Use of menopausal hormone therapy beyond age 65 years and its effects on women's health outcomes by types, routes, and doses

Sep 21, 2026

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Objectives: Assess the use of menopausal hormone therapy beyond age 65 years and its health implications by estrogen/progestogen types, administration routes, and dose strengths. Methods: Prescription drug and encounter records of 10 million senior Medicare women (2007-2020) with Cox regression adjusting for time-varying characteristics. Outcomes include all-cause mortality, five cancers, six cardiovascular diseases, and dementia. Results show therapy effects varying by regimen; low-dose and non-oral routes often associate with larger risk reductions.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages9

Reading Time23 min

AccessFree to download

Objectives

Methods

Results

Estrogen monotherapy beyond 65

Estrogen and progestogen combination therapy

Conclusions

Menopause: The Journal of The Menopause Society Vol. 31, No. 5, pp. 363-371 DOI: 10.1097/GME.0000000000002335 Copyright © 2024 The Author(s) . Published by Wolters Kluwer Health, Inc. on behalf of The Menopause Society. ORIGINAL STUDY Use of menopausal hormone therapy beyond age 65 years and its effects on women's health outcomes by types, routes, and doses Seo H. Baik, PhD, Fitsum Baye, MS, and Clement J. McDonald, MD Abstract Objectives: The study aims to assess the use of menopausal hormone therapy beyond age 65 years and its health implications by types of estrogen/progestogen, routes of administration, and dose strengths. Methods: Using prescription drug and encounter records of 10 million senior Medicare women from 2007-2020 and Cox regression analyses adjusted for time-varying characteristics of the women, we examined the effects of different preparations of menopausal hormone therapy on all-cause mortality, five cancers, six cardiovascular diseases, and dementia. Results: Compared with never use or discontinuation of menopausal hormone therapy after age 65 years, the use of estrogen monotherapy beyond age 65 years was associated with significant risk reductions in mortality (19% or adjusted hazards ratio, 0.81; 95% CI, 0.79-0.82), breast cancer (16%), lung cancer (13%), colorectal cancer (12%), congestive heart failure (CHF) (5%), venous thromboembolism (3%), atrial fibrillation (4%), acute myocardial infarction (11%), and dementia (2%) . For the use of estrogen and progestogen combo-therapy, both E+ progestin and E+ progesterone were associated with increased risk of breast cancer by 10%-19%, but such risk can be mitigated using low dose of transdermal or vaginal E+ progestin. Moreover, E+ progestin exhibited significant risk reductions in endometrial cancer (45% or adjusted hazards ratio, 0.55; 95% CI, 0.50-0.60), ovarian cancer (21%), ischemic heart disease (5%), CHF (5%), and venous thromboembolism (5%), whereas E+ progesterone exhibited risk reduction only in CHF (4%). Conclusions: Among senior Medicare women, the implications of menopausal hormone therapy use beyond age 65 years vary by types, routes, and strengths. In general, risk reductions appear to be greater with low rather than medium or high doses, vaginal or transdermal rather than oral preparations, and with E2 rather than conjugated estrogen. Key Words: Cancers – Cardiovascular conditions – Dementia – Menopausal hormone therapy – Survival. n 2002, the Women's Health Initiative (WHI) trial reported that menopausal estrogen + progestogen therapy (EPT) in irsremenasence,e1opoauihsnolagwsihcc,e sre63 ytroks Theee,arsanprccsreopasroreensd tharyentere-t negative outcomes in a dramatic manner that some described as misleading.2,3 However, most of these negative results lost Received November 29, 2023; revised and accepted January 2, 2024. From the Lister Hill National Center for Biomedical Communications, National Library of Medicine, US National Institutes of Health, Bethesda, MD. Funding/support: This research was supported by the Intramural Research Program of the National Library of Medicine, National Institutes of Health. Financial disclosures/conflicts of interest: None reported. Disclaimers: Three previous editions of the paper have been published on two preprint servers, Authorea ([https://doi.org/10.22541/au.167895234.48153899/v1](https://doi.org/10.22541/au.167895234.48153899/v1), [https://doi.org/10.22541/au.161873076.60547427/v1](https://doi.org/10.22541/au.161873076.60547427/v1)) and MedRxiv ([https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.1101/2022.05.25.22275595](10.1101/2022.05.25.22275595)). Previous editions included different number of women and/or different number of distinct hormone therapy preparations. significance when corrected for multiple testing.1 The second WHI study in 2004 examined the effect of estrogen therapy (ET) on these same outcomes in similar aged but hysterectomized women

FAQs

What was the study’s primary objective?

To evaluate how menopausal hormone therapy use beyond age 65 years relates to women’s health outcomes, considering types of estrogen/progestogen, routes, and dose strengths.

How was the study conducted?

It used prescription drug and encounter records of 10 million senior Medicare women from 2007–2020, with Cox regression analyses adjusted for time-varying characteristics.

What overall pattern did the study find regarding risk reductions?

Implications varied by regimen, with generally greater risk reductions seen with low rather than medium/high doses, vaginal or transdermal rather than oral preparations, and E2 rather than conjugated estrogen.

Sep 21, 2026

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