Progesterone administration antagonizes the effect of estradiol on endothelium‐dependent vasodilation in young healthy women

Abstract

PurposeTo examine the acute effects of progesterone and estrogen on endothelium‐dependent vasodilation in healthy reproductive‐aged women.MethodsWe suppressed endogenous estrogens and progesterone in 16 premenopausal women for 10 days using a gonadotropin‐releasing hormone antagonist (GnRHa). On day 4, subjects were tested and then supplemented either 0.1 mg estradiol (GnRHA+E2; N=8) transdermally or 200 mg progesterone (GnRHa+P4; N=8) orally per day. On day 7 subjects were tested and began supplementation with both hormones (GnRHa+P4+E2), and were tested again on day 10. Flow‐mediated vasodilation (FMD) of the brachial artery was assessed using B‐mode arterial ultrasound, combined with synchronized Doppler analysis.ResultsSignificant differences were observed when comparing FMD in GnRHa (7.85 ± 2.77%) and GnRHa+E2 conditions (10.14 ± 1.40%; p<0.05). The E2 increase was abolished when progesterone was also supplemented (6.27 ± 2.41%). In contrast, GnRHa+P4 (6.66 ± 2.56%) did not significantly alter FMD from GnRHa (7.80 ± 2.76%) and GnRHa+P4+E2 (7.40 ± 3.02%). However, a multi‐level prediction model demonstrates progesterone (p<0.02) and estradiol (p<0.01) predict FMD within subjects.ConclusionThese data suggest that acute progesterone administration antagonizes the effect of estrogen on endothelium‐dependent vasodilation.Supported by NIH Grant HL081671.