Exemestane, sold by Pfizer as Aromasin, is an oral aromatase inhibitor: a drug that blocks the enzyme that turns androgens into estrogens. The FDA approved it in 1999 for advanced breast cancer and in 2005 for early breast cancer, in both cases only for postmenopausal women.
Unlike anastrozole and letrozole, exemestane is a steroid. It is structurally related to androstenedione, the enzyme’s natural substrate, and it inactivates the enzyme irreversibly. Outside oncology it is used to control estrogen during anabolic steroid use, but there are no trials in that setting. The main dosing study in males lasted 10 days and enrolled 12 young volunteers.
This page summarizes what the FDA label, clinical trials and anti-doping rules report. It is for education only and is not medical advice.
| Property | Detail |
|---|---|
| Drug class | Steroidal, irreversible aromatase inactivator (“suicide” inhibitor) |
| Brand / approval | Aromasin (Pfizer), NDA 020753, approved October 21, 1999; generics available |
| Route | Oral tablet, taken once daily after a meal |
| Strength | 25 mg |
| Labeled dose | 25 mg once daily; 50 mg once daily with a strong CYP3A4 inducer |
| Half-life (label) | About 24 h (terminal, healthy postmenopausal women) |
| Estrogen suppression (label) | 85–95% fall in plasma estrogens at 25 mg/day; whole-body aromatization cut by 98% |
| US status | Prescription only; approved indications are limited to postmenopausal women with breast cancer |
| WADA status | Named under S4 Hormone and Metabolic Modulators (aromatase inhibitors) on the 2026 Prohibited List |
What it is
Exemestane’s chemical name is 6-methylenandrosta-1,4-diene-3,17-dione: formula C₂₀H₂₄O₂, molecular weight 296.4 g/mol (FDA label; PubChem). It is androstenedione with two changes: an extra double bond in the A-ring and a methylene group at carbon 6.
Aromatase converts androstenedione and testosterone to estrone and estradiol. After menopause, this conversion in peripheral tissues is the main source of circulating estrogen. The label describes exemestane as a false substrate: the enzyme starts to process it, and the resulting intermediate binds irreversibly to the active site and inactivates the enzyme. This is called “suicide inhibition.” Anastrozole and letrozole, by contrast, are nonsteroidal aromatase inhibitors (Goss et al., JCO 2013).
The label states that exemestane does not bind steroid receptors to any meaningful degree, except for a slight affinity for the androgen receptor: 0.28% of that of dihydrotestosterone (DHT). Its main metabolite, 17-hydroexemestane, binds the androgen receptor 100 times more strongly than the parent drug. In breast cancer cell culture, this metabolite acted as an androgen at low nanomolar concentrations (Ariazi et al., Mol Cancer Ther 2007). The MA.27 investigators described exemestane as “a mild androgen” (Goss et al., JCO 2013). Whether this matters clinically in men has not been studied.
Pharmacokinetics
From the current Aromasin label (FDA label):
| Parameter | Value |
|---|---|
| Fraction absorbed | About 42% of a radiolabeled dose |
| Time to peak (tmax) | 2.9 h in healthy women; 1.2 h in women with breast cancer |
| Effect of a high-fat meal | AUC up 59%, peak level up 39% vs fasting |
| Protein binding | 90% (albumin and α1-acid glycoprotein) |
| Terminal half-life | About 24 h |
| Metabolism | Extensive; CYP3A4 (oxidation at carbon 6) and aldo-keto reductases (17-keto reduction) |
| Excretion | 42% in urine, 42% in feces over 1 week; under 1% excreted unchanged |
| Hepatic or renal impairment | AUC about 3 times higher; no dose change considered necessary |
Estrogen suppression lasts longer than the half-life alone would suggest. After a single 25 mg dose, maximum estrogen suppression came 2–3 days later and persisted for 4–5 days. The label also reports that a single 25 mg dose in fasted healthy men (mean age 32) gave pharmacokinetics similar to those in postmenopausal women.
