Raloxifene

updated

Raloxifene is an FDA-approved medicine for osteoporosis in postmenopausal women and for reducing invasive breast cancer risk in those at high risk, backed by the 7,705-woman MORE trial and the 19,747-woman STAR trial. Its label says there is no indication for use in men and that use in men is not recommended. The claim that it shrinks established gynecomastia better than tamoxifen traces to one retrospective chart review of 38 adolescents, and a PubMed search on 9 October 2026 found no randomized or prospective comparison.

Selective estrogen receptor modulator (SERM)

  • FDA approved EVISTA under NDA 020815 on 9 December 1997; section 5.10 of the label says there is no indication for use in men and that use in men is not recommended.
  • In MORE (7,705 postmenopausal women with osteoporosis), raloxifene for 3 years lowered first vertebral fractures from 4.3% to 1.9%.
  • In STAR (19,747 postmenopausal women at increased risk), raloxifene was not superior to tamoxifen: invasive breast cancer 4.4 versus 4.3 per 1,000 women per year.
  • The boxed warning covers deep vein thrombosis, pulmonary embolism and death from stroke; 59 (1.2%) raloxifene versus 39 (0.8%) placebo patients died of stroke over a mean 5.6 years in women.
  • The supplier claim traces to a retrospective chart review of 38 adolescents with non-randomized drug choice, whose authors wrote that further study is required.
  • A PubMed search on 9 October 2026 returned 5 records on raloxifene and gynecomastia, and ClinicalTrials.gov returned 0 registered studies.

What is raloxifene approved to do?

FDA approved EVISTA (raloxifene) on 9 December 1997 for osteoporosis in postmenopausal women and for reducing invasive breast cancer risk in postmenopausal women with osteoporosis or at high risk. The label states there is no indication for use in men and that use in men is not recommended.

The EVISTA label covers treatment and prevention of osteoporosis in postmenopausal women and reducing invasive breast cancer risk in postmenopausal women with osteoporosis or at high risk. Section 5.10 states there is no indication for use in men, that it has not been adequately studied in men, and that its use is not recommended. Pediatric safety and effectiveness are not established. The label version used here took effect on 11 February 2026.

FDA approved EVISTA under NDA 020815 on 9 December 1997 (Eli Lilly). Approvals outside the United States are not covered here.

Raloxifene base is C28H27NO4S (473.6 g/mol, CAS 84449-90-1, PubChem CID 5035). The salt in EVISTA is raloxifene hydrochloride (C28H28ClNO4S, 510.0 g/mol, CAS 82640-04-8, CID 54900), and label tablet strengths are stated for the hydrochloride.

EVISTA label, version effective 11 February 2026: indication, boxed warning, men, PK

FDA prescribing information

DailyMed, U.S. National Library of Medicine. EVISTA (raloxifene hydrochloride) oral tablets, prescribing information, label version effective 11 February 2026. Set ID fcaaa6dc-74e8-4fb8-800c-5574bf0f8de9.

The label approves EVISTA for treatment and prevention of osteoporosis in postmenopausal women and for reducing invasive breast cancer risk in postmenopausal women with osteoporosis or at high risk. Its boxed warning covers increased risk of deep vein thrombosis, pulmonary embolism and death from stroke: in postmenopausal women with or at risk of coronary disease, 59 (1.2%) raloxifene and 39 (0.8%) placebo patients died of stroke over a mean 5.6 years (HR 1.49, 95% CI 1.00 to 2.24). Section 5.10 states there is no indication for use in men, that it has not been adequately studied in men, and that its use is not recommended; pediatric safety and effectiveness are not established. About 60% of an oral dose is absorbed but absolute bioavailability is 2% because of extensive glucuronide conjugation, the plasma elimination half-life is 27.7 hours, and exposure normalized for lean body weight did not differ between age-matched female and male volunteers.

Participants / model
Postmenopausal women; age-matched male and female volunteers for PK
Treatment
EVISTA oral tablets (raloxifene hydrochloride)
Follow-up
Label version effective 11 February 2026
Study design
FDA prescribing information
Funding
not stated in the source

The boxed-warning risks come from women. The label recommends against use in men.

Read the original source
Drugs@FDA: EVISTA approved 9 December 1997

Regulatory record

U.S. Food and Drug Administration. Drugs@FDA application record for NDA 020815 (EVISTA). Date read from the openFDA Drugs@FDA record.

FDA approved EVISTA under NDA 020815 on 9 December 1997 (Eli Lilly).

Participants / model
Not a clinical population
Treatment
Drug application
Follow-up
Approved 1997
Study design
FDA application record
Funding
not stated in the source

This record gives the approval date and applicant. Indications come from the product label.

Read the original source
PubChem: raloxifene and raloxifene hydrochloride identity

Chemical identity record

National Library of Medicine. PubChem compound records CID 5035 (raloxifene) and CID 54900 (raloxifene hydrochloride).

Raloxifene base: PubChem CID 5035, C28H27NO4S, 473.6 g/mol, CAS 84449-90-1. Raloxifene hydrochloride, the salt in EVISTA: CID 54900, C28H28ClNO4S, 510.0 g/mol, CAS 82640-04-8. Label tablet strengths are stated for the hydrochloride, so salt and free-base masses differ.

Participants / model
Chemical identity, not a clinical population
Treatment
Defined molecule and salt
Follow-up
Not applicable
Study design
NLM chemical record
Funding
not stated in the source

Identity record only; it says nothing about efficacy or safety.

Read the original source

What did the large fracture and breast cancer trials find?

In MORE, 3 years of raloxifene in 7,705 postmenopausal women with osteoporosis lowered first vertebral fractures from 4.3% to 1.9%. In STAR, raloxifene was not superior to tamoxifen for invasive breast cancer in 19,747 women at increased risk.

In MORE (7,705 postmenopausal women with osteoporosis), raloxifene 60 mg a day for 3 years raised spine and hip bone mineral density by 2 to 3% and lowered first vertebral fractures from 4.3% to 1.9% (relative risk reduction 55%).

