Tamoxifen is an oral selective estrogen receptor modulator (SERM): a drug that blocks estrogen’s effects in some tissues, such as the breast, while mimicking estrogen in others, such as the uterus. It was first sold in the US as Nolvadex, approved in December 1977 under an application now held by AstraZeneca. It has been a standard hormonal treatment for estrogen receptor-positive breast cancer for decades and is also approved to lower breast cancer risk in high-risk women.
Outside oncology, tamoxifen is used off-label in men for gynecomastia (male breast tissue growth) and male infertility, and it is widely self-administered by anabolic steroid users as “post-cycle therapy” (PCT). None of these male uses is an FDA-approved indication, and no controlled trial has tested tamoxifen for recovery after anabolic steroid use. The FDA label carries a boxed warning for uterine cancer, stroke and pulmonary embolism in the risk-reduction setting.
This page summarizes what the FDA labels, clinical trials and guidelines report. It is for education only and is not medical advice.
| Property | Detail |
|---|---|
| Drug class | Nonsteroidal SERM (triphenylethylene derivative) |
| Brands / approval | Nolvadex (AstraZeneca), NDA 017970, approved 1977, now discontinued in the US; generic tablets; Soltamox oral solution (NDA 021807) |
| Route | Oral (tablet or solution) |
| Strengths | 10 mg and 20 mg tablets; oral solution 20 mg per 10 mL |
| Labeled dose | 20–40 mg/day for metastatic breast cancer; 20 mg/day for adjuvant therapy, DCIS and risk reduction |
| Half-life (label) | Terminal half-life of about 5–7 days; ≈14 days for the main metabolite, N-desmethyltamoxifen |
| Key mechanism fact | CYP2D6 converts it to endoxifen and 4-hydroxytamoxifen, minor metabolites with ≈100-fold greater estrogen receptor affinity |
| US status | Prescription only; not a controlled substance (DEA schedule: none) |
| WADA status | Prohibited at all times (S4.2, anti-estrogenic substances) |
What it is
Tamoxifen’s chemical name is (Z)-2-[4-(1,2-diphenyl-1-butenyl)phenoxy]-N,N-dimethylethanamine, formula C₂₆H₂₉NO, molecular weight 371.5 g/mol (PubChem). Medicines contain it as tamoxifen citrate (563.6 g/mol). A 20 mg tablet therefore contains 30.4 mg of the citrate salt (tamoxifen tablets label).
It is not a steroid. It is a nonsteroidal “antiestrogen” from the same chemical family as clomiphene and toremifene.
The compound, coded ICI 46,474, came out of 1960s industry research on nonsteroidal antiestrogens. These drugs blocked fertility in laboratory rats, so a “morning-after” pill was the first goal. In subfertile women, however, antiestrogens induced ovulation instead, and ICI 46,474 was reinvented as a breast cancer treatment (Jordan, Br J Pharmacol 2006). It later became the first drug approved by the FDA to reduce breast cancer incidence in high-risk women (Jordan, Nat Rev Drug Discov 2003).
How a SERM works
Tamoxifen competes with estrogen for the estrogen receptor (Soltamox label). Whether it blocks or activates the receptor depends on the tissue:
| Tissue | Tamoxifen’s effect | Consequence |
|---|---|---|
| Breast | Blocks estrogen | Basis of breast cancer treatment and of its use for gynecomastia |
| Hypothalamus and pituitary | Blocks estrogen’s negative feedback | LH, FSH and testosterone rise in men |
| Uterus | Partial estrogen-like action | Endometrial thickening, polyps and cancer |
| Liver | Estrogen-like action | IGF-1 falls and SHBG rises |
Pharmacokinetics
From the FDA labels (tablets; Soltamox):
| Parameter | Value |
|---|---|
| Peak after a single 20 mg dose | ≈40 ng/mL (range 35–45), about 5 h after dosing |
| Terminal half-life, tamoxifen | About 5–7 days |
| Half-life, N-desmethyltamoxifen | Approximately 14 days |
| Time to steady state | About 4 weeks (tamoxifen); about 8 weeks (N-desmethyltamoxifen) |
| Steady state on 20 mg/day for 3 months | 122 ng/mL tamoxifen; 353 ng/mL N-desmethyltamoxifen |
| Steady state, active metabolites | Endoxifen 29.1 ng/mL; 4-hydroxytamoxifen 3.7 ng/mL |
| Excretion | ≈65% of a dose excreted over 2 weeks, mainly in feces |
| Food | No effect on absorption (oral solution) |
The long half-life means it takes about a month to reach steady state, and the drug clears slowly after the last dose. The labels advise avoiding pregnancy during treatment and for 2 months after stopping.
