Newly identified gene variant may render hormonal birth control less effective

Credit: Gabriela Sanda from Pixabay

Temperatures are getting cooler and days are getting shorter—fall is definitely here. With the dawn of October, many are ready for the month-long campaign devoted to raising awareness for women’s health. While pink ribbons and highlights in advancements in breast cancer research may abound in the coming weeks, a recent study published in the Journal of Obstetrics and Gynecology reminds us to consider another area of women’s health this month—that of her own fertility.

Hormonal contraceptive users can expect a highly effective means of preventing pregnancy when taken ‘perfectly’. Perfect use of hormonal birth control is estimated to be 99% effective at preventing pregnancy. However, typical use estimations come in at 91-92% effective. In other words, about 9 out of every 100 women can expect to conceive while using oral contraceptives. User error is typically cited as the cause of the discrepancy in efficacy, but as Lazorwitz et al report, a woman’s genes can play a novel role in achieving pregnancy even while using hormonal contraceptives.  

The study followed 350 ethnically diverse women aged 18-45 who had a contraceptive implant in place for 1-3 years.  The researchers chose to study women who used the Nexplanon implant—an implant that releases the progestin etonogestrel which prevents the release of an egg from the ovary (ovulation). The research strategy involved studying 120 single nucleotide polymorphisms in 14 candidate genes reported to be involved in the metabolism and regulation of estrogens and progestins. The group identified a variant (CYP3A7*1C) in which the metabolism, or break-down, of etonogestrel is enhanced, thereby accelerating the clearance of the hormone responsible for suppressing ovulation. CYP3A7 belongs to the cytochrome P450 family (a group of detoxifying enzymes found in the liver), and is typically only expressed in fetal livers. Adults with the CYP3A7*1C allele, however, express this fetal isoform, resulting in the production of enzymes that increase the breakdown of hormones like estrogen and progestin. In fact, 27.8% of CYP3A7*1C carriers enrolled in the study had serum etonogestrel concentrations that fell below the level recommended by the manufacturer for consistent suppression of ovulation.

The authors conclude by advocating for a personalized approach to women’s health care. However, the findings of this study demonstrate some of the failings of hormonal contraceptives. Given recent studies suggesting hormonal contraceptives increase risk of depression, particularly among adolescents, women could benefit from alternatives to hormonal birth control. It appears women may agree—between 40% and 60% of women indicate they are interested in learning more from their physicians about alternatives to hormonal contraceptives. With the recent FDA approval of the fertility app, Natural Cycles, women have gained more access to resources helping them understand their own fertility. Fertility awareness methods can have efficacy rates similar to conventional methods of contraception and may be an alternative for women who are seeking a more personalized approach when it comes to understanding how their own body functions.

By Sadie Dierschke, Editor in Chief

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