Ethinyl estradiol-to-desogestrel ratio impacts endothelial function in young women

Abstract

Background Ethinyl estradiol (EE) and progestins have the ability to alter endothelial function. The type of progestin and the ratio of EE to progestin used in oral contraceptive pills (OCPs) may determine how they affect the arterial vasculature. Study Design In this study, we investigated endothelial function across a cycle in very low dose (VLD) and low dose (LD) combination EE and desogestrel (DSG) OCP users during two phases: active (VLD=20 mcg EE/150 mcg DSG; LD=30 mcg EE/150 mcg DSG) and pill-free. Endothelial function was also measured during an EE-only hormone phase (10 mcg EE) in group VLD. Results Endothelium-dependent vasodilation was greater during the active phase compared to the pill-free phase in group LD (9.02±0.72% vs. 7.33±0.84%; p=.029). This phase difference was not observed in group VLD (5.86±0.63% vs. 6.56±0.70%; p=.108). However, endothelium-dependent vasodilation was higher during the EE-only phase, compared to the active and pill-free phases (8.92±0.47% vs. 5.86±0.63%, and 6.56±0.70%; pb.001) in group VLD. Conclusions These data suggest DSG may antagonize the vasodilatory activity of EE and that this effect is further modulated by the EE-toDSG ratio.

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

“…Our laboratory has previously shown a negative impact of desogestrel, levonorgestrel, and MPA (all combined with varying doses of ethinyl estradiol) on FMD levels (25,26,47). Lizarelli et al (22) also discovered similar responses in FMD in young women, showing that levonorgestrel (when combined with ethinyl estradiol) and depot MPA decrease FMD, compared with that in age-matched controls.…”

“…Data were collected and analyzed for 9-min postadministration. The administration of nitroglycerine elicits maximum dilation of the conduit arteries (25,26,47,48). EIVD is calculated as the percent change between baseline diameter and peak dilation post-nitroglycerine administration:…”

“…However, cardiovascular responses to different types of exogenous progestogen administration widely vary (1,7,23,36). Our laboratory has previously shown that levonorgestrel, desogestrel, and medroxyprogesterone acetate (MPA) all antagonized the effects of ethinyl estradiol on FMD (25,26,47). Conversely, etonorgestrel (via a vaginal ring) and drospirenone did not (24, 48).…”

“…However, it is unclear whether the lower FMD during the mid-luteal phase, compared with the ovulation phase (high estrogen, low progesterone), is due to the rise in progesterone or the lowered estrogen during this phase. The administration of estradiol has also been demonstrated to increase FMD compared with hormone-suppressed values (5,10,11,25,26,47). However, cardiovascular responses to different types of exogenous progestogen administration widely vary (1,7,23,36).…”

Differential effects of the type of oral contraceptive and menstrual phase on endothelial function in healthy young women

“…Studies investigating endothelial function in premenopausal women must be carefully designed to account for cyclic changes in estrogen, a potent vasoactive hormone (2) . A small number of studies have used flow mediated dilatation (FMD) to investigate the effect of menstrual cycle phase on endothelial function in premenopausal women; both free-cycling (3) , and those taking two different formulations of oral contraceptives (OC) (4,5) . These studies confirmed the oestrogen-correlated variation in FMD response in free-cycling women, but have also indicated that the response in women taking OC depends on the type of progestin.…”