Afimoxifene (4-hydroxytamoxifen)

updated

Afimoxifene (4-hydroxytamoxifen) is the estrogen receptor antagonist metabolite of tamoxifen, tested as a skin gel in women with breast conditions, and no FDA approval was found. The larger 2023 randomized trial in women with ductal carcinoma in situ did not meet its noninferiority margin against oral tamoxifen. A PubMed search on 10 October 2026 found no trial or case series in men, in gynecomastia or in anabolic steroid users.

Estrogen receptor antagonist (tamoxifen metabolite)

  • No FDA approval was found: openFDA Drugs@FDA returned no record for afimoxifene or 4-hydroxytamoxifen, and DailyMed returned no label for afimoxifene, on 10 October 2026.
  • In a 100-woman presurgical trial in ER-positive DCIS, 4-hydroxytamoxifen gel did not meet the noninferiority margin against oral tamoxifen: Ki-67 was 3.3% higher on gel (80% CI 2.1% to 4.6%) against a 2.6% margin in 75 evaluable women.
  • In 27 women with DCIS, mean plasma 4-hydroxytamoxifen was 0.2 ng/mL on gel and 1.1 ng/mL on oral tamoxifen, while breast adipose tissue levels were similar (5.8 and 5.4 ng/g).
  • A phase 3 dense-breast trial of a 0.2% gel (BHR-700, 223 enrolled) was terminated early by the sponsor, and its registry says the primary density outcome was not collected.
  • A PubMed search on 10 October 2026 for 4-hydroxytamoxifen or afimoxifene with gynecomastia, male breast, anabolic steroid, bodybuilding or post-cycle terms returned 5 records, and none was a trial or case series in men.
  • The trial abstracts reviewed do not state which isomer the gel used, so a vendor product is not shown to match it.

What is afimoxifene, and has anyone approved it?

Afimoxifene is 4-hydroxytamoxifen, the estrogen receptor antagonist metabolite of tamoxifen. No FDA approval was found: openFDA and DailyMed returned no record on 10 October 2026, and a 2005 review calls 4-hydroxytamoxifen for gynecomastia investigational.

Afimoxifene and 4-hydroxytamoxifen are one compound under two names, and the studies also write 4-OHT. PubChem keeps separate records for the isomers. (Z)-4-hydroxytamoxifen is C26H29NO2 (387.5 g/mol, CAS 68047-06-3, PubChem CID 449459), afimoxifene with the isomer unspecified is CID 63062 (CAS 68392-35-8), and the (E) isomer is CID 5352135 (CAS 174592-47-3). The trial abstracts reviewed do not state the isomer, so a vendor product cannot be matched to the studied gel from these sources.

openFDA Drugs@FDA returned no record for afimoxifene or 4-hydroxytamoxifen, and DailyMed returned no label for afimoxifene, both on 10 October 2026. A 2005 review in men with prostate cancer states that aromatase inhibitors and 4-hydroxytamoxifen for gynecomastia are investigational. In women with breast conditions it is an investigational drug, not an approved product. The studies below tested it as a skin gel.

PubChem: separate records for the (Z), unspecified and (E) isomers

Chemical identity record

National Library of Medicine. PubChem compound records CID 449459 ((Z)-4-hydroxytamoxifen), CID 63062 (afimoxifene, isomer unspecified) and CID 5352135 ((E) isomer).

PubChem keeps separate records for the isomers. (Z)-4-hydroxytamoxifen: CID 449459, C26H29NO2, 387.5 g/mol, CAS 68047-06-3 (the first CAS-like synonym listed; PubChem lists other CAS-like numbers for the same record). Afimoxifene with the isomer unspecified: CID 63062, CAS 68392-35-8. The (E) isomer: CID 5352135, CAS 174592-47-3. The trial abstracts reviewed do not state the isomer, so a vendor product cannot be matched to the studied gel from these sources.

Participants / model
Chemical identity, not a clinical population
Treatment
Defined molecule, three PubChem records
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
Drugs@FDA and DailyMed, 10 October 2026: no record; 2005 review: investigational

Regulatory record

Dobs A et al. J Urol. 2005;174(5):1737-42. PMID 16217274.

openFDA Drugs@FDA returned no record for afimoxifene or 4-hydroxytamoxifen, and DailyMed returned no label for afimoxifene, both on 10 October 2026. A 2005 review in men with prostate cancer states that aromatase inhibitors and 4-hydroxytamoxifen for gynecomastia are investigational. The compound is an investigational drug in women with breast conditions, not an approved product.

Participants / model
Not a clinical population; the review concerns men with prostate cancer
Treatment
Drug applications and labels; 4-hydroxytamoxifen for gynecomastia (review)
Follow-up
Searches run on 10 October 2026
Study design
FDA record searches and a narrative review
Funding
not stated in the source

The absence of a record is a US-scoped statement. Approvals outside the United States are not covered.

Read the original source

What did the presurgical gel trials in women find?

Three randomized presurgical trials in women with breast cancer or DCIS tested 4-hydroxytamoxifen gel against oral tamoxifen. In the larger 2023 trial the gel did not meet noninferiority, and plasma drug levels were lower on gel in the two trials that report them.

The largest was a randomized, double-blind phase 2 trial in 100 women who started treatment for ER-positive ductal carcinoma in situ (90 completed, 75 evaluable). Gel (2 mg a day per breast) did not meet the noninferiority margin against oral tamoxifen 20 mg a day: post-treatment Ki-67 was 3.3% higher on gel (80% CI 2.1% to 4.6%) against a 2.6% margin. The 12-gene DCIS Score fell by 16 on oral tamoxifen and 1.8 on gel. Breast endoxifen was minimal on gel (median 0.3 ng/g) versus 13.0 ng/g on oral tamoxifen, and breast 4-hydroxytamoxifen was similar (3.8 versus 5.7 ng/g, not significant). Oral tamoxifen changed plasma proteins and vasomotor symptoms, and the gel arm had minimal changes. The trial is registered as NCT02993159.

A randomized, double-blind phase 2 trial in 27 pre- and postmenopausal women with DCIS gave 4 mg a day of gel or 20 mg a day of oral tamoxifen for 6 to 10 weeks before surgery. Ki-67 fell by 3.4% on gel and 5.1% on oral tamoxifen (between-group P = 0.99). Mean plasma 4-hydroxytamoxifen was 0.2 ng/mL on gel and 1.1 ng/mL on oral tamoxifen (P = 0.0003), while breast adipose tissue levels were similar (5.8 and 5.4 ng/g).