A dedicated study in young males reported a shorter half-life. In 10 healthy males from a cohort aged 14–26, a single 25 mg dose peaked at 1 hour and had a terminal half-life of 8.9 h (Mauras et al., JCEM 2003). The abstract does not explain the difference from the label’s 24 h figure.
Hormone effects in postmenopausal women
The label reports the following at 25 mg/day or across the studied dose range of 0.5–600 mg/day:
- Estrogens: suppression starts at 5 mg/day and reaches at least 85–95% at 25 mg/day.
- Adrenal hormones: no effect on cortisol or aldosterone, even at 200 mg/day.
- Androgens: small falls in testosterone at up to 25 mg/day; rises in testosterone and androstenedione at 200 mg/day or more.
- SHBG (sex hormone-binding globulin, the protein that carries testosterone in blood): a dose-dependent fall from 2.5 mg/day upward.
- LH and FSH: slight increases, from reduced estrogen feedback on the pituitary.
- Thyroid: no significant effect at 25 mg/day.
Approved medical use
The FDA label covers two uses (FDA label):
- Advanced breast cancer in postmenopausal women whose disease has progressed on tamoxifen (original approval, October 21, 1999).
- Adjuvant treatment of early breast cancer in postmenopausal women with estrogen-receptor-positive disease who have taken tamoxifen for 2–3 years and switch to exemestane to complete 5 years of hormonal therapy. FDA approved this indication on October 5, 2005 (FDA approval letter, S-006).
The dose is one 25 mg tablet daily after a meal. The label states that Aromasin is not indicated for breast cancer in premenopausal women, and that safety and effectiveness in children have not been established. It has no approved use in men.
What the research shows
Early breast cancer after tamoxifen (IES)
The Intergroup Exemestane Study randomized 4,742 postmenopausal women who were disease-free after 2–3 years of tamoxifen. They either switched to exemestane or stayed on tamoxifen to complete 5 years (Coombes et al., NEJM 2004). At a median follow-up of 30.6 months:
| Outcome | Exemestane | Tamoxifen |
|---|---|---|
| First events (recurrence, new contralateral cancer or death) | 183 | 266 |
| Disease-free survival hazard ratio | 0.68 (95% CI 0.56–0.82) | Reference |
| Absolute disease-free survival gain at 3 years | 4.7% (95% CI 2.6–6.8) | — |
| Contralateral breast cancer | 9 | 20 |
| Deaths | 93 | 106 (not significantly different) |
The label adds a longer overall survival update at 119 months of median follow-up. Deaths were 19.9% with exemestane and 21.5% with tamoxifen, with no significant difference.
Exemestane alone vs tamoxifen first (TEAM)
The TEAM trial randomized 9,779 postmenopausal women with hormone-receptor-positive early breast cancer to 5 years of exemestane 25 mg/day, or to tamoxifen followed by exemestane (van de Velde et al., Lancet 2011). Disease-free survival at 5 years was 86% vs 85% (HR 0.97, 95% CI 0.88–1.08). The side-effect profiles differed:
| Adverse event | Exemestane alone | Tamoxifen then exemestane |
|---|---|---|
| Musculoskeletal events | 50% | 44% |
| Gynecological symptoms | 11% | 20% |
| Venous thrombosis | 1% | 2% |
| Endometrial abnormalities | under 1% | 4% |
| Hypertension | 6% | 5% |
| Hyperlipidemia | 5% | 3% |
In this table, musculoskeletal events, hypertension and hyperlipidemia were reported more often with exemestane alone; the sequential arm had more gynecological, clotting and endometrial events.
Exemestane vs anastrozole (MA.27)
MA.27 was the first head-to-head test of a steroidal against a nonsteroidal aromatase inhibitor. It randomized 7,576 postmenopausal women (median age 64.1) to 5 years of exemestane or anastrozole (Goss et al., JCO 2013). At a median follow-up of 4.1 years, 4-year event-free survival was 91% vs 91.2% (HR 1.02, 95% CI 0.87–1.18). Neither drug was superior.