STAR was a randomized double-blind head-to-head trial of raloxifene 60 mg versus tamoxifen 20 mg in 19,747 postmenopausal women at increased breast cancer risk (median 4.3 years). Raloxifene was not superior: invasive breast cancer rates were 4.4 versus 4.3 per 1,000 women per year, the noninferiority analysis was consistent with raloxifene losing up to 35% of tamoxifen's effect, and noninvasive breast cancers were fewer on tamoxifen.

Both trials were in postmenopausal women. Neither describes men or gynecomastia.

MORE: 7,705 women, fractures; STAR: 19,747 women, raloxifene versus tamoxifen

FDA prescribing information

DailyMed, U.S. National Library of Medicine. EVISTA (raloxifene hydrochloride) prescribing information, label version effective 11 February 2026, section 14 (MORE and STAR trials). Set ID fcaaa6dc-74e8-4fb8-800c-5574bf0f8de9.

In MORE (7,705 postmenopausal women with osteoporosis), raloxifene for 3 years raised spine and hip bone mineral density by 2 to 3% and lowered first vertebral fractures from 4.3% to 1.9% (relative risk reduction 55%). In STAR, a randomized double-blind head-to-head trial of raloxifene versus tamoxifen in 19,747 postmenopausal women at increased breast cancer risk (median 4.3 years), raloxifene was not superior: invasive breast cancer rates were 4.4 versus 4.3 per 1,000 women per year, the noninferiority analysis was consistent with raloxifene losing up to 35% of tamoxifen's effect, and noninvasive breast cancers were fewer on tamoxifen.

Participants / model
Postmenopausal women: 7,705 with osteoporosis (MORE) and 19,747 at increased breast cancer risk (STAR)
Treatment
Oral raloxifene 60 mg daily; tamoxifen 20 mg daily in STAR
Follow-up
MORE 3 years; STAR median 4.3 years
Study design
Phase 3 randomized trials, results read from label section 14
Funding
not stated in the source

Women only. STAR measured breast cancer, not gynecomastia.

Read the original source

Does raloxifene shrink established gynecomastia better than tamoxifen?

Not shown. The claim traces to one non-randomized chart review of 38 adolescents whose authors said further study was needed. A PubMed search on 9 October 2026 found no randomized or prospective comparison, and no study in adults or steroid users.

Sellers prefer raloxifene over tamoxifen for established glandular gynecomastia and say it shrinks existing tissue better. The only comparative source found is a retrospective chart review of 38 consecutive patients with persistent pubertal gynecomastia at one pediatric endocrinology clinic, who received reassurance alone or a 3- to 9-month course of tamoxifen or raloxifene. Mean breast nodule diameter fell 2.1 cm (95% CI 1.7 to 2.7) on tamoxifen and 2.5 cm (1.7 to 3.3) on raloxifene; some improvement occurred in 86% on tamoxifen and 91% on raloxifene, and a decrease of more than 50% in 86% on raloxifene versus 41% on tamoxifen. No side effects were seen.

Drug choice was not randomized, per-group numbers are not given in the abstract, and the authors wrote that further study is required to determine that this is truly a treatment effect. The patients were adolescents with a mean age of 14.6 years.

A PubMed search on 9 October 2026 for raloxifene with gynecomastia returned 5 records: the chart review, a published comment on it, one case report and two reviews. A ClinicalTrials.gov search the same day returned 0 registered studies. No randomized or prospective comparison of raloxifene with tamoxifen for gynecomastia, and no study in adults or steroid users, was found. The one case report is a healthy 20-year-old man whose finasteride-associated gynecomastia regressed but did not resolve after 6 months of raloxifene and was later removed surgically; it had no comparator.

The one large randomized head-to-head comparison found is STAR, in postmenopausal women. It measured breast cancer, not gynecomastia, and raloxifene was not superior to tamoxifen there.

38 adolescents, retrospective chart review: raloxifene or tamoxifen for 3 to 9 months

Human study

Lawrence SE et al. J Pediatr. 2004;145(1):71-6. PMID 15238910.

Mean breast nodule diameter fell 2.1 cm (95% CI 1.7 to 2.7) on tamoxifen and 2.5 cm (1.7 to 3.3) on raloxifene. Some improvement occurred in 86% on tamoxifen and 91% on raloxifene, and a decrease of more than 50% in 86% on raloxifene versus 41% on tamoxifen. No side effects were seen. Drug choice was not randomized, per-group numbers are not given in the abstract, and the authors wrote that further study is required to determine that this is truly a treatment effect.

Participants / model
38 adolescents with persistent pubertal gynecomastia (treated subjects mean age 14.6, duration 28.3 months)
Treatment
Oral tamoxifen or raloxifene for 3 to 9 months, or reassurance alone; doses not given in the abstract
Follow-up
3 to 9 months of treatment
Study design
Retrospective chart review at one pediatric endocrinology clinic
Funding
not stated in the source

This is the only comparative source found behind the supplier claim. Drug choice was not randomized, and the abstract gives no per-group numbers.

Read the original source
PubMed search, 9 October 2026: 5 records; ClinicalTrials.gov: 0 studies

PubMed search record

PubMed search run on 9 October 2026: raloxifene AND (gynecomastia OR gynaecomastia). 5 records returned. ClinicalTrials.gov search for "raloxifene gynecomastia" on the same date: 0 registered studies.

The PubMed search returned 5 records: the chart review on this page, a published comment on it, one case report, and two reviews. A ClinicalTrials.gov search for raloxifene gynecomastia on the same date returned 0 registered studies. No randomized or prospective comparison of raloxifene with tamoxifen for gynecomastia, and no study in adults or steroid users, was found.

Participants / model
Records returned, not a population
Treatment
Not applicable
Follow-up
Searches run on 9 October 2026
Study design
Literature and registry search
Funding
not stated in the source

A search result shows what PubMed and ClinicalTrials.gov returned on that date. It is not proof that no unindexed study exists.