In 55 postmenopausal women with invasive ER-positive breast cancer, randomized to gel at 0.5, 1 or 2 mg a day, oral tamoxifen 20 mg a day, or no treatment for 2 to 3 weeks, gel at 1.0 and 2.0 mg a day lowered tumor proliferation markers (Ki-67 and PCNA) with approximate equivalence to oral tamoxifen and had no effect on apoptotic markers. Plasma 4-hydroxytamoxifen was consistently higher with oral tamoxifen.

All three trials enrolled women, and none tested the gel in men.

100 women with DCIS: gel did not meet noninferiority to oral tamoxifen

Randomized controlled trial

Khan SA et al. JAMA Surg. 2023;158(12):1265-1273. PMID 37870954.

The gel did not meet the noninferiority margin against oral tamoxifen: in 75 evaluable women, post-treatment Ki-67 was 3.3% higher on gel (80% CI 2.1% to 4.6%) against a 2.6% margin. The 12-gene DCIS Score fell by 16 on oral tamoxifen and 1.8 on gel. Breast endoxifen was minimal on gel (median 0.3 ng/g) versus 13.0 ng/g on oral tamoxifen, and breast 4-hydroxytamoxifen was similar (3.8 versus 5.7 ng/g, not significant). Oral tamoxifen changed plasma proteins and vasomotor symptoms, and the gel arm had minimal changes.

Participants / model
100 women who started treatment for ER-positive ductal carcinoma in situ (90 completed, 75 evaluable)
Treatment
Transdermal 4-hydroxytamoxifen gel 2 mg a day per breast versus oral tamoxifen 20 mg a day
Follow-up
4 to 10 weeks
Study design
Randomized double-blind phase 2 presurgical trial
Funding
not stated in the source

Women with ductal carcinoma in situ. The result does not describe men.

Read the original source
27 women with DCIS: similar Ki-67 fall, lower plasma drug on gel

Randomized controlled trial

Lee O et al. Clin Cancer Res. 2014;20(14):3672-82. PMID 25028506.

4-hydroxytamoxifen gel and oral tamoxifen lowered Ki-67 by 3.4% and 5.1% (between-group P = 0.99). Mean plasma 4-hydroxytamoxifen was 0.2 ng/mL on gel and 1.1 ng/mL on oral tamoxifen (P = 0.0003), while breast adipose tissue levels were similar (5.8 and 5.4 ng/g). SHBG, factor VIII and von Willebrand factor rose and IGF-1 fell with oral tamoxifen but not with gel. Hot flashes were similar in both groups.

Participants / model
27 pre- and postmenopausal women with DCIS
Treatment
Transdermal 4-hydroxytamoxifen gel 4 mg a day versus oral tamoxifen 20 mg a day
Follow-up
6 to 10 weeks
Study design
Randomized double-blind phase 2 presurgical trial
Funding
not stated in the source

This supports lower plasma exposure with the gel in women, not any effect in men.

Read the original source
55 postmenopausal women: gel at 1 and 2 mg a day lowered Ki-67 and PCNA, close to oral tamoxifen

Randomized controlled trial

Rouanet P et al. J Clin Oncol. 2005;23(13):2980-7. PMID 15860853.

Gel at 1.0 and 2.0 mg a day lowered tumor proliferation markers (Ki-67 and PCNA) with approximate equivalence to oral tamoxifen and had no effect on apoptotic markers. Plasma 4-hydroxytamoxifen was consistently higher with oral tamoxifen. Hot flushes were as common at the two higher gel doses as with tamoxifen.

Participants / model
55 postmenopausal women with invasive ER-positive breast cancer
Treatment
Percutaneous 4-hydroxytamoxifen gel 0.5, 1 or 2 mg a day, oral tamoxifen 20 mg a day, or no treatment
Follow-up
2 to 3 weeks
Study design
Randomized presurgical trial
Funding
not stated in the source

A short presurgical study in women with invasive breast cancer.

Read the original source

What did the breast pain and dense-breast studies find?

A phase II trial in premenopausal women found the 4 mg a day gel improved the cyclical breast pain score by 12.71 mm over placebo. A phase 3 dense-breast trial was stopped by the sponsor with no efficacy result, and a registry-posted phase 2 showed no clear density advantage for the gel.

In a phase II trial in premenopausal women with moderate to severe cyclical mastalgia, afimoxifene gel at 4 mg a day for 4 menstrual cycles improved the pain score over placebo by 12.71 mm on a visual analog scale (95% CI 0.96 to 24.47 mm, P = 0.034), and tenderness and nodularity also improved. A 2 mg a day arm was also tested. The abstract does not state the number of participants. This is breast pain in women with a hormone-cycle condition, not gynecomastia.

A phase 3 trial of BHR-700 (0.2% 4-hydroxytamoxifen gel, 4 mg per breast per day) against placebo for reducing mammographic density in 223 enrolled women with dense breasts (BI-RADS C or D) was terminated early by the sponsor, which cited an administrative change in development strategy. The registry states the primary outcome, percent density reduction at 52 weeks, was not collected and cannot be reported (NCT03199963). A registration for a stopped trial is not evidence of efficacy.

A phase 2 randomized placebo-controlled prevention trial from MD Anderson (NCT03063619, 194 enrolled, completed 26 October 2021) posted mean percent change in mammographic density at month 12 in 123 evaluable women: -6.30 (SD 9.11) on gel versus -5.77 (SD 11.24) on placebo in the craniocaudal view, and -2.81 (SD 6.74) versus -5.43 (SD 9.08) in the mediolateral oblique view. The registry posts no between-group test. A PubMed search on 10 October 2026 found no peer-reviewed report of this trial, so the numbers are registry statements only. They do not show a clear density advantage for the gel.

Cyclical mastalgia: 4 mg a day gel eased breast pain by 12.71 mm over placebo

Randomized controlled trial

Mansel R et al. Breast Cancer Res Treat. 2007;106(3):389-97. PMID 17351746.

The 4 mg a day afimoxifene gel improved the pain score over placebo by 12.71 mm on a visual analog scale (95% CI 0.96 to 24.47 mm, P = 0.034), and tenderness and nodularity also improved. The abstract reports no change in menstrual pattern or plasma hormone levels and no drug-related serious adverse events.

