Medical Academic (MA): How common is the use of GLP1-RAs and tirzepatide among women of reproductive age?

Dr Malikah van der Schyff (MvdS): Current estimates suggest that ~12% of women of reproductive age are taking these medicines for weight management or type 2 diabetes (T2DM), although I suspect the true figure is considerably higher. Commonly prescribed agents include semaglutide, liraglutide, dulaglutide and tirzepatide, which acts as a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist (GLP1-RA).

MA: How do these medicines influence fertility?

MvdS: One of the most important messages for clinicians is that these medicines can improve fertility, particularly in women with polycystic metabolic–ovarian syndrome (PMOS), formerly known as polycystic ovary syndrome. Rapid weight loss improves ovulation, meaning women who previously struggled to conceive may become unexpectedly fertile. We have seen increasing numbers of unplanned pregnancies, many of which patients describe as ‘welcome surprises’.

Weight loss also alters hormone metabolism. As adipose tissue breaks down, endogenous oestrogen levels increase, which may contribute to endometrial hyperplasia, heavier menstrual bleeding or breakthrough bleeding in women taking combined oral contraceptives.

MA: Why are oral contraceptives a concern in women taking these medicines?

MvdS: These medicines delay gastric emptying, slowing the movement of food and medicines through the gastrointestinal (GI) tract. This can potentially affect the absorption of orally administered medicines, particularly those absorbed within the first four hours after ingestion.

For semaglutide, liraglutide and dulaglutide, available evidence suggests contraceptive efficacy is probably maintained because modern oestrogens and progestogens have relatively long half-lives. However, we cannot assume there is no risk, particularly as contraceptive failures are often under-reported. In my own practice, I have noticed more breakthrough bleeding in women taking oral contraceptives together with these medicines. In addition, nausea, vomiting and diarrhoea can further compromise absorption, creating another potential pathway for contraceptive failure.

MA: Does tirzepatide require different counselling?

MvdS: Yes. Tirzepatide appears to have a greater effect on gastric emptying than the other medicines in this class, making it the drug of greatest concern when oral contraception is being used. The manufacturer's prescribing information advises women to use a non-oral contraceptive or add a barrier method for four weeks after starting tirzepatide and again for four- weeks after every dose increase. This recommendation reflects both its greater effect on gastric emptying and the limited clinical data currently available.

MA: What do current international guidelines recommend?

MvdS: Guidance from organisations such as the United States Food and Drug Administration (FDA) and the American College of Obstetricians and Gynecologists (ACOG) suggests that women who are stable on combined hormonal contraception generally do not require routine backup contraception. The effectiveness of combined hormonal contraceptives depends more on hormone half-life than on minor changes in absorption. These medicines are also not regarded as having the narrow therapeutic index seen with certain other orally administered drugs. Nevertheless, some guidance recommends considering additional contraception for seven days when initiating therapy or increasing the dose. Importantly, even though no confirmed contraceptive failures have been reported, healthcare professionals still have a responsibility to counsel patients about the potential risks and uncertainties.

MA: Which contraceptive methods do you prefer for women taking these medicines?

MvdS: Long-acting reversible contraceptives remain my preferred option because they completely bypass the GI tract and eliminate concerns about absorption. This includes contraceptive implants and intrauterine systems. Transdermal patches and vaginal rings are also attractive alternatives because they avoid GI absorption. Where possible, I tend to steer patients away from oral contraceptives and instead discuss these longer-acting or non-oral options as first-line choices.

If a woman chooses to remain on combined hormonal contraception, it is important to counsel her about what to do if vomiting occurs and to discuss the additional precautions required with tirzepatide.

MA: What advice should clinicians provide to women planning pregnancy?

MvdS: Firstly, every woman starting one of these medicines should be informed that fertility may improve significantly, particularly if she has PMOS. This conversation should take place before treatment begins. Women wishing to conceive should discontinue treatment at least two months before attempting pregnancy because these medicines have long elimination half-lives. They should also begin folic acid supplementation together with a prenatal multivitamin, and women with T2DM should be transitioned to insulin before conception where appropriate. These discussions should be carefully documented, covering both contraception and future fertility planning.

MA: What do we know about their safety during pregnancy and breastfeeding?

MvdS: Animal studies have demonstrated embryo toxicity, but there are currently insufficient human data to establish safety during pregnancy. Most women discontinue treatment as soon as pregnancy is recognised, and any pregnancy occurring during treatment should be reported to the relevant pregnancy registry. These medicines are also not recommended during breastfeeding. They are excreted into animal milk, and because we lack adequate human safety data, my recommendation is straightforward: they should not be used while breastfeeding.

MA: Are there any other important clinical considerations?

MvdS: Yes. One issue that is increasingly relevant involves anaesthesia. Because delayed gastric emptying increases the risk of aspiration, some anaesthetists recommend stopping these medicines for several weeks before elective surgery. Perhaps the most practical message is to ask every patient directly whether they are taking an injectable medicine for weight management or diabetes. Many patients simply do not think to mention it. Once you know they are taking one of these medicines, review their contraceptive method, ask about GI side effects such as nausea, vomiting or diarrhoea, and consider whether a longer-acting or non-oral contraceptive would provide better protection. Ultimately, our role extends beyond prescribing. We need to counsel patients about both the potential for improved fertility and the possible impact these medicines may have on contraceptive effectiveness so that they can make informed decisions about their reproductive health.

Conclusion

As the use of injectable weight-loss and diabetes therapies continues to increase among women of reproductive age, healthcare professionals must be aware of their implications for fertility, contraceptive efficacy and pregnancy planning. Dr van der Schyff discusses how these medicines may improve fertility, affect the absorption of oral contraceptives through delayed gastric emptying, and influence contraceptive choice. She highlights the importance of proactive counselling, considering long-acting reversible and other non-oral contraceptive methods, providing pre-conception advice, and discussing pregnancy, breastfeeding and perioperative management to support safe, individualised reproductive care.

Dr van der Schyff recently presented a thought-provoking webinar entitled Current contraceptive practice: Balancing efficacy and patient needs, sponsored by Acino, part of Arcera. To watch a replay of the webinar, click here https://event.webinarjam.com/9pqmp/login/xq0nqalk3uvwof18ns9s9 . Don’t forget to let John Woodford know that you watched the replay to earn your CEU. Send an email to john.woodford@media24.com. Include the name of the webinar, the date (27 July) and your MP number. If you are not registered with the HPCSA, you can request a certificate of attendance from John to submit to your council. 

Dr Malikah van der Schyff is a Cape Town-based Obstetrician and Gynaecologist with more than two decades of experience in women’s healthcare. She is a dedicated women’s health advocate, activist, and minimally invasive gynaecological surgeon with a strong passion for advancing patient-centred care, reproductive health, menopause management, and healthcare leadership in South Africa.  Dr van der Schyff holds leadership positions in several prominent medical organisations where she is contributing to professional development, healthcare advocacy, and policy advancement. She is the immediate past president of the  South African Menopause Society and is a key opinion leader in mature women’s health. Alongside her leadership and advocacy work, she continues her private clinical practice in obstetrics and gynaecology in Cape Town, where she remains committed to delivering compassionate, evidence-based care to women across all stages of life.

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