Human experience shows us that contraception isn’t always foolproof, but a new study is the first to ever highlight a genetic explanation for why birth control doesn’t always work as intended.

 

New research suggests some women with a particular genetic variant could potentially be at a greater risk of becoming pregnant even while using some hormone-based birth control methods – due to a gene that breaks down the chemicals in the contraceptives.

“The findings mark the first time a genetic variant has been associated with birth control,” says obstetrician-gynaecologist Aaron Lazorwitz from the University of Colorado School of Medicine.

Lazorwitz and his team enrolled 350 women of reproductive age in a pharmacogenomic study, to identify whether genetic variants can influence etonogestrel concentrations among contraceptive implant users.

Etonogestrel is a synthetic version of the female sex hormone, progesterone, which naturally prevents ovulation during pregnancy or after ovulation has already occurred.

In the experiment, each of the participants used an etonogestrel implant for birth control for 12–36 months, and were genotyped as part of the study, along with giving blood samples.

In addition to finding that BMI and duration of implant use were associated with etonogestrel concentration, the team discovered three genetic variants that were also linked.

One of these, a gene called CYP3A7*1C, turned up in just over 5 percent of the women tested. Ordinarily, this gene is active in foetuses, but is turned off before birth.

 

In a minority of cases, though, the gene stays on, resulting in adult expression of an enzyme called CYP3A7, which can alter steroid hormone metabolism.

Such an imbalance, the researchers hypothesise, could explain why over a quarter (27.8 percent) of the participants with the genetic variant in the study had etonogestrel concentrations in their blood that fell below the threshold for consistent ovulatory suppression.

“That enzyme breaks down the hormones in birth control and may put women at a higher risk of pregnancy while using contraceptives, especially lower dose methods,” Lazorwitz says.

It’s a potentially huge finding, but the researchers are eager to emphasise a lot more work needs to be done to study the implications of this.

“We want to reassure women that it is just too early to recommend any screening or changes in treatment based upon our findings alone,” Lazorwitz told ScienceAlert.

“We need to duplicate and validate these findings in more women and with different birth control methods, like the pill.”

While it’s possible women with the CYP3A7*1C gene who take the pill for contraception might also face a hypothetically higher risk of pregnancy, most women who use contraceptives needn’t be concerned, the researchers say, either because of hormone levels or because of the way different contraceptives work.

 

“For most women, the implant has more than enough extra hormone in it that we don’t expect this genetic variant alone to effect its ability to prevent pregnancy,” Lazorwitz told ScienceAlert.

“For the IUDs, they don’t rely upon hormones in the system that are broken down by this genetic variant as they work locally inside the woman’s uterus.”

In terms of the broader context, then, it’s too early to definitively conclude that carriers of this genetic variant are more likely to become pregnant on contraception than women without CYP3A7*1C – as that’s well beyond the scope of this particular clinical trial.

But the gene – which is also associated with leukaemia, in addition to breast and lung cancer – nonetheless does look like it may pose a hypothetically greater risk of pregnancy for some women, even if we can’t quantify that risk yet.

Because of that, the findings definitely warrant further examination, especially given we now have evidence showing the same birth control methods might not work equally well for all women who take them.

We also need to know more about other genetic variants too. This study predominantly examined women who identified themselves as white, and 51.4 percent of the participants reported having a Hispanic or Latina ethnicity, which could also affect the results.

“The biggest takeaway is that we’ve assumed for so long that if a woman taking birth control gets pregnant, then she must have done something wrong,” Lazorwitz told Wired.

“Instead, maybe we need to pay more attention as physicians to other things that might be going on, like genetics, so we can give better, more individualised treatment to women, instead of just blindly adhering to the motto that if you just throw some hormones at it, that usually fixes the problem.”

The findings are reported in Obstetrics & Gynecology.

 



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