Read the original source
Case report: one 20-year-old man, regression but not resolution

Case report

Farkas HS et al. JCEM Case Rep. 2024;2(5):luae050. PMID 38660487.

A healthy 20-year-old man developed gynecomastia after 1 month of low-dose finasteride. It was unchanged 5 months after finasteride was stopped, regressed but did not resolve after 6 months of raloxifene, and was removed by bilateral mammoplasty a year later.

Participants / model
One 20-year-old man with finasteride-associated gynecomastia
Treatment
Oral raloxifene for 6 months; dose not given in the abstract
Follow-up
6 months of raloxifene
Study design
Case report
Funding
not stated in the source

One case, no comparator.

Read the original source
MORE: 7,705 women, fractures; STAR: 19,747 women, raloxifene versus tamoxifen

FDA prescribing information

DailyMed, U.S. National Library of Medicine. EVISTA (raloxifene hydrochloride) prescribing information, label version effective 11 February 2026, section 14 (MORE and STAR trials). Set ID fcaaa6dc-74e8-4fb8-800c-5574bf0f8de9.

In MORE (7,705 postmenopausal women with osteoporosis), raloxifene for 3 years raised spine and hip bone mineral density by 2 to 3% and lowered first vertebral fractures from 4.3% to 1.9% (relative risk reduction 55%). In STAR, a randomized double-blind head-to-head trial of raloxifene versus tamoxifen in 19,747 postmenopausal women at increased breast cancer risk (median 4.3 years), raloxifene was not superior: invasive breast cancer rates were 4.4 versus 4.3 per 1,000 women per year, the noninferiority analysis was consistent with raloxifene losing up to 35% of tamoxifen's effect, and noninvasive breast cancers were fewer on tamoxifen.

Participants / model
Postmenopausal women: 7,705 with osteoporosis (MORE) and 19,747 at increased breast cancer risk (STAR)
Treatment
Oral raloxifene 60 mg daily; tamoxifen 20 mg daily in STAR
Follow-up
MORE 3 years; STAR median 4.3 years
Study design
Phase 3 randomized trials, results read from label section 14
Funding
not stated in the source

Women only. STAR measured breast cancer, not gynecomastia.

Read the original source

What do the guideline and reviews say about drug treatment for gynecomastia?

A European guideline recommends against SERMs, aromatase inhibitors and non-aromatizable androgens for gynecomastia in general, and a systematic review judged the drug data partial and insufficient. Tamoxifen, not raloxifene, was the drug used in most included studies.

The European Academy of Andrology guideline recommends against using SERMs, aromatase inhibitors or non-aromatizable androgens to treat gynecomastia in general (strong recommendation, low-quality evidence). It states that more than 90% of pubertal gynecomastia resolves on its own within 24 months and reserves surgery for long-lasting gynecomastia that does not regress.

A systematic review of drug treatment for pubertal gynecomastia screened 1,425 publications and included 24, 16 of them on SERMs and the rest on aromatase inhibitors or androgens. It judged the data partial and insufficient, found tamoxifen was the drug used in most included studies, and noted that high-quality studies are lacking.

European Academy of Andrology guideline: no SERMs or aromatase inhibitors for gynecomastia in general

Human study

Kanakis GA et al. Andrology. 2019;7(6):778-793. PMID 31099174.

The guideline recommends against using SERMs, aromatase inhibitors or non-aromatizable androgens to treat gynecomastia in general (strong recommendation, low-quality evidence), states that more than 90% of pubertal gynecomastia resolves on its own within 24 months, and reserves surgery for long-lasting gynecomastia that does not regress.

Participants / model
Boys and men with gynecomastia (guideline scope)
Treatment
Not drug-specific
Follow-up
Not applicable
Study design
Clinical practice guideline (GRADE)
Funding
not stated in the source

A treatment recommendation for gynecomastia in general. It is not specific to raloxifene.

Read the original source
Systematic review: 24 of 1,425 publications included, data partial and insufficient

Systematic review and meta-analysis

Berger O et al. Front Pediatr. 2022;10:978311. PMID 36389365.

The review screened 1,425 publications and included 24, 16 of them on SERMs and the rest on aromatase inhibitors or androgens. It judged the data partial and insufficient, found tamoxifen was the drug used in most included studies, and noted that high-quality studies are lacking.

Participants / model
Adolescents with pubertal gynecomastia
Treatment
Oral SERMs, aromatase inhibitors or androgens
Follow-up
Not applicable
Study design
Systematic review
Funding
not stated in the source

Adolescent population. Tamoxifen, not raloxifene, was the drug used in most included studies.

Read the original source

What does raloxifene do to hormones and bones in men?

In healthy men raloxifene raised LH, FSH and testosterone, less than tamoxifen did, and it did not lower IGF-I. In 30 healthy older men the authors saw no clear benefit. In 48 men on a GnRH agonist, it raised hip bone density over 12 months.

In a randomized open-label crossover in 10 healthy men, 2 weeks each of raloxifene (60 and 120 mg a day) and tamoxifen (10 and 20 mg a day) both raised LH, FSH and testosterone, with smaller mean rises on raloxifene (testosterone 25% versus 40%; LH 30% versus 70%). Raloxifene, unlike tamoxifen, did not lower IGF-I. In 284 subfertile men with idiopathic oligozoospermia treated with tamoxifen 20 mg (94 men), toremifene 60 mg (99) or raloxifene 60 mg (91) once daily, all three raised gonadotropins, with larger rises on tamoxifen and toremifene than on raloxifene. The abstract does not describe randomization or give hormone values.

In a double-blind trial in 30 healthy men aged 60 to 70, raloxifene 120 mg a day (15 men) versus placebo (15) for 3 months raised LH by 29%, FSH by 21%, total testosterone by 20%, free testosterone by 16% and estradiol by 21%. Total cholesterol fell from 5.7 to 5.5 mmol/L, and total PSA rose 17%. The authors saw no clear benefit of raloxifene in ageing men.

