Pharmacological interactions and menopausal hormone therapy: a review

Importance and objective: Menopausal hormone therapy (HT) is widely used, and there are several statements of international scientific societies to guide prescribers; however, a summary of existing literature about possible drug interactions with HT does not exist, although many midlife women take medications for other conditions. Therefore, our objective was to create a document that presents and synthesizes the most relevant interactions. The impact of the interaction itself and the number of candidates for HT who are likely to use other treatments are considered based on the best available evidence.

Methods: A systematic review was performed to determine the best evidence of interaction effects on relevant outcomes of interest for decision making. A working framework was developed to formulate explicit and reasoned recommendations according to four predefined categories for coadministration: (1) can be used without expected risks, (2) acceptable use (no evidence of negative interaction), (3) alternative treatment should be considered, and (4) nonuse without express justification. The project protocol was registered in the Open Science Framework platform (doi: 10.17605/OSF.IO/J6WBC ) and in PROSPERO (registration number CRD42020166658).

Results: Studies targeting our objective are scarce, but 23 pharmacological groups were assigned to one of the predefined categories of recommendation for concomitant use of HT. Vaginal HT was assigned to category 1 for 21 of the analyzed pharmacological groups. For oral and transdermal HT (estrogen-only or combined) and tibolone, there were 12 pharmacological groups assigned to category 1, 12 to category 2, 5 to category 3, and 4 to category 4. Results are shown in crossed-tables that are useful for counseling and prescription.

Discussion and conclusions: Available evidence of HT interactions with other drugs is scarce and mainly indirect. It comes from biological plausibility, knowledge of extensive concomitant use without reported incidents, and/or extrapolation from hormonal contraception, but there are pharmacological groups in all categories showing that information is useful. These eligibility criteria summarize it and can help in the decision process of HT coadministration with other drugs. Decisions should be taken based on these recommendations but also individualized risk/benefit evaluation, according to underlying pathology, patient's clinical requirements, and the existence or nonexistence of alternatives.