Hormone Therapy in Menopause: Concepts, Controversies, and Approach to Treatment

Endocr Rev. 2021 Nov 16;42(6):720-752. doi: 10.1210/endrev/bnab011.


Hormone therapy (HT) is an effective treatment for menopausal symptoms, including vasomotor symptoms and genitourinary syndrome of menopause. Randomized trials also demonstrate positive effects on bone health, and age-stratified analyses indicate more favorable effects on coronary heart disease and all-cause mortality in younger women (close proximity to menopause) than in women more than a decade past menopause. In the absence of contraindications or other major comorbidities, recently menopausal women with moderate or severe symptoms are appropriate candidates for HT. The Women's Health Initiative (WHI) hormone therapy trials-estrogen and progestin trial and the estrogen-alone trial-clarified the benefits and risks of HT, including how the results differed by age. A key lesson from the WHI trials, which was unfortunately lost in the posttrial cacophony, was that the risk:benefit ratio and safety profile of HT differed markedly by clinical characteristics of the participants, especially age, time since menopause, and comorbidity status. In the present review of the WHI and other recent HT trials, we aim to provide readers with an improved understanding of the importance of the timing of HT initiation, type and route of administration, and of patient-specific considerations that should be weighed when prescribing HT.

Keywords: hormone therapy; menopause; timing hypothesis.

Publication types

  • Review

MeSH terms

  • Estrogen Replacement Therapy*
  • Estrogens / therapeutic use
  • Female
  • Hormone Replacement Therapy
  • Humans
  • Menopause*
  • Women's Health


  • Estrogens