Raloxifene is an oral selective estrogen receptor modulator (SERM): a drug that acts like estrogen in some tissues, such as bone, while blocking estrogen in others, such as the breast and uterus. Eli Lilly sells it as Evista, first approved by the FDA in December 1997, and generic tablets are also available. Its approved uses are all in postmenopausal women: treating and preventing osteoporosis, and lowering the risk of invasive breast cancer.

Outside those uses, raloxifene appears in steroid-using communities as an alternative to tamoxifen for gynecomastia (male breast tissue growth) and as a “post-cycle therapy” (PCT) drug. The FDA label states plainly that there is no indication for raloxifene in men and that it has not been adequately studied in men. The label also carries a boxed warning for blood clots and for death from stroke.

This page summarizes what the FDA label, the large clinical trials and the small studies in men report. It is for education only and is not medical advice.

Property	Detail
Drug class	Nonsteroidal SERM (benzothiophene)
Brand / approval	Evista (Eli Lilly), NDA 020815, approved December 9, 1997; generic tablets available
Route	Oral tablet
Strength	60 mg raloxifene hydrochloride (≈55.7 mg raloxifene base)
Labeled dose	60 mg once daily, with or without food
Half-life (label)	27.7 h after a single dose; 32.5 h with repeated dosing
Key mechanism fact	Estrogen-like in bone; estrogen-blocking in breast and uterus; cleared by glucuronidation, not by cytochrome P450 enzymes
Boxed warning	Venous thromboembolism (blood clots) and death from stroke
US status	Prescription only; not a controlled substance; no approved use in men
WADA status	Prohibited at all times (S4.2, anti-estrogenic substances)

What it is

Raloxifene is used as its hydrochloride salt, formula C₂₈H₂₇NO₄S·HCl, molecular weight 510.05 g/mol (Evista label). The free base weighs 473.6 g/mol (PubChem). Each 60 mg tablet is the molar equivalent of 55.71 mg of raloxifene base.

It is not a steroid. Unlike tamoxifen and clomiphene, which are triphenylethylenes, raloxifene belongs to the benzothiophene class (Evista label).

How it works

Raloxifene binds the estrogen receptor. Whether that switches estrogen signaling on or off depends on which helper proteins (coactivators or corepressors) the receptor recruits in a given tissue. According to the label:

Bone: it acts like estrogen. It lowers bone resorption and turnover, raises bone mineral density (BMD) and reduces vertebral fractures.
Breast and uterus: it acts as an antagonist. Clinical trials found no estrogen-like effect on breast tissue or the uterine lining.
Hypothalamus and pituitary: in men it raises LH (luteinizing hormone), FSH (follicle-stimulating hormone) and testosterone, a sign that it partly blocks estrogen’s brake on these hormones. The effect is smaller than with tamoxifen (see below).

How it compares with tamoxifen and clomiphene

The library has separate pages for tamoxifen, clomiphene and toremifene. The differences that matter most:

Feature	Raloxifene	Tamoxifen	Clomiphene
Chemical family	Benzothiophene	Triphenylethylene	Triphenylethylene
US-approved use	Osteoporosis; breast cancer risk reduction (postmenopausal women)	Breast cancer treatment and risk reduction	Ovulatory dysfunction in women seeking pregnancy
Half-life (labels)	≈28–33 h	≈5–7 days; ≈14 days for N-desmethyltamoxifen	Zuclomiphene detectable for over a month
Metabolism	Glucuronidation; no CYP450 metabolites detected	Substrate of CYP3A, 2C9 and 2D6	—
Effect on the uterus	Antagonist; endometrial thickness no different from placebo	Boxed warning for uterine malignancies	—
LH / testosterone rise in healthy men, 2 weeks	+30% / +25%	+70% / +40%	—

Sources: Evista label; tamoxifen label; clomiphene label; Birzniece et al., JCEM 2010.

Pharmacokinetics

Raloxifene is an unusual oral drug: most of it is absorbed, but almost none reaches the circulation unchanged. The label reports the following (Evista label):

Absorption. About 60% of an oral dose is absorbed, but extensive first-pass glucuronidation leaves an absolute bioavailability of only 2%. A high-fat meal raises peak levels by 28% and total exposure by 16%, which the label does not consider clinically meaningful.
Recycling. Raloxifene and its glucuronides convert back and forth and recirculate through the bile and gut (enterohepatic cycling). This is what stretches the half-life to about a day.
Binding. About 95% is bound to plasma proteins (albumin and α1-acid glycoprotein), but not to SHBG.
Metabolism. Only glucuronide conjugates were found. The label calls this “strong evidence” that raloxifene is not metabolized by cytochrome P450 enzymes.
Excretion. Mainly in feces; under 0.2% appears unchanged in urine.
Men vs women. Exposure and clearance, adjusted for lean body weight, did not differ significantly between age-matched men and women.