In an open-label 12-month trial, 48 men with nonmetastatic prostate cancer on a GnRH agonist were randomized to raloxifene 60 mg a day or no raloxifene. Total hip bone mineral density rose 1.1% on raloxifene and fell 2.6% without it (P < 0.001); lumbar spine bone mineral density rose 1.0% versus fell 1.0% (P = 0.07). This is a bone outcome in androgen-deprived men, not a breast outcome.

10 healthy men, 2 weeks each: smaller rises with raloxifene than tamoxifen

Randomized controlled trial

Birzniece V et al. J Clin Endocrinol Metab. 2010;95(12):5443-8. PMID 20843951.

Raloxifene and tamoxifen both raised LH, FSH and testosterone, with smaller mean rises on raloxifene (testosterone 25% versus 40%; LH 30% versus 70%). Raloxifene, unlike tamoxifen, did not lower IGF-I.

Participants / model
10 healthy men
Treatment
Oral raloxifene 60 and 120 mg daily and tamoxifen 10 and 20 mg daily
Follow-up
2 weeks per drug
Study design
Randomized open-label crossover study
Funding
not stated in the source

Short hormone study in healthy men.

Read the original source
284 subfertile men: gonadotropin rises larger on tamoxifen and toremifene than raloxifene

Human study

Tsourdi E et al. Fertil Steril. 2009;91(4 Suppl):1427-30. PMID 18692782.

All three drugs raised gonadotropins, with larger rises on tamoxifen and toremifene than on raloxifene. The abstract does not describe randomization or give hormone values.

Participants / model
284 consecutive subfertile men with idiopathic oligozoospermia (94 on tamoxifen, 99 on toremifene, 91 on raloxifene)
Treatment
Oral tamoxifen 20 mg, toremifene 60 mg or raloxifene 60 mg once daily
Follow-up
Not stated in the abstract
Study design
Comparative clinical study
Funding
not stated in the source

The abstract does not describe randomization or give hormone values.

Read the original source
30 healthy men aged 60 to 70, 3 months: LH, FSH, testosterone and estradiol up

Randomized controlled trial

Duschek EJ et al. Eur J Endocrinol. 2004;150(4):539-46. PMID 15080785.

Raloxifene raised LH by 29%, FSH by 21%, total testosterone by 20%, free testosterone by 16% and estradiol by 21%; total cholesterol fell from 5.7 to 5.5 mmol/L, and total PSA rose 17%. The authors saw no clear benefit of raloxifene in ageing men.

Participants / model
30 healthy men aged 60 to 70 (15 on raloxifene, 15 on placebo)
Treatment
Oral raloxifene 120 mg daily or placebo
Follow-up
3 months
Study design
Double-blind randomized trial
Funding
not stated in the source

Healthy older men, not men with gynecomastia.

Read the original source
48 men on a GnRH agonist, 12 months: hip bone density up 1.1% versus down 2.6%

Randomized controlled trial

Smith MR et al. J Clin Endocrinol Metab. 2004;89(8):3841-6. PMID 15292315.

Total hip bone mineral density rose 1.1% on raloxifene and fell 2.6% without it (P < 0.001); lumbar spine bone mineral density rose 1.0% versus fell 1.0% (P = 0.07).

Participants / model
48 men with nonmetastatic prostate cancer on a GnRH agonist
Treatment
Oral raloxifene 60 mg daily or no raloxifene
Follow-up
12 months
Study design
Randomized open-label trial
Funding
not stated in the source

This is a bone outcome in androgen-deprived men, not a breast outcome.

Read the original source

How does raloxifene work, and what does the body do with it?

In the male studies raloxifene is compared with tamoxifen, and it raised LH, FSH and testosterone less than tamoxifen did. Its absolute oral bioavailability is 2% because of extensive glucuronide conjugation, and its plasma elimination half-life is 27.7 hours.

The male studies on this page treat raloxifene as a SERM comparable to tamoxifen. In 10 healthy men and in 284 subfertile men it raised gonadotropins less than tamoxifen did, and unlike tamoxifen it did not lower IGF-I in the crossover. The label text used for this page does not describe the receptor mechanism further.

About 60% of an oral dose is absorbed, but absolute bioavailability is 2% because of extensive glucuronide conjugation. The plasma elimination half-life is 27.7 hours, and exposure normalized for lean body weight did not differ between age-matched female and male volunteers.

EVISTA label, version effective 11 February 2026: indication, boxed warning, men, PK

FDA prescribing information

DailyMed, U.S. National Library of Medicine. EVISTA (raloxifene hydrochloride) oral tablets, prescribing information, label version effective 11 February 2026. Set ID fcaaa6dc-74e8-4fb8-800c-5574bf0f8de9.

The label approves EVISTA for treatment and prevention of osteoporosis in postmenopausal women and for reducing invasive breast cancer risk in postmenopausal women with osteoporosis or at high risk. Its boxed warning covers increased risk of deep vein thrombosis, pulmonary embolism and death from stroke: in postmenopausal women with or at risk of coronary disease, 59 (1.2%) raloxifene and 39 (0.8%) placebo patients died of stroke over a mean 5.6 years (HR 1.49, 95% CI 1.00 to 2.24). Section 5.10 states there is no indication for use in men, that it has not been adequately studied in men, and that its use is not recommended; pediatric safety and effectiveness are not established. About 60% of an oral dose is absorbed but absolute bioavailability is 2% because of extensive glucuronide conjugation, the plasma elimination half-life is 27.7 hours, and exposure normalized for lean body weight did not differ between age-matched female and male volunteers.

Participants / model
Postmenopausal women; age-matched male and female volunteers for PK
Treatment
EVISTA oral tablets (raloxifene hydrochloride)
Follow-up
Label version effective 11 February 2026
Study design
FDA prescribing information
Funding
not stated in the source

The boxed-warning risks come from women. The label recommends against use in men.

