Contraceptive: Why ‘the pill’ does make some women put on weight

Many women are adamant that taking the contraceptive pill makes them gain weight – yet researchers have repeatedly not been able to find a link.

But a new study suggests that some women do put on weight while on the pill, and their genes are to blame.

Furthermore, genes could explain why some women become pregnant even though they’re on the pill.

This understanding could eventually lead to more “tailormade” contraception that works best for the individual woman.

Hormonal contraceptives, such as the pill, implant and certain types of coil, work by preventing ovulation and thickening mucus on the cervix (this blocks sperm reaching an egg).

While many women are happy with their birth control, for some it is a hit-and-miss affair.

Many put up with side-effects including weight gain.

A small minority become pregnant, despite using the contraception correctly.

Now researchers at the Yale School of Medicine have discovered a link between weight gain and a common form of hormonal contraception containing progestins.

These are synthetic compounds that mimic progesterone, a hormone that suppresses ovulation.

They looked at 276 women using implants containing etonogestrel, a progestin.

Those who had a certain variant of the ESR1 gene were more likely to gain weight.

Aaron Lazorwitz, an assistant professor of obstetrics, gynaecology and reproductive sciences at Yale School of Medicine, who led the research, told Good Health: “This could indicate a biological process whereby genetic differences are causing specific women to be at higher risk for weight gain when using hormonal contraception.”

While it’s not clear why (one theory is the genes alter the way oestrogen interacts with progesterone receptors), “we know that high levels of oestrogenic activity seem to cause more weight-related issues compared to progestins”, he adds.

“This could help explain why studies seem to show an overall minimal amount of weight change with hormonal contraception, given these genetic variants would be found only in a small proportion of women.”

In other words, while some women do gain weight on the pill, many don’t – so the results of large studies come out showing little difference overall.

The more options people have to take control of their fertility and avoid unwanted pregnancy, the better.

The discovery “holds a lot of promise as a way to help predict a very bothersome side-effect for a lot of women”, adds Dr Lazorwitz.

Another important finding from the same research team at Yale, is that a mutation of a different gene, CYP3A7, may increase the metabolism of etonogestrel, making it pass out of the body more quickly before it has time to suppress ovulation.

Around 5 per cent of women carry this mutation, and could be at greater risk of “contraceptive failure” and becoming pregnant.

Although his research focused on implants, which are placed under the skin, Dr Lazorwitz says etonogestrel works similarly to other contraceptives including the pill.

“The hormones in pills and implants are metabolised in similar ways and have similar actions in the body, and so I expect the influence of genetic differences to be similar between them,” he says.

Dr Lazorwitz says his findings underline the need for a more personalised view of contraception – the current trial-and-error approach can mean women typically try three or four methods before finding one that works for them, a 2020 poll found.

“We currently have no means to predict an individual woman’s risks of contraceptive failure or side-effects when selecting a contraceptive method and I am hopeful that genetics will help us fix this long-standing issue in women’s healthcare,” he says.

New technology means it’s possible to offer more personalised contraception for women – which, in turn, would lead to “fewer side-effects and greater satisfaction”, adds Dr Michelle Griffin, an obstetrician and gynaecologist and director of MFG Health Consulting, which advises women’s health businesses.

Genetic testing for contraception is already available in the US, although nothing yet exists commercially to test specifically for the CYP3A7 mutation, says Dr Lazorwitz.

However, he says there is no reason why future tests shouldn’t be available to look for the CYP3A7 mutation alongside other genetic markers.

He adds that other genetic tests could also be beneficial – for instance, to identify if a woman carries a genetic variant that might put her at greater risk of blood clotting when taking a hormonal contraceptive.

Dr Griffin adds that while genetic testing is “very much in the research phase”, in future it might also help prevent the “blame” mentality often applied to women who become pregnant despite being on contraception: “I’ve had patients who report they took their birth control pill every day and still had an unintended pregnancy”.

The British Pregnancy Advisory Service (BPAS), an abortion care service, said 51 per cent of the 60,592 women it treated in 2016 (its most recent statistics) were using at least one form of contraception when they became pregnant.

Each woman seeking contraception should be treated as a unique individual, says Dr Ali Kubba, a gynaecologist and contraception specialist based in London.

This entails getting a detailed lifestyle and sexual history from patients, which can be a problem in busy NHS clinics, he adds.

He says that gene testing alone may not be a solution because contraception failure can have several causes.

“An extreme example is Ozempic, which can sometimes cause vomiting which affects the absorption of the hormones of the oral contraceptive,” he says.

(Women affected should be offered non-oral contraceptive alternatives such as the patch; but this doesn’t often happen, he adds.)

Dr Kubba stresses that more research is needed into the links between genetics and weight gain linked to hormonal contraceptives.

“It’s important that we don’t put too much weight on a single lab study [the Yale research],” he says.

More contraceptive options are also needed to help men control their fertility, adds Heidi Stewart, chief executive of BPAS.

“The more options people have to take control of their fertility and avoid unwanted pregnancy, the better.”