‘Doctor, I’m on Mounjaro – will it interfere with my HRT?’

Incretin-based therapies like semaglutide and tirzepatide have taken the world by storm - splashed across headlines, hailed as game-changers, and now likely being discussed over brunch. But beneath the hype lies important clinical nuance, especially when they cross paths with HRT.

Both semaglutide and tirzepatide are once-weekly injections approved in the UK for treating obesity and type 2 diabetes. They are agonists of GLP-1, which is an incretin hormone, helping to: increase satiety, reduce our appetite, reduce glucagon secretion, slow gastric emptying, and tirzepatide goes the extra mile as it is also a GIP analogue to enhance insulin secretion further. 

Now, meet Maria, a 50-year-old lawyer managing her menopausal symptoms with oral utrogestan and transdermal oestrogen. All is well at her 3-month HRT review… until she casually mentions she's now using tirzepatide from a reputable private clinic. (Cue the internal alarm bells)

As of December 2024, over 500,000 individuals in the UK were estimated to be accessing incretin-based therapies privately. Recent projections indicate this figure may now exceed 1 million, with the majority obtaining treatment through online providers.

Why the Concern?

Incretin-based therapies like tirzepatide delay gastric emptying. This can interfere with drug absorption, a fact we already know from data showing up to a 66% reduction in peak levels of the combined oral contraceptive (COC). [Read Dr Rob Walker’s brilliant Blog on contraception while on tirzepatide]. So, if tirzepatide can do that to COCs, what might it do to oral progestogens like utrogestan? (The million-dollar question)

What's the Risk? 

While specific data for HRT is lacking, extrapolated evidence suggests that delayed gastric emptying could reduce oral progesterone absorption, potentially compromising endometrial protection. And in women who have obesity, this risk becomes even more clinically significant.

Thankfully, the British Menopause Society (BMS) has produced clear, pragmatic guidance for how to manage patients like Maria who are taking oral utrogestan with transdermal oestrogen alongside incretin-based therapies:

Practical Recommendations:

1. Use the 52mg levonorgestrel IUD
   • The 52mg levonorgestrel IUD is unaffected by incretin-based therapies
   • It offers reliable endometrial protection (and contraception, if needed)
   • The BMS expert opinion suggests this is likely to be the most sensible option for patients like Maria to replace her oral utrogestan with a 52mg levonorgestrel IUD
2. If Maria prefers to remain on her oral utrogestan…
   • Temporarily increase the dose of oral progestogen for 4 weeks after starting (or adjusting) the incretin-based therapy
   • Repeat with each dose change until a stable dose of the incretin-based therapy is achieved
3. Consider transdermal combined HRT preparations
   • Absorption is unlikely to be unaffected by the incretin-based therapies, though direct evidence remains limited

And don’t forget about oestrogen: transdermal oestrogen administration is preferred when using incretin-based therapies, as it bypasses absorption issues and reduces VTE risk (always a bonus).

In summary, incretin-based therapies are revolutionising metabolic care, but they introduce new complexities in HRT management. Until we have stronger data, the key is informed counselling, evidence-based pragmatism, and shared decision-making with patients.