Read the original source
10 healthy men, 2 weeks each: smaller rises with raloxifene than tamoxifen

Randomized controlled trial

Birzniece V et al. J Clin Endocrinol Metab. 2010;95(12):5443-8. PMID 20843951.

Raloxifene and tamoxifen both raised LH, FSH and testosterone, with smaller mean rises on raloxifene (testosterone 25% versus 40%; LH 30% versus 70%). Raloxifene, unlike tamoxifen, did not lower IGF-I.

Participants / model
10 healthy men
Treatment
Oral raloxifene 60 and 120 mg daily and tamoxifen 10 and 20 mg daily
Follow-up
2 weeks per drug
Study design
Randomized open-label crossover study
Funding
not stated in the source

Short hormone study in healthy men.

Read the original source
284 subfertile men: gonadotropin rises larger on tamoxifen and toremifene than raloxifene

Human study

Tsourdi E et al. Fertil Steril. 2009;91(4 Suppl):1427-30. PMID 18692782.

All three drugs raised gonadotropins, with larger rises on tamoxifen and toremifene than on raloxifene. The abstract does not describe randomization or give hormone values.

Participants / model
284 consecutive subfertile men with idiopathic oligozoospermia (94 on tamoxifen, 99 on toremifene, 91 on raloxifene)
Treatment
Oral tamoxifen 20 mg, toremifene 60 mg or raloxifene 60 mg once daily
Follow-up
Not stated in the abstract
Study design
Comparative clinical study
Funding
not stated in the source

The abstract does not describe randomization or give hormone values.

Read the original source
European Academy of Andrology guideline: no SERMs or aromatase inhibitors for gynecomastia in general

Human study

Kanakis GA et al. Andrology. 2019;7(6):778-793. PMID 31099174.

The guideline recommends against using SERMs, aromatase inhibitors or non-aromatizable androgens to treat gynecomastia in general (strong recommendation, low-quality evidence), states that more than 90% of pubertal gynecomastia resolves on its own within 24 months, and reserves surgery for long-lasting gynecomastia that does not regress.

Participants / model
Boys and men with gynecomastia (guideline scope)
Treatment
Not drug-specific
Follow-up
Not applicable
Study design
Clinical practice guideline (GRADE)
Funding
not stated in the source

A treatment recommendation for gynecomastia in general. It is not specific to raloxifene.

Read the original source

What risks do the label and the studies report?

The EVISTA boxed warning covers deep vein thrombosis, pulmonary embolism and death from stroke: 59 (1.2%) versus 39 (0.8%) placebo patients died of stroke over a mean 5.6 years. Those risks come from women, and the label says use in men is not recommended.

The boxed warning covers increased risk of deep vein thrombosis, pulmonary embolism and death from stroke. In postmenopausal women with or at risk of coronary disease, 59 (1.2%) raloxifene and 39 (0.8%) placebo patients died of stroke over a mean 5.6 years (HR 1.49, 95% CI 1.00 to 2.24). These risks come from women.

Section 5.10 states there is no indication for use in men, that raloxifene has not been adequately studied in men, and that its use is not recommended.

In the retrospective chart review of 38 adolescents, no side effects were seen, but the review was non-randomized and small. In 30 healthy men aged 60 to 70, raloxifene raised estradiol by 21% and total PSA by 17% over 3 months.

EVISTA label, version effective 11 February 2026: indication, boxed warning, men, PK

FDA prescribing information

DailyMed, U.S. National Library of Medicine. EVISTA (raloxifene hydrochloride) oral tablets, prescribing information, label version effective 11 February 2026. Set ID fcaaa6dc-74e8-4fb8-800c-5574bf0f8de9.

The label approves EVISTA for treatment and prevention of osteoporosis in postmenopausal women and for reducing invasive breast cancer risk in postmenopausal women with osteoporosis or at high risk. Its boxed warning covers increased risk of deep vein thrombosis, pulmonary embolism and death from stroke: in postmenopausal women with or at risk of coronary disease, 59 (1.2%) raloxifene and 39 (0.8%) placebo patients died of stroke over a mean 5.6 years (HR 1.49, 95% CI 1.00 to 2.24). Section 5.10 states there is no indication for use in men, that it has not been adequately studied in men, and that its use is not recommended; pediatric safety and effectiveness are not established. About 60% of an oral dose is absorbed but absolute bioavailability is 2% because of extensive glucuronide conjugation, the plasma elimination half-life is 27.7 hours, and exposure normalized for lean body weight did not differ between age-matched female and male volunteers.

Participants / model
Postmenopausal women; age-matched male and female volunteers for PK
Treatment
EVISTA oral tablets (raloxifene hydrochloride)
Follow-up
Label version effective 11 February 2026
Study design
FDA prescribing information
Funding
not stated in the source

The boxed-warning risks come from women. The label recommends against use in men.

Read the original source
38 adolescents, retrospective chart review: raloxifene or tamoxifen for 3 to 9 months

Human study

Lawrence SE et al. J Pediatr. 2004;145(1):71-6. PMID 15238910.

Mean breast nodule diameter fell 2.1 cm (95% CI 1.7 to 2.7) on tamoxifen and 2.5 cm (1.7 to 3.3) on raloxifene. Some improvement occurred in 86% on tamoxifen and 91% on raloxifene, and a decrease of more than 50% in 86% on raloxifene versus 41% on tamoxifen. No side effects were seen. Drug choice was not randomized, per-group numbers are not given in the abstract, and the authors wrote that further study is required to determine that this is truly a treatment effect.

Participants / model
38 adolescents with persistent pubertal gynecomastia (treated subjects mean age 14.6, duration 28.3 months)
Treatment
Oral tamoxifen or raloxifene for 3 to 9 months, or reassurance alone; doses not given in the abstract
Follow-up
3 to 9 months of treatment
Study design
Retrospective chart review at one pediatric endocrinology clinic
Funding
not stated in the source

This is the only comparative source found behind the supplier claim. Drug choice was not randomized, and the abstract gives no per-group numbers.

