Androgen Effects on Baroreflex Sensitivity in Women with AE‐PCOS

Abstract

Polycystic ovary syndrome (PCOS) is a reproductive endocrinopathy affecting approximately 10% of reproductive age women. Hyperandrogenism in women may be associated with increased sympathetic activity and impaired blood pressure (BP) regulation. Women with the Androgen-Excess PCOS (AE-PCOS) phenotype can have severe clinical metabolic and cardiovascular comorbidities, including elevated BP. We tested the hypothesis that androgen exposure in AE-PCOS increases BP and impairs BP regulation, as indexed by sympathetic baroreflex sensitivity (BRS). We measured BRS in 5 women with AE-PCOS (mean±SD, age=25±5 y; BMI=40±2 kg/m2) at Baseline (BSL), after 4 days of reproductive hormone suppression with a gonadotropin-releasing hormone (GnRH) antagonist (ANT, 250 μg/day) and 4 days of GnRH ant+testosterone (T, 5 mg/day). Before participating, subjects were screened to demonstrate insulin resistance using an oral glucose tolerance test (AUC=25949±11038 IU for insulin, AUC=23385±2561 mg/dl for glucose). Muscle sympathetic nerve activity (MSNA), expressed in bursts/100 heartbeat (Hb), and diastolic BP (DBP) were measured during the Modified Oxford technique, and sympathetic BR gain (MSNA/DBP) served as an index of sympathetic BRS. We also assessed integrated BR gain with forearm vascular resistance changes as a function of lower body negative pressure (LBNP). Reproductive hormone suppression decreased resting mean arterial pressure compared to BSL (114±10 mm Hg) under both ANT (107±2 mm Hg) and T conditions (106±9 mm Hg, P=0.04). Sympathetic BR gain during ANT was greater compared to BSL (-0.922±0.506 vs. -0.800±0.542 bursts/100 Hb/mm Hg, respectively), and gain was unaffected when androgens were reintroduced (T=-0.819±0.276 bursts/100 Hb, P=0.29). Integrated BRS during LBNP was unaffected by hormone treatment (BSL=0.911±0.653; ANT=0.794±0.967; T= 1.002±0.367 units/mm Hg). In obese, insulin resistant women with AE-PCOS, suppressing testosterone and estrogen (E2) improved arterial BR control of MSNA, while testosterone administration did not restore BR control. Thus, our initial hypothesis that T impairs baroreflex control of MSNA is not supported by these data but suggests that the continued suppression of E2 during ANT and ANT+T may play a more important role. The potential impact of E2 could be a promising clinical intervention and will be directly tested in our future studies.