The toxicity profiles differed only modestly:
- less frequent with exemestane: osteoporosis or osteopenia, high triglycerides, high cholesterol and vaginal bleeding;
- less frequent with anastrozole: mild liver test abnormalities and rare atrial fibrillation;
- similar: hot flashes and joint or muscle symptoms.
Overall, 31.6% of patients stopped treatment because of side effects, other illness or refusal.
Breast cancer prevention (MAP.3)
MAP.3 randomized 4,560 postmenopausal women at moderately increased risk to exemestane 25 mg/day or placebo (Goss et al., NEJM 2011). At a median of 35 months, there were 11 invasive breast cancers on exemestane and 32 on placebo. The annual incidence was 0.19% vs 0.55%, a 65% relative reduction (HR 0.35, 95% CI 0.18–0.70). Adverse events of any kind occurred in 88% vs 85% (p = 0.003). The authors found no significant differences in fractures, cardiovascular events or other cancers over this short follow-up. Prevention is not an FDA-labeled indication.
Premenopausal women with ovarian suppression (TEXT and SOFT)
Before menopause the ovary is the main source of estrogen, and the label states that Aromasin is not indicated in premenopausal women. In the combined TEXT and SOFT analysis, 4,690 premenopausal women had their ovarian function suppressed and received either exemestane or tamoxifen for 5 years (Pagani et al., NEJM 2014). Five-year disease-free survival was 91.1% vs 87.3% (HR 0.72, 95% CI 0.60–0.85). Overall survival did not differ (HR 1.14, 95% CI 0.86–1.51). This use is not on the US label.
Men
We found no efficacy trials of exemestane in men, and none in men using anabolic steroids. The main dosing study was a randomized crossover in 12 healthy males aged 14–26 who took 25 mg and 50 mg daily for 10 days each, separated by a 14-day washout (Mauras et al., JCEM 2003):
| Measure | 25 mg/day | 50 mg/day |
|---|---|---|
| Estradiol change (24 h after last dose) | −38% | −32% |
| Testosterone change | +60% | +56% |
| Lipids and IGF-I | No change | No change |
The 50 mg dose gave no extra estradiol suppression. Peak estradiol suppression after a single 25 mg dose was 62% at 12 hours. Testosterone likely rose because lower estrogen reduces feedback on the pituitary; the label describes the same mechanism for the LH and FSH rises seen in women. The study was too short to assess bone, lipids over time or safety, and the authors stated that long-term efficacy and safety needed further study.
The only randomized trial of an aromatase inhibitor in older men used a different drug, anastrozole 1 mg/day, for 1 year in 69 men aged 60 or over with low or borderline testosterone (Burnett-Bowie et al., JCEM 2009). Testosterone rose, but spine bone mineral density fell compared with placebo (p = 0.0014). The authors concluded that aromatase inhibition does not improve skeletal health in these men. Whether exemestane has the same effect in men has not been tested.
About “suicide inhibitors don’t cause estrogen rebound” or “Aromasin is the bone-friendly AI.” These claims circulate widely in steroid-use communities. No study has measured estrogen rebound after stopping exemestane in men. In women, exemestane lowered bone density compared with placebo (see below), and in MA.27 its bone advantage over anastrozole was modest and, in the investigators’ words, “requires confirmation.”
Side effects and risks
The Aromasin label has no boxed warning. Its warnings cover bone loss, vitamin D assessment, lab abnormalities, use in premenopausal women and harm to a fetus.
Bone loss
Lowering estrogen speeds up bone loss. In label study 027, women on exemestane lost 3.5% of lumbar spine and 4.6% of femoral neck bone mineral density (BMD) over 24 months, compared with 2.4% and 2.6% on placebo (FDA label). In IES, clinical fractures occurred in 4.2% of women on exemestane vs 3.1% on tamoxifen.
