Short-term oral progesterone administration antagonizes the effect of transdermal estradiol on endothelium-dependent vasodilation in young healthy women

Abstract

Very few studies have explored the cardiovascular effects of progesterone in premenopausal women. This study aimed to examine the short-term effects of oral progesterone alone, transdermal estrogen alone, and progesterone and estrogen combined on flow-mediated dilation (FMD) in healthy reproductive-aged women. We suppressed endogenous estrogens and progesterone in 17 premenopausal women for 10-12 days using a gonadotropin-releasing hormone antagonist. On day 4 (hormone suppression condition), subjects were tested (n = 17) and were then supplemented with either 200 mg micronized progesterone (n = 8) orally or 0.1 mg estradiol (n = 9) transdermally per day. On day 7 (progesterone-first or estradiol-first condition), subjects were tested and began supplementation with both hormones (n = 17) and were tested again on day 10 (combined hormone condition). FMD of the brachial artery was assessed using B-mode arterial ultrasound, combined with synchronized Doppler analysis. As a result, significant differences in FMD were observed between hormone suppression (7.85 ± 1.06%) and estrogen-first conditions (10.14 ± 1.40%; P < 0.05). The estradiol-induced increase was abolished when oral progesterone was also supplemented (6.27 ± 0.96%). In contrast, we observed a trend toward a decrease in FMD with unopposed progesterone administration, but no statistically significant differences were found between the progesterone-first (6.66 ± 1.23%), hormone suppression (7.80 ± 1.23%), and combined hormone conditions (7.40 ± 1.29%). In conclusion, these data suggest that short-term oral micronized progesterone administration antagonizes the beneficial effect of transdermal estradiol on FMD.

Fig. 1.

Study design. Subjects are tested under hormone suppression, progesterone-first or estrogen-first, and combined progesterone-estrogen conditions. Testing occurred on days 4, 7, and 10. GnRHa, hormone suppression via gonadotropin release hormone antagonist; P₄, progesterone; E₂, estradiol.

Fig. 2.

Flow-mediated dilation (FMD) and hormone condition. A: FMD was higher in the estrogen-first (GnRHa + E₂) condition than in the suppressed hormone state (GnRHa, P = 0.037) and combined hormones condition (GnRHa + P₄ + E₂, P = 0.001). B: no statistical differences in FMD were found between hormone suppression (GnRHa), progesterone-first (GnRHa + P₄), and combined progesterone-estrogen conditions (GnRHa + P₄ + E₂), P > 0.05, although there was a trend toward a decreased FMD in the progesterone-first condition. Values are means ± SE. *P < 0.05.