LAUSR

Polycystic Ovary Syndrome (PCOS) is characterized by hyperandrogenism and ovulatory dysfunction. PCOS women have elevated prevalence of cardiometabolic risk factors that worsen after menopause. Liraglutide (Lira), a glucagon-like peptide-1 receptor agonist, have shown beneficial metabolic effects in small clinic trials in reproductive-age PCOS women. We have shown that chronic hyperandrogenemia in an experimental model of postmenopausal PCOS (PCOS) is associated with an adverse cardiometabolic profile and upregulation of the intrarenal renin angiotensin system (RAS). We analyzed the effect of Lira in the cardiometabolic profile, intrarenal RAS and blood pressure (BP) in postmenopausal PCOS. Four week-old female Sprague Dawley rats were treated with dihydrotestosterone or placebo for 17 months. Lira administration during the last 3 weeks caused a bigger reduction in food intake, body weight, fat mass and HOMA-IR index in PCOS than in control rats. Moreover, Lira improved dyslipidemia and elevated leptin levels in PCOS. In contrast, Lira decreased intrarenal expression of RAS components only in the control group. Lira transiently increased heart rate and decreased BP in control rats. However, Lira did not modify BP but increased heart rate in PCOS. The ACE inhibitor enalapril abolished the BP differences between PCOS and control rats. However, Lira co-administration with enalapril further reduced BP only in control rats. In summary, Lira exhibit beneficial effects in several cardiometabolic risk factors in postmenopausal PCOS. However, hyperandrogenemia blunted the BP lowering effect of Lira in postmenopausal PCOS. Androgen-induced activation of intrarenal RAS may play a major role mediating increases in BP in postmenopausal PCOS.