The liver enzyme CYP3A4 oxidizes the methylidene group in position 6, and the 17-keto group (on the five-membered ring) is reduced by aldo-keto reductases to an alcohol. Of the resulting metabolites, 40% are excreted via the urine and 40% via the feces within a week. The original substance accounts for only 1% of excretion in the urine. The terminal half-life is 24 hours. Chemistry Exemestane is known chemically as 6-methylideneandrosta-1,4-diene-3,17-dione. Like the aromatase inhibitors formestane and atamestane, exemestane is a steroid that is structurally similar to 4-androstenedione, the natural substrate of aromatase. It is distinguished from the natural substance only by the methylidene group in position 6 and an additional double bond in position 1. Pure exemestane is a white to off-white powder that is soluble in DMSO to at least 20 mg/mL. Optical rotation [α]D is +250 to 300° (per g/100 cm³ and decimetre at 589 nm wavelength). Society and culture Performance enhancement Exemestane has been used in doping to raise luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels, which in turn increases the ratio of male over female sexual hormones and so improves performance. The drug also counteracts gynecomastia as well as fat and water retention following excessive aromatase production due to testosterone doping. Along with other aromatase inhibitors, exemestane is on the World Anti-Doping Agency's list of prohibited substances. Research Oral exemestane 25 mg/day for 2–3 years of adjuvant therapy was generally more effective than 5 years of continuous adjuvant tamoxifen in the treatment of postmenopausal women with early-stage estrogen receptor-positive/unknown receptor status breast in a large well-designed trial. Preliminary data from the open-label TEAM trial comparing exemestane with tamoxifen indicated in 2009 that exemestane 25 mg/day is also effective in the primary adjuvant treatment of early-stage breast cancer in postmenopausal women. Interim phase III trial results in 2011 showed that adding