Genes may explain why some women on the Pill still get pregnant

(Reuters Health) - It’s long been assumed that women who get pregnant on birth control pills somehow erred, possibly by forgetting a dose. But a new study suggests some women may inherit genes that break down contraceptive hormones more rapidly, leaving them with hormone levels that are too low to prevent pregnancy, according to a report published in Obstetrics & Gynecology.

Researchers found that women with a certain genetic variant metabolized estrogen and progesterone so quickly that it could put them at risk for pregnancy if they were taking low-dose birth control pills.

“If a woman came in and said she was taking birth control and got pregnant we assumed she did something wrong, missed a pill or wasn’t using the method like she was supposed to,” said the study’s lead author, Dr. Aaron Lazorwitz of the University of Colorado School of Medicine. “We need to believe the patient and to understand that there are other things outside of her control, like genetics, that could cause birth control to fail.”

The new research ought to start a trend, Lazorwitz said. “Women’s health hasn’t had a lot of this kind of research done yet,” he added. “It’s time we catch up with research in other medications that have shown that genetics can affect how the body breaks them down.”

To take a closer look at the issue, Lazorwitz and his colleagues recruited 350 women with an etonogestrel implant in place for at least a year and no more than 36 months. The long-lasting contraceptive comes in the form of a small plastic strip that is injected into the skin of a woman’s upper arm and slowly releases pregnancy-preventing hormones over the course of three years.

The researchers chose to study the impact of genetics on hormone metabolism in women using the implant because “it was much easier to study and there was no concern about anyone missing a dose,” Lazorwitz said. “We eventually want to bring this kind of research to women who are using the pill to see if they have the same effects. We had to start somewhere and this was a really good population to start with.”

Lazorwitz and his colleagues focused on a gene, called CYP3A7*1C, that is turned on in all fetuses but switches off in most infants. In some women, the gene never switched off. Instead, it continues to make the CYP3A7 protein, which breaks down the hormones used in birth control, Lazorwitz said.

When the researchers tested volunteers’ hormone levels, they found that more than one in four women with the CYP3A7*1C genetic variant did not have high enough levels of etonogestrel to prevent ovulation.

The new study “is groundbreaking,” said Dr. Anne Davis, an obstetrician-gynecologist at NewYork-Presbyterian/Columbia University Irving Medical Center. “The reason it is so important is that hormonal contraception is commonly used by millions and millions of women in the United States and around the world.”

It provides “a glimpse into the next questions we should be asking as to how we can improve care,” said Davis, who was not affiliated with the new research. “Birth control pills have been around for ages but there are two hard nuts to crack. First, we know if we give two people exactly the same birth control pill and measure how much medication is in their bodies, it can be wildly different. And that’s left doctors trying to come up with a reason scratching their heads.”

There is also the issue of side effects that vary from woman to woman, Davis added. “One woman will say I took this medication and I feel lousy,” she added. “Another will say it works great, I’m not pregnant; my periods are easier; and my skin has cleared up.”

“Knowing that there is a difference in how people metabolize hormones sets the stage for more research that can help us understand the experiences of women better and that can help us give the right medication to the right patient,” Davis said.

SOURCE: Obstetrics & Gynecology, online March 12, 2019.