Exemestane

What exemestane is

Exemestane is a steroidal, irreversibly acting aromatase inhibitor and is prescription-only. It is approved for postmenopausal women with hormone-dependent breast cancer: as adjuvant treatment after two to three years of tamoxifen and in advanced disease after tamoxifen.

What is rated is the state of knowledge. For the approved use it is good, with two large randomized trials. For use in men – with low testosterone or for “estrogen control” alongside anabolic steroids – it is almost empty. The two other aromatase inhibitors, anastrozole and letrozole, have been studied considerably better in men.

How it works

The enzyme aromatase converts androgens into estrogens. Exemestane is chemically related to the natural substrate androstenedione. According to the US prescribing information, the enzyme processes it as a false substrate; the intermediate product binds permanently to the active site and shuts the enzyme down, which is referred to as “suicide inhibition”. At the approved dose, estrogens in postmenopausal women fall by at least 85 to 95 percent, and total aromatization in the body by 98 percent.

Unlike anastrozole and letrozole, exemestane is a steroid. It barely binds to the androgen receptor itself, at 0.28 percent of the binding of dihydrotestosterone; its breakdown product 17-dihydroexemestane binds about 100 times more strongly. In addition, SHBG falls in a dose-dependent manner. What this means clinically in men has not been studied.

What the studies show

IES: switching from tamoxifen to exemestane

Coombes 2007 (Lancet) randomized 4,724 postmenopausal women who were disease-free after two to three years of tamoxifen: switch to exemestane or continue tamoxifen up to a total of five years. After a mean of 55.7 months there were 354 versus 455 events, hazard ratio 0.76 (0.66 to 0.88; p = 0.0001). Deaths: 222 versus 261, hazard ratio 0.85 (0.71 to 1.02; p = 0.08); excluding the 122 patients with an estrogen receptor-negative tumor, 0.83 (p = 0.05). The authors speak of a modest survival benefit.

MAP.3: prevention

Goss 2011 (NEJM) gave 4,560 postmenopausal women with at least one risk factor exemestane or placebo in a double-blind design. After a mean of 35 months: 11 versus 32 invasive breast cancers, a relative reduction of the annual rate by 65 percent. Side effects were reported by 88 versus 85 percent (p = 0.003); there were no significant differences in fractures, cardiovascular events, other cancers and treatment-related deaths.

Mauras 2003: the only study in men

Mauras 2003 (J Clin Endocrinol Metab) gave 12 healthy young men aged 14 to 26 two doses of exemestane in a crossover design for 10 days each. Estradiol fell by 38 and 32 percent respectively, testosterone rose by 60 and 56 percent respectively. Blood lipids and IGF-1 remained unchanged. The half-life was 8.9 hours. The authors state that efficacy and safety with longer use need further study.

What estradiol deficiency does in men

Direct data on exemestane are missing, but the consequences of estrogen deficiency in men have been measured in studies with anastrozole. In 400 healthy men whose own hormone production was suppressed and replaced with testosterone gel, estrogen deficiency mainly explained the increase in body fat and contributed to the decline in sexual function (Finkelstein 2013). When aromatization was blocked, bone mineral density of the spine measured by CT fell markedly, regardless of the testosterone dose (Finkelstein 2016). Estradiol above 10 pg/ml together with testosterone above 200 ng/dl was generally sufficient to prevent increased bone resorption and falling bone mineral density.

Where the data stop

• Men over more than ten days. There is no study on bone, heart, blood lipids or sexual function with longer use.
• Alongside anabolic steroids. No controlled studies on lowering estradiol during anabolic steroid use were found in the research.
• Comparison with other aromatase inhibitors in men. Whether exemestane has advantages over anastrozole or letrozole in men has not been compared.
• The androgenic effect of the breakdown product. The receptor binding has been described in the laboratory; its significance in men is open.

Status, approval and legal

Exemestane is approved as Aromasin for the treatment of breast cancer in postmenopausal women. The US prescribing information names two indications: adjuvant treatment of estrogen receptor-positive early breast cancer after two to three years of tamoxifen up to a total of five years, and advanced breast cancer after tamoxifen. The approved dose is 25 mg once daily after a meal.

In Germany, exemestane is prescription-only (Annex 1 of the Prescription Drugs Ordinance, AMVV). Use in men is not approved.

In sport, exemestane is on the World Anti-Doping Agency’s 2026 Prohibited List under S4.1 aromatase inhibitors and is prohibited at all times, in and out of competition. In Germany it is listed in the annex of the Anti-Doping Act under hormone and metabolic modulators; this means that acquisition and possession in non-small quantities for the purpose of doping in sport are also prohibited.

Safety

In women, bone mineral density falls. In a sub-analysis of IES, it decreased by 3.1 percent at the lumbar spine after 24 months, compared with 0.2 percent on tamoxifen, and by 4.2 versus 0.3 percent at the femoral neck. The US prescribing information recommends, in osteoporosis or risk of osteoporosis, a bone density measurement at the start and a check of vitamin D levels before treatment begins. In MAP.3 there was no significant increase in fractures or cardiovascular events over three years.

For men there are no safety data beyond ten days. Studies with anastrozole show that estrogen deficiency in men affects body fat, sexual function and bone, even with sufficient testosterone. If you are prescribed an aromatase inhibitor, the question of bone mineral density and blood lipids belongs in the conversation.

Sources

• Coombes RC et al., Lancet 2007 – IES, switch to exemestane after 2–3 years of tamoxifen, 4,724 women
• Goss PE et al., N Engl J Med 2011 – MAP.3, exemestane for breast cancer prevention, 4,560 women
• Mauras N et al., J Clin Endocrinol Metab 2003 – pharmacokinetics and dose finding of exemestane in young men, crossover with 12 men, 10 days
• Finkelstein JS et al., N Engl J Med 2013 – testosterone, estradiol, body composition, strength and sexual function in 400 healthy men
• Finkelstein JS et al., J Clin Invest 2016 – testosterone, estradiol and bone in 400 healthy men
• US prescribing information Aromasin (DailyMed) – indications, dose, mechanism of action, bone mineral density
• German Prescription Drugs Ordinance (AMVV), Annex 1 – prescription requirement
• WADA Prohibited List 2026, informational German translation by NADA – S4.1 aromatase inhibitors, prohibited at all times
• German Anti-Doping Act, Annex – III. Hormone and metabolic modulators, 1. Aromatase inhibitors