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Raloxifene hydrochloride (Evista) — a benzothiophene SERM
A second-generation selective estrogen receptor modulator (SERM) approved for postmenopausal osteoporosis and for reducing the risk of invasive breast cancer in high-risk and osteoporotic postmenopausal women. In the pivotal MORE trial it cut vertebral-fracture risk and reduced invasive (largely ER-positive) breast cancer by ~70%; CORE extended the breast-cancer benefit to 8 years, and the STAR trial showed it roughly matched tamoxifen for invasive-breast-cancer prevention with less uterine cancer. It is used OFF-LABEL by some men for gynecomastia (a small pediatric series found it shrank pubertal breast tissue). The honest limits are non-negotiable: the RUTH trial found NO reduction in coronary events but a significant increase in FATAL STROKE and venous thromboembolism, raloxifene does NOT reduce hip or non-vertebral fractures, and it commonly causes hot flushes and leg cramps. It is NOT a supplement and NOT a longevity drug.
Prescription medication — not a dietary supplement
Raloxifene (Evista) is a prescription (or investigational) drug, not a supplement. It is included here for reference because people research and discuss it (often used off-label) — not as a recommendation. Take it only under a qualified clinician's supervision and only as prescribed; do not source it from grey-market vendors, where identity, purity, and dosing are unverified. The evidence below reflects its clinical trials.
What the evidence says
Most Raloxifene (Evista) studies are mechanism or observational rather than RCTs that measure a clinical effect — keep findings provisional.
Most evidence is from high-quality meta-analyses and randomised trials published 1999–2025 with a typical study size of 7,705 participants.
Based on 366 studies · 17 meta-analyses · 340 RCTs · 15,448 total participants
Confidence
High confidenceBy outcome
Raloxifene has strong, randomized, outcome-level evidence for its APPROVED uses: the pivotal MORE trial cut vertebral-fracture risk and reduced invasive (ER-positive) breast cancer by ~70%, CORE extended the breast-cancer benefit to 8 years, the STAR trial showed it roughly matched tamoxifen for preventing invasive breast cancer with less uterine cancer and fewer clots, and a 9-trial individual-participant SERM meta-analysis confirms a ~38% breast-cancer reduction over 10 years. The score is held in the emerging band by mandatory, well-documented limits: the RUTH trial found NO reduction in coronary events but a SIGNIFICANT increase in FATAL STROKE (HR 1.49) and venous thromboembolism (HR 1.44); raloxifene does NOT reduce hip or non-vertebral fractures; and it commonly causes hot flushes and leg cramps. The off-label male/gynecomastia use is poorly evidenced (a small retrospective pediatric series only). Strong for vertebral fracture and breast-cancer risk reduction; real clot/stroke risk and no cardiovascular or hip-fracture benefit. NOT a supplement, NOT a longevity drug.
373 rigorous studies
348 randomized trials · 17 meta-analyses · 19 systematic reviews
Our evidence rating for Raloxifene (Evista) is accountable to this entire body of rigorous research indexed in PubMed — not a hand-picked subset.
PubMed · as of Jul 2026
5 trials ongoing or recruiting · 59 completed on ClinicalTrials.gov
12 of the completed trials have posted results
Registered trials show research momentum for Raloxifene (Evista), not proof of effect — a registration is a plan, and posted results are sponsor-reported, not peer-reviewed. They are never counted toward the evidence rating above.
