ReviewClinical pharmacology : advances and applications2026
Cardiovascular and Metabolic Outcomes of Hormone Replacement Therapy in Women Aged 65 Years and Older: A Systematic Review of Randomized Clinical Trials.
Review in Clinical pharmacology : advances and applications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Authors and funding
5 authors.
Funding
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Abstract
Background: The cardiovascular, kidney, and metabolic effects of hormone replacement therapy (HRT) in postmenopausal women, particularly those who initiate treatment after age 65, remain incompletely characterized. The objective of this systematic review was to evaluate evidence on these outcomes, with a focus on women aged 65 years and older. Methods: PubMed, Embase, Scopus, and the Cochrane Library were searched for studies published between January 1, 2021, and February 28, 2026. Eligible studies included randomized controlled trials and secondary or post-trial analyses evaluating HRT in postmenopausal women, particularly women aged 65 years and older. Outcomes included cardiovascular, renal, and metabolic endpoints. Risk of bias was assessed using RoB 2 where applicable, and evidence was synthesized narratively. The review protocol was registered in PROSPERO (CRD420261338310). Results: Of 1701 records identified, 6 reports met the inclusion criteria, all derived from three parent trials: the Women's Health Initiative Hormone Therapy Trials (WHI-HT), Early versus Late Intervention Trial with Estradiol (ELITE), and Kronos Early Estrogen Prevention Study (KEEPS). HRT effects varied by regimen and timing. In WHI-HT analyses, conjugated equine estrogens (CEE), alone or with medroxyprogesterone acetate (MPA), lowered low-density lipoprotein cholesterol (LDL-C) but increased triglycerides and systolic blood pressure; CEE plus MPA had a less favorable coronary profile than CEE alone. ELITE supported less favorable vascular effects with later initiation, while KEEPS showed neutral long-term findings. No trial was designed specifically for women aged ≥65 years, and evidence in this age group was limited to subgroup analyses of broader postmenopausal women. Additionally, no studies included renal outcomes. Conclusion: Future prospective studies should evaluate cardiovascular, kidney, and metabolic outcomes across HRT regimens and timing in older postmenopausal women to guide individualized treatment decisions.
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