Reappraising 21 years of the WHI study: Putting the findings in context for clinical practice

Menopausal hormone treatment (MHT) is recommended for the management of menopause symptoms. The Women's Health Initiative (WHI) placebo-controlled randomised study examined the effects of continuous combined or estrogen-only MHT on the risk of non-communicable diseases (NCDs) in post-menopausal women. The study was terminated prematurely after an interim analysis showed an increased risk of breast cancer diagnosis, which led to a rapid decrease in MHT use worldwide. Subsequently, limitations of the study design and its interpretation in the context of other clinical studies has contributed to a more nuanced appreciation of the risk-benefit profile of differing MHT regimens regarding risk associated with the class of progestogen prescribed, its pattern of prescription, duration of use and timing of initiation related to menopause onset. This review provides a contextual interpretation of the WHI placebo-controlled study and evaluates the impact of bioidentical MHT, with a focus on combined therapies containing micronised progesterone, on the risk of chronic NCDs in post-menopausal women.

Automated summary

Menopausal hormone treatment (MHT) is recommended for managing menopause symptoms, but the Women's Health Initiative (WHI) study showed an increased risk of breast cancer with MHT, leading to a decrease in its use globally. However, further evaluation considering different MHT regimens has shed light on a more nuanced understanding of the risk-benefit profile, particularly regarding progestogen type, prescription pattern, duration of use, and timing of initiation. This review provides a contextual interpretation of the WHI study and evaluates the impact of bioidentical MHT on the risk of chronic non-communicable diseases in post-menopausal women.