CYP2D6 and endoxifen
Several liver enzymes metabolize tamoxifen: CYP3A, CYP2D6, CYP2C9, CYP2C19 and CYP2B6. Two minor metabolites, endoxifen and 4-hydroxytamoxifen, have about 100-fold greater affinity for the estrogen receptor than tamoxifen itself. CYP2D6 is the key enzyme for making endoxifen, and its activity varies genetically. In the WHEL study cited in the Soltamox label, mean endoxifen levels were:
| CYP2D6 phenotype | n | Mean endoxifen (ng/mL) |
|---|---|---|
| Ultrarapid metabolizers | 27 | 22.8 |
| Normal metabolizers | 1,097 | 15.9 |
| Intermediate metabolizers | 164 | 8.1 |
| Poor metabolizers | 82 | 5.6 |
Strong CYP2D6 inhibitors such as paroxetine also lower endoxifen (14.8 vs 26.7 ng/mL in one comparison). The label states that the effect of CYP2D6 genotype or inhibitors on tamoxifen’s clinical efficacy “is not well established,” because studies disagree.
Approved medical use
The current labels approve tamoxifen for:
- metastatic breast cancer in women and men;
- adjuvant treatment of early-stage estrogen receptor-positive breast cancer, including to reduce cancer in the opposite breast;
- ductal carcinoma in situ (DCIS), after surgery and radiation, to reduce the risk of invasive breast cancer;
- reducing breast cancer incidence in high-risk women.
| Setting | Labeled dose |
|---|---|
| Metastatic breast cancer | 20–40 mg/day; doses over 20 mg split morning and evening |
| Adjuvant treatment | 20 mg/day for 5–10 years (Soltamox label) |
| DCIS | 20 mg/day for 5 years |
| Risk reduction in high-risk women | 20 mg/day for 5 years |
The labels note that doses above 20 mg/day gave no additional benefit in the adjuvant setting. For male breast cancer, the label cites published reports in which 66 of 132 evaluable men (50%) responded to tamoxifen (tamoxifen tablets label).
The original Nolvadex tablets (NDA 017970) are listed as discontinued. FDA has determined in the Federal Register that they were not withdrawn for safety or effectiveness reasons, and generics remain approved (Drugs@FDA).
What the research shows
Breast cancer treatment
The Early Breast Cancer Trialists’ Collaborative Group pooled individual patient data from 20 trials (n = 21,457) of about 5 years of tamoxifen vs no tamoxifen (EBCTCG, Lancet 2011). In estrogen receptor-positive disease (n = 10,645):
| Outcome | Rate ratio, tamoxifen vs control |
|---|---|
| Recurrence, years 0–4 | 0.53 |
| Recurrence, years 5–9 | 0.68 |
| Recurrence, years 10–14 | 0.97 (no further gain or loss) |
| Breast cancer mortality, years 0–4 | 0.71 |
| Breast cancer mortality, years 5–9 | 0.66 |
| Breast cancer mortality, years 10–14 | 0.68 |
So 5 years of tamoxifen cut breast cancer deaths by about a third for at least 15 years. In estrogen receptor-negative disease, it had little or no effect.
The ATLAS trial randomized 12,894 women who had already completed 5 years of tamoxifen to continue to 10 years or stop (Davies et al., Lancet 2013). Among the 6,846 women with ER-positive disease, continuing lowered:
- recurrence during years 5–14, from 25.1% to 21.4%;
- breast cancer mortality during years 5–14, from 15.0% to 12.2%.
