Autonomic Dysfunction in Women with Androgen Excess PCOS

Abstract

Polycystic ovary syndrome (PCOS) is the most common reproductive endocrinopathy, affecting approximately 10% of reproductive age women. Further, 75% of women with PCOS have the more severe phenotype, Androgen Excess‐PCOS (AE‐PCOS), that is dominated by clinical and biochemical manifestations of hyperandrogenism. AE‐PCOS is also associated with elevated blood pressure (BP), which we hypothesized is the result of androgen‐associated impairments in autonomic function. Thus, we tested the hypothesis that androgen excess is associated with impaired baroreflex sensitivity (BRS) in women with AE‐PCOS. We tested four obese women with AE‐PCOS (age 30±3 y; BMI 39±11 kg/m2) at 0, HDT, ‐20, ‐30 lower body negative pressure (LBNP) under three conditions: Baseline (BL), during hormone suppression with a GnRH antagonist (GnRH ant, 7 days, 250 μg/day), and with GnRH ant+testosterone (T, 4 days, 5 mg/day). Women were mildly hypertensive at rest at BL, but BP increased following hormone suppression with the GnRH ant and remained elevated with T (93±7, 105±5, 105±9 mm Hg for BL, GnRH ant, and T, respectively, P=0.02). Blood pressure was well maintained during LBNP under the three hormone conditions. Forearm vascular resistance (FVR) increased during LBNP under each condition, but the increase was greatest during GnRH ant and T (Δ54±19, Δ235±145, Δ104±64 units for BL, GnRH ant, and T, respectively, P=0.04). The resulting BRS slopes were greater in GnRH ant (−5.2 units/mm Hg) compared to BL (−1.6 units/mm Hg), demonstrating concomitant testosterone and estrogen suppression improved BRS in women with AE‐PCOS. When we restored androgens, the BRS slope was again attenuated (T= −1.7 units/mm Hg), suggesting an important role for androgens in autonomic function in AE‐PCOS. GnRH ant increased resting BP independent of T in AE‐PCOS, which is likely a function of the continued estrogen suppression. Thus, hypertension associated with AE‐PCOS appears closely associated with estrogen suppression and independent of testosterone‐induced changes in BRS. In summary, both estrogens and androgens contribute to BP regulation in women with AE‐PCOS. Women with AE‐PCOS frequently present with mild hypertension that is driven by altered estrogen and testosterone exposures. Treating hypertension is crucial for preventing cardiovascular disease in this vulnerable population.Support or Funding InformationR01 HL135089