Natural Fluctuations in Progesterone Do Not Impact Vascular Function in Healthy Premenopausal Women

Abstract

Endogenous sex hormone concentrations vary across the menstrual cycle of naturally menstruating premenopausal women and may elicit concomitant changes in vascular function. Specifically, estrogen (E2) may enhance vascular function, partially by increasing nitric oxide bioavailability. In contrast, the influence of progesterone (P4) on vascular function remains unclear, with some data suggesting it increases nitric oxide bioavailability and other data suggesting it antagonizes the dilatory effects of E2. The objective of the study was to elucidate potential effects of P4 on the macrovascular function of healthy premenopausal women in the presence of relatively lower E2 concentrations. It was hypothesized that measures of macrovascular function would be similar between the early follicular (EF) and early luteal (EL) phases of healthy premenopausal women, despite a significant increase in the progesterone‐to‐estrogen ratio from the EF to the EL phase. Sex hormones and vascular function were measured in ten healthy premenopausal women (22±2 y) during the EF phase (within 5 days of the onset of menstruation) and the EL phase (4±2 days post‐ovulation) of a single menstrual cycle. Serum concentrations of E2 and P4 were analyzed using enzyme‐linked immunosorbent assays. Independent concentrations of E2 and P4 were calculated, as well as P4:E2. Macrovascular function was assessed via brachial artery flow‐mediated dilation (FMD). %FMD was calculated as the percent change in brachial artery diameter following an ischemic stimulus. Data were compared between phases with paired t‐tests. Serum concentrations of E2 and P4 increased from the EF to the EL phase (91.8±34.5 vs. 120.9±32.6 pg/mL, p=0.01 and 1.4±0.6 vs. 5.1±3.6 ng/mL, p=0.01, respectively). The P4:E2 increased significantly from the EF to the EL phase as a result of the P4 surge in the EL phase (15.5±4.8 vs. 42.9±30.5, p=0.02). %FMD did not differ between the EF and EL phases (9.6±4.4 vs. 9.5±3.5 %, p=0.97). In conclusion, the macrovascular function of healthy premenopausal women is similar between the EF and EL phases despite significant increases in the P4:E2. Findings may suggest that P4 does not play an antagonist role on E2 and may have a synergistic effect on increasing %FMD among decreased concentrations of E2.