The cost was more endometrial cancer (cumulative risk 3.1% vs 1.6%; RR 1.74, 95% CI 1.30–2.34) and more pulmonary embolism (RR 1.87, 95% CI 1.13–3.07). Ischemic heart disease was lower (RR 0.76, 95% CI 0.60–0.95).
Breast cancer prevention
The NSABP P-1 trial randomized 13,388 high-risk women to tamoxifen 20 mg/day or placebo for 5 years (Fisher et al., JNCI 1998). Results:
- Invasive breast cancer fell by 49%: cumulative incidence through 69 months was 22.0 vs 43.4 per 1,000 women.
- Only ER-positive tumors were prevented: they fell by 69%, while ER-negative tumors were unchanged.
- Endometrial cancer roughly doubled: risk ratio 2.53 (95% CI 1.35–4.97), mostly in women aged 50 or older.
In the NSABP B-24 trial of 1,804 women with DCIS, tamoxifen reduced invasive breast cancer by 43% (RR 0.57, 95% CI 0.39–0.84), but it was not shown to improve survival (tamoxifen tablets label).
Gynecomastia from antiandrogen therapy
The best controlled evidence for tamoxifen against gynecomastia comes from men with prostate cancer taking bicalutamide 150 mg/day. Bicalutamide blocks androgen receptors, and breast enlargement and breast pain are frequent side effects. This is a different setting from anabolic steroid use, so the results may not transfer directly.
A double-blind, placebo-controlled trial randomized 282 men on bicalutamide to tamoxifen at five doses or placebo for 12 months (Fradet et al., Eur Urol 2007):
| Daily tamoxifen dose | Men with breast events (gynecomastia or breast pain) at 6 months |
|---|---|
| Placebo | 96.7% |
| 1 mg | 86.2% |
| 2.5 mg | 60.0% |
| 5 mg | 55.3% |
| 10 mg | 23.5% |
| 20 mg | 8.8% |
The effect was clearly dose-dependent. Once tamoxifen was stopped and bicalutamide continued for another 12 months, breast events became common again in all groups. Hot flushes increased at tamoxifen doses of 5 mg or more.
A second randomized trial compared bicalutamide alone, bicalutamide plus tamoxifen 10 mg/day, and bicalutamide plus a single dose of breast radiotherapy (Perdonà et al., Lancet Oncol 2005):
| Arm | n | Gynecomastia | Breast pain |
|---|---|---|---|
| Bicalutamide alone | 51 | 35 (69%) | 29 (57%) |
| + Tamoxifen 10 mg/day | 50 | 4 (8%) | 3 (6%) |
| + Radiotherapy | 50 | 17 (34%) | 15 (30%) |
A systematic review of four randomized trials found that tamoxifen cut the risk of gynecomastia at 6 months by about 90% compared with no treatment (RR 0.10, 95% CI 0.05–0.22). It also outperformed the aromatase inhibitor anastrozole for prevention (RR 0.22, 95% CI 0.08–0.58). Long-term effects on cancer outcomes were unclear (Kunath et al., BMC Med 2012).
Established, idiopathic and pubertal gynecomastia
The evidence for treating gynecomastia that has already developed, outside the antiandrogen setting, is weaker:
- Pubertal gynecomastia. A systematic review found six studies and no randomized controlled trials. Results looked promising, but the studies had methodological flaws (Lapid et al., J Pediatr Endocrinol Metab 2013).
- Adult idiopathic gynecomastia. In an uncontrolled cohort of 81 men given tamoxifen 10 mg daily, 90.1% had complete resolution (Mannu et al., Breast J 2018). Without a control group, spontaneous regression cannot be ruled out.
The European Academy of Andrology guideline recommends watchful waiting after stopping the substance that caused gynecomastia. It does not recommend SERMs, aromatase inhibitors or non-aromatizable androgens for gynecomastia in general. It suggests surgery for long-lasting gynecomastia that does not regress (Kanakis et al., Andrology 2019).
