Testosterone-associated blood pressure dysregulation in women with androgen excess polycystic ovary syndrome

We tested the hypothesis that hyperandrogenemia in androgen excess polycystic ovary syndrome ( AE-PCOS) is a primary driver in blood pressure (BP) dysregulation via altered sympathetic nervous system activity (SNSA), reduced integrated baroreflex gain and increased renin-angiotensin system ( RAS) activation. We measured resting SNSA (microneurography), integrated baroreflex gain, and RAS with lower body negative pressure in obese insulin- resistant (IR) women with AEPCOS [n = 8, 23 +/- 4 yr; body mass index (BMI) = 36.3 +/- 6.4 kg/m(2)] and obese IR controls (n = 7, control, 29 +/- 7 yr; BMI = 34.9 +/- 6.8 kg/m(2)), at baseline (BSL), after 4 days of gonadotropin-releasing hormone antagonist (ANT, 250 mu g/day) and 4 days of ANT + testosterone (ANT + T, 5 mg/day) administration. Resting BP was similar between groups for systolic blood pressure (SBP; 137 +/- 14 vs. 135 +/- 14 mmHg, AE-PCOS, control) and diastolic BP (89 +/- 21 vs. 76 +/- 10 mmHg, AE-PCOS, control). BSL integrated baroreflex gain was similar between groups [ 1.4 +/- 0.9 vs. 1.0 +/- 1.3 forearm vascular resistance (FVR) U/mmHg], but AE-PCOS had lower SNSA (10.3 +/- 2.0 vs. 14.4 +/- 4.4 burst/100 heartbeats, P = 0.04). In AE-PCOS, T suppression increased integrated baroreflex gain, which was restored to BSL with ANT + T (4.3 +/- 6.5 vs. 1.5 +/- 0.8 FVR U/mmHg, ANT, and ANT + T, P = 0.04), with no effect in control. ANT increased SNSA in AE-PCOS (11.2 +/- 2.4, P = 0.04). Serum aldosterone was greater in AE-PCOS versus control (136.5 +/- 60.2 vs. 75.7 +/- 41.4 pg/ mL, AE-PCOS, control, P = 0.04) at BSL but was unaffected by intervention. Serum angiotensin-converting enzyme was greater in AE-PCOS versus control (101.9 +/- 93.4 vs. 38.2 +/- 14.7 pg/mL, P = 0.04) and reduced by ANT in AE-PCOS (77.7 +/- 76.5 vs. 43.4 +/- 27.3 lg/L, ANT, and ANT + T, P = 0.04) with no impact on control. Obese, IR women with AE-PCOS showed decreased integrated baroreflex gain and increased RAS activation compared with control. NEW & NOTEWORTHY Here we present evidence for an important role of testosterone in baroreflex control of blood pressure and renal responses to baroreceptor unloading in women with a common, high-risk androgen excess polycystic ovary syndrome (AE-PCOS) phenotype. These data indicate a direct effect of testosterone on the vascular system of women with AE-PCOS independent of body mass index (BMI) and insulin-resistant (IR). Our study indicates that hyperandrogenemia is a central underlining mechanism of heightened cardiovascular risk in women with PCOS.