Oral contraceptive pills (OCPs) are a popular contraception method. Currently, lower-dose ethinyl estradiol formulations are most commonly prescribed, although they have been linked to increased arterial vascular risk. The aim of this study was to investigate endothelial function in healthy young women using lower-dose ethinyl estradiol OCPs. We examined flow-mediated, endothelium-dependent and nitroglycerin-mediated, endothelium-independent vasodilation of the brachial artery, comparing two doses of ethinyl estradiol/levonorgestrel OCPs in 15 healthy young women on two study days: once during the active phase and once during the placebo phase of an OCP cycle. Group low dose (LD) (n=7) active pills contained 150 microg levonorgestrel/30 microg ethinyl estradiol versus Group very low dose (VLD) (n=8) with 100 microg levonorgestrel/20 microg ethinyl estradiol. Endothelium-dependent vasodilation was lower during the active phase in Group VLD (5.33 +/- 1.77% vs. 7.23 +/- 2.60%; P=0.024). This phase difference was not observed in Group LD (8.00 +/- 0.970% vs. 7.61 +/- 1.07%; P=0.647). Endothelium-independent vasodilation did not differ between phases in either group. Finally, we measured endothelium-dependent vasodilation in two additional women who received 10 microg of unopposed ethinyl estradiol. Endothelium-dependent vasodilation was increased by unopposed ethinyl estradiol compared with the placebo phase (10.88 +/- 2.34% vs. 6.97 +/- 1.83%). These results suggest that levonorgestrel may antagonize the activity of ethinyl estradiol. Thus both the progestin type and estradiol dose need to be considered when assessing arterial vascular risk of OCP use in women.

Meendering JR, Torgrimson BN, Miller NP, Kaplan PF, Minson CT. Estrogen, medroxyprogesterone acetate, endothelial function, and markers of cardiovascular risk in young women. Am J Physiol Heart Circ Physiol 294: H1630-H1637, 2008. First published February 15, 2008 doi:10.1152/ajpheart.01314.2007.-Medroxyprogesterone acetate (MPA) is widely known for its use in combination hormone therapy for postmenopausal women. However, MPA is also commonly used in young women for contraception and treatment of a number of gynecological conditions. Despite its widespread use, the cardiovascular effects of MPA in young women are unclear. Therefore, the purpose of this study was to determine the acute effects of MPA when used in combination with estradiol on markers of cardiovascular risk in young women. We suppressed endogenous estrogens and progesterone in 10 premenopausal women using a gonadotropin-releasing hormone antagonist (GnRHa) for 10 days. On day 4 of GnRHa subjects received 0.1 mg of estradiol (GnRHaϩE2), and on day 7 5 mg of MPA was added (GnRHaϩE2ϩMPA). Endothelium-dependent vasodilation and endothelium-independent vasodilation of the brachial artery, lipids, homocysteine, high-sensitivity C-reactive protein, and endothelin-1 were assessed during treatment with GnRHa, GnRHaϩE2, and GnRHaϩE2ϩMPA. Four additional subjects were tested to validate the efficacy of the GnRHa model and confirm the findings. Endothelium-dependent vasodilation was greater during GnRHaϩE2 than during GnRHa or GnRHaϩE2ϩMPA (P ϭ 0.006). Endothelin-1 was lower during GnRHaϩE2 than GnRHa alone (P ϭ 0.039). Endothelin-1 increased with the addition of MPA and was not significantly different from GnRHa alone. There were no differences in the other markers of cardiovascular risk between hormone treatment days. These data suggest that acute MPA administration negates the beneficial effects of estradiol on endothelium-dependent vasodilation in young women. In addition, these data suggest that estradiol decreases endothelin-1 concentrations and the addition of MPA may counteract the effect of estradiol on endothelin-1. endothelium; hormones; flow-mediated vasodilation; endothelin-1; progestins THERE IS SUBSTANTIAL EVIDENCE to suggest that estrogens have a cardioprotective influence in women by improving endothelial function (11,14,19,24) and low-density lipoprotein (LDL) concentrations (45) while decreasing concentrations of endothelin-1 (ET-1) (4,26,31,32,56) and homocysteine (9). In contrast, medroxyprogesterone acetate (MPA) has been shown to counteract the beneficial effects of estrogens in animals (1, 52) and in some studies in postmenopausal women (18,44,49). Recently, the estrogen plus MPA arm of the Women's Health Initiative clinical trial was terminated because of a trend toward negative cardiovascular outcomes (37). These findings raise questions about the use of progestins, and specifically MPA, in hormone treatments.In addition to postmenopausal women, premenopausal women are also commonly prescribed MPA. MPA is used in the injectable prog...

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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.