Testosterone effects on autonomic function in women with androgen excess polycystic ovary syndrome

Women with androgen excess-polycystic ovarian syndrome (AE-PCOS) present with increased blood pressure (BP) and impaired cardiovascular autonomic control. We tested the hypothesis that androgens play an obesity-independent role in impaired baroreflex (BR) sensitivity and renin-angiotensin system (RAS) control of BP in women with AE-PCOS. We measured the sympathetic baroreflex (sBR) and cardiovagal baroreflex (cvBR) with the modified Oxford procedure, and integrated baroreflex (iBR) and the RAS response to lower body negative pressure (LBNP) in obese, insulin resistant (IR) women with AE-PCOS (n=9; age=23±4 y; BMI=36.3±6.4 kg/m2) and obese, IR controls (CTL) (n=7; age=29±7 y; BMI=34.9±6.8 kg/m2). Studies were conducted at baseline (BSL), after 4 days of reproductive hormone suppression with a gonadotropin-releasing hormone antagonist (ANT, 250 μg/day), and after 4 days of ANT+testosterone (ANT+T, 5 mg/day). At BSL, AE-PCOS and CTL had similar systolic BP (137±14 vs.133±14 mmHg, respectively) and diastolic BP (76±8 vs.63±12 mmHg, respectively). Resting MSNA burst incidence was lower (10.3±3.1 vs. 14.3±4.4 bursts-1×100 hb, P=0.04), but total MSNA activity was greater in AE-PCOS compared to CTL (249±112 vs. 156±44 bursts/min, respectively, P=0.04). Hormone intervention did not impact resting MSNA or BP in either group. In the AE-PCOS group, sBR gain increased during modified Oxford with ANT suppression of T, but sBR gain was restored to BSL when T was reintroduced (-0.48±0.15, -0.63±0.19, and -0.50±0.15 bursts -1 ·100 hb·mmHg -1 for BSL, ANT and ANT+T, respectively, P=0.01). Hormone interventions did not impact sBR gain in CTL (-0.48±0.06, -0.47±0.10, and -0.46±0.09 bursts -1 ·100 hb·mmHg -1 for BSL, ANT and ANT+T, respectively). iBR gain for AE-PCOS and CTL was similar at BSL (1.4±0.9 vs. 1.0±1.3 FVR unit/mmHg, respectively). In AE-PCOS, T suppression increased iBR gain, which was restored to BSL with ANT+T (4.3±6.5 vs.1.5±0.8 FVR unit/mmHg for ANT and ANT+T respectively, P<0.04), with no effect in CTL (1.9 ± 3.0 vs. 0.7±0.9 FVR unit/mmHg for ANT and ANT+T, respectively). cvBR gain was unaffected by group or treatment. Serum aldosterone was greater in AE-PCOS vs CTL (136.5±60.2 vs. 75.7±41.4 pg/ml, respectively, P<0.04), but unaffected by hormone intervention. Serum angiotensin converting enzyme (S [ACE] ) in AE-PCOS was greater compared to CTL at BSL (101.9±93.4 vs. 38.2 ±14.7 pg/ml, respectively, P<0.04). In AE-PCOS, S [ACE] was reduced by ANT (77.7 ±76.5 and 40.6±10.6 μg/L for ANT vs. ANT+T, respectively, P<0.04), but hormone intervention did not impact CTL (43.4±27.3 and 40.6±1 μg/L for ANT vs. ANT+T, respectively, P<0.04). These data suggest the milieu of AE-PCOS increases susceptibility to T driven autonomic perturbations as T elevation had differential effects in AE-PCOS vs. CTL. Our data indicate a powerful relationship among elevated androgens, autonomic function, and the kidney.NIH HL135089/P20GM 121334 National Institutes of Health, NHLBI HL135089 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.