Differential cardiometabolic outcomes of leuprolide versus spironolactone in women with polycystic ovary syndrome

Background: Polycystic ovary syndrome (PCOS) is a common endocrine disorder with systemic implications including dyslipidemia, hypertension, and chronic kidney disease. We explored the metabolic effects of leuprolide and spironolactone beyond their use for managing hyperandrogenic symptoms in PCOS. Methods: We used the TriNetX Research Network to identify patients aged 18 to 50 years diagnosed with PCOS and stratified them by use of leuprolide or spironolactone. The cohorts were matched for demographics, comorbidities, and confounding medications and each had 2078 patients. Outcomes included rates of hypercholesterolemia, lipid profiles, lipid-lowering agent use, hypertension, antihypertensive medications, obesity, hyperglycemia, chronic kidney disease, and major adverse cardiovascular events. Results: Over a 5-year examination period, leuprolide carried lower risks than spironolactone for hypercholesterolemia (risk ratio [RR] 0.46; 95% confidence interval [CI], 0.39-0.54), low high-density lipoprotein (RR 0.41; CI, 0.35-0.48), and elevated low-density lipoprotein (RR 0.39; CI, 0.26-0.58). Risks were also reduced for hypertension (RR 0.73; CI, 0.61-0.87), antihypertensive use (RR 0.86; CI, 0.75-0.99), and lipid-lowering therapy (RR 0.79; CI, 0.63-0.99). No significant differences appeared for chronic kidney disease, major adverse cardiovascular events, hyperglycemia, or obesity. Conclusion: Leuprolide therapy was associated with improved lipid and hypertension outcomes compared to spironolactone. These findings support leuprolide's potential role in broader metabolic management of PCOS.