Informational only. Not medical advice.INFORMATIONAL PLATFORM ONLY — NOT MEDICAL ADVICE, DIAGNOSIS, OR TREATMENT
Informational only. Not medical advice.INFORMATIONAL PLATFORM ONLY — NOT MEDICAL ADVICE, DIAGNOSIS, OR TREATMENT
Head-to-head comparison of 4-Hydroxytamoxifen (Afimoxifene) and Endoxifen — mechanism, side effects, legal status, and pricing.
4-Hydroxytamoxifen (afimoxifene) is a non-peptide selective estrogen receptor modulator (SERM) and triphenylethylene derivative that serves as a major, highly potent active metabolite of tamoxifen. It is not an approved drug in the US or elsewhere; human data are limited to investigational Phase II trials of a topical gel formulation for cyclical mastalgia and breast density reduction. Tamoxifen and other SERMs are prohibited at all times under WADA category S4.2 (anti-estrogenic substances); as tamoxifen's active metabolite and an anti-estrogenic SERM, 4-hydroxytamoxifen would very likely be captured by similar-structure-or-effect language, though explicit naming was not confirmed.
Endoxifen is a non-steroidal triphenylethylene selective estrogen receptor modulator (SERM) and the active secondary metabolite of tamoxifen. It is not FDA-approved and remains investigational, studied in multiple Phase 1 and Phase 2 human trials for endocrine-refractory ER-positive breast cancer, desmoid tumors, and other hormone-receptor-positive solid tumors. Endoxifen is sold by research-chemical suppliers labeled for laboratory use only, not for human consumption.
4-Hydroxytamoxifen (Afimoxifene)
Endoxifen
Category
Legal Status
Mechanism
Side Effects
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4-Hydroxytamoxifen (Afimoxifene)
No pricing data yet.
Check 4-Hydroxytamoxifen (Afimoxifene) prices →Endoxifen
COA corpus from Disclosed Labs — independently tested batches only.
4-Hydroxytamoxifen (Afimoxifene)
1
COAs
98.9%
Avg purity
1
Labs
Endoxifen
2
COAs
99.5%
Avg purity
2
Labs
No human data exist for oral administration; all human evidence comes from investigational topical gel trials. A randomized, double-blind Phase II trial in premenopausal women with cyclical mastalgia (2 mg vs 4 mg vs placebo gel over 4 menstrual cycles) found the 4 mg dose significantly improved pain scores versus placebo with no serious drug-related adverse events and no observed changes in menstrual pattern or plasma hormone levels. Additional Phase II trials have evaluated topical 4-hydroxytamoxifen gel for reducing mammographic breast density and as a presurgical/DCIS intervention, though current trial status is unconfirmed. In MCF-7 human breast cancer cells in vitro, 4-hydroxytamoxifen competitively inhibits estrogen receptor signaling, inducing growth arrest and apoptosis. In ovariectomized Sprague-Dawley rats, 4-hydroxytamoxifen produced uterotrophic changes (increased luminal epithelial cell height) but far less uterine weight gain than estradiol, consistent with partial-agonist rather than full-agonist activity. In mouse uterus, 4-hydroxytamoxifen exposure is uterotrophic (estrogen-agonist-like), contrasting with more antagonist-dominant behavior in rat uterus.
Key references
No FDA approval or approval in any jurisdiction; endoxifen is investigational only. Human trials: Goetz et al. 2017 Phase 1 in endocrine-refractory metastatic ER-positive breast cancer (20–160 mg/day oral, no maximum tolerated dose, 3 partial responses, clinical benefit rate 26.3%); Takebe et al. 2021 Phase 1 in gynecologic, desmoid, and hormone-receptor-positive solid tumors (20–360 mg/day, no MTD, partial responses in desmoid tumors); Alliance A011203 randomized Phase 2 found Z-endoxifen not superior to tamoxifen overall but showed PFS benefit in CDK4/6-inhibitor-naive patients (HR 0.42). Preclinical: in ovariectomized mice, oral Z-endoxifen increased cancellous and cortical bone mass; in rats, reduced bone turnover and protected against bone loss; in MCF7 xenografts, showed superior antitumor activity versus tamoxifen, letrozole, and exemestane.
4-Hydroxytamoxifen (Afimoxifene) and Endoxifen are both in the Hormone category and may have overlapping mechanisms. Researchers should review both profiles carefully, understand the mechanisms of action, and monitor the relevant biomarkers when combining compounds in the same class. As always, consult a licensed healthcare provider before making any decisions about combining research compounds.
This platform provides informational tools only, not medical advice. This comparison is for educational purposes only. Consult a licensed provider.
Contraindications
Lab Testing
Key references
Disclosed Labs