Read the original source
30 healthy men aged 60 to 70, 3 months: LH, FSH, testosterone and estradiol up

Randomized controlled trial

Duschek EJ et al. Eur J Endocrinol. 2004;150(4):539-46. PMID 15080785.

Raloxifene raised LH by 29%, FSH by 21%, total testosterone by 20%, free testosterone by 16% and estradiol by 21%; total cholesterol fell from 5.7 to 5.5 mmol/L, and total PSA rose 17%. The authors saw no clear benefit of raloxifene in ageing men.

Participants / model
30 healthy men aged 60 to 70 (15 on raloxifene, 15 on placebo)
Treatment
Oral raloxifene 120 mg daily or placebo
Follow-up
3 months
Study design
Double-blind randomized trial
Funding
not stated in the source

Healthy older men, not men with gynecomastia.

Read the original source

Why does raloxifene sit in A tier?

The A rests on an FDA approval since 1997 and two large trials in postmenopausal women. The label says there is no indication in men, and the claim that raloxifene beats tamoxifen for gynecomastia traces to one non-randomized review of 38 adolescents.

The A applies to the approved uses in postmenopausal women, backed by the 7,705-woman MORE trial and the 19,747-woman STAR trial. The supplier's use is off-label, and the label says use in men is not recommended.

The claim that raloxifene is preferred over tamoxifen for established gynecomastia is not supported as stated. It traces to one non-randomized chart review whose authors called for further study, and in STAR, the large randomized comparison in women, raloxifene was not superior to tamoxifen. A PubMed search on 9 October 2026 found no randomized or prospective comparison and no adult or steroid-user data beyond one case report.

EVISTA label, version effective 11 February 2026: indication, boxed warning, men, PK

FDA prescribing information

DailyMed, U.S. National Library of Medicine. EVISTA (raloxifene hydrochloride) oral tablets, prescribing information, label version effective 11 February 2026. Set ID fcaaa6dc-74e8-4fb8-800c-5574bf0f8de9.

The label approves EVISTA for treatment and prevention of osteoporosis in postmenopausal women and for reducing invasive breast cancer risk in postmenopausal women with osteoporosis or at high risk. Its boxed warning covers increased risk of deep vein thrombosis, pulmonary embolism and death from stroke: in postmenopausal women with or at risk of coronary disease, 59 (1.2%) raloxifene and 39 (0.8%) placebo patients died of stroke over a mean 5.6 years (HR 1.49, 95% CI 1.00 to 2.24). Section 5.10 states there is no indication for use in men, that it has not been adequately studied in men, and that its use is not recommended; pediatric safety and effectiveness are not established. About 60% of an oral dose is absorbed but absolute bioavailability is 2% because of extensive glucuronide conjugation, the plasma elimination half-life is 27.7 hours, and exposure normalized for lean body weight did not differ between age-matched female and male volunteers.

Participants / model
Postmenopausal women; age-matched male and female volunteers for PK
Treatment
EVISTA oral tablets (raloxifene hydrochloride)
Follow-up
Label version effective 11 February 2026
Study design
FDA prescribing information
Funding
not stated in the source

The boxed-warning risks come from women. The label recommends against use in men.

Read the original source
MORE: 7,705 women, fractures; STAR: 19,747 women, raloxifene versus tamoxifen

FDA prescribing information

DailyMed, U.S. National Library of Medicine. EVISTA (raloxifene hydrochloride) prescribing information, label version effective 11 February 2026, section 14 (MORE and STAR trials). Set ID fcaaa6dc-74e8-4fb8-800c-5574bf0f8de9.

In MORE (7,705 postmenopausal women with osteoporosis), raloxifene for 3 years raised spine and hip bone mineral density by 2 to 3% and lowered first vertebral fractures from 4.3% to 1.9% (relative risk reduction 55%). In STAR, a randomized double-blind head-to-head trial of raloxifene versus tamoxifen in 19,747 postmenopausal women at increased breast cancer risk (median 4.3 years), raloxifene was not superior: invasive breast cancer rates were 4.4 versus 4.3 per 1,000 women per year, the noninferiority analysis was consistent with raloxifene losing up to 35% of tamoxifen's effect, and noninvasive breast cancers were fewer on tamoxifen.

Participants / model
Postmenopausal women: 7,705 with osteoporosis (MORE) and 19,747 at increased breast cancer risk (STAR)
Treatment
Oral raloxifene 60 mg daily; tamoxifen 20 mg daily in STAR
Follow-up
MORE 3 years; STAR median 4.3 years
Study design
Phase 3 randomized trials, results read from label section 14
Funding
not stated in the source

Women only. STAR measured breast cancer, not gynecomastia.

Read the original source
38 adolescents, retrospective chart review: raloxifene or tamoxifen for 3 to 9 months

Human study

Lawrence SE et al. J Pediatr. 2004;145(1):71-6. PMID 15238910.

Mean breast nodule diameter fell 2.1 cm (95% CI 1.7 to 2.7) on tamoxifen and 2.5 cm (1.7 to 3.3) on raloxifene. Some improvement occurred in 86% on tamoxifen and 91% on raloxifene, and a decrease of more than 50% in 86% on raloxifene versus 41% on tamoxifen. No side effects were seen. Drug choice was not randomized, per-group numbers are not given in the abstract, and the authors wrote that further study is required to determine that this is truly a treatment effect.

Participants / model
38 adolescents with persistent pubertal gynecomastia (treated subjects mean age 14.6, duration 28.3 months)
Treatment
Oral tamoxifen or raloxifene for 3 to 9 months, or reassurance alone; doses not given in the abstract
Follow-up
3 to 9 months of treatment
Study design
Retrospective chart review at one pediatric endocrinology clinic
Funding
not stated in the source

This is the only comparative source found behind the supplier claim. Drug choice was not randomized, and the abstract gives no per-group numbers.

Read the original source
PubMed search, 9 October 2026: 5 records; ClinicalTrials.gov: 0 studies

PubMed search record

PubMed search run on 9 October 2026: raloxifene AND (gynecomastia OR gynaecomastia). 5 records returned. ClinicalTrials.gov search for "raloxifene gynecomastia" on the same date: 0 registered studies.