Participants / model
Premenopausal women with moderate to severe cyclical mastalgia
Treatment
Transdermal hydroalcoholic gel, 2 or 4 mg a day, or placebo
Follow-up
4 menstrual cycles
Study design
Phase II randomized placebo-controlled trial
Funding
not stated in the source

The abstract does not give the number of participants. This is breast pain in women with a hormone-cycle condition, not gynecomastia.

Read the original source
Dense-breast phase 3: stopped early by the sponsor, no efficacy result

Trial registry record

ClinicalTrials.gov, U.S. National Library of Medicine. Study record NCT03199963.

A phase 3 trial of BHR-700 (0.2% 4-hydroxytamoxifen gel, 4 mg per breast per day) against placebo for reducing mammographic density in women with dense breasts (BI-RADS C or D) was terminated early by the sponsor, which cited an administrative change in development strategy. Posted results are limited to safety: serious adverse events in 5 of 149 on gel and 0 of 73 on placebo in the blinded phase, with no deaths. The registry states the primary outcome (percent density reduction at 52 weeks) was not collected and cannot be reported.

Participants / model
223 enrolled women with dense breasts, aged 35 to 75 years
Treatment
4-hydroxytamoxifen gel, 8 mg a day total, 52 weeks planned, versus placebo
Follow-up
52 weeks planned; terminated early
Study design
Phase 3 randomized placebo-controlled trial, terminated by the sponsor
Funding
not stated in the source

A registration for a stopped trial is not evidence of efficacy.

Read the original source
Dense-breast phase 2: no clear density advantage for the gel, no publication found

Trial registry record

ClinicalTrials.gov, U.S. National Library of Medicine. Study record NCT03063619.

A phase 2 randomized placebo-controlled prevention trial from MD Anderson (194 enrolled, completed 2021-10-26) posted a mean percent change in mammographic density at month 12 in 123 evaluable women. Craniocaudal view: -6.30 (SD 9.11) on 4-hydroxytamoxifen gel versus -5.77 (SD 11.24) on placebo. Mediolateral oblique view: -2.81 (SD 6.74) versus -5.43 (SD 9.08). The registry posts no between-group test. No peer-reviewed report of this trial was found in PubMed: a search run 10 October 2026 for hydroxytamoxifen[tiab] OR afimoxifene[tiab] with topical, transdermal or gel and randomized or trial returned 7 records (none is this trial), and the 15 most relevant of 25 records for hydroxytamoxifen or afimoxifene with mammographic density or dense breast were also reviewed and none is a report of it. The posted means do not show a clear density advantage for the gel.

Participants / model
194 enrolled women aged 40 to 69 years with mammographically dense breasts; 123 evaluable
Treatment
Topical 4-hydroxytamoxifen gel once daily to each breast, up to 52 weeks, versus placebo
Follow-up
Up to 52 weeks; completed 26 October 2021
Study design
Phase 2 randomized placebo-controlled prevention trial, registry-posted results, no publication found
Funding
not stated in the source

The registry posts no between-group test, and no peer-reviewed report was found, so these numbers are registry statements only.

Read the original source

Does 4-hydroxytamoxifen prevent gynecomastia or support post-cycle recovery?

No study found tests it. A PubMed search on 10 October 2026 for hydroxytamoxifen or afimoxifene with gynecomastia, male breast, anabolic steroid, bodybuilding or post-cycle terms returned 5 records, and none was a trial or case series of 4-hydroxytamoxifen in men, in gynecomastia or in anabolic steroid users.

Sellers market 4-hydroxytamoxifen to prevent and treat gynecomastia, to block breast estrogen receptors during anabolic steroid cycles, to support post-cycle therapy, and as a topical that limits systemic effects.

The 5 records were a molecular imaging database entry on radiolabeled tamoxifen, the 2005 prostate-cancer gynecomastia review, a doping-control urine immunoassay for 4-hydroxylated SERM metabolites, a nanoparticle formulation study in breast cancer cells, and a prostate cancer cell-line study. The doping-control abstract says athletes use antiestrogens against anabolic steroid-related gynecomastia, but it tests an assay, not a treatment. A second search for tamoxifen with gynecomastia and topical, transdermal, percutaneous or gel terms returned 2 records, a 2025 narrative review of testosterone-replacement adverse effects and the same cell-line study, and neither tested a topical tamoxifen or 4-hydroxytamoxifen product in men.

A ClinicalTrials.gov search on 10 October 2026 for 4-hydroxytamoxifen or afimoxifene returned 19 records. The nine registered studies of the gel all list female participants only, in breast cancer, DCIS, high-risk or dense breast, atypia or mastalgia studies. A search for afimoxifene and gynecomastia returned no records, and a search for gynecomastia with tamoxifen, hydroxytamoxifen, afimoxifene or endoxifen returned 3 records, all oral Nolvadex or bicalutamide studies in prostate cancer.

The topical point rests on gel applied to the breast in women. Mean plasma 4-hydroxytamoxifen was 0.2 versus 1.1 ng/mL in 27 women, and SHBG, factor VIII and von Willebrand factor rose and IGF-1 fell with oral tamoxifen but not with gel. That supports lower plasma exposure in women, not any effect in men. The abstracts do not state which isomer or salt the gel used, and no source gives gel stability, dose accuracy or purity for vendor products, so a vendor powder or research product is not shown to match the studied gel.

PubMed searches, 10 October 2026: 5 records and 2 records, none testing the supplier claims

PubMed search record

PubMed searches run on 10 October 2026: (hydroxytamoxifen OR afimoxifene OR 4-OHT) AND (gynecomastia OR gynaecomastia OR "male breast" OR "anabolic steroid" OR bodybuilding OR "post-cycle" OR "post cycle") (5 records); tamoxifen[tiab] AND gynecomastia[tiab] AND (topical OR transdermal OR percutaneous OR gel) (2 records).

The first search returned 5 records: a molecular imaging database entry on radiolabeled tamoxifen, the 2005 prostate-cancer gynecomastia review, a doping-control urine immunoassay for 4-hydroxylated SERM metabolites (its abstract says athletes use antiestrogens against anabolic steroid-related gynecomastia, but it tests an assay, not a treatment), a nanoparticle formulation study in breast cancer cells, and a prostate cancer cell-line study. None was a trial or case series of 4-hydroxytamoxifen for gynecomastia, in men, or in anabolic steroid users. The second search returned 2 records, a 2025 narrative review of testosterone-replacement adverse effects that says gynecomastia is usually managed with aromatase inhibitors and tamoxifen, and the same cell-line study; neither tested a topical tamoxifen or 4-hydroxytamoxifen product in men. No evidence was found for gynecomastia treatment or prevention, anabolic steroid cycle protection, or post-cycle therapy with 4-hydroxytamoxifen.