Hormones in healthy men
Because tamoxifen blocks estrogen feedback at the hypothalamus and pituitary, it raises the body’s own testosterone. In a randomized crossover study, 10 healthy men took tamoxifen (10 and 20 mg/day) and raloxifene (60 and 120 mg/day) for 2 weeks each (Birzniece et al., JCEM 2010):
| Measure | Tamoxifen | Raloxifene |
|---|---|---|
| LH | +70% | +30% |
| Testosterone | +40% | +25% |
| IGF-1 (at the higher dose) | −25% | No significant change |
| SHBG (at the higher dose) | +20% | No significant change |
Both drugs raised LH, FSH and testosterone, but tamoxifen had the larger effect. The IGF-1 drop reflects tamoxifen’s estrogen-like action in the liver. Whether this matters for muscle has not been studied.
Male infertility
A meta-analysis of 11 randomized trials of clomiphene or tamoxifen in men with idiopathic low sperm count or motility found a higher pregnancy rate with treatment (pooled OR 2.42, 95% CI 1.47–3.94). Sperm concentration, motility, FSH and testosterone also rose (Chua et al., Andrology 2013). The analysis pooled both drugs, so it does not isolate tamoxifen’s effect.
Recovery after anabolic steroid use
About tamoxifen as “PCT.” Tamoxifen is often presented online as a proven way to restart testosterone production after a steroid cycle. A 2014 review in Fertility and Sterility set out to perform a meta-analysis of treatments for anabolic steroid-induced hypogonadism, but no quality studies met the inclusion criteria. Its recommendations, which include SERMs, rest on expert opinion (Rahnema et al., Fertil Steril 2014).
The hormone rise seen in healthy men and in infertile men shows that tamoxifen can stimulate the testicular axis. It does not show how fast or how completely a steroid-suppressed axis recovers with tamoxifen compared with no treatment, because that has not been tested in a controlled trial.
Side effects and risks
Boxed warning
For women with DCIS and women at high risk of breast cancer, the label warns of serious and sometimes fatal uterine cancer, stroke and pulmonary embolism. The incidence rates in NSABP P-1 were (Soltamox label):
| Event | Tamoxifen (per 1,000 women-years) | Placebo (per 1,000 women-years) |
|---|---|---|
| Endometrial adenocarcinoma | 2.20 | 0.71 |
| Uterine sarcoma | 0.17 | 0.04 |
| Stroke | 1.43 | 1.00 |
| Pulmonary embolism | 0.75 | 0.25 |
The label states that for women already diagnosed with breast cancer, the benefits outweigh these risks.
Blood clots
Tamoxifen raises the risk of deep vein thrombosis and pulmonary embolism, and the risk rises further when it is combined with chemotherapy. In NSABP P-1, pulmonary embolism occurred in 18 women on tamoxifen vs 6 on placebo (RR 3.01, 95% CI 1.15–9.27); three were fatal, all in the tamoxifen arm.
Eyes
The labels report cataracts, corneal changes, reduced color vision, retinal vein thrombosis and retinopathy. In NSABP P-1, cataract surgery was more common on tamoxifen (201 vs 129 women; RR 1.58, 95% CI 1.26–1.97) (Soltamox label).
Liver
Tamoxifen can raise liver enzymes. Rarely it has been linked to fatty liver, cholestasis, hepatitis and hepatic necrosis, including a few deaths. The label recommends periodic liver function tests and blood counts. In rats, tamoxifen caused liver tumors at all tested doses; in one Swedish trial using 40 mg/day, 3 liver cancers occurred on tamoxifen vs 1 in the observation group.
Effects in men
Data in men come mostly from case series and trials in prostate or breast cancer:
- Sexual function. The label reports loss of libido and impotence severe enough to stop treatment in some male patients.
- Hormones. In oligospermic men, LH, FSH, testosterone and estrogen levels rose on tamoxifen.
