Systematic review- hormone replacement therapy in postmenopausal women with medical co-morbidities

Safety and efficacy of HRT in women with chronic medical conditions remain incompletely understood. As life expectancy rises and the use of HRT becomes more common, condition-specific recommendations are crucial to support clinical decisions.

Systematic review on disease-specific effects of HRT in peri- and postmenopausal women with chronic medical disorders.

Comprehensive search of PubMed, Embase, Cochrane Central Register of Controlled Trials, and Web of Science was conducted from inception to 31 August 2025. Cross reference was undertaken.

Systematic reviews, meta-analysis, Randomised controlled trials, cohort, and case-control studies examining oral, transdermal, or other HRT formulations in peri- or postmenopausal women with chronic diseases were included. Case reports, editorials, conference abstracts, and non-English publications were excluded.

Titles, abstracts, and full-text articles were independently evaluated by three reviewers. Data extraction included study design, participant characteristics, HRT regimen, and outcomes.

Fifty-four studies met inclusion criteria, covering neurological (epilepsy, migraine, Alzheimer's, Parkinson's, multiple sclerosis, meningioma), metabolic, cardiovascular, autoimmune, renal, hepatic, and endocrine conditions. Oral estrogen formulations may increase risk whereas transdermal preparations may confer lower thrombotic and hepatic risk (limited evidence). Neurological benefits were observed in Parkinson's disease and multiple sclerosis, but evidence was limited for Alzheimer's disease and migraine. HRT was generally safe in stable autoimmune conditions. Cardiovascular safety is supported in women without pre-existing disease.

HRT should be individualised according to comorbidities, formulation, and route, with preference for transdermal or low-dose regimens in high-risk populations.

Registration: PROSPERO ID CRD420251233527.