Does Ozempic boost fertility? What the science says Research shows it is plausible, but more data is needed
Blockbuster weight-loss drugs have been linked to unexplained pregnancies
Women have taken to social media to report unplanned pregnancies while taking weight-loss and diabetes medications such as Wegovy.Credit: Michelle Gibson/Getty
Injectable weight-loss and diabetes drugs Ozempic and Wegovy have become household names across the world. But, amongst the buzz surrounding these medicines, reports of a serious side effect soon surfaced. Women described unplanned pregnancies on social media, attributing their ‘Ozempic babies’ to the new drugs.
Some women report that they got pregnant while taking the birth-control pill. Others were previously diagnosed as infertile, but say that they conceived after taking a course of the drugs.
Scientists say that the reports are plausible. They have several hypotheses about why the drugs — which belong to a group known as GLP-1 agonists — boost fertility, but until more data are available, the exact mechanism remains unknown.
“We are in a data-free zone when it comes to GLP-1s and fertility and pregnancy,” says Beverly Tchang, an endocrinologist at Weill Cornell Medicine in New York.
The GLP-1 drugs deliver a synthetic version of a naturally occurring hormone called glucagon-like peptide 1, which conveys the feeling of being full after eating. The drug binds to the same receptor as the hormone, but degrades more slowly, suppressing appetite for longer.
When GLP-1 drugs were approved for weight management in the United States a few years ago, demand skyrocketed. Semaglutide — sold by Novo Nordisk as Wegovy for weight loss, and already marketed under the brand name Ozempic as a treatment for type 2 diabetes — was followed by tirzepatide, a drug produced by Eli Lilly that targets GLP-1 receptors along with another type of receptor.
A spokesperson for Novo Nordisk said that they had not tested semaglutide in pregnant people or individuals intending to become pregnant. However, because “there are limited clinical-trial data with semaglutide use in pregnant women”, the company recommends stopping the drug two months before a pregnancy to avoid exposing a fetus to the effects of the drug.
Consequential delays
Scientists are investigating the idea that GLP-1 might be associated with unexpected pregnancies. Overweight and obese people often experience disruptions in their menstrual cycle caused by hormonal imbalances or inflammation. “The female reproductive system is very sensitive and responsive to metabolic health, energy balance and nutrition,” says Nicole Templeman, a cell biologist at the University of Victoria in Canada. The weight loss triggered by GLP-1 drugs might restore regular ovulation for some women.
But she says the effects could also extend beyond weight loss. “GLP-1 receptors have their own effects in the reproductive system that seem to be independent of weight loss,” says Templeman.
Indeed, people on GLP-1 drugs have reported pregnancies despite taking oral contraceptives. Eli Lilly, the company that manufactures tirzepatide, advises people on oral contraceptives to use backup methods of birth control for four weeks after starting tirzepatide, or if they increase their dosage.
A spokesperson for Eli Lilly said that the company studied drug interactions as part of the standard US Food and Drug Administration (FDA) approval process. They found that tirzepatide changes the way oral contraceptives are absorbed, potentially making them less effective.
GLP-1 drugs slow the rate at which food and medications empty out of the stomach and into the intestines, which is where oral contraceptives are absorbed into the bloodstream. Eli Lilly data for tirzepatide showed that it reduced the maximum concentration of contraceptive in the blood by up to 66% after a single dose.
“So, over half of it is gone, which is a big problem,” says Jessica Skelley, a pharmacologist at Samford University in Birmingham, Alabama. Oral contraceptives are concentration dependent: “if there is not enough of them in the body, they can’t effectively provide contraceptive benefit”, Skelley adds.
Semaglutide seemed to affect the concentration of hormonal contraception less markedly than tirzepatide did, but Skelley says it could still be an issue because the two drugs work in a similar manner.
Beyond digestion
Outside of digestion, GLP-1 is known to have effects on other physiological systems. In 2015, Federico Mallo, an endocrinologist at the University of Vigo in Italy, and his team published a study in which they found that dosing female rats with GLP-1 stimulated the production of luteinizing hormone (LH)2. A surge in LH is known to trigger ovulation in both rats and humans. Rats given GLP-1 had increased numbers of viable offspring when compared with untreated rats.
“We are quite sure that GLP-1 receptor analogues are promoting fertility because they are able to increase the pre-ovulatory LH peak,” he says.
Although rats are not mini humans, Mallo says, they do have menstrual cycles with similar phases to those of humans. Mallo, like other researchers, was not surprised to hear about human pregnancies after GLP-1 drug use.
Meanwhile, in a Nature Metabolism study1 published on 20 May 2024, a team based in China identified a species of gut bacteria that regulates natural GLP-1 production in mice. These bacteria, Bacteroides vulgatus, suppressed production of the GLP-1 hormone, disrupting ovarian function in the mice. When the researchers treated the mice with a GLP-1 drug, they began ovulating once again.
The impact of GLP-1 drugs on fertility is a “topical conversation”, says Alyse Goldberg, an endocrinologist and fertility specialist at the University of Toronto in Canada. Data from the journal JAMA suggest that young people of reproductive age are increasingly taking these drugs. Of the 162,439 people aged 18–25 who picked up a GLP-1 prescription in 2023, more than 75% were female.
“If people are losing weight and regaining ovulation, there is a risk of pregnancy if they’re not properly counselled,” she says. As for more data on the effect of GLP-1 drugs on fertility, Goldberg says, “We’re all waiting with bated breath.”
doi: https://doi.org/10.1038/d41586-024-02045-w
This story originally appeared on: Nature - Author:Gillian Dohrn