The PubMed search returned 5 records: the chart review on this page, a published comment on it, one case report, and two reviews. A ClinicalTrials.gov search for raloxifene gynecomastia on the same date returned 0 registered studies. No randomized or prospective comparison of raloxifene with tamoxifen for gynecomastia, and no study in adults or steroid users, was found.

Participants / model
Records returned, not a population
Treatment
Not applicable
Follow-up
Searches run on 9 October 2026
Study design
Literature and registry search
Funding
not stated in the source

A search result shows what PubMed and ClinicalTrials.gov returned on that date. It is not proof that no unindexed study exists.

Read the original source

Studies and sources

EVISTA label, version effective 11 February 2026: indication, boxed warning, men, PK

FDA prescribing information

DailyMed, U.S. National Library of Medicine. EVISTA (raloxifene hydrochloride) oral tablets, prescribing information, label version effective 11 February 2026. Set ID fcaaa6dc-74e8-4fb8-800c-5574bf0f8de9.

The label approves EVISTA for treatment and prevention of osteoporosis in postmenopausal women and for reducing invasive breast cancer risk in postmenopausal women with osteoporosis or at high risk. Its boxed warning covers increased risk of deep vein thrombosis, pulmonary embolism and death from stroke: in postmenopausal women with or at risk of coronary disease, 59 (1.2%) raloxifene and 39 (0.8%) placebo patients died of stroke over a mean 5.6 years (HR 1.49, 95% CI 1.00 to 2.24). Section 5.10 states there is no indication for use in men, that it has not been adequately studied in men, and that its use is not recommended; pediatric safety and effectiveness are not established. About 60% of an oral dose is absorbed but absolute bioavailability is 2% because of extensive glucuronide conjugation, the plasma elimination half-life is 27.7 hours, and exposure normalized for lean body weight did not differ between age-matched female and male volunteers.

Participants / model
Postmenopausal women; age-matched male and female volunteers for PK
Treatment
EVISTA oral tablets (raloxifene hydrochloride)
Follow-up
Label version effective 11 February 2026
Study design
FDA prescribing information
Funding
not stated in the source

The boxed-warning risks come from women. The label recommends against use in men.

Read the original source
MORE: 7,705 women, fractures; STAR: 19,747 women, raloxifene versus tamoxifen

FDA prescribing information

DailyMed, U.S. National Library of Medicine. EVISTA (raloxifene hydrochloride) prescribing information, label version effective 11 February 2026, section 14 (MORE and STAR trials). Set ID fcaaa6dc-74e8-4fb8-800c-5574bf0f8de9.

In MORE (7,705 postmenopausal women with osteoporosis), raloxifene for 3 years raised spine and hip bone mineral density by 2 to 3% and lowered first vertebral fractures from 4.3% to 1.9% (relative risk reduction 55%). In STAR, a randomized double-blind head-to-head trial of raloxifene versus tamoxifen in 19,747 postmenopausal women at increased breast cancer risk (median 4.3 years), raloxifene was not superior: invasive breast cancer rates were 4.4 versus 4.3 per 1,000 women per year, the noninferiority analysis was consistent with raloxifene losing up to 35% of tamoxifen's effect, and noninvasive breast cancers were fewer on tamoxifen.

Participants / model
Postmenopausal women: 7,705 with osteoporosis (MORE) and 19,747 at increased breast cancer risk (STAR)
Treatment
Oral raloxifene 60 mg daily; tamoxifen 20 mg daily in STAR
Follow-up
MORE 3 years; STAR median 4.3 years
Study design
Phase 3 randomized trials, results read from label section 14
Funding
not stated in the source

Women only. STAR measured breast cancer, not gynecomastia.

Read the original source
Drugs@FDA: EVISTA approved 9 December 1997

Regulatory record

U.S. Food and Drug Administration. Drugs@FDA application record for NDA 020815 (EVISTA). Date read from the openFDA Drugs@FDA record.

FDA approved EVISTA under NDA 020815 on 9 December 1997 (Eli Lilly).

Participants / model
Not a clinical population
Treatment
Drug application
Follow-up
Approved 1997
Study design
FDA application record
Funding
not stated in the source

This record gives the approval date and applicant. Indications come from the product label.

Read the original source
38 adolescents, retrospective chart review: raloxifene or tamoxifen for 3 to 9 months

Human study

Lawrence SE et al. J Pediatr. 2004;145(1):71-6. PMID 15238910.

Mean breast nodule diameter fell 2.1 cm (95% CI 1.7 to 2.7) on tamoxifen and 2.5 cm (1.7 to 3.3) on raloxifene. Some improvement occurred in 86% on tamoxifen and 91% on raloxifene, and a decrease of more than 50% in 86% on raloxifene versus 41% on tamoxifen. No side effects were seen. Drug choice was not randomized, per-group numbers are not given in the abstract, and the authors wrote that further study is required to determine that this is truly a treatment effect.

Participants / model
38 adolescents with persistent pubertal gynecomastia (treated subjects mean age 14.6, duration 28.3 months)
Treatment
Oral tamoxifen or raloxifene for 3 to 9 months, or reassurance alone; doses not given in the abstract
Follow-up
3 to 9 months of treatment
Study design
Retrospective chart review at one pediatric endocrinology clinic
Funding
not stated in the source

This is the only comparative source found behind the supplier claim. Drug choice was not randomized, and the abstract gives no per-group numbers.

Read the original source
European Academy of Andrology guideline: no SERMs or aromatase inhibitors for gynecomastia in general

Human study

Kanakis GA et al. Andrology. 2019;7(6):778-793. PMID 31099174.

The guideline recommends against using SERMs, aromatase inhibitors or non-aromatizable androgens to treat gynecomastia in general (strong recommendation, low-quality evidence), states that more than 90% of pubertal gynecomastia resolves on its own within 24 months, and reserves surgery for long-lasting gynecomastia that does not regress.