Parameter (healthy postmenopausal women)	Single dose	Multiple doses
Mean half-life	27.7 h	32.5 h
Observed half-life range	10.7–273 h	15.8–86.6 h
Apparent oral clearance	44.1 L/kg·h	47.4 L/kg·h
Apparent volume of distribution	2348 L/kg	2853 L/kg

Within-person variability is high, about 30% for most parameters. Organ impairment raises exposure:

Group	Change vs healthy volunteers
Mild liver impairment (Child-Pugh A), 60 mg single dose	Plasma levels ≈150% higher; clearance 56% lower
Moderate or severe kidney impairment (10 men), 120 mg single dose	Total exposure (AUC) 122% higher

Approved medical use

The FDA label lists three indications, all in postmenopausal women (Evista label):

treatment and prevention of osteoporosis;
reduction in risk of invasive breast cancer in women with osteoporosis;
reduction in risk of invasive breast cancer in women at high risk of it.

The labeled dose for all three is one 60 mg tablet daily. The label lists important limits: raloxifene is not for treating breast cancer, preventing its recurrence or lowering the risk of noninvasive breast cancer. It is not recommended for premenopausal women, and it should not be used to prevent heart disease. The optimal treatment length for breast cancer risk reduction is not known.

The US Preventive Services Task Force recommends that clinicians offer risk-reducing medicines such as tamoxifen, raloxifene or aromatase inhibitors to women at increased breast cancer risk and low risk of side effects. It recommends against their routine use in women who are not at increased risk (USPSTF, JAMA 2019).

What the research shows

Osteoporosis and fractures (MORE)

The Multiple Outcomes of Raloxifene Evaluation (MORE) randomized 7705 postmenopausal women with osteoporosis in 25 countries to 60 mg/day, 120 mg/day or placebo for 3 years. All took calcium and vitamin D (Ettinger et al., JAMA 1999). Results for the approved 60 mg dose, from the label:

Outcome (60 mg vs placebo)	Raloxifene	Placebo	Relative risk reduction (95% CI)
New vertebral fracture, no fracture at baseline	1.9%	4.3%	55% (29–71%)
New vertebral fracture, ≥1 fracture at baseline	14.1%	20.2%	30% (14–44%)
New painful (clinical) vertebral fracture	1.8%	3.1%	41% (17–59%)

Compared with placebo, the 60 mg dose raised BMD by 2.1% at the femoral neck and 2.6% at the spine. Raloxifene did not significantly reduce nonvertebral fractures (both doses combined: RR 0.9, 95% CI 0.8–1.1). In three prevention trials in younger postmenopausal women, it raised hip, spine and total-body BMD compared with calcium alone (Evista label).

Breast cancer risk reduction

Breast cancer was a secondary outcome in MORE and then the focus of three further trials:

Trial	Population, n	Comparison	Invasive breast cancer result
MORE (Cummings et al., JAMA 1999)	Women with osteoporosis, 7705; median 40 months	Raloxifene (both doses) vs placebo	RR 0.24 (95% CI 0.13–0.44)
CORE (Martino et al., JNCI 2004)	MORE participants continued 4 more years	60 mg vs placebo	HR 0.41 (0.24–0.71) during CORE; HR 0.34 (0.22–0.50) over 8 years
RUTH (Barrett-Connor et al., NEJM 2006)	Women with or at high risk of heart disease, 10,101; median 5.6 years	60 mg vs placebo	HR 0.56 (0.38–0.83)
STAR, first report (Vogel et al., JAMA 2006)	High-risk women, 19,747	60 mg raloxifene vs 20 mg tamoxifen	RR 1.02 (0.82–1.28), no difference
STAR, 81-month update (Vogel et al., Cancer Prev Res 2010)	Same trial, longer follow-up	Raloxifene vs tamoxifen	RR 1.24 (1.05–1.47), raloxifene less effective

Three consistent findings run through these trials:

The benefit is limited to estrogen receptor-positive cancer. In MORE, ER-positive cancer fell by 90% (RR 0.10), while ER-negative cancer did not change (RR 0.88, 95% CI 0.26–3.0).
It does not prevent noninvasive cancer as well as tamoxifen. STAR found more noninvasive breast cancers with raloxifene (RR 1.40, 95% CI 0.98–2.00, not significant).
It keeps most, not all, of tamoxifen’s effect. In the STAR update, raloxifene retained about 76% of tamoxifen’s effect on invasive cancer, with less uterine toxicity (see below).

