Semaglutide is a medication belonging to the class of glucagon-like peptide-1 (GLP-1) receptor agonists. It mimics the naturally occurring GLP-1 hormone, regulating blood sugar levels and appetite. The U.S. Food and Drug Administration (FDA) has approved it for treating Type 2 diabetes and for chronic weight management in adults with obesity or those who are overweight. As its use expands among people of reproductive age, questions have arisen about its influence on fertility.
Current Clinical Evidence on Fertility
Current human clinical data do not indicate that semaglutide directly causes infertility in either men or women. Clinical trials have not been specifically designed to study the ability to conceive, as patients who were pregnant or planning pregnancy were typically excluded for ethical and safety reasons. This results in a significant lack of robust, long-term human data focused directly on reproductive outcomes.
The primary concern regarding semaglutide and reproduction centers on potential fetal harm (teratogenicity) if the drug is present during pregnancy, not on the ability to become pregnant. Preclinical studies in animals, particularly at high doses, have shown risks of adverse fetal development, including skeletal and visceral abnormalities. These findings relate to the drug’s safety during gestation, which is distinct from its effect on the capacity to conceive.
How Weight Loss Influences Reproductive Health
The most significant factor influencing fertility outcomes for individuals taking semaglutide is often the weight loss achieved. Obesity is a well-established cause of reproductive dysfunction in both sexes, frequently leading to infertility. In women, excess body fat disrupts hormonal balance, causing conditions like anovulation (where an egg is not released) and irregular menstrual cycles.
Effective weight loss, which can be substantial with semaglutide, frequently improves or restores ovulatory function. Even a modest reduction of 5% to 10% of body weight can normalize menstrual cycles and improve the metabolic profile in women with polycystic ovary syndrome (PCOS). For men, obesity-related metabolic dysfunction contributes to hypogonadism and poor sperm quality, which often improves following significant weight reduction. This powerful indirect benefit of metabolic improvement may mask any subtle, direct effects the drug might have on the reproductive system.
Mechanism of Action and Hormonal Interaction
Semaglutide binds to GLP-1 receptors, which are found throughout the body, including in reproductive tissues like the ovaries and testes. This suggests a potential for interaction with the hormonal pathways that regulate fertility, known as the hypothalamic-pituitary-gonadal (HPG) axis. Semaglutide improves insulin sensitivity and metabolic health, which acts as a powerful lever for hormonal normalization.
In women with PCOS, semaglutide-induced metabolic improvements decrease androgen levels, such as testosterone, which often interfere with ovulation. Studies in men show mixed results regarding a direct impact on male sex hormones. While some data suggest a correlation between GLP-1 agonist use and hypogonadism, other findings show no adverse effects on sperm parameters. Overall, the drug’s influence on reproductive hormones appears largely mediated through correcting underlying metabolic dysfunction, rather than direct negative interference with the HPG axis.
Guidance on Conception and Pregnancy Planning
Due to limited data on human pregnancy safety and findings from animal studies showing potential for fetal harm, semaglutide is not safe for use during pregnancy. For individuals planning to conceive, the most important step is to stop the medication well in advance. The drug has a long half-life, meaning it remains active in the body for an extended period.
Manufacturers recommend discontinuing semaglutide at least two months before attempting conception to ensure it is fully cleared from the system. This period allows for sufficient washout time, given the drug’s half-life is approximately one week. Individuals who become pregnant while taking semaglutide should immediately stop the medication and contact their healthcare provider to discuss the pregnancy and alternatives for managing their underlying condition.