Participants / model
Records reviewed, not a population
Treatment
Not applicable
Follow-up
Searches run on 10 October 2026
Study design
Literature search
Funding
not stated in the source

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

Read the original source
ClinicalTrials.gov, 10 October 2026: 19 records, none testing the gel in men

Trial registry record

ClinicalTrials.gov searches run on 10 October 2026: "4-hydroxytamoxifen OR afimoxifene" (19 records); "afimoxifene gynecomastia" (no records); "gynecomastia AND (tamoxifen OR hydroxytamoxifen OR afimoxifene OR endoxifen)" (3 records).

The search for 4-hydroxytamoxifen or afimoxifene returned 19 records. The nine that tested the afimoxifene or 4-OHT gel (NCT03063619, NCT03199963, NCT00272714, NCT00084344, NCT00952731, NCT02993159, NCT04009044, NCT04570956 and the CR1447 study NCT02067741) all list female participants only, in breast cancer, DCIS, high-risk or dense breast, atypia or mastalgia studies. NCT04009044 (156 estimated, active, not recruiting) studies drug delivery to normal and irradiated breast. The other 10 were oral tamoxifen, endoxifen-supplementation or unrelated studies. A second search, afimoxifene gynecomastia, returned no records, and a third, gynecomastia with tamoxifen, hydroxytamoxifen, afimoxifene or endoxifen, returned 3 records, all oral Nolvadex or bicalutamide studies in prostate cancer (NCT00233610, NCT00866554, NCT00637871), none of 4-hydroxytamoxifen.

Participants / model
Records reviewed, not a population
Treatment
Not applicable
Follow-up
Searches run on 10 October 2026
Study design
Registry search
Funding
not stated in the source

A search result shows what the registry returned on that date. It is not proof that no unlisted study exists.

Read the original source
27 women with DCIS: similar Ki-67 fall, lower plasma drug on gel

Randomized controlled trial

Lee O et al. Clin Cancer Res. 2014;20(14):3672-82. PMID 25028506.

4-hydroxytamoxifen gel and oral tamoxifen lowered Ki-67 by 3.4% and 5.1% (between-group P = 0.99). Mean plasma 4-hydroxytamoxifen was 0.2 ng/mL on gel and 1.1 ng/mL on oral tamoxifen (P = 0.0003), while breast adipose tissue levels were similar (5.8 and 5.4 ng/g). SHBG, factor VIII and von Willebrand factor rose and IGF-1 fell with oral tamoxifen but not with gel. Hot flashes were similar in both groups.

Participants / model
27 pre- and postmenopausal women with DCIS
Treatment
Transdermal 4-hydroxytamoxifen gel 4 mg a day versus oral tamoxifen 20 mg a day
Follow-up
6 to 10 weeks
Study design
Randomized double-blind phase 2 presurgical trial
Funding
not stated in the source

This supports lower plasma exposure with the gel in women, not any effect in men.

Read the original source
100 women with DCIS: gel did not meet noninferiority to oral tamoxifen

Randomized controlled trial

Khan SA et al. JAMA Surg. 2023;158(12):1265-1273. PMID 37870954.

The gel did not meet the noninferiority margin against oral tamoxifen: in 75 evaluable women, post-treatment Ki-67 was 3.3% higher on gel (80% CI 2.1% to 4.6%) against a 2.6% margin. The 12-gene DCIS Score fell by 16 on oral tamoxifen and 1.8 on gel. Breast endoxifen was minimal on gel (median 0.3 ng/g) versus 13.0 ng/g on oral tamoxifen, and breast 4-hydroxytamoxifen was similar (3.8 versus 5.7 ng/g, not significant). Oral tamoxifen changed plasma proteins and vasomotor symptoms, and the gel arm had minimal changes.

Participants / model
100 women who started treatment for ER-positive ductal carcinoma in situ (90 completed, 75 evaluable)
Treatment
Transdermal 4-hydroxytamoxifen gel 2 mg a day per breast versus oral tamoxifen 20 mg a day
Follow-up
4 to 10 weeks
Study design
Randomized double-blind phase 2 presurgical trial
Funding
not stated in the source

Women with ductal carcinoma in situ. The result does not describe men.

Read the original source

How does 4-hydroxytamoxifen work, and how much reaches the blood?

It is the estrogen receptor antagonist metabolite of tamoxifen. In women the gel gave lower plasma drug than oral tamoxifen while breast tissue levels of 4-hydroxytamoxifen were similar, and no half-life or peak time appears in the sources reviewed.

4-hydroxytamoxifen is the estrogen receptor antagonist metabolite of tamoxifen. The breast trials tested whether a gel applied to the breast could match oral tamoxifen on proliferation markers with lower plasma exposure. In ER-positive disease the gel lowered Ki-67 in 27 women with DCIS and lowered Ki-67 and PCNA with approximate equivalence to oral tamoxifen in 55 postmenopausal women, while the larger 100-woman DCIS trial did not meet noninferiority.

Plasma 4-hydroxytamoxifen was 0.2 ng/mL on gel and 1.1 ng/mL on oral tamoxifen in 27 women, with breast adipose tissue levels of 5.8 and 5.4 ng/g. In the 100-woman trial, breast 4-hydroxytamoxifen was 3.8 ng/g on gel and 5.7 ng/g on oral tamoxifen (not significant), while breast endoxifen was median 0.3 ng/g on gel versus 13.0 ng/g on oral tamoxifen. No half-life, time to peak or bioavailability is given in the sources reviewed, and no pharmacokinetic data in men were found.

55 postmenopausal women: gel at 1 and 2 mg a day lowered Ki-67 and PCNA, close to oral tamoxifen

Randomized controlled trial

Rouanet P et al. J Clin Oncol. 2005;23(13):2980-7. PMID 15860853.

Gel at 1.0 and 2.0 mg a day lowered tumor proliferation markers (Ki-67 and PCNA) with approximate equivalence to oral tamoxifen and had no effect on apoptotic markers. Plasma 4-hydroxytamoxifen was consistently higher with oral tamoxifen. Hot flushes were as common at the two higher gel doses as with tamoxifen.

