You know those tales from friends of friends who got pregnant while on birth control? In rare instances, it might not have been user error, but rather because of their genes, new research suggests.
A study published last week in Obstetrics & Gynecology found that 5 percent of women are carriers of a genetic variant—CYP3A7*1C—that may affect the way the body metabolizes the hormones used in contraceptive methods. If the levels of these hormones dips too low, in theory they may not prevent the release of an egg (aka suppress ovulation), potentially putting people at risk for unintended pregnancy.
In the study, researchers looked at 350 people with the birth control implant Nexplanon, which is inserted into your arm and releases the hormone progestin (this prevents the ovaries from releasing an egg and protects from pregnancy for five years). Nexplanon is more than 99 percent effective. “We picked the implant not because it fails, but because it doesn’t fail,” says Aaron Lazorwitz, first author of the study and an assistant professor of obstetrics and gynecology at the University of Colorado School of Medicine.
What’s more, the implant releases the same amount of hormone daily in each woman, and it was easy to measure the amount of hormone released, as the specific type of progestin, known as etonogestrel, isn't made by the body. Next, scientists looked at 120 specific genetic variants that past research suggested could affect the breakdown of these hormones.
They found that some carriers of the genetic variant CYP3A7*1C had lower levels of the hormone in their blood, on average. Specifically, among the 5 percent of women in the study who are carriers of the gene, 27.8 percent had hormone levels that dropped below the threshold set for the contraceptive to be effective. (That number for etonogestrel is 90 picograms per milliliter, or pg/mL.)
How could genes affect your birth control?
Lazorwitz suspects that women who have this variant make an enzyme that’s typically not expressed in adults (it’s commonly found in fetuses) that breaks down steroid hormones faster. If these “birth control” hormones are metabolized too quickly, it’s possible that ovulation could occur and people could be at risk for pregnancy. However, Lazorwitz says that even when women’s levels dip below 90 pg/mL, the implant “still seems to work.”
This level is the manufacturer’s safe number for suppressing ovulation, as it’s the lowest effective level that’s been established in studies. The actual cut-off is likely lower, Lazorwitz says, but we don’t know where the real floor is. “The point is that there is a portion of women who are carriers of this gene who are getting into a worrisome range [where] we don’t know when the contraception will stop working,” he says. Still—and if you take anything away from this news, let it be this—even if you have this genetic variant, you are likely still well-protected against pregnancy.
However, this genetic difference could account for the rare failure of an extremely reliable method like the implant. Another factor to consider is that even if the ovaries do somehow release an egg, the hormone in the implant makes cervical mucus hostile to penetration by sperm, says Mary Jane Minkin, clinical professor of obstetrics, gynecology and reproductive sciences at the Yale School of Medicine, who wasn’t involved in the study. It’s a built-in backup protection that’s certainly handy.
There's another "maybe" that concerns Lazorwitz, however. It’s possible that these genetic variants may have even more of an effect on low-dose hormonal methods, like the low-dose, progestin-only “mini pill.” That said, more research needs to be done to know for sure. Though Lazorwitz’s research focuses on how contraceptives interact with other drugs, it was only recently that he started to look at how genes might impact hormonal contraception, he explained to Wired. Scientists knew from previous research that CYP3A variants can change drug metabolism, and this is the first study to identify a genetic variant associated with birth control. Future research, he told the publication, will analyze a larger group of women with whole-genome sequencing to see if there are other variants that impact birth control.
The study also noted that other factors can affect a woman’s hormone levels on the contraceptive implant, including a higher BMI and longer duration of implant use. However, taken alone, these do not cause contraception failure, Lazorwitz says.
If you have the implant and love it, stay on it
So, where do you go from here? After all, no one’s testing women for these genetic variants, or will be any time soon—we’re not there yet. “While this is very early research that suggests we may be moving toward individualized pharmacogenetics [how genes affect drugs], it’s not ready for primetime in clinical care,” says Nancy Stanwood, section chief of family planning at the Yale School of Medicine.
In fact, Stanwood says, data on the implant’s efficacy should make women completely comfortable to continue to use it: Its failure rate is 5 in 10,000—more effective than an IUD. “If you have the implant, you can celebrate. There was nothing in the genetic testing that lead to a concerning change in hormone levels. Women should know that they’re protected,” she says.
“I have never seen a true failure of the birth control implant,” Stanwood adds; “true failure” meaning pregnancy while on the implant. (FYI, fertility makes its incredibly speedy return after you take it out, and you can get pregnant as quickly as a few days later.)
Popping the birth control pill is another story, because it adds in the potential for user error. You have to remember to take it daily, and in the case of the mini pill, commit to taking it at exactly the same time each day.
Before clinicians were aware that genes impact how our bodies break down certain drugs, it was assumed that unintended pregnancies among women using hormonal birth control were the woman’s fault. “We know that’s no longer true, but still, most people who do get pregnant didn’t take it consistently,” she says. On average, Stanwood says, new pill-users report missing about four pills per pack. Forgetting to take just one or two could lead to an egg being release, she says, and thus, a potential pregnancy.
That blame game, though, is also completely unfair, Stanwood says. “Telling a woman she’s noncompliant because she didn’t take the pill puts the burden on the patient. Maybe it didn’t fit her life, and it’s the birth control method that’s the problem.”
Working with your doctor to figure out the right method for you—a set-it-and-forget-it implant or IUD, versus a pill, patch, or ring, which are more convenient to start and stop as you wish—is the most important piece of this puzzle. You may not be able to control your genes, but at least you can control that choice.
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