Research · PMID 41307293
Reviewed by Neal Rouzier, MD, Preventive Medicine · Sep 2026
Long-term hormone therapy for perimenopausal and postmenopausal women.
The Cochrane database of systematic reviews · November 2025 · Magdalena Bofill Rodriguez, Li Ning Yong, Sanja Mirkov, Christine Bekos, Anne Lethaby, et al.
What this study found
Long-term follow-up of women using hormone therapy suggests that the risk profiles vary between combined hormone therapy and oestrogen-only therapy. Oestrogen-only hormone therapy probably makes little to no difference to coronary events, and probably increases the risk of stroke and gallbladder disease.
How RAGMD uses this study
Clinical questions this paper informs
Synthesis lives on the evidence question — this page shows where the study sits in that analysis.
Core study
Is there a critical timing window for cardiovascular benefit from HRT?
The critical-window concept proposes that starting HRT closer to menopause may yield different cardiovascular effects than starting later. WHI subgroup analyses inform but do not prove this hypothesis for routine practice.
Open evidence analysisPrimary study
Does menopausal hormone therapy prevent osteoporosis and fractures?
Estrogen-based therapy reduces bone loss and fracture risk in postmenopausal women, with benefit most established during early postmenopause. Guidelines support HRT for fracture prevention primarily when indicated for vasomotor symptoms or in high-risk women.
Open evidence analysisPrimary study
Does hormone therapy improve sleep disturbance in menopause?
Menopausal hormone therapy can improve sleep when vasomotor symptoms are a major driver of disruption. Benefits for primary insomnia without hot flashes are less consistent across trials.
Open evidence analysisCore study
Does testosterone therapy improve sexual function in postmenopausal women?
Testosterone therapy modestly improves sexual desire and related distress in selected postmenopausal women with hypoactive sexual desire disorder, particularly after oophorectomy. Monitoring for androgenic side effects and long-term safety is recommended.
Open evidence analysisCore study
Does menopause cause weight gain and can hormone therapy help?
Menopause is associated with central adiposity and lean mass loss independent of aging alone. Hormone therapy is not a weight-loss treatment but may attenuate some menopause-related body composition shifts in selected women.
Open evidence analysisSupporting literature
Does hormone replacement therapy increase breast cancer risk?
Combined estrogen-progestin therapy is associated with a small increased breast cancer risk in WHI and observational data. Estrogen-alone in hysterectomized women showed lower risk in WHI, but interpretation depends on regimen, duration, and individual risk factors.
Open evidence analysisSupporting literature
What therapies are most effective for vasomotor symptoms in perimenopause?
Systemic hormone therapy remains the most effective treatment for moderate-to-severe vasomotor symptoms across the menopause transition. When estrogen is declined or contraindicated, evidence-supported non-hormonal options—including fezolinetant and selected SSRIs/SNRIs—reduce symptoms, though with generally smaller effect than estrogen.
Open evidence analysisSupporting literature
Is fezolinetant effective for menopausal hot flashes?
Fezolinetant, a neurokinin-3 receptor antagonist, reduced moderate-to-severe vasomotor symptoms in randomized trials of postmenopausal women. It offers a non-hormonal option when estrogen is contraindicated or declined.
Open evidence analysisSupporting literature
Does hormone therapy help depression or anxiety during perimenopause?
Some trials suggest estrogen-based therapy may help depressive symptoms during the menopause transition, particularly when vasomotor symptoms coexist. It is not a substitute for standard treatment of major depressive disorder.
Open evidence analysisSupporting literature
Is menopause associated with cognitive changes or brain fog?
Many women report subjective cognitive difficulty during perimenopause, often linked to sleep disruption and vasomotor symptoms. Objective cognitive testing shows subtle changes in some cohorts, but HRT is not established as a treatment for brain fog alone.
Open evidence analysis