Heart disease (RUTH)

Raloxifene has estrogen-like effects on lipid metabolism (Cummings et al., JAMA 1999), so it was tested as a heart drug. In RUTH, it had no effect on coronary events (533 vs 553 events; HR 0.95, 95% CI 0.84–1.07) and no effect on death from any cause (Barrett-Connor et al., NEJM 2006). The label therefore says it should not be used to prevent cardiovascular disease.

Hormones in healthy men

Four small controlled studies have measured raloxifene’s hormonal effects in men. None was in steroid users, and none measured muscle, strength or body composition.

Study	Design, n	Dose, duration	LH	Total testosterone	Estradiol	Other findings
Birzniece et al., JCEM 2010	Randomized open-label crossover vs tamoxifen, 10 healthy men	60 and 120 mg/day over 2 weeks	+30%	+25%	—	No significant change in IGF-1 (tamoxifen: −25%)
Duschek et al., Eur J Endocrinol 2004	Double-blind RCT, 30 men aged 60–70	120 mg/day, 3 months	+29%	+20%	+21%	FSH +21%; SHBG +7%; PSA +17%; HDL trended down
Uebelhart et al., JBMR 2004	Double-blind crossover, 43 eugonadal men aged 49–70	120 mg/day, 6 weeks	—	+13%	+11%	Osteocalcin −13%; the anti-resorptive effect was seen only in men with low baseline estradiol
Doran et al., JBMR 2001	Randomized blinded, 50 elderly men	60 mg/day, 6 months	—	No significant change vs placebo	No significant change vs placebo	No effect on bone markers or lipids

Two points stand out. First, raloxifene’s effect on the testicular axis is real but modest, and smaller than tamoxifen’s in a head-to-head crossover. Second, because it raises testosterone, it also raised estradiol in two of these studies, since more testosterone is available for conversion to estrogen. Duschek and colleagues concluded there were “no clear beneficial effects” in ageing men.

Men on androgen deprivation therapy

In an open-label trial, 48 men with nonmetastatic prostate cancer on a GnRH agonist (which shuts down testosterone production) were randomized to raloxifene 60 mg/day or no raloxifene for 12 months (Smith et al., JCEM 2004). Total hip BMD rose 1.1% with raloxifene and fell 2.6% without it (p under 0.001). The difference at the spine (+1.0% vs −1.0%) was not significant (p = 0.07).

Gynecomastia

The only published clinical data come from adolescents. A retrospective chart review of 38 consecutive boys with persistent pubertal gynecomastia compared reassurance alone with 3–9 months of tamoxifen or raloxifene (Lawrence et al., J Pediatr 2004):

Outcome	Tamoxifen	Raloxifene
Mean reduction in breast nodule diameter	2.1 cm (95% CI 1.7–2.7)	2.5 cm (95% CI 1.7–3.3)
Any improvement	86%	91%
Reduction greater than 50%	41%	86%

The authors noted that further study was needed to confirm this was a true treatment effect. Pubertal gynecomastia usually resolves on its own: in more than 90% of cases within 24 months, according to the European Academy of Andrology (EAA) guideline. That guideline concludes that SERMs, aromatase inhibitors and non-aromatizable androgens are “not justified in general” for gynecomastia and names surgery as the treatment of choice for long-lasting cases (Kanakis et al., Andrology 2019). No controlled trial has tested raloxifene for gynecomastia caused by anabolic steroids.

Recovery after anabolic steroid use

About raloxifene as “PCT.” Online sources often present raloxifene as a gentler or “gains-friendly” alternative to tamoxifen for restarting testosterone after a steroid cycle, pointing to its lack of effect on IGF-1. The IGF-1 difference is real in one 10-man crossover study, but no study has tested whether it matters for muscle. More importantly, no controlled study has tested raloxifene, or any SERM, for recovery after anabolic steroid use. A 2014 review intended as a meta-analysis of treatments for steroid-induced hypogonadism found that no quality studies met the inclusion criteria (Rahnema et al., Fertil Steril 2014).

The healthy-men studies show that raloxifene can raise LH and testosterone in an intact axis. They do not show how fast or how fully a steroid-suppressed axis recovers with raloxifene compared with no treatment.

Side effects and risks

Boxed warning

The label’s boxed warning covers two risks (Evista label):

Venous thromboembolism (VTE): deep vein thrombosis (a clot in a leg vein) and pulmonary embolism (a clot that travels to the lungs). Women with current or past VTE should not take raloxifene.
Death from stroke in women with heart disease or at increased risk of coronary events.

