Peptide & Experimental
Raloxifene
Selective estrogen receptor modulator (SERM), prescription-only · Evista, Optruma, raloxifene hydrochloride
Raloxifene is a selective estrogen receptor modulator, approved for the treatment and prevention of osteoporosis in women after menopause. It reduces vertebral fractures and breast cancer, but not hip fractures or heart attacks, and it increases the risk of thrombosis – all measured in trials with tens of thousands of women. In men it is used off-label against breast gland enlargement; there is no controlled study for this.
What raloxifene is and how it works
Raloxifene is a selective estrogen receptor modulator, SERM for short, and prescription-only. In the EU it is approved as Evista for the treatment and prevention of osteoporosis in women after menopause and is intended for long-term use.
The active substance occupies the estrogen receptor and acts in a tissue-dependent way: estrogen-like on bone, as an antagonist on the breast and uterus. In this way it slows bone loss without stimulating the lining of the uterus; in the MORE trial, raloxifene caused neither bleeding nor breast pain. This is the most important difference from tamoxifen, which has a partly estrogen-like effect on the uterus.
In men, the effect has hardly been studied. In a double-blind study with 30 men aged 60 to 70, testosterone rose by 20 percent compared with placebo over three months under raloxifene, whereas IGF-1 fell by 24.5 percent. The authors attribute the drop in IGF-1 to the partly estrogen-like effect, as is also known from orally taken estrogens.
What is well supported
- Fewer vertebral fractures. In MORE, with 7,705 women with osteoporosis, the proportion with a new vertebral fracture over three years fell from 10.1 to 6.6 percent, relative risk 0.7. Fractures outside the spine did not become less frequent.
- Less breast cancer. In RUTH, with 10,101 women, invasive breast cancer occurred 44 percent less often; in STAR, with 19,747 women, raloxifene was as effective as tamoxifen in this respect. Across all SERM prevention trials with 83,399 women, breast cancer fell by 38 percent (Cuzick 2013).
- The thrombosis risk is quantified. In MORE, venous thromboembolism occurred about three times as often as under placebo; in RUTH there were 1.2 additional cases per 1,000 women per year.
- Assessed by regulators. The European Medicines Agency approved Evista on August 5, 1998; the assessment report and contraindications are public.
What the studies show
MORE: vertebral fractures in 7,705 women
Ettinger 1999 randomized postmenopausal women with osteoporosis to two raloxifene doses or placebo; all also received calcium and vitamin D. After 36 months, 10.1 percent under placebo had a new vertebral fracture, compared with 6.6 percent under the approved dose (relative risk 0.7; 95 percent confidence interval 0.5 to 0.8). For fractures outside the spine there was no difference (relative risk 0.9). Bone density rose by 2.1 percent at the femoral neck and 2.6 percent at the spine. Venous thromboembolism was about three times as frequent (relative risk 3.1).
RUTH: heart and breast in 10,101 women
Barrett-Connor 2006 studied women with coronary heart disease or several risk factors over a median of 5.6 years. The primary endpoint of coronary events remained unchanged (hazard ratio 0.95). Invasive breast cancer fell (40 versus 70 cases, HR 0.56), as did clinical vertebral fractures (HR 0.65). On the other side were more fatal strokes (59 versus 39, HR 1.49) and more venous thromboembolism (103 versus 71, HR 1.44). All-cause mortality did not differ.
STAR: raloxifene versus tamoxifen in 19,747 women
Vogel 2006 compared both substances over five years in postmenopausal women at increased risk of breast cancer. Invasive breast cancer occurred equally often (163 versus 168 cases, relative risk 1.02). Under raloxifene there were fewer thromboembolic events (relative risk 0.70) and fewer cataracts (0.79), but somewhat more non-invasive breast cancer, narrowly short of statistical significance. Uterine cancer: 23 cases under raloxifene, 36 under tamoxifen, also not significant.
Lawrence 2004: pubertal gynecomastia
Retrospective analysis of 38 adolescents with persistent pubertal gynecomastia who were either only reassured or treated with tamoxifen or raloxifene. The lump shrank by an average of 2.5 cm under raloxifene and 2.1 cm under tamoxifen; by more than half in 86 versus 41 percent. No side effects were observed. The authors themselves write that further studies are needed to establish a true treatment effect.
Where the data stop
- Hip fractures and the heart. Raloxifene reduces vertebral fractures, but not fractures outside the spine, and it does not protect against coronary events.
- Gynecomastia in men. There is no randomized study, neither for pubertal gynecomastia nor for breast gland enlargement caused by anabolic steroids. The only analysis is retrospective and concerns adolescents.
- Healthy men. The randomized study with 30 older men ran for three months. How the thrombosis risk and the lowered IGF-1 play out with longer use has not been studied.
- Origin of the product. The data apply to the tested medicine, not to products from the gray market.
Status, approval and legal
Evista was approved by the European Medicines Agency on August 5, 1998, for the treatment and prevention of osteoporosis in women after menopause. The approved dose is one 60 mg tablet once daily. Raloxifene is prescription-only. There is no approval for men; use against gynecomastia is an unapproved use.
The WADA Prohibited List 2026 lists raloxifene under S4.2, the anti-estrogenic substances, banned in and out of competition and for all athletes. In the annex of the German Anti-Doping Act it is listed among the anti-estrogenic substances.