The MAP.3 bone substudy followed 351 healthy postmenopausal women for 2 years, all taking calcium and vitamin D (Cheung et al., Lancet Oncol 2012):
| Site | Exemestane | Placebo | Difference (95% CI) |
|---|---|---|---|
| Distal radius, total volumetric BMD | −6.1% | −1.8% | −4.3% (−5.3 to −3.2) |
| Distal radius, cortical thickness | −7.9% | −1.1% | −6.8% (−8.5 to −5.0) |
| Lumbar spine, areal BMD | −2.4% | −0.5% | −1.9% (−2.9 to −1.0) |
| Femoral neck, areal BMD | −2.4% | −0.8% | −1.6% (−2.7 to −0.6) |
The label advises bone density testing at the start of treatment in women with or at risk of osteoporosis, and checking 25-hydroxy vitamin D before starting.
Common side effects
In the IES trial (2,252 women on exemestane vs 2,280 on tamoxifen), the label lists these rates:
| Side effect | Exemestane | Tamoxifen |
|---|---|---|
| Hot flushes | 21% | 20% |
| Fatigue | 16% | 15% |
| Joint pain (arthralgia) | 15% | 9% |
| Headache | 13% | 11% |
| Insomnia | 12% | 9% |
| Increased sweating | 12% | 10% |
| Hypertension | 10% | 8% |
| Dizziness | 10% | 8% |
Carpal tunnel syndrome (2.4% vs 0.2%) and paresthesia, a pins-and-needles sensation (2.6% vs 0.9%), were also more common on exemestane. Discontinuation for side effects was 6% vs 5%. In the placebo-controlled study 027, hair loss (alopecia) occurred in 15% vs 4.1%.
Heart and blood vessels
In IES, cardiac ischemic events (heart attack, angina and myocardial ischemia) occurred in 1.6% on exemestane vs 0.6% on tamoxifen, and heart failure in 0.4% vs 0.3%. The label notes 6 deaths from stroke on exemestane vs 2 on tamoxifen, and 5 deaths from heart failure vs 2. Tamoxifen, in turn, caused more blood clots (2.0% vs 0.9%).
Lipids
In study 027, HDL (“good”) cholesterol fell by 6–9% on exemestane. Total cholesterol, LDL and triglycerides did not change (FDA label). In the 10-day study in young males, lipids did not change (Mauras et al., JCEM 2003). There are no long-term lipid data in men.
Liver and other lab changes
The label reports the following in early breast cancer:
- Bilirubin elevations in 5% on exemestane vs 0.8% on tamoxifen (IES), and 7% vs 0% on placebo (study 027).
- Alkaline phosphatase elevations in 15% vs 2.6% (IES).
- Creatinine elevations in 6% vs 4.3% (IES).
Hepatitis, including cholestatic hepatitis, has been reported after approval. In advanced breast cancer, about 20% of patients had grade 3 or 4 lymphocytopenia (a low count of lymphocytes, a type of white blood cell), but 89% of them had low counts before starting.
Interactions
- Strong CYP3A4 inducers (rifampicin, phenytoin, carbamazepine, phenobarbital, St. John’s wort) lower exemestane levels. Rifampicin cut exemestane’s peak level by 41% and AUC by 54%, so the label raises the dose to 50 mg/day.
- Estrogen-containing drugs should not be combined with exemestane because they counteract it.
- CYP3A4 inhibitors: ketoconazole had no significant effect.
- Exemestane does not inhibit the major CYP enzymes, so it is unlikely to raise levels of other drugs.
Who should not use it
- People with known hypersensitivity to exemestane or any tablet ingredient (the only formal contraindication).
- Pregnant women: exemestane can harm a fetus. The label advises a pregnancy test within 7 days before starting, and contraception during treatment and for 1 month after the last dose.
- Breastfeeding women, during treatment and for 1 month after.
- Premenopausal women, unless ovarian function is suppressed as part of a specialist regimen.
The label also notes that, based on animal studies, exemestane may impair fertility in males and females.
Overdose
The label reports that single doses up to 800 mg in healthy women, and 600 mg/day for 12 weeks in women with advanced breast cancer, were well tolerated. There is no specific antidote.