Blood clots

VTE is the most serious side effect in every large trial:

Trial	VTE result
MORE, 60 mg vs placebo (label)	26 vs 11 women; HR 2.4 (95% CI 1.2–4.5); ≈1 in 100 women over 2.6 years
RUTH	103 vs 71 events; HR 1.44 (1.06–1.95)
STAR update, vs tamoxifen	RR 0.75 (0.60–0.93), fewer clots than tamoxifen

The label says the risk is highest in the first 4 months and similar in size to that of hormone therapy. It advises stopping raloxifene at least 72 hours before and during prolonged immobilization, such as after surgery or on bed rest. Retinal vein thrombosis is also listed.

Stroke

In RUTH, 59 women on raloxifene and 39 on placebo died of stroke (HR 1.49, 95% CI 1.00–2.24; absolute increase 0.7 per 1000 woman-years). The total number of strokes did not differ significantly (249 vs 224; HR 1.10, 95% CI 0.92–1.32) (Barrett-Connor et al., NEJM 2006).

Common side effects

From the label’s placebo-controlled osteoporosis trials (60 mg/day):

Effect	MORE (treatment): raloxifene	MORE: placebo	Prevention trials: raloxifene	Prevention trials: placebo
Hot flashes	9.7%	6.4%	24.6%	18.3%
Leg cramps	7.0%	3.7%	5.9%	1.9%
Peripheral edema (swelling)	5.2%	4.4%	3.3%	1.9%
Flu syndrome	13.5%	11.4%	14.6%	13.5%
Sweating	2.5%	2.0%	3.1%	1.7%

In RUTH, gallstones were also more common (3.3% vs 2.6%). Raloxifene did not cause breast pain or vaginal bleeding more often than placebo.

Uterus and eyes compared with tamoxifen

Raloxifene’s main safety advantage over tamoxifen is in the uterus. In the STAR update, raloxifene had fewer endometrial cancers (RR 0.55, 95% CI 0.36–0.83) and much less uterine hyperplasia (RR 0.19) than tamoxifen (Vogel et al., Cancer Prev Res 2010). The first STAR report also found fewer cataracts (RR 0.79, 95% CI 0.68–0.92) (Vogel et al., JAMA 2006).

Effects specific to men

The label does not recommend use in men. In the small studies above, raloxifene raised estradiol by 11–21%, raised PSA (prostate-specific antigen) by 17% and showed a trend toward lower HDL in older men (Duschek et al., Eur J Endocrinol 2004). In male mice given high doses for 21 months, testicular and prostate tumors increased; this is an animal finding with unknown relevance to people (Evista label).

Interactions

The label lists (Evista label):

Cholestyramine (a cholesterol-binding resin): cuts raloxifene absorption and recycling by 60%; not recommended together.
Warfarin: a 10% drop in prothrombin time in a single-dose study; clotting tests should be checked when starting or stopping raloxifene.
Highly protein-bound drugs such as diazepam, diazoxide and lidocaine: use with caution.
Systemic estrogens: combined use is not recommended.

Because raloxifene is not metabolized by CYP450 enzymes, it lacks the CYP2D6 issue that affects tamoxifen.

Who should not use it

The label contraindicates raloxifene in:

current or past VTE, including retinal vein thrombosis;
pregnancy, because it may harm the fetus.

It also advises caution or avoidance in premenopausal women, liver impairment, moderate or severe kidney impairment, women at risk of stroke and anyone facing prolonged immobilization. Safety in children has not been established.

Legal status and use in sport

In the US, raloxifene is a prescription drug with no DEA schedule. The 2026 WADA Prohibited List names it under S4.2 (anti-estrogenic substances), banned in and out of competition. It is a “specified substance” (WADA 2026 Prohibited List).

Key takeaways

An osteoporosis and breast cancer prevention drug for postmenopausal women. Raloxifene 60 mg/day cut new vertebral fractures by 30–55% in MORE and lowered ER-positive invasive breast cancer, but did not reduce nonvertebral fractures.
Short half-life, low bioavailability. Only 2% of an oral dose reaches the blood unchanged, the half-life is about 28–33 hours, and it is cleared by glucuronidation rather than CYP enzymes.
Gentler on the uterus than tamoxifen, but somewhat less effective. In STAR it had fewer clots, endometrial cancers and cataracts, and retained about 76% of tamoxifen’s breast cancer benefit over the long term.
Clots and fatal stroke are the main risks. VTE risk was 2–3 times higher than with placebo in MORE, and RUTH found more fatal strokes in women with heart disease.
Thin evidence in men. It modestly raised LH and testosterone (and estradiol) in small studies. The gynecomastia data come from one retrospective review in teenagers, and no study has tested it after anabolic steroid use.

Sources

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Food and Drug Administration. Drugs@FDA: Evista (raloxifene hydrochloride), NDA 020815. FDA.
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Mylan Pharmaceuticals. Tamoxifen citrate tablets USP, prescribing information. DailyMed.
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Raloxifene