Safety
The most important risk is venous thromboembolism, that is, thromboses and pulmonary embolisms: in MORE about three times as frequent as under placebo, in RUTH 1.2 additional cases per 1,000 women per year. RUTH also saw more fatal strokes, in absolute terms 0.7 per 1,000 woman-years, without an increase in strokes overall.
According to the EMA, the most common side effects are hot flashes and flu-like symptoms. Among other things, raloxifene must not be used in cases of previous or existing thrombosis and pulmonary embolism, liver disease, severe kidney disease, unexplained uterine bleeding or uterine cancer, and possible pregnancy. It belongs in the hands of a physician.
BK-Score Well supported, heavily overhyped
| Human evidence | 8 | |
|---|---|---|
| Mechanism | 8 | |
| Safety data | 9 | |
| Hype gap | 4 | |
| Track record of use | 9 |
Evidence 8, because the approved use is established in large randomized trials – in MORE with 7,705 women, the proportion with a new vertebral fracture fell from 10.1 to 6.6 percent (Ettinger 1999), and RUTH and STAR, with almost 30,000 women combined, confirm the effect on breast cancer – whereas use in men rests on a retrospective analysis of 38 adolescents and a three-month study of 30 older men. Mechanism 8, because the tissue-dependent action on the estrogen receptor is well described, but the effects in men hardly at all. Safety 9, because thromboembolism and fatal strokes are quantified in trials with more than 37,000 women combined; that means well studied, not harmless. Hype 4, because raloxifene is used in the strength-training scene against breast gland enlargement caused by anabolic steroids, although there is no controlled study on this and the only randomized study in healthy men found IGF-1 to be 24.5 percent lower (Duschek 2005). Use 9, because raloxifene has been approved in the EU since 1998 and is intended for long-term use. Direction mixed: proven benefit in osteoporosis and breast cancer prevention, proven thrombosis risk, hardly any data for use in men.
The score rates the state of knowledge, not the substance. “Safety data 9” means well studied – not harmless. “Track record of use 9” means used long and widely – that is not proof of efficacy.
Subjective assessment by Biohacking Kompakt based on published scoring rules – not a scientific rating and not a medical recommendation. Rules and all ratings (German)
Frequently asked questions about raloxifene
What is raloxifene approved for?
For the treatment and prevention of osteoporosis in women after menopause. Evista has been approved in the EU since August 5, 1998; the approved dose is one 60 mg tablet once daily. According to the EMA, a clear reduction in vertebral fractures is established, but not in hip fractures.
Does raloxifene lower the risk of breast cancer?
Yes. In the RUTH trial with 10,101 women, invasive breast cancer occurred 44 percent less often, in absolute terms 1.2 fewer cases per 1,000 women per treatment year. In the STAR trial with 19,747 women, raloxifene was as effective as tamoxifen in this respect, with fewer thromboembolic events and cataracts.
What is the difference from tamoxifen?
Both are selective estrogen receptor modulators. Tamoxifen has a partly estrogen-like effect on the lining of the uterus and increases the cancer risk there; raloxifene does not stimulate the lining. In the head-to-head STAR trial, both prevented the same amount of invasive breast cancer, and raloxifene caused fewer thromboembolic events and cataracts.
Does raloxifene help against gynecomastia in men?
There is no controlled study on this. In a retrospective analysis of 38 adolescents with persistent pubertal gynecomastia, the lump shrank by more than half in 86 percent under raloxifene, without randomization. In 30 older men, testosterone rose by 20 percent under raloxifene, while IGF-1 fell by 24.5 percent. In Germany it is not approved for men.
What are the risks of raloxifene?
In the MORE trial, venous thromboembolism occurred about three times as often as under placebo. In RUTH there were more fatal strokes, in absolute terms 0.7 additional per 1,000 woman-years. Common side effects are hot flashes and flu-like symptoms. Raloxifene is banned in sport: WADA list 2026, S4.2, in and out of competition.
Related
- Related topicTamoxifen
- Related topicExemestane
- Related topicAnastrozole
- Related topicClomiphene
- Related topicAbaloparatide
- Related topicLetrozole
Sources
- EMA – Evista (raloxifene), European public assessment report and summary
- Ettinger B et al., JAMA 1999 – MORE, raloxifene and vertebral fractures, 7,705 women with osteoporosis
- Barrett-Connor E et al., N Engl J Med 2006 – RUTH, raloxifene, cardiovascular events and breast cancer, 10,101 women
- Vogel VG et al., JAMA 2006 – STAR, tamoxifen versus raloxifene for breast cancer prevention, 19,747 women
- Cuzick J et al., Lancet 2013 – meta-analysis of the SERM prevention trials, 83,399 women
- Duschek EJ et al., Maturitas 2005 – raloxifene, testosterone and IGF-1 in 30 older men, randomized, double-blind
- Lawrence SE et al., J Pediatr 2004 – raloxifene and tamoxifen in pubertal gynecomastia, retrospective, 38 patients
- Smith MR et al., J Clin Endocrinol Metab 2004 – raloxifene against bone loss under GnRH agonists, 48 men with prostate cancer
- WADA Prohibited List 2026, S4.2 anti-estrogenic substances – official publication in the German Federal Law Gazette II 2025 No. 312
- German Anti-Doping Act, annex – III. Hormone and metabolic modulators, 2. Anti-estrogenic substances
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Information only, not medical advice and not a usage or dosage recommendation. Prescription-only and unapproved substances belong in the hands of a physician. Last updated: 2026-10-09.