Berbrier Danielle E, Leone Cheryl A, Adler Tessa E, Bender Jeffrey R, Taylor Hugh S, Stachenfeld Nina S, Usselman Charlotte W
Cardiovascular Health and Autonomic Regulation Laboratory, Department of Kinesiology and Physical Education, McGill University, Montreal, Quebec, Canada.
The John B. Pierce Laboratory, Yale School of Medicine, New Haven, Connecticut, United States.
J Appl Physiol (1985). 2023 Apr 1;134(4):868-878. doi: 10.1152/japplphysiol.00583.2022. Epub 2023 Mar 2.
Polycystic ovary syndrome (PCOS) is associated with endothelial dysfunction; whether this is attributable to comorbid hyperandrogenism and/or obesity remains to be established. Therefore, we ) compared endothelial function between lean and overweight/obese (OW/OB) women with and without androgen excess (AE)-PCOS and ) 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: = 7; OW/OB: = 7) and 14 controls (CTRL; lean: = 7, OW/OB: = 7) at baseline (BSL) and following 7 days of ethinyl estradiol supplementation (EE; 30 µg/day) 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 versus both lean CTRL (5.2 ± 1.5 vs. 10.3 ± 2.6%, < 0.01) and OW/OB AE-PCOS (5.2 ± 1.5 vs. 6.6 ± 0.9%, = 0.048). A negative correlation between BSL %FMD and free testosterone was observed in lean AE-PCOS only ( = 0.68, = 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%, < 0.01), had no impact on %FMD in lean AE-PCOS (5.17 ± 1.5 vs. 5.17 ± 1.1%, = 0.99), and reduced %FMD in lean CTRL (10.3 ± 2.6 vs. 7.6 ± 1.2%, = 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. We present evidence for marked endothelial dysfunction in lean women with androgen excess polycystic ovary syndrome (AE-PCOS) that is ) associated with free testosterone levels, ) impaired relative to overweight/obese women with AE-PCOS, and ) unchanged following short-term ethinyl estradiol supplementation. These data indicate an important direct effect of androgens on the vascular system in women with AE-PCOS. Our data also suggest that the relationship between androgens and vascular health differs between phenotypes of AE-PCOS.
多囊卵巢综合征（PCOS）与内皮功能障碍有关；这是否归因于合并的高雄激素血症和/或肥胖仍有待确定。因此，我们：比较了有和没有雄激素过多（AE）-PCOS的瘦型与超重/肥胖（OW/OB）女性之间的内皮功能；研究了雄激素作为这些女性内皮功能潜在调节因子的作用。在基线（BSL）以及补充乙炔雌二醇（EE；30μg/天）7天后，对14例AE-PCOS女性（瘦型：n = 7；OW/OB：n = 7）和14例对照（CTRL；瘦型：n = 7，OW/OB：n = 7）进行血流介导的血管舒张（FMD）测试，以评估血管舒张治疗对内皮功能的影响；在每个时间点，我们评估反应性充血期间直径的峰值增加（%FMD）、剪切速率和低血流介导的血管收缩（%LFMC）。与瘦型CTRL（5.2±1.5对10.3±2.6%，P < 0.01）和OW/OB AE-PCOS（5.2±1.5对6.6±0.9%，P = 0.048）相比，瘦型AE-PCOS的BSL %FMD降低。仅在瘦型AE-PCOS中观察到BSL %FMD与游离睾酮之间呈负相关（r = 0.68，P = 0.02）。EE增加了两个OW/OB组的%FMD（CTRL：7.6±0.6对10.4±2.5%，AE-PCOS：6.6±0.9对9.6±1.7%，P < 0.01），对瘦型AE-PCOS的%FMD无影响（5.17±1.5对5.17±1.1%，P = 0.99），并降低了瘦型CTRL的%FMD（10.3±2.6对7.6±1.2%，P = 0.03）。总体而言，这些数据表明，患有AE-PCOS的瘦型女性比其OW/OB对应者表现出更严重的内皮功能障碍。此外，内皮功能障碍似乎在瘦型AE-PCOS中由循环雄激素介导，而在OW/OB AE-PCOS中则不然，这表明这些表型的AE-PCOS在内皮病理生理学上存在差异。我们提供证据表明，患有雄激素过多多囊卵巢综合征（AE-PCOS）的瘦型女性存在明显的内皮功能障碍，其：与游离睾酮水平相关；相对于患有AE-PCOS的超重/肥胖女性受损；在短期补充乙炔雌二醇后无变化。这些数据表明雄激素对患有AE-PCOS的女性血管系统有重要的直接影响。我们的数据还表明，雄激素与血管健康之间的关系在AE-PCOS的不同表型之间存在差异。
