Glucagon-like peptide-1 receptor agonists (GLP-1s or GLP-1RAs) and hormone replacement therapy (HRT)

Glucagon-like peptide-1 receptor agonists (GLP-1s or GLP-1RAs) and hormone replacement therapy (HRT)

The British Menopause Society has stated (1):

• concerns related to concurrent use of HRT and semaglutide or tirzepatide relate primarily to endometrial protection and a potential risk of reduced absorption of oral progestogens used within HRT regimens
  • incretin-based therapies delay gastric emptying and therefore may reduce the absorption of any oral component of HRT
  • extrapolating from data on COC effects indicates that using non-oral progestogen for 4 weeks after initiation and for 4 weeks after each dose escalation with incretin-based therapies may be needed for effective endometrial protection
    • from a pragmatic perspective, with several potential dose changes, a non-oral route for the progestogen component of HRT would be preferable throughout treatment with incretin-based therapies
      • the 52 mg levonorgestrel-releasing intrauterine device provides contraception in perimenopausal women, and endometrial protection for the estrogen component of HRT, unaffected by concomitant use of incretin-based therapies - likely to be the most comprehensive option for endometrial protection in women using combined HRT concomitantly with incretin-based therapies for obesity/diabetes (expert opinion), particularly since this group of women are already at increased risk of endometrial pathology
    • where oral progestogen is preferred by patients on HRT, there are no data to inform the dose adjustment required for endometrial protection in high-risk women, including those treated with ncretin-based therapies
      • a suggested approach is to temporarily increase the dose of oral progestogen for 4 weeks after commencing incretin-based therapies, and maintain a higher dose of progestogen with each dose increment on incretin-based therapy until a stable dose is achieved
    • women who continue to have unscheduled bleeding despite modifying their progestogen intake while using incretin-based therapies, or where there is a concern about the clinical presentation, bleeding amount, or pattern, should be assessed to exclude endometrial pathology
      • it may be prudent to consider investigations earlier than stated in national guidance in high-risk women (expert opinion)

Reference:

1. British Menopause Society (April 2025). Use of incretin-based therapies in women using hormone replacement therapy (HRT).