- Tolerability. A review of trials in men found that under 5% withdrew because of side effects. Most withdrawals were men with breast cancer, and cardiovascular events were the most common reason. Long-term safety data in men are lacking (Wibowo et al., Andrology 2016).
Other effects
- Hot flashes are the most common side effect. In NSABP P-1 they occurred in 80% of women on tamoxifen vs 68% on placebo; severe hot flashes in 45% vs 28%.
- Blood counts. Platelets can fall, usually to 50,000–100,000/mm³.
- Triglycerides. Rare large rises, sometimes with pancreatitis.
- Hypercalcemia in some patients with bone metastases, within weeks of starting.
- Very high doses. Tremor, unsteady gait, dizziness and QT prolongation were seen at doses at least 6 times the maximum recommended dose.
Interactions
| Drug | Interaction (label) |
|---|---|
| Warfarin and other coumarins | Marked increase in anticoagulant effect; contraindicated for DCIS and risk-reduction use |
| Rifampin (strong CYP3A4 inducer) | Tamoxifen AUC down 86% and peak down 55%; avoid strong CYP3A4 inducers |
| Strong CYP2D6 inhibitors (e.g. paroxetine) | Lower endoxifen levels; clinical impact not well established |
| Anastrozole | Anastrozole levels down 27%; combination showed no benefit and should be avoided |
| Letrozole | Letrozole levels down 38%; combination not recommended |
Who should not use it
The labels list these contraindications and cautions:
- known hypersensitivity to tamoxifen;
- for DCIS or risk reduction: a need for warfarin-type anticoagulants, or a history of deep vein thrombosis or pulmonary embolism;
- pregnancy: tamoxifen can harm the fetus, and women should use non-hormonal contraception during treatment and for 2 months afterwards;
- breastfeeding.
Legal status and use outside medicine
In the US, tamoxifen is a prescription drug with no DEA schedule (DailyMed). In sport, the 2026 WADA Prohibited List names tamoxifen under S4.2 (anti-estrogenic substances), banned in and out of competition (WADA 2026 Prohibited List).
Self-directed PCT is common among steroid users. In an anonymous survey of 470 men who used anabolic steroids, 56.5% of those who had tried to stop reported using some form of PCT, which the authors describe as typically involving hCG and SERMs (Grant et al., Subst Abuse Treat Prev Policy 2023). Benefits in the survey were self-reported.
Product from outside pharmacies is unreliable. A Polish medicines control laboratory tested 63 seized samples sold for PCT, including tamoxifen and clomiphene. In 34.9% of them, the declared active ingredient was absent. Some samples contained no active ingredient at all, and others contained undeclared drugs (Blazewicz et al., Front Chem 2025).
Key takeaways
- A breast cancer drug with decades of trial data. Five years of tamoxifen cut breast cancer deaths by about a third in ER-positive disease, and it halved invasive cancer in high-risk women in NSABP P-1.
- Long-acting, with active metabolites. The half-life is about 5–7 days (about 14 days for its main metabolite), and CYP2D6 converts it to the more potent endoxifen.
- Strong evidence for preventing antiandrogen gynecomastia. In men on bicalutamide, 20 mg/day cut breast events from 97% to 9% at 6 months. Evidence for shrinking established gynecomastia is mostly uncontrolled, and the EAA guideline does not recommend SERMs in general.
- Raises testosterone, but untested as PCT. Tamoxifen raised LH by about 70% and testosterone by about 40% in healthy men. No controlled trial has tested it for recovery after anabolic steroids.
- Real risks. Blood clots, uterine cancer, cataracts and rare liver injury are documented. In men, loss of libido and impotence have led to stopping treatment.
Sources
- Mylan Pharmaceuticals. Tamoxifen citrate tablets USP, prescribing information (ANDA 074732). DailyMed.
- Mayne Pharma. Soltamox (tamoxifen citrate) oral solution, prescribing information (NDA 021807). DailyMed.
- Food and Drug Administration. Drugs@FDA: Nolvadex (tamoxifen citrate), NDA 017970. FDA.