Participants / model
55 postmenopausal women with invasive ER-positive breast cancer
Treatment
Percutaneous 4-hydroxytamoxifen gel 0.5, 1 or 2 mg a day, oral tamoxifen 20 mg a day, or no treatment
Follow-up
2 to 3 weeks
Study design
Randomized presurgical trial
Funding
not stated in the source

A short presurgical study in women with invasive breast cancer.

Read the original source
27 women with DCIS: similar Ki-67 fall, lower plasma drug on gel

Randomized controlled trial

Lee O et al. Clin Cancer Res. 2014;20(14):3672-82. PMID 25028506.

4-hydroxytamoxifen gel and oral tamoxifen lowered Ki-67 by 3.4% and 5.1% (between-group P = 0.99). Mean plasma 4-hydroxytamoxifen was 0.2 ng/mL on gel and 1.1 ng/mL on oral tamoxifen (P = 0.0003), while breast adipose tissue levels were similar (5.8 and 5.4 ng/g). SHBG, factor VIII and von Willebrand factor rose and IGF-1 fell with oral tamoxifen but not with gel. Hot flashes were similar in both groups.

Participants / model
27 pre- and postmenopausal women with DCIS
Treatment
Transdermal 4-hydroxytamoxifen gel 4 mg a day versus oral tamoxifen 20 mg a day
Follow-up
6 to 10 weeks
Study design
Randomized double-blind phase 2 presurgical trial
Funding
not stated in the source

This supports lower plasma exposure with the gel in women, not any effect in men.

Read the original source
100 women with DCIS: gel did not meet noninferiority to oral tamoxifen

Randomized controlled trial

Khan SA et al. JAMA Surg. 2023;158(12):1265-1273. PMID 37870954.

The gel did not meet the noninferiority margin against oral tamoxifen: in 75 evaluable women, post-treatment Ki-67 was 3.3% higher on gel (80% CI 2.1% to 4.6%) against a 2.6% margin. The 12-gene DCIS Score fell by 16 on oral tamoxifen and 1.8 on gel. Breast endoxifen was minimal on gel (median 0.3 ng/g) versus 13.0 ng/g on oral tamoxifen, and breast 4-hydroxytamoxifen was similar (3.8 versus 5.7 ng/g, not significant). Oral tamoxifen changed plasma proteins and vasomotor symptoms, and the gel arm had minimal changes.

Participants / model
100 women who started treatment for ER-positive ductal carcinoma in situ (90 completed, 75 evaluable)
Treatment
Transdermal 4-hydroxytamoxifen gel 2 mg a day per breast versus oral tamoxifen 20 mg a day
Follow-up
4 to 10 weeks
Study design
Randomized double-blind phase 2 presurgical trial
Funding
not stated in the source

Women with ductal carcinoma in situ. The result does not describe men.

Read the original source

What risks and side effects were reported?

In women, hot flashes were as common on gel as on oral tamoxifen in two trials, and the stopped phase 3 posted serious adverse events in 5 of 149 on gel and 0 of 73 on placebo. No safety data in men were found, and vendor products are not shown to match the studied gel.

Hot flashes were similar in the gel and oral tamoxifen groups in the 27-woman trial, and hot flushes were as common at the two higher gel doses as with tamoxifen in the 55-woman trial. In the 100-woman trial, oral tamoxifen changed plasma proteins and vasomotor symptoms, and the gel arm had minimal changes.

In the blinded phase of the stopped phase 3 dense-breast trial, serious adverse events occurred in 5 of 149 women on gel and 0 of 73 on placebo, with no deaths. The registry posts only safety results for that trial. The mastalgia trial abstract reports no change in menstrual pattern or plasma hormone levels and no drug-related serious adverse events.

All of these data are from women. No safety data in men, in gynecomastia or in anabolic steroid users were found. A vendor powder or research product is not shown to match the studied gel, and its purity and dose accuracy are unknown.

27 women with DCIS: similar Ki-67 fall, lower plasma drug on gel

Randomized controlled trial

Lee O et al. Clin Cancer Res. 2014;20(14):3672-82. PMID 25028506.

4-hydroxytamoxifen gel and oral tamoxifen lowered Ki-67 by 3.4% and 5.1% (between-group P = 0.99). Mean plasma 4-hydroxytamoxifen was 0.2 ng/mL on gel and 1.1 ng/mL on oral tamoxifen (P = 0.0003), while breast adipose tissue levels were similar (5.8 and 5.4 ng/g). SHBG, factor VIII and von Willebrand factor rose and IGF-1 fell with oral tamoxifen but not with gel. Hot flashes were similar in both groups.

Participants / model
27 pre- and postmenopausal women with DCIS
Treatment
Transdermal 4-hydroxytamoxifen gel 4 mg a day versus oral tamoxifen 20 mg a day
Follow-up
6 to 10 weeks
Study design
Randomized double-blind phase 2 presurgical trial
Funding
not stated in the source

This supports lower plasma exposure with the gel in women, not any effect in men.

Read the original source
55 postmenopausal women: gel at 1 and 2 mg a day lowered Ki-67 and PCNA, close to oral tamoxifen

Randomized controlled trial

Rouanet P et al. J Clin Oncol. 2005;23(13):2980-7. PMID 15860853.

Gel at 1.0 and 2.0 mg a day lowered tumor proliferation markers (Ki-67 and PCNA) with approximate equivalence to oral tamoxifen and had no effect on apoptotic markers. Plasma 4-hydroxytamoxifen was consistently higher with oral tamoxifen. Hot flushes were as common at the two higher gel doses as with tamoxifen.

Participants / model
55 postmenopausal women with invasive ER-positive breast cancer
Treatment
Percutaneous 4-hydroxytamoxifen gel 0.5, 1 or 2 mg a day, oral tamoxifen 20 mg a day, or no treatment
Follow-up
2 to 3 weeks
Study design
Randomized presurgical trial
Funding
not stated in the source

A short presurgical study in women with invasive breast cancer.

Read the original source
100 women with DCIS: gel did not meet noninferiority to oral tamoxifen

Randomized controlled trial

Khan SA et al. JAMA Surg. 2023;158(12):1265-1273. PMID 37870954.

The gel did not meet the noninferiority margin against oral tamoxifen: in 75 evaluable women, post-treatment Ki-67 was 3.3% higher on gel (80% CI 2.1% to 4.6%) against a 2.6% margin. The 12-gene DCIS Score fell by 16 on oral tamoxifen and 1.8 on gel. Breast endoxifen was minimal on gel (median 0.3 ng/g) versus 13.0 ng/g on oral tamoxifen, and breast 4-hydroxytamoxifen was similar (3.8 versus 5.7 ng/g, not significant). Oral tamoxifen changed plasma proteins and vasomotor symptoms, and the gel arm had minimal changes.