Participants / model
Boys and men with gynecomastia (guideline scope)
Treatment
Not drug-specific
Follow-up
Not applicable
Study design
Clinical practice guideline (GRADE)
Funding
not stated in the source

A treatment recommendation for gynecomastia in general. It is not specific to raloxifene.

Read the original source
Systematic review: 24 of 1,425 publications included, data partial and insufficient

Systematic review and meta-analysis

Berger O et al. Front Pediatr. 2022;10:978311. PMID 36389365.

The review screened 1,425 publications and included 24, 16 of them on SERMs and the rest on aromatase inhibitors or androgens. It judged the data partial and insufficient, found tamoxifen was the drug used in most included studies, and noted that high-quality studies are lacking.

Participants / model
Adolescents with pubertal gynecomastia
Treatment
Oral SERMs, aromatase inhibitors or androgens
Follow-up
Not applicable
Study design
Systematic review
Funding
not stated in the source

Adolescent population. Tamoxifen, not raloxifene, was the drug used in most included studies.

Read the original source
Case report: one 20-year-old man, regression but not resolution

Case report

Farkas HS et al. JCEM Case Rep. 2024;2(5):luae050. PMID 38660487.

A healthy 20-year-old man developed gynecomastia after 1 month of low-dose finasteride. It was unchanged 5 months after finasteride was stopped, regressed but did not resolve after 6 months of raloxifene, and was removed by bilateral mammoplasty a year later.

Participants / model
One 20-year-old man with finasteride-associated gynecomastia
Treatment
Oral raloxifene for 6 months; dose not given in the abstract
Follow-up
6 months of raloxifene
Study design
Case report
Funding
not stated in the source

One case, no comparator.

Read the original source
10 healthy men, 2 weeks each: smaller rises with raloxifene than tamoxifen

Randomized controlled trial

Birzniece V et al. J Clin Endocrinol Metab. 2010;95(12):5443-8. PMID 20843951.

Raloxifene and tamoxifen both raised LH, FSH and testosterone, with smaller mean rises on raloxifene (testosterone 25% versus 40%; LH 30% versus 70%). Raloxifene, unlike tamoxifen, did not lower IGF-I.

Participants / model
10 healthy men
Treatment
Oral raloxifene 60 and 120 mg daily and tamoxifen 10 and 20 mg daily
Follow-up
2 weeks per drug
Study design
Randomized open-label crossover study
Funding
not stated in the source

Short hormone study in healthy men.

Read the original source
30 healthy men aged 60 to 70, 3 months: LH, FSH, testosterone and estradiol up

Randomized controlled trial

Duschek EJ et al. Eur J Endocrinol. 2004;150(4):539-46. PMID 15080785.

Raloxifene raised LH by 29%, FSH by 21%, total testosterone by 20%, free testosterone by 16% and estradiol by 21%; total cholesterol fell from 5.7 to 5.5 mmol/L, and total PSA rose 17%. The authors saw no clear benefit of raloxifene in ageing men.

Participants / model
30 healthy men aged 60 to 70 (15 on raloxifene, 15 on placebo)
Treatment
Oral raloxifene 120 mg daily or placebo
Follow-up
3 months
Study design
Double-blind randomized trial
Funding
not stated in the source

Healthy older men, not men with gynecomastia.

Read the original source
284 subfertile men: gonadotropin rises larger on tamoxifen and toremifene than raloxifene

Human study

Tsourdi E et al. Fertil Steril. 2009;91(4 Suppl):1427-30. PMID 18692782.

All three drugs raised gonadotropins, with larger rises on tamoxifen and toremifene than on raloxifene. The abstract does not describe randomization or give hormone values.

Participants / model
284 consecutive subfertile men with idiopathic oligozoospermia (94 on tamoxifen, 99 on toremifene, 91 on raloxifene)
Treatment
Oral tamoxifen 20 mg, toremifene 60 mg or raloxifene 60 mg once daily
Follow-up
Not stated in the abstract
Study design
Comparative clinical study
Funding
not stated in the source

The abstract does not describe randomization or give hormone values.

Read the original source
48 men on a GnRH agonist, 12 months: hip bone density up 1.1% versus down 2.6%

Randomized controlled trial

Smith MR et al. J Clin Endocrinol Metab. 2004;89(8):3841-6. PMID 15292315.

Total hip bone mineral density rose 1.1% on raloxifene and fell 2.6% without it (P < 0.001); lumbar spine bone mineral density rose 1.0% versus fell 1.0% (P = 0.07).

Participants / model
48 men with nonmetastatic prostate cancer on a GnRH agonist
Treatment
Oral raloxifene 60 mg daily or no raloxifene
Follow-up
12 months
Study design
Randomized open-label trial
Funding
not stated in the source

This is a bone outcome in androgen-deprived men, not a breast outcome.

Read the original source
PubChem: raloxifene and raloxifene hydrochloride identity

Chemical identity record

National Library of Medicine. PubChem compound records CID 5035 (raloxifene) and CID 54900 (raloxifene hydrochloride).

Raloxifene base: PubChem CID 5035, C28H27NO4S, 473.6 g/mol, CAS 84449-90-1. Raloxifene hydrochloride, the salt in EVISTA: CID 54900, C28H28ClNO4S, 510.0 g/mol, CAS 82640-04-8. Label tablet strengths are stated for the hydrochloride, so salt and free-base masses differ.

Participants / model
Chemical identity, not a clinical population
Treatment
Defined molecule and salt
Follow-up
Not applicable
Study design
NLM chemical record
Funding
not stated in the source

Identity record only; it says nothing about efficacy or safety.

Read the original source

Why is Raloxifene in A tier?

A fits an approved drug promoted for an off-label use. Raloxifene has been FDA-approved since 1997 with two large trials in postmenopausal women, but its label says use in men is not recommended. The claim that it beats tamoxifen for gynecomastia is not supported as stated: it traces to one non-randomized chart review of 38 adolescents.