- National Center for Biotechnology Information. Tamoxifen, PubChem CID 2733526. PubChem.
- Jordan VC. Tamoxifen (ICI46,474) as a targeted therapy to treat and prevent breast cancer. Br J Pharmacol. 2006;147(Suppl 1):S269–S276. PubMed.
- Jordan VC. Tamoxifen: a most unlikely pioneering medicine. Nat Rev Drug Discov. 2003;2(3):205–213. PubMed.
- Early Breast Cancer Trialists’ Collaborative Group (EBCTCG), Davies C, Godwin J, Gray R, et al. Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials. Lancet. 2011;378(9793):771–784. PubMed.
- Davies C, Pan H, Godwin J, et al. Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial. Lancet. 2013;381(9869):805–816. PubMed.
- Fisher B, Costantino JP, Wickerham DL, et al. Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst. 1998;90(18):1371–1388. PubMed.
- Fradet Y, Egerdie B, Andersen M, et al. Tamoxifen as prophylaxis for prevention of gynaecomastia and breast pain associated with bicalutamide 150 mg monotherapy in patients with prostate cancer: a randomised, placebo-controlled, dose-response study. Eur Urol. 2007;52(1):106–114. PubMed.
- Perdonà S, Autorino R, De Placido S, et al. Efficacy of tamoxifen and radiotherapy for prevention and treatment of gynaecomastia and breast pain caused by bicalutamide in prostate cancer: a randomised controlled trial. Lancet Oncol. 2005;6(5):295–300. PubMed.
- Kunath F, Keck B, Antes G, et al. Tamoxifen for the management of breast events induced by non-steroidal antiandrogens in patients with prostate cancer: a systematic review. BMC Med. 2012;10:96. PubMed.
- Lapid O, van Wingerden JJ, Perlemuter L. Tamoxifen therapy for the management of pubertal gynecomastia: a systematic review. J Pediatr Endocrinol Metab. 2013;26(9–10):803–807. PubMed.
- Mannu GS, Sudul M, Bettencourt-Silva JH, et al. Role of tamoxifen in idiopathic gynecomastia: a 10-year prospective cohort study. Breast J. 2018;24(6):1043–1045. PubMed.
- Kanakis GA, Nordkap L, Bang AK, et al. EAA clinical practice guidelines-gynecomastia evaluation and management. Andrology. 2019;7(6):778–793. PubMed.
- Birzniece V, Sata A, Sutanto S, Ho KK. Neuroendocrine regulation of growth hormone and androgen axes by selective estrogen receptor modulators in healthy men. J Clin Endocrinol Metab. 2010;95(12):5443–5448. PubMed.
- Chua ME, Escusa KG, Luna S, et al. Revisiting oestrogen antagonists (clomiphene or tamoxifen) as medical empiric therapy for idiopathic male infertility: a meta-analysis. Andrology. 2013;1(5):749–757. PubMed.
- Rahnema CD, Lipshultz LI, Crosnoe LE, et al. Anabolic steroid-induced hypogonadism: diagnosis and treatment. Fertil Steril. 2014;101(5):1271–1279. PubMed.
- Wibowo E, Pollock PA, Hollis N, Wassersug RJ. Tamoxifen in men: a review of adverse events. Andrology. 2016;4(5):776–788. PubMed.
- Grant B, Kean J, Vali N, et al. The use of post-cycle therapy is associated with reduced withdrawal symptoms from anabolic-androgenic steroid use: a survey of 470 men. Subst Abuse Treat Prev Policy. 2023;18(1):66. PubMed.
- Blazewicz A, Poplawska M, Daniszewska B, et al. Illegal and falsified medicines self-administrated in not approved post-cycle therapy after the cessation of anabolic-androgenic steroids - qualitative analysis. Front Chem. 2025;13:1536858. PubMed.
- World Anti-Doping Agency. World Anti-Doping Code International Standard: Prohibited List 2026 (in effect January 1, 2026). WADA.