Hormone Replacement Therapy (Female)

Transdermal estradiol avoids first-pass liver effects. Start within 10 years of menopause for best outcomes. Oral micronized progesterone for endometrial protection. Updated August 16, 2026 (context, not a change in recommendation): Nature Aging 2026 (Carleton et al.) profiled age-associated differences in ER-positive breast cancer using an aged rat model, human patient tissue and patient-derived organoids, and found that systemic and local chronic inflammation together with altered ENDOGENOUS estrogen disposition create a tumour-permissive breast microenvironment in older women. Read this carefully before it reaches patients in distorted form: the study concerns host aging biology and endogenous hormone metabolism, it tested no exogenous hormone therapy, and it says nothing about whether menopausal hormone therapy raises or lowers this risk. It does not alter HRT risk-benefit counselling, which should continue to rest on the randomised and observational literature already summarised above. Its practical value is as a reminder that inflammatory and metabolic status in older women is part of the breast-cancer risk conversation independent of hormone exposure.