Browse these trials on ClinicalTrials.govClinicalTrials.gov · as of Sep 2026
Raloxifene hydrochloride (Evista) is a second-generation, benzothiophene selective estrogen receptor modulator (SERM) — a drug that acts as an estrogen AGONIST in some tissues (notably bone, where it preserves bone mineral density) and an estrogen ANTAGONIST in others (breast and, importantly, the endometrium, where unlike tamoxifen it does not behave as an agonist). It is FDA-approved for two indications: treatment and prevention of postmenopausal osteoporosis, and reduction of the risk of invasive breast cancer in postmenopausal women with osteoporosis or at high risk of breast cancer. Both approvals rest on large randomized trials. The pivotal Multiple Outcomes of Raloxifene Evaluation (MORE) trial randomized 7,705 postmenopausal women with osteoporosis to raloxifene or placebo and showed that raloxifene reduced the risk of new vertebral fractures (RR ~0.7 at 60 mg/day, ~0.5 at 120 mg/day) and increased bone mineral density. The same trial population delivered the breast-cancer signal: invasive breast cancer was reduced by about 70% (RR 0.24 in the first report; 72% by the 4-year analysis), an effect confined to estrogen-receptor-positive disease. The Continuing Outcomes Relevant to Evista (CORE) extension carried that benefit out to 8 years (invasive breast cancer reduced 66%, ER-positive 76% over both trials), and the head-to-head STAR (Study of Tamoxifen and Raloxifene) trial in 19,747 high-risk postmenopausal women found raloxifene roughly equivalent to tamoxifen for preventing invasive breast cancer, with fewer uterine cancers and fewer thromboembolic events than tamoxifen — though it was somewhat less effective against noninvasive (in situ) disease. A 2013 individual-participant meta-analysis of nine SERM prevention trials confirmed the class reduces breast-cancer incidence by ~38% over 10 years. This is genuinely strong, randomized, outcome-level evidence for the approved indications — the strong end of the picture.
The honest counterweight is equally well-documented and is the reason the score sits in the emerging band. The Raloxifene Use for The Heart (RUTH) trial randomized 10,101 postmenopausal women with or at high risk of coronary heart disease to raloxifene or placebo over a median 5.6 years specifically to test a cardiovascular benefit — and found NONE: there was no significant effect on coronary events (hazard ratio 0.95). Worse, raloxifene significantly increased the risk of FATAL STROKE (HR 1.49) and venous thromboembolism — deep-vein thrombosis and pulmonary embolism (HR 1.44) — while again reducing breast cancer and clinical vertebral fractures. So the same tissue-selective agonism that protects bone makes raloxifene pro-thrombotic in the clotting system, exactly as with tamoxifen. Two further hard limits matter: raloxifene reduces VERTEBRAL fractures but has NOT been shown to reduce hip or other non-vertebral fractures (the SERM meta-analysis found only a small, marginal non-vertebral effect), so it is not a complete osteoporosis solution; and it commonly causes hot flushes and leg cramps. Pregnancy is an absolute contraindication.
The off-label male use is the weak end. Because gynecomastia is estrogen-driven and raloxifene antagonizes the estrogen receptor in breast tissue, it has been tried for male breast enlargement. The evidence is thin: the best-known data are a small retrospective pediatric chart review of persistent pubertal gynecomastia in which raloxifene (and tamoxifen) shrank breast-nodule diameter, with raloxifene producing a higher proportion of major responses — but this was 38 boys, retrospective, and the authors themselves flagged that prospective confirmation is needed. There are essentially no controlled trials of raloxifene for adult male gynecomastia, anti-estrogen 'on-cycle' use, or bodybuilding contexts; that use is poorly evidenced and off-label. Overall, raloxifene is a well-proven prescription drug for postmenopausal bone and breast-cancer-risk outcomes whose benefits are real but bounded (no hip-fracture, no cardiovascular benefit) and whose venous-thromboembolic and fatal-stroke risks are documented in its own pivotal trials. It is a prescription SERM, not a dietary supplement, and not a longevity agent.
In bone, raloxifene acts as an estrogen AGONIST — it slows bone resorption and preserves bone mineral density, which is why it reduces vertebral-fracture risk and treats postmenopausal osteoporosis.
In breast tissue raloxifene ANTAGONIZES the estrogen receptor, starving estrogen-driven (ER-positive) tumor growth — the basis for its breast-cancer-risk reduction and its off-label use against estrogen-driven gynecomastia. Unlike tamoxifen, it is NOT an endometrial agonist, so it carries less uterine-cancer risk.
The same tissue-selective estrogen agonism that protects bone makes raloxifene pro-thrombotic — it raises the risk of venous thromboembolism (deep-vein thrombosis, pulmonary embolism) and fatal stroke, documented in its own pivotal trials. This is the mandatory counterweight to the bone and breast benefits.
How Raloxifene (Evista) works — from molecular targets to health outcomes. Click an edge to see supporting research.This visualization is in beta — pathways are being refined and expanded.
This is the approved population — raloxifene reduces vertebral fractures and invasive ER-positive breast cancer. Weigh the clot/fatal-stroke risk, and note it does NOT reduce hip fractures (a bisphosphonate or denosumab may be preferred if hip-fracture protection is the priority).
