Effects of androgen excess and body mass index on endothelial function in women with polycystic ovary syndrome

Abstract

Polycystic ovary syndrome (PCOS) is associated with endothelial dysfunction; whether this is attributable to co-morbid hyperandrogenism and/or obesity remains to be established. Therefore, we (1) compared endothelial function between lean and overweight/obese (OW/OB) women with and without androgen excess (AE)-PCOS and (2) examined androgens as potential modulators of endothelial function in these women. The flow-mediated dilation (FMD) test was applied in 14 women with AE-PCOS (lean: n=7; OW/OB: n=7) and 14 controls (CTRL; lean: n=7, OW/OB: n=7) at baseline (BSL) and following 7-days of ethinyl estradiol supplementation (EE; 30mg/day) in order to assess the effect of a vasodilatory therapeutic on endothelial function; at each time point we assessed peak increases in diameter during reactive hyperemia (%FMD), shear rate, and low flow-mediated constriction (%LFMC). BSL %FMD was attenuated in lean AE-PCOS vs both lean CTRL (5.2±1.5 vs 10.3±2.6%, P<0.01) and OW/OB AE-PCOS (5.2±1.5 vs 6.6±0.9%, P=0.048). A negative correlation between BSL %FMD and free testosterone was observed in lean AE-PCOS only (R2=0.68, P=0.02). EE increased %FMD in both OW/OB groups (CTRL: 7.6±0.6 vs 10.4±2.5%, AE-PCOS: 6.6±0.9 vs 9.6±1.7%, P<0.01), had no impact on %FMD in lean AE-PCOS (5.17±1.5 vs 5.17±1.1%, P=0.99), and reduced %FMD in lean CTRL (10.3±2.6 vs 7.6±1.2%, P=0.03). Collectively, these data indicate that lean women with AE-PCOS exhibit more severe endothelial dysfunction than their OW/OB counterparts. Furthermore, endothelial dysfunction appears to be mediated by circulating androgens in lean but not in OW/OB AE-PCOS, suggesting a difference in the endothelial pathophysiology of AE-PCOS between these phenotypes.

Is polycystic ovary syndrome associated with elevated muscle sympathetic nerve activity?

“…potent CVD risk factors (Amiri et al, 2020;Barber & Franks, 2021;Berbrier et al, 2023;Goodarzi et al, 2011;Sprung et al, 2013), which likely contribute to an increased incidence of cardiovascular morbidity.…”

“…Moreover, insulin resistance affects approximately 50–70% of females with PCOS, independent of body mass index (BMI; Goodarzi et al., 2011 ). Females with PCOS are also at an increased risk of developing endothelial dysfunction (Berbrier et al., 2023 ; Sprung et al., 2013 ), an early marker of atherosclerosis. All of these pathologies are well‐established CVD risk factors, and given their prevalence in PCOS, create a concerning profile of CVD risk in females with PCOS.…”

“…Most studies include only premenopausal females, in whom CVD mortality is relatively infrequent. Nevertheless, there is compelling evidence that PCOS is associated with the presence of potent CVD risk factors (Amiri et al., 2020 ; Barber & Franks, 2021 ; Berbrier et al., 2023 ; Goodarzi et al., 2011 ; Sprung et al., 2013 ), which likely contribute to an increased incidence of cardiovascular morbidity.…”

“…The most well‐established vascular consequence of PCOS is endothelial dysfunction. Females with PCOS exhibit endothelial dysfunction regardless of BMI (Sprung et al., 2013 ), and the magnitude of endothelial dysfunction has been associated with circulating androgens in lean females (Berbrier et al., 2023 ).…”

Diyet ileri glikasyon son ürünleri (AGE) ve kadın infertilitesi

“…The presence of endothelial dysfunction in individuals with PCOS has been found to potentially elevate the likelihood of developing cardiovascular disease. Furthermore, this dysfunction has been seen to be linked with hyperandrogenism (80,81). Insulin resistance, hyperandrogenism, and obesity are considered as potential mediators of endothelial function in PCOS (82).…”