Participants / model
100 women who started treatment for ER-positive ductal carcinoma in situ (90 completed, 75 evaluable)
Treatment
Transdermal 4-hydroxytamoxifen gel 2 mg a day per breast versus oral tamoxifen 20 mg a day
Follow-up
4 to 10 weeks
Study design
Randomized double-blind phase 2 presurgical trial
Funding
not stated in the source

Women with ductal carcinoma in situ. The result does not describe men.

Read the original source
Dense-breast phase 3: stopped early by the sponsor, no efficacy result

Trial registry record

ClinicalTrials.gov, U.S. National Library of Medicine. Study record NCT03199963.

A phase 3 trial of BHR-700 (0.2% 4-hydroxytamoxifen gel, 4 mg per breast per day) against placebo for reducing mammographic density in women with dense breasts (BI-RADS C or D) was terminated early by the sponsor, which cited an administrative change in development strategy. Posted results are limited to safety: serious adverse events in 5 of 149 on gel and 0 of 73 on placebo in the blinded phase, with no deaths. The registry states the primary outcome (percent density reduction at 52 weeks) was not collected and cannot be reported.

Participants / model
223 enrolled women with dense breasts, aged 35 to 75 years
Treatment
4-hydroxytamoxifen gel, 8 mg a day total, 52 weeks planned, versus placebo
Follow-up
52 weeks planned; terminated early
Study design
Phase 3 randomized placebo-controlled trial, terminated by the sponsor
Funding
not stated in the source

A registration for a stopped trial is not evidence of efficacy.

Read the original source
Cyclical mastalgia: 4 mg a day gel eased breast pain by 12.71 mm over placebo

Randomized controlled trial

Mansel R et al. Breast Cancer Res Treat. 2007;106(3):389-97. PMID 17351746.

The 4 mg a day afimoxifene gel improved the pain score over placebo by 12.71 mm on a visual analog scale (95% CI 0.96 to 24.47 mm, P = 0.034), and tenderness and nodularity also improved. The abstract reports no change in menstrual pattern or plasma hormone levels and no drug-related serious adverse events.

Participants / model
Premenopausal women with moderate to severe cyclical mastalgia
Treatment
Transdermal hydroalcoholic gel, 2 or 4 mg a day, or placebo
Follow-up
4 menstrual cycles
Study design
Phase II randomized placebo-controlled trial
Funding
not stated in the source

The abstract does not give the number of participants. This is breast pain in women with a hormone-cycle condition, not gynecomastia.

Read the original source
PubChem: separate records for the (Z), unspecified and (E) isomers

Chemical identity record

National Library of Medicine. PubChem compound records CID 449459 ((Z)-4-hydroxytamoxifen), CID 63062 (afimoxifene, isomer unspecified) and CID 5352135 ((E) isomer).

PubChem keeps separate records for the isomers. (Z)-4-hydroxytamoxifen: CID 449459, C26H29NO2, 387.5 g/mol, CAS 68047-06-3 (the first CAS-like synonym listed; PubChem lists other CAS-like numbers for the same record). Afimoxifene with the isomer unspecified: CID 63062, CAS 68392-35-8. The (E) isomer: CID 5352135, CAS 174592-47-3. The trial abstracts reviewed do not state the isomer, so a vendor product cannot be matched to the studied gel from these sources.

Participants / model
Chemical identity, not a clinical population
Treatment
Defined molecule, three PubChem records
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 does afimoxifene sit in C tier?

C fits randomized human data in women with thin and mixed results. The gel gave lower plasma exposure than oral tamoxifen, but one trial missed noninferiority, a phase 3 was stopped without efficacy data, and nothing tests it in men.

The C reflects four randomized trials in women (three presurgical and one for breast pain), two registry-posted placebo-controlled studies, and a plausible mechanism. The 2023 DCIS trial did not meet noninferiority to oral tamoxifen, the dense-breast phase 3 was stopped for administrative reasons with no efficacy data, and the dense-breast phase 2 posted means with no clear separation.

The supplier claims for gynecomastia, steroid-cycle protection and post-cycle recovery are not supported: no study was found in men, in gynecomastia or in anabolic steroid users. The grade covers the studied use in women, not the supplier's.

100 women with DCIS: gel did not meet noninferiority to oral tamoxifen

Randomized controlled trial

Khan SA et al. JAMA Surg. 2023;158(12):1265-1273. PMID 37870954.

The gel did not meet the noninferiority margin against oral tamoxifen: in 75 evaluable women, post-treatment Ki-67 was 3.3% higher on gel (80% CI 2.1% to 4.6%) against a 2.6% margin. The 12-gene DCIS Score fell by 16 on oral tamoxifen and 1.8 on gel. Breast endoxifen was minimal on gel (median 0.3 ng/g) versus 13.0 ng/g on oral tamoxifen, and breast 4-hydroxytamoxifen was similar (3.8 versus 5.7 ng/g, not significant). Oral tamoxifen changed plasma proteins and vasomotor symptoms, and the gel arm had minimal changes.

Participants / model
100 women who started treatment for ER-positive ductal carcinoma in situ (90 completed, 75 evaluable)
Treatment
Transdermal 4-hydroxytamoxifen gel 2 mg a day per breast versus oral tamoxifen 20 mg a day
Follow-up
4 to 10 weeks
Study design
Randomized double-blind phase 2 presurgical trial
Funding
not stated in the source

Women with ductal carcinoma in situ. The result does not describe men.

Read the original source
Dense-breast phase 3: stopped early by the sponsor, no efficacy result

Trial registry record

ClinicalTrials.gov, U.S. National Library of Medicine. Study record NCT03199963.

A phase 3 trial of BHR-700 (0.2% 4-hydroxytamoxifen gel, 4 mg per breast per day) against placebo for reducing mammographic density in women with dense breasts (BI-RADS C or D) was terminated early by the sponsor, which cited an administrative change in development strategy. Posted results are limited to safety: serious adverse events in 5 of 149 on gel and 0 of 73 on placebo in the blinded phase, with no deaths. The registry states the primary outcome (percent density reduction at 52 weeks) was not collected and cannot be reported.