Legal status and use outside medicine
In the US, exemestane is a prescription drug (FDA label). FDA lists Pfizer’s NDA 020753 and several generic ANDAs (openFDA Drugs@FDA).
In sport, the 2026 WADA Prohibited List names exemestane among the aromatase inhibitors in class S4, Hormone and Metabolic Modulators. Our source is a reproduction by the German Sport University Cologne, which hosts a WADA-accredited laboratory (DSHS Köln).
Key takeaways
- A steroidal, irreversible aromatase inhibitor. Exemestane permanently inactivates the aromatase enzyme and lowers estrogens by 85–95% at the labeled 25 mg/day.
- Approved only for breast cancer in postmenopausal women. It has no approved use in men, and the main dosing study in males lasted 10 days in 12 young volunteers.
- As effective as other options in breast cancer. It cut recurrence by about a third vs continued tamoxifen (IES) and matched anastrozole (MA.27).
- Bone loss is the main long-term risk. Bone density fell faster than with placebo, even with calcium and vitamin D supplements.
- “Bone-friendly” and “no rebound” claims are unproven. Its weak androgenic metabolite has not been shown to protect bone or lipids in men.
- Banned in sport. WADA lists exemestane by name under S4.
Sources
- Pfizer (Pharmacia & Upjohn). Aromasin (exemestane) tablets prescribing information, revised 12/2024. DailyMed.
- Food and Drug Administration. Approval letter, NDA 20-753/S-006 (Aromasin adjuvant indication), October 5, 2005. FDA.
- Food and Drug Administration. Drugs@FDA application records for exemestane (NDA 020753, original approval October 21, 1999, and generic ANDAs). openFDA.
- National Center for Biotechnology Information. PubChem Compound Summary for CID 60198, Exemestane. PubChem.
- Coombes RC, Hall E, Gibson LJ, et al. A randomized trial of exemestane after two to three years of tamoxifen therapy in postmenopausal women with primary breast cancer. N Engl J Med. 2004;350(11):1081–1092. PubMed.
- van de Velde CJ, Rea D, Seynaeve C, et al. Adjuvant tamoxifen and exemestane in early breast cancer (TEAM): a randomised phase 3 trial. Lancet. 2011;377(9762):321–331. PubMed.
- Goss PE, Ingle JN, Pritchard KI, et al. Exemestane versus anastrozole in postmenopausal women with early breast cancer: NCIC CTG MA.27—a randomized controlled phase III trial. J Clin Oncol. 2013;31(11):1398–1404. PubMed.
- Goss PE, Ingle JN, Alés-Martínez JE, et al. Exemestane for breast-cancer prevention in postmenopausal women. N Engl J Med. 2011;364(25):2381–2391. PubMed.
- Cheung AM, Tile L, Cardew S, et al. Bone density and structure in healthy postmenopausal women treated with exemestane for the primary prevention of breast cancer: a nested substudy of the MAP.3 randomised controlled trial. Lancet Oncol. 2012;13(3):275–284. PubMed.
- Pagani O, Regan MM, Walley BA, et al. Adjuvant exemestane with ovarian suppression in premenopausal breast cancer. N Engl J Med. 2014;371(2):107–118. PubMed.
- Mauras N, Lima J, Patel D, et al. Pharmacokinetics and dose finding of a potent aromatase inhibitor, aromasin (exemestane), in young males. J Clin Endocrinol Metab. 2003;88(12):5951–5956. PubMed.
- Ariazi EA, Leitão A, Oprea TI, et al. Exemestane’s 17-hydroxylated metabolite exerts biological effects as an androgen. Mol Cancer Ther. 2007;6(11):2817–2827. PubMed.
- Burnett-Bowie SA, McKay EA, Lee H, Leder BZ. Effects of aromatase inhibition on bone mineral density and bone turnover in older men with low testosterone levels. J Clin Endocrinol Metab. 2009;94(12):4785–4792. PubMed.
- German Sport University Cologne, Institute of Biochemistry. S4 – Hormones and Metabolic Modulators (WADA Prohibited List, January 1, 2026). DSHS Köln.