Microvascular endothelial function is preserved during short-term estrogen suppression with Elagolix® in women with endometriosis

Cardiovascular disease (CVD) risk is elevated in women with endometriosis (ENDO). Because estrogen is cardioprotective in some women, this CVD risk might be exacerbated by common ENDO treatments that suppress estrogen. The purpose of this study was to determine the impact of short-term estrogen suppression on peripheral microvascular endothelial function in women with ENDO. We hypothesized that estrogen suppression would impair endothelium-dependent vasodilation in ENDO (n = 8, 29 ± 7 y, 23.3 + 2.5 kg x m2) and controls (CON, n = 12, 27 ± 6 y, 23.1 ± 5.1 kg x m2). Trials were conducted with (POST) and without (PRE) 4 days of estrogen suppression (400 mg/day gonadotropin-releasing hormone antagonist, Elagolix®) in the early follicular phase of separate menstrual cycles in both groups. The cutaneous circulation was used as a model of microvascular vasodilatory function. Laser Doppler flowmetry (LDF) was continuously measured during graded perfusions of acetylcholine (Ach, 1x10-10 – 1x10-1 M) and estradiol (E2, 10-100 nM or 1x10-9-x10-7 M) through intradermal microdialysis. Maximal vasodilation was elicited via 28 mM sodium nitroprusside perfusion with local heating (42C). Cutaneous vascular conductance was calculated as LDF/mean arterial pressure. Dose response curves were generated with nonlinear modeling of normalized data with constraints and compared via median effective ACh and E2 dose (ED50) and HillSlope. Data are presented as mean ± SD and alpha = 0.05. With Ach perfusions, Elagolix® lowered Ach ED50 in CON (PRE, -3.17 ± 1.21 logM; POST, -2.49 ± 0.89 logM; ANOVA, P=0.02), but had no impact on Ach ED50 in ENDO (PRE, -2.83 ± 1.27 logM; POST, -3.49 ± 1.51 logM; ANOVA, P = 0.54). HillSlope was unaffected by Elagolix® in both ENDO (PRE, 2.32 ± 2.67; POST 2. 31 ± 2.35) and CON (PRE, 1.48 ± 2.28; POST, 1.65 ± 1.46; ANOVA, P = 0.25). Elagolix® had no impact on E2 ED50 in ENDO (PRE, 1.95 ± 0.25 logM; POST, 1.99 ± 0.27 logM,) or CON (PRE, 2.07 ± 0.77 logM; POST, 2.13 ± 0.14 logM; ANOVA, P = 0.11). HillSlope was also unaffected by Elagolix® in ENDO (PRE, 7.94 ± 5.83; POST, 6.88 ± 4.55) and CON (PRE, 9.45 ± 7.50; POST, 8.14 ± 5.06; ANOVA, P = 0.54). Contrary to our hypothesis, these data indicate that peripheral endothelial function is not compromised in women with ENDO compared to CON. Further, peripheral microvascular endothelial function is preserved during short-term estrogen suppression treatment in these patients. Future studies with longer estrogen suppression are needed to determine long-term cardiovascular effects of this treatment in women with endometriosis. NIH 1R01HL161000; NCT 2000022193. 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.