Polycystic ovary syndrome was associated with a higher prevalence of hypertension compared to age-matched controls (34% vs. 25%) and underuse of ACE inhibitors or ARBs (18% vs. 16%).
Cross-Sectional (n=3,035)
Does hyperandrogenemia activate the renin-angiotensin system to drive hypertension in PCOS, and does enalapril mitigate this effect?
Hyperandrogenemia in PCOS activates the renin-angiotensin system to drive hypertension, which can be mitigated by ACE inhibition, highlighting a potential targeted therapeutic approach.
Absolute Event Rate: 34% vs 25%
Background: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder affecting 5–20% of reproductive-aged women. It is characterized by hyperandrogenemia, metabolic dysfunction, and increased hypertension risk. Although obesity and insulin resistance may contribute to elevated blood pressure (BP), mechanisms linking hyperandrogenemia to cardiovascular risk in PCOS remain unclear. Activation of the renin–angiotensin system (RAS) has been reported in PCOS, suggesting a major role of RAS signaling in androgen-driven hypertension. Aim: To test whether hyperandrogenemia activates systemic and intrarenal RAS in a time-dependent manner and whether angiotensin-converting enzyme (ACE) inhibition mitigates the associated BP increase. We also aim to assess hypertension prevalence and antihypertensive use in women with PCOS versus age-matched controls. Methods: Two complementary experiments were conducted. In the first, 80 female Sprague Dawley rats (n=20 per time point: 2, 4, 8, and 12 weeks post-DHT; 10 DHT and 10 placebo each) were used to assess DHT by Radioimmunoassay, intrarenal AR and AGT mRNA by digital PCR, and AGT protein by automated Western blotting. Serum and urinary AGT were measured by ELISA. In the second, 40 rats received vehicle or DHT with or without the ACE inhibitor enalapril for 90 days. BP was measured by radiotelemetry, and ACE activity in plasma and kidney by fluorometric assays. These mechanistic findings were complemented with cross-sectional data from 3,035 women with PCOS in the UMMC Research Data Warehouse as well as female controls matched on age and race. Statistics used t-tests or 2-way ANOVA. Cross-sectional data were analyzed using R and multivariable logistic regression to evaluate hypertension in PCOS patients. Results: DHT significantly increased circulating DHT (~1.5–2-fold, p< 0.05) and elevated renal AR expression in cortex (~9-fold) and medulla (~2-fold). Intrarenal AGT mRNA was strongly upregulated in DHT rats (~16–30-fold, p< 0.05), whereas AGT protein was unchanged, suggesting post-transcriptional regulation. Serum and urinary AGT were also higher by ~2-fold and ~10–30-fold (p< 0.05), indicating systemic and intrarenal RAS activation, evident as early as two weeks. In radiotelemetry studies, DHT increased mean arterial pressure (116 ± 1 vs. 107 ± 1 mmHg, p< 0.05), an effect abolished by enalapril (82 ± 1 vs. 116 ± 1 mmHg, p< 0.05). Although DHT did not alter ACE activity, enalapril suppressed ACE activity in plasma, cortex, and medulla by ~2–4-fold (p< 0.05). Women with PCOS had higher BMI (38 ± 10 vs. 31 ± 9 kg/m 2 ), systolic BP (128 ± 13 vs. 123 ± 13 mmHg), and more frequent hypertension (34% vs. 25%) than age-matched controls. Of those with HTN, PCOS women were prescribed with ACE inhibitor or ARB use in a low percentage (18% vs. 16%), with greater use of calcium channel blockers (22% vs. 15%) and diuretics (23% vs. 16%) as compared to control hypertensive women. Conclusion: Chronic hyperandrogenemia activates systemic and intrarenal RAS, elevating AGT and BP, while enalapril mitigates these effects. Early increases in serum, urinary, and renal AGT identify it as a potential biomarker of RAS dysregulation in PCOS and support RAS-targeted interventions. Clinical data likewise show increased hypertension risk in PCOS and underuse of ACE inhibitors. Together, preclinical and clinical findings reinforce a mechanistic link between androgen excess and RAS-driven cardiovascular dysfunction, highlighting hyperandrogenemia-induced RAS activation as a driver of cardiometabolic risk in women with PCOS. Funding: This work was supported by R01HL171494, R01HL144847, T32HL105324, P20GM121334, P50MD017338, P30GM149404, U54 GM115428, and 1-26-PDF-0678 This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
Cardozo et al. (Fri,) conducted a cross-sectional in Polycystic ovary syndrome (PCOS) (n=3,035). Polycystic ovary syndrome vs. Age- and race-matched controls was evaluated on Hypertension prevalence. Polycystic ovary syndrome was associated with a higher prevalence of hypertension compared to age-matched controls (34% vs. 25%) and underuse of ACE inhibitors or ARBs (18% vs. 16%).