Participants / model
223 enrolled women with dense breasts, aged 35 to 75 years
Treatment
4-hydroxytamoxifen gel, 8 mg a day total, 52 weeks planned, versus placebo
Follow-up
52 weeks planned; terminated early
Study design
Phase 3 randomized placebo-controlled trial, terminated by the sponsor
Funding
not stated in the source

A registration for a stopped trial is not evidence of efficacy.

Read the original source
Dense-breast phase 2: no clear density advantage for the gel, no publication found

Trial registry record

ClinicalTrials.gov, U.S. National Library of Medicine. Study record NCT03063619.

A phase 2 randomized placebo-controlled prevention trial from MD Anderson (194 enrolled, completed 2021-10-26) posted a mean percent change in mammographic density at month 12 in 123 evaluable women. Craniocaudal view: -6.30 (SD 9.11) on 4-hydroxytamoxifen gel versus -5.77 (SD 11.24) on placebo. Mediolateral oblique view: -2.81 (SD 6.74) versus -5.43 (SD 9.08). The registry posts no between-group test. No peer-reviewed report of this trial was found in PubMed: a search run 10 October 2026 for hydroxytamoxifen[tiab] OR afimoxifene[tiab] with topical, transdermal or gel and randomized or trial returned 7 records (none is this trial), and the 15 most relevant of 25 records for hydroxytamoxifen or afimoxifene with mammographic density or dense breast were also reviewed and none is a report of it. The posted means do not show a clear density advantage for the gel.

Participants / model
194 enrolled women aged 40 to 69 years with mammographically dense breasts; 123 evaluable
Treatment
Topical 4-hydroxytamoxifen gel once daily to each breast, up to 52 weeks, versus placebo
Follow-up
Up to 52 weeks; completed 26 October 2021
Study design
Phase 2 randomized placebo-controlled prevention trial, registry-posted results, no publication found
Funding
not stated in the source

The registry posts no between-group test, and no peer-reviewed report was found, so these numbers are registry statements only.

Read the original source
PubMed searches, 10 October 2026: 5 records and 2 records, none testing the supplier claims

PubMed search record

PubMed searches run on 10 October 2026: (hydroxytamoxifen OR afimoxifene OR 4-OHT) AND (gynecomastia OR gynaecomastia OR "male breast" OR "anabolic steroid" OR bodybuilding OR "post-cycle" OR "post cycle") (5 records); tamoxifen[tiab] AND gynecomastia[tiab] AND (topical OR transdermal OR percutaneous OR gel) (2 records).

The first search returned 5 records: a molecular imaging database entry on radiolabeled tamoxifen, the 2005 prostate-cancer gynecomastia review, a doping-control urine immunoassay for 4-hydroxylated SERM metabolites (its abstract says athletes use antiestrogens against anabolic steroid-related gynecomastia, but it tests an assay, not a treatment), a nanoparticle formulation study in breast cancer cells, and a prostate cancer cell-line study. None was a trial or case series of 4-hydroxytamoxifen for gynecomastia, in men, or in anabolic steroid users. The second search returned 2 records, a 2025 narrative review of testosterone-replacement adverse effects that says gynecomastia is usually managed with aromatase inhibitors and tamoxifen, and the same cell-line study; neither tested a topical tamoxifen or 4-hydroxytamoxifen product in men. No evidence was found for gynecomastia treatment or prevention, anabolic steroid cycle protection, or post-cycle therapy with 4-hydroxytamoxifen.

Participants / model
Records reviewed, not a population
Treatment
Not applicable
Follow-up
Searches run on 10 October 2026
Study design
Literature search
Funding
not stated in the source

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

Read the original source

Studies and sources

PubChem: separate records for the (Z), unspecified and (E) isomers

Chemical identity record

National Library of Medicine. PubChem compound records CID 449459 ((Z)-4-hydroxytamoxifen), CID 63062 (afimoxifene, isomer unspecified) and CID 5352135 ((E) isomer).

PubChem keeps separate records for the isomers. (Z)-4-hydroxytamoxifen: CID 449459, C26H29NO2, 387.5 g/mol, CAS 68047-06-3 (the first CAS-like synonym listed; PubChem lists other CAS-like numbers for the same record). Afimoxifene with the isomer unspecified: CID 63062, CAS 68392-35-8. The (E) isomer: CID 5352135, CAS 174592-47-3. The trial abstracts reviewed do not state the isomer, so a vendor product cannot be matched to the studied gel from these sources.

Participants / model
Chemical identity, not a clinical population
Treatment
Defined molecule, three PubChem records
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
Drugs@FDA and DailyMed, 10 October 2026: no record; 2005 review: investigational

Regulatory record

Dobs A et al. J Urol. 2005;174(5):1737-42. PMID 16217274.

openFDA Drugs@FDA returned no record for afimoxifene or 4-hydroxytamoxifen, and DailyMed returned no label for afimoxifene, both on 10 October 2026. A 2005 review in men with prostate cancer states that aromatase inhibitors and 4-hydroxytamoxifen for gynecomastia are investigational. The compound is an investigational drug in women with breast conditions, not an approved product.

Participants / model
Not a clinical population; the review concerns men with prostate cancer
Treatment
Drug applications and labels; 4-hydroxytamoxifen for gynecomastia (review)
Follow-up
Searches run on 10 October 2026
Study design
FDA record searches and a narrative review
Funding
not stated in the source

The absence of a record is a US-scoped statement. Approvals outside the United States are not covered.

Read the original source
100 women with DCIS: gel did not meet noninferiority to oral tamoxifen

Randomized controlled trial

Khan SA et al. JAMA Surg. 2023;158(12):1265-1273. PMID 37870954.

The gel did not meet the noninferiority margin against oral tamoxifen: in 75 evaluable women, post-treatment Ki-67 was 3.3% higher on gel (80% CI 2.1% to 4.6%) against a 2.6% margin. The 12-gene DCIS Score fell by 16 on oral tamoxifen and 1.8 on gel. Breast endoxifen was minimal on gel (median 0.3 ng/g) versus 13.0 ng/g on oral tamoxifen, and breast 4-hydroxytamoxifen was similar (3.8 versus 5.7 ng/g, not significant). Oral tamoxifen changed plasma proteins and vasomotor symptoms, and the gel arm had minimal changes.