Poorly evidenced — the only notable data are a small retrospective pediatric series in persistent pubertal gynecomastia. Off-label, with no controlled trials in adult men; the venous-thromboembolism risk still applies. Use only under medical supervision.
Higher-risk — raloxifene is contraindicated with prior venous thromboembolism and increased fatal stroke in high-CV-risk women in RUTH. Often a poor fit; discuss before use.
Not indicated; contraindicated in pregnancy and breastfeeding (can harm the fetus).
Raloxifene can modestly decrease prothrombin time; monitor INR when starting or stopping. The underlying pro-thrombotic risk of raloxifene also matters in anticoagulated patients.
Cholestyramine reduces raloxifene absorption by about 60% and interrupts its enterohepatic cycling; co-administration is not recommended.
Concomitant use with systemic estrogen is not recommended; overlapping or opposing effects on the estrogen axis with other hormonal agents are not well validated.
Tip: A documented risk elevated in the pivotal trials (RUTH HR 1.44). Seek urgent care for leg swelling/pain, chest pain, or breathlessness; contraindicated with a prior clot history. Consider stopping before prolonged immobilization.
Tip: RUTH found no increase in overall stroke rate but a significant increase in FATAL stroke (HR 1.49) in women at high cardiovascular risk. Weigh carefully in anyone with stroke risk factors.
Tip: A common SERM effect, often most noticeable early in treatment; usually tolerable.
Tip: Frequently reported; usually mild but can affect adherence.
Tip: Generally mild; discuss with the prescribing clinician if bothersome.
Raloxifene (Evista) has an evidence score of 5.3/10 — moderate evidence based on 171 indexed studies, including 1 meta-analysis. A second-generation selective estrogen receptor modulator (SERM) approved for postmenopausal osteoporosis and for reducing the risk of invasive breast cancer in high-risk and osteoporotic postmenopausal women. In the pivotal MORE trial it cut vertebral-fracture risk and reduced invasive (largely ER-positive) breast cancer by ~70%; CORE extended the breast-cancer benefit to 8 years, and the STAR trial showed it roughly matched tamoxifen for invasive-breast-cancer prevention with less uterine cancer. It is used OFF-LABEL by some men for gynecomastia (a small pediatric series found it shrank pubertal breast tissue). The honest limits are non-negotiable: the RUTH trial found NO reduction in coronary events but a significant increase in FATAL STROKE and venous thromboembolism, raloxifene does NOT reduce hip or non-vertebral fractures, and it commonly causes hot flushes and leg cramps. It is NOT a supplement and NOT a longevity drug. Representative study: PMID 23639488.
The commonly studied dose of Raloxifene (Evista) is Approved (postmenopausal women) / off-label (male) — clinician-directed. For osteoporosis treatment/prevention and breast-cancer risk reduction the standard, validated dose is 60 mg once daily (the MORE, CORE, RUTH and STAR trials all used 60 mg/day; MORE also tested 120 mg/day with no clear added fracture benefit and more side effects). For off-label male gynecomastia the small published pediatric series used roughly 60 mg/day; there is no FDA-approved male dose and the male evidence is thin and retrospective.. Individual needs vary — start at the lower end of the range and adjust based on how you respond.
Timing is flexible for Raloxifene (Evista) — consistent daily use matters more than the time of day. Taken as a single 60 mg oral tablet once daily, with or without food, at any time of day.
Raloxifene (Evista) should be used with caution — talk to a healthcare provider before taking it. The most commonly reported side effects are hot flushes / vasomotor symptoms, leg cramps, venous thromboembolism (DVT, pulmonary embolism). Use caution if any of these apply to you: Active or past history of venous thromboembolism (deep-vein thrombosis, pulmonary embolism, retinal-vein thrombosis) — raloxifene raises clot risk; Pregnancy and breastfeeding (can harm the fetus; contraindicated); Women of childbearing potential / premenopausal women (not indicated).
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Reviewed by Dr. Baher Al Hakim · Last reviewed June 2026 · evidence from 367 studies · how we score · editorial policy
This information is for educational purposes only. It is not a substitute for professional medical advice. Always consult a qualified healthcare provider before starting, stopping, or changing any supplement or medication.
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