Hormone Therapy in Menopause: Concepts, Controversies, and Approach to Treatment
Abstract
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.
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Estrogen replacement therapy can effectively manage menopause symptoms and post-menopausal osteoporosis, but its benefits must be weighed against heightened risks of blood clots, stroke, and breast cancer, especially with long-term use.
“Although estrogen replacement therapy (or hormone replacement therapy) can effectively manage menopause symptoms and post-menopausal osteoporosis, its benefits must be weighed against the heightened risks of blood clots, stroke, and breast cancer, especially with long-term use [50, 51].”
The balance of risks and benefits associated with hormone replacement therapy varies considerably based on individual physiology, time since menopause onset, and the specific type of hormone replacement therapy.
“The balance of risks and benefits associated with hormone replacement therapy varies considerably based on individual physiology, time since menopause onset, and the specific type of hormone replacement therapy [50].”
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- Authors
- Flores, V. A., Pal, L., & Manson, J. E.
- Affiliations
- Yale University (US)
- Brigham and Women's Hospital (US)
- Corresponding author
- Flores, Valerie A
- Venue
- Endocrine Reviews
- Publisher
- The Endocrine Society
- Published
- 2021-04-15
- Volume
- 42
- Issue
- 6
- Pages
- 720-752
- ISSN
- 0163-769X (ISSN-L)
- 1945-7189
- OpenAlex
- W3155312871
- Cited by
- 174
- References
- 343
- Citations by year
- 2026: 40 · 2025: 45 · 2024: 44 · 2023: 30 · 2022: 13 · 2021: 2
- FWCI
- 3.45
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Endocrine Reviews (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Keywords
- hormone therapy, menopause, vasomotor symptoms, genitourinary syndrome of menopause, bone health, coronary artery disease, all-cause mortality, Women's Health Initiative, estrogen-progestin, estrogen-only therapy, timing of hormone therapy initiation, route of administration, risk-benefit assessment
- MeSH terms
- Estrogens, Female, Humans, Menopause, Estrogen Replacement Therapy, Women's Health, Hormone Replacement Therapy
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