A New Contraceptive Pill Containing 17β-Estradiol and Nomegestrol Acetate

Abstract

Most combined oral contraceptive pills contain ethinyl estradiol (EE) with progestins. In order to minimize the pill's cardiovascular risks, the concept of using 17β-estradiol (E2), the endogenous estradiol, arose in the 1970s. Many attempts to develop a pill containing 17β-E2 have failed as cycle control was low. The first pill containing 17β-E2 was launched in 2011. This monophasic pill contains 24 pills with 1.5 mg 17β-E2 and 2.5 mg nomegestrol acetate, and four placebo pills. Studies conducted in Europe and the USA demonstrate that its Pearl index is 0.38 and 1.13, respectively. It has less influence on hemostasis, fibrinolysis markers, lipids and carbohydrate metabolism than the combined oral contraceptive levonorgestrel/EE (150 g/30 g and 100 µg/20 µg). Withdrawal bleedings are shorter and lighter as compared with women using drospirenone/EE (3 mg/ 30 µg). The number of women without withdrawal bleeding is approximately 30% after 12 months. Even though its contraindications are identical to other combined oral contraceptives, this nomegestrol acetate/E2 pill should be considered to be of interest for many women.

Potentially effective therapy of heavy menstrual bleeding with an oestradiol-nomegestrol acetate oral contraceptive: a pilot study

“…In contrast, a study comparing a COCP using a 24/4 regimen with the same COCP on a 21/7-day regimen [23] found no difference in bleeding patterns suggesting that the improvement in HMB in our study was not due to the 24/4 regimen but resulted from the oestradiol-17β-based formulation of the COCP.…”

FSRH Guideline (January 2019, amended October 2023) Combined Hormonal Contraception

“…Theoretically, estradiol COC could have improved safety profiles compared to formulations containing EE or mestranol due to reduced thrombotic and metabolic effects 5. This has not yet been established: although limited evidence suggests that estradiol COC is safe to use and highly effective in preventing unintended pregnancy,6 further research will be required to assess the safety profile of estradiol COC relative to that of EE COC.…”

Use of Hormone Replacement in Females with Endocrine Disorders

“…The most recent contraceptive pills contain 10–35 µg of EE instead of an equivalent of 100–150 µg in the initial pills which were available during the 1960s. Some COCPs containing EV or 17β-E2 have been available for some years [3]. EE is available not only in oral COCPs but in contraceptive patches as well as in contraceptive rings.…”

“…Studies performed in postmenopausal women, on hormonal menopausal replacement therapy, have shown that at least 12 days of progestin per month are necessary to avoid the risk of endometrial carcinoma [3]. However, data are extrapolated from postmenopausal women since no data have been available so far in young patients using HRT.…”