New Data Show Novel Combined Oral Contraceptive Has Limited Changes in Endocrine Markers

Research on a novel, investigational combined oral contraceptive (COC; Nextstellis®, Mayne Pharma) containing drospirenone (DRSP) and estetrol (E4) showed that the treatment resulted in limited changes in endocrine markers, according to data presented at the annual meeting of the International Society for the Study of Women's Sexual Health.

The data showed that the COC had lower increases in hormone-binding globulins compared with COCs based on ethinyl-estradiol (EE), which is a synthetic estrogen used in all but one of the currently available COCs on the market.

Since some COCs have been found to decrease circulating androgens and increase hormone-binding globulins, these endocrine changes have resulted in some patients experiencing hormonal imbalance and certain adverse effects, such as acne, excess facial and body hair, or changes in libido.

"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," said Andrew London, MD, assistant professor of OB/GYN at the Johns Hopkins School of Medicine, in a press 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."

In the randomized, open-label, 3-arm parallel phase 2 study, researchers assessed the changes observed from the baseline serum concentration of various endocrine and liver protein markers at cycles 3 and 6 during a 24/4-day regimen of 6 consecutive cycles of 28-day treatment periods. Participants received either the novel COC, a COC formulation containing EE combined with either levonorgestrel (LNG/EE), or drospirenone (DRSP/EE).

When comparing the results, the researchers found that there was a significant increase in sex hormone-binding globulin at cycles 3 (240%) and 6 (251%) with DRSP/EE compared to baseline (52%) or those observed with the novel COC (55%). For LNG/EE, the results were not significantly different at cycle 3 or 6.

Additionally, the researchers found that at cycle 6, there was a decrease in total testosterone (31%) and free testosterone with the novel COC (50%). These results were not significantly different from those with LNG/EE, at 38% and 50% respectively, or with DRSP/EE, at 33% and 71% respectively. At cycle 3, the researchers found no decreases in any group.

At cycle 6, the researchers observed that the novel COC had a significantly lower impact on dehydroepiandrosterone sulfate levels at 10% than DRSP/EE at 27%; however, no differences were noted between DRSP/E4 and LNG/EE.

"This exciting new data 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," said Scott Richards, CEO of Mayne Pharma, in the press release.

REFERENCE

New Data Show NEXTSTELLIS® Has Selective Impact On Endocrine Markers Compared With Common Combined Oral Contraceptives. Raleigh, NC: Mayne Pharma; March 6, 2021. https://www.prnewswire.com/news-releases/new-data-show-nextstellis-has-selective-impact-on-endocrine-markers-compared-with-common-combined-oral-contraceptives-301241886.html. Accessed on March 8, 2021.