What are the main benefits of HRT for menopausal women?
HRT is highly effective for the most common menopausal symptoms. A comprehensive umbrella review of 60 systematic reviews found that HRT reduced the frequency of hot flashes by 57% (risk ratio 0.43) and their severity by 71% (risk ratio 0.29) compared to placebo [1]. It also significantly improved vaginal atrophy, sexual function, and sleep quality. A 2024 clinical trial of 152 women found that those on HRT had a 96% overall treatment effectiveness rate compared to 87% with conventional treatment alone, with significant improvements in mood and sleep scores [3].
Beyond symptom relief, HRT provides important long-term bone protection. The same umbrella review showed HRT reduced the risk of all fractures by 28% (risk ratio 0.72) based on 30 trials involving over 43,000 women [1]. This is particularly valuable for women at risk of osteoporosis. Additionally, some evidence suggests cardiovascular benefits when HRT is started early: a 2021 review of the Women's Health Initiative trials emphasized that women who began HRT within 10 years of menopause had more favorable effects on heart disease and overall mortality compared to those starting later [11].
What are the risks and downsides of HRT?
The most clearly established risks are blood clots and stroke. The umbrella review found that HRT increased the risk of stroke by 17% (risk ratio 1.17) and venous thromboembolism (blood clots in veins) by 60% (risk ratio 1.60) based on large randomized trials [1]. The risk of blood clots was highest with oral estrogen, but a 2021 study of over 51,000 women veterans found that transdermal (skin patch) estrogen did not significantly lower clot risk compared to oral forms, contradicting some earlier beliefs [2]. Gallbladder disease requiring surgery was also increased with HRT [1].
Cancer risk is the most common concern among women considering HRT. A 2025 survey of 71 women found that 48% cited cancer risk as their primary worry about HRT [5]. The umbrella review confirmed that combined estrogen-progestin therapy increases breast cancer risk, while estrogen-only therapy does not increase breast cancer risk but does increase ovarian cancer risk [1]. However, a large Danish study on melanoma found that while HRT users had a 21% higher risk of being diagnosed with melanoma, this was likely due to increased healthcare surveillance rather than a true causal effect, and HRT did not worsen melanoma survival [4]. For women with a history of cancer, a 2024 Lancet review noted that HRT appears safe for many cancer survivors, though it is typically avoided in hormone-sensitive cancers like breast cancer [10].
Who should and should not use HRT?
The ideal candidates for HRT are healthy women under age 60 (or within 10 years of menopause) who have moderate to severe menopausal symptoms. A 2021 expert review emphasized that the risk-benefit ratio is most favorable for this group, with lower risks of heart disease and mortality compared to women starting HRT more than a decade after menopause [11]. HRT is also considered safe for women with certain chronic conditions: a 2024 meta-analysis of 19 studies found no increased risk of heart attack in women with diabetes who used HRT (pooled relative risk 0.83) [6]. For women with schizophrenia, a 2026 case series of 5 women found HRT was well-tolerated and improved mood and social functioning [7].
HRT is generally not recommended for women with a history of breast cancer, uterine cancer, blood clots, stroke, or unexplained vaginal bleeding. For women who cannot take standard HRT, alternatives exist. A 2024 Lancet review noted that non-hormonal treatments and vaginal estrogen are safe options for many cancer survivors [10]. Additionally, a 2025 literature review suggested that selective estrogen receptor modulators (SERMs) like raloxifene may offer a safer alternative for women with psychosis who need estrogen-like effects without the full risks of HRT [9]. Importantly, compounded 'bioidentical' hormones sold by compounding pharmacies lack FDA approval and evidence of safety or effectiveness; a 2023 clinical guideline strongly recommends FDA-approved formulations instead [8].
Sources used in this answer
Menopausal hormone therapy and women’s health: An umbrella review
Umbrella review of 60 systematic reviews found HRT reduces hot flashes by 57% and fractures by 28%, but increases stroke by 17% and blood clots by 60%.
Comparative venous thromboembolic safety of oral and transdermal postmenopausal hormone therapies among women Veterans
Among 51,571 women veterans, risk of blood clots was similar for oral conjugated estrogen, oral estradiol, and transdermal estradiol (hazard ratios ~0.95-0.96).
Effects of hormone replacement therapy on mood and sleep quality in menopausal women
Randomized trial of 152 women found HRT improved mood and sleep scores significantly, with 96% treatment effectiveness vs 87% for conventional care, and no difference in side effects.
Hormone replacement therapy and the risk of melanoma in post-menopausal women.
Danish case-control study of 8,279 melanoma cases found a 21% higher risk with HRT use, but no dose-response and no effect on survival, suggesting detection bias.
Patients' Concerns for Hormone-Replacement Therapy for Menopause.
Survey of 71 women found 48% cited cancer risk as their primary concern about HRT, and non-users had significantly milder menopausal symptoms than users.
Cardiovascular risk of hormone replacement therapy in menopausal women with diabetes: a systematic review and meta-analysis of clinical trials and observational studies
Meta-analysis of 19 studies found no increased risk of heart attack in women with diabetes using HRT (pooled relative risk 0.83).
Practical Approach to Hormone Replacement Therapy for (Peri) Menopausal Women With Schizophrenia Spectrum Disorders: A Case Series.
Case series of 5 women with schizophrenia found HRT was well-tolerated and improved mood, energy, and social functioning in most.
Compounded Bioidentical Menopausal Hormone Therapy
Clinical guideline states compounded bioidentical hormones lack FDA approval and evidence of safety; FDA-approved formulations are recommended.
Comparing Hormone Therapies in Peri- and Post-Menopausal Women With Psychosis: A Literature Review
Literature review found both HRT and SERMs improve psychotic symptoms in menopausal women, with SERMs offering better long-term safety.
Managing menopause after cancer
Lancet review states HRT is effective for menopausal symptoms and appears safe for many cancer survivors, but is typically avoided in hormone-sensitive cancers.
Hormone Therapy in Menopause: Concepts, Controversies, and Approach to Treatment
Review of WHI trials emphasizes HRT's risk-benefit ratio is most favorable for women under 60 or within 10 years of menopause onset.