterone, testosterone), metabolic (fasting glucose, HbA1c, insulin, HOMA-IR), lipid (cholesterol, triglycerides, HDL), adipokine (leptin), and hematological parameters were assessed. Group comparisons were performed using independent t-test/Mann-Whitney test as appropriate. Correlation analysis explored inter-relationships among variables, and multivariate logistic regression identified independent predictors of PCOS. RESULTS Compared with controls, PCOS women had significantly higher BMI (26.3 +/- 5.3 vs. 23.4 +/- 3.2 kg/m2; p=0.014), WHR (0.861 +/- 0.061 vs. 0.799 +/- 0.060; p<0.001), LH (7.5 +/- 3.7 vs. 5.3 +/- 2.2 mIU/mL; p=0.006), LH/FSH ratio (1.37 +/- 0.76 vs. 0.76 +/- 0.32; p<0.001), estrogen (54.5 +/- 18.2 vs. 38.0 +/- 11.1 pg/mL; p<0.001), testosterone (49.7 +/- 25.1 vs. 34.5 +/- 14.0 ng/dL; p=0.001), fasting insulin (11.55 +/- 10.8 vs. 5.63 +/- 2.6 uIU/mL; p=0.004), HOMA-IR (2.47 +/- 2.4 vs. 1.17 +/- 0.54; p=0.007), and leptin (31.3 +/- 17.4 vs. 16.4 +/- 10.5 ng/mL; p<0.001), with significantly lower FSH (5.6 +/- 1.7 vs. 7.2 +/- 1.9 mIU/mL; p<0.001) and HDL (43.0 +/- 10.0 vs. 54.3 +/- 15.3 mg/dL; p<0.001). Correlation analysis revealed positive associations between BMI and leptin, insulin, and HOMA-IR; WHR and testosterone; TLC and leptin/WHR; and LH/FSH ratio and estrogen, while HDL correlated negatively with HOMA-IR and TLC. Logistic regression identified leptin (OR = 1.105, 95% CI 1.016-1.201, p=0.020) and LH/FSH ratio (OR = 18.48, 95% CI 1.82-187.7, p=0.014) as independent predictors of PCOS. CONCLUSION Normoglycemic PCOS women show distinct hormonal, metabolic, and adipokine alterations, with leptin and LH/FSH emerging as robust independent predictors. These findings highlight the early convergence of adiposity, insulin resistance, inflammation, and gonadotropin imbalance in PCOS, underscoring the need for early biomarker-based risk stratification and intervention even before the onset of overt glycemic abnormalities.
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Abstract

BACKGROUND Polycystic ovary syndrome (PCOS) is a multifaceted disorder characterized by reproductive, metabolic, and endocrine disturbances. While insulin resistance (IR) is recognized as a central feature, the interplay of adipokines, lipid metabolism, gonadotropin imbalance, and inflammation in normoglycemic PCOS women remains underexplored.

Methods

A case-control study was conducted on 30 newly diagnosed normoglycemic women with PCOS (Rotterdam criteria, 2003) and 30 age-matched healthy controls. Anthropometric, hormonal (LH, FSH, LH/FSH ratio, prolactin, estrogen, progesterone, testosterone), metabolic (fasting glucose, HbA1c, insulin, HOMA-IR), lipid (cholesterol, triglycerides, HDL), adipokine (leptin), and hematological parameters were assessed. Group comparisons were performed using independent t-test/Mann-Whitney test as appropriate. Correlation analysis explored inter-relationships among variables, and multivariate logistic regression identified independent predictors of PCOS.

Results

Compared with controls, PCOS women had significantly higher BMI (26.3 +/- 5.3 vs. 23.4 +/- 3.2 kg/m2; p=0.014), WHR (0.861 +/- 0.061 vs. 0.799 +/- 0.060; p<0.001), LH (7.5 +/- 3.7 vs. 5.3 +/- 2.2 mIU/mL; p=0.006), LH/FSH ratio (1.37 +/- 0.76 vs. 0.76 +/- 0.32; p<0.001), estrogen (54.5 +/- 18.2 vs. 38.0 +/- 11.1 pg/mL; p<0.001), testosterone (49.7 +/- 25.1 vs. 34.5 +/- 14.0 ng/dL; p=0.001), fasting insulin (11.55 +/- 10.8 vs. 5.63 +/- 2.6 uIU/mL; p=0.004), HOMA-IR (2.47 +/- 2.4 vs. 1.17 +/- 0.54; p=0.007), and leptin (31.3 +/- 17.4 vs. 16.4 +/- 10.5 ng/mL; p<0.001), with significantly lower FSH (5.6 +/- 1.7 vs. 7.2 +/- 1.9 mIU/mL; p<0.001) and HDL (43.0 +/- 10.0 vs. 54.3 +/- 15.3 mg/dL; p<0.001). Correlation analysis revealed positive associations between BMI and leptin, insulin, and HOMA-IR; WHR and testosterone; TLC and leptin/WHR; and LH/FSH ratio and estrogen, while HDL correlated negatively with HOMA-IR and TLC. Logistic regression identified leptin (OR = 1.105, 95% CI 1.016-1.201, p=0.020) and LH/FSH ratio (OR = 18.48, 95% CI 1.82-187.7, p=0.014) as independent predictors of PCOS.

Conclusion

Normoglycemic PCOS women show distinct hormonal, metabolic, and adipokine alterations, with leptin and LH/FSH emerging as robust independent predictors. These findings highlight the early convergence of adiposity, insulin resistance, inflammation, and gonadotropin imbalance in PCOS, underscoring the need for early biomarker-based risk stratification and intervention even before the onset of overt glycemic abnormalities. Competing Interest Statement The authors have declared no competing interest. Funding Statement No external funding was received for this study. Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study protocol was approved by the Institutional Ethics Committee of Lady Hardinge Medical College, New Delhi. The approval id is as follow: LHMC/ECHR/2014/178 I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data Availability All data produced in the present study are available upon reasonable request to the authors

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