Participants / model
100 women who started treatment for ER-positive ductal carcinoma in situ (90 completed, 75 evaluable)
Treatment
Transdermal 4-hydroxytamoxifen gel 2 mg a day per breast versus oral tamoxifen 20 mg a day
Follow-up
4 to 10 weeks
Study design
Randomized double-blind phase 2 presurgical trial
Funding
not stated in the source

Women with ductal carcinoma in situ. The result does not describe men.

Read the original source
27 women with DCIS: similar Ki-67 fall, lower plasma drug on gel

Randomized controlled trial

Lee O et al. Clin Cancer Res. 2014;20(14):3672-82. PMID 25028506.

4-hydroxytamoxifen gel and oral tamoxifen lowered Ki-67 by 3.4% and 5.1% (between-group P = 0.99). Mean plasma 4-hydroxytamoxifen was 0.2 ng/mL on gel and 1.1 ng/mL on oral tamoxifen (P = 0.0003), while breast adipose tissue levels were similar (5.8 and 5.4 ng/g). SHBG, factor VIII and von Willebrand factor rose and IGF-1 fell with oral tamoxifen but not with gel. Hot flashes were similar in both groups.

Participants / model
27 pre- and postmenopausal women with DCIS
Treatment
Transdermal 4-hydroxytamoxifen gel 4 mg a day versus oral tamoxifen 20 mg a day
Follow-up
6 to 10 weeks
Study design
Randomized double-blind phase 2 presurgical trial
Funding
not stated in the source

This supports lower plasma exposure with the gel in women, not any effect in men.

Read the original source
55 postmenopausal women: gel at 1 and 2 mg a day lowered Ki-67 and PCNA, close to oral tamoxifen

Randomized controlled trial

Rouanet P et al. J Clin Oncol. 2005;23(13):2980-7. PMID 15860853.

Gel at 1.0 and 2.0 mg a day lowered tumor proliferation markers (Ki-67 and PCNA) with approximate equivalence to oral tamoxifen and had no effect on apoptotic markers. Plasma 4-hydroxytamoxifen was consistently higher with oral tamoxifen. Hot flushes were as common at the two higher gel doses as with tamoxifen.

Participants / model
55 postmenopausal women with invasive ER-positive breast cancer
Treatment
Percutaneous 4-hydroxytamoxifen gel 0.5, 1 or 2 mg a day, oral tamoxifen 20 mg a day, or no treatment
Follow-up
2 to 3 weeks
Study design
Randomized presurgical trial
Funding
not stated in the source

A short presurgical study in women with invasive breast cancer.

Read the original source
Cyclical mastalgia: 4 mg a day gel eased breast pain by 12.71 mm over placebo

Randomized controlled trial

Mansel R et al. Breast Cancer Res Treat. 2007;106(3):389-97. PMID 17351746.

The 4 mg a day afimoxifene gel improved the pain score over placebo by 12.71 mm on a visual analog scale (95% CI 0.96 to 24.47 mm, P = 0.034), and tenderness and nodularity also improved. The abstract reports no change in menstrual pattern or plasma hormone levels and no drug-related serious adverse events.

Participants / model
Premenopausal women with moderate to severe cyclical mastalgia
Treatment
Transdermal hydroalcoholic gel, 2 or 4 mg a day, or placebo
Follow-up
4 menstrual cycles
Study design
Phase II randomized placebo-controlled trial
Funding
not stated in the source

The abstract does not give the number of participants. This is breast pain in women with a hormone-cycle condition, not gynecomastia.

Read the original source
Dense-breast phase 3: stopped early by the sponsor, no efficacy result

Trial registry record

ClinicalTrials.gov, U.S. National Library of Medicine. Study record NCT03199963.

A phase 3 trial of BHR-700 (0.2% 4-hydroxytamoxifen gel, 4 mg per breast per day) against placebo for reducing mammographic density in women with dense breasts (BI-RADS C or D) was terminated early by the sponsor, which cited an administrative change in development strategy. Posted results are limited to safety: serious adverse events in 5 of 149 on gel and 0 of 73 on placebo in the blinded phase, with no deaths. The registry states the primary outcome (percent density reduction at 52 weeks) was not collected and cannot be reported.

Participants / model
223 enrolled women with dense breasts, aged 35 to 75 years
Treatment
4-hydroxytamoxifen gel, 8 mg a day total, 52 weeks planned, versus placebo
Follow-up
52 weeks planned; terminated early
Study design
Phase 3 randomized placebo-controlled trial, terminated by the sponsor
Funding
not stated in the source

A registration for a stopped trial is not evidence of efficacy.

Read the original source
Dense-breast phase 2: no clear density advantage for the gel, no publication found

Trial registry record

ClinicalTrials.gov, U.S. National Library of Medicine. Study record NCT03063619.

A phase 2 randomized placebo-controlled prevention trial from MD Anderson (194 enrolled, completed 2021-10-26) posted a mean percent change in mammographic density at month 12 in 123 evaluable women. Craniocaudal view: -6.30 (SD 9.11) on 4-hydroxytamoxifen gel versus -5.77 (SD 11.24) on placebo. Mediolateral oblique view: -2.81 (SD 6.74) versus -5.43 (SD 9.08). The registry posts no between-group test. No peer-reviewed report of this trial was found in PubMed: a search run 10 October 2026 for hydroxytamoxifen[tiab] OR afimoxifene[tiab] with topical, transdermal or gel and randomized or trial returned 7 records (none is this trial), and the 15 most relevant of 25 records for hydroxytamoxifen or afimoxifene with mammographic density or dense breast were also reviewed and none is a report of it. The posted means do not show a clear density advantage for the gel.

Participants / model
194 enrolled women aged 40 to 69 years with mammographically dense breasts; 123 evaluable
Treatment
Topical 4-hydroxytamoxifen gel once daily to each breast, up to 52 weeks, versus placebo
Follow-up
Up to 52 weeks; completed 26 October 2021
Study design
Phase 2 randomized placebo-controlled prevention trial, registry-posted results, no publication found
Funding
not stated in the source

The registry posts no between-group test, and no peer-reviewed report was found, so these numbers are registry statements only.

Read the original source

Why is Afimoxifene (4-hydroxytamoxifen) in C tier?

C fits a compound with randomized human trials in women and a plausible mechanism, but with thin and mixed results. The larger 2023 DCIS trial did not meet noninferiority to oral tamoxifen, the dense-breast phase 3 was stopped with no efficacy data, and a placebo-controlled phase 2 posted no clear density advantage. No study tests it in men, in gynecomastia or in anabolic steroid users, so the supplier claims rest on data from women.