Investigational Oral Contraceptive Has Selective Impact On Endocrine Markers

A new, next-generation combined oral contraceptive (COC) containing estetrol (E4) 15 mg and drospirenone (DRSP) 3 mg has less impact on endocrine markers, including lower increases in hormone-binding globulins, compared with COCs that include ethinyl-estradiol (EE), new research indicates.

The limited endocrine effects of the E4/DRSP COC are "very reassuring," Dr. Andrew London, assistant professor of obstetrics and gynecology at The Johns Hopkins School of Medicine in Baltimore, Maryland, told Reuters Health by phone.

It will be "very exciting to have a new oral contraceptive that decreases endocrine side effects as well as provides effective contraception," said Dr. London.

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At the International Society for the Study of Women's Sexual Health (ISSWSH) virtual meeting, Dr. London reported data from a randomized, open-label trial looking at the endocrine and metabolic effects of E4/DRSP (at cycle three and six) compared to that of a COC formulation containing EE combined with either levonorgestrel (LNG/EE) or drospirenone (DRSP/EE).

There were 38 women in the E4/DRSP group, and 29 and 31, respectively, in the LNG/EE and DRSP/EE groups. Among the key findings from the study:

- A significant increase in sex-hormone-binding globulin (SHBG) at cycle three (240%) and six (251%) with DRSP/EE as compared to baseline or those observed with E4/DRSP (52% and 55%). The change in SHBG with LNG/EE was not significantly different at cycle three or six.

- At cycle six, the decrease in total testosterone and free testosterone with E4/DRSP (31% and 50%) was not significantly different from those noted with LNG/EE (38% and 50%) or DRSP/EE (33% and 71%). At cycle three, there were no decreases noted in any group.

- At cycle six, E4/DRSP had a significantly lower impact on dehydroepiandrosterone sulfate (DHEA-S) levels than DRSP/EE (10% vs. 27%), with no differences noted between DRSP/E4 and LNG/EE.

The E4/DRSP oral contraceptive (Nextstellis) was developed by Mayne Pharma's development and manufacturing partner Mithra Pharmaceuticals SA and is currently being reviewed by the U.S. Food and Drug Administration (FDA).

The new drug application is based on results from two phase-3 clinical studies involving more than 3,725 women aged 16 to 50 years. If approved, Nextstellis would be the first contraceptive product containing E4 and the first new estrogen introduced in the United States for contraceptive use in roughly 50 years.

In a news release, Scott Richards, Mayne Pharma CEO, said the "exciting new data" on endocrine parameters of E4/DRSP "adds to the solid safety and tolerability profile of Nextstellis and the growing body of clinical evidence that this unique combination with a new form of estrogen, may be a promising novel oral contraceptive option for women."

"When prescribing COCs, practitioners must have a good understanding of how these therapies may impact other hormones in the body in order to make an informed prescribing decision for their patients," Dr. London added in the release.

"Based on our findings, treatment with DRSP/E4 has limited effects on some of these endocrine parameters compared to the tested EE-containing products, giving DRSP/E4 a different and potentially favorable endocrine profile compared to those EE-based COCs," he said.

The study was funded by Mayne Pharma. Dr. London has financial ties to Mithra Women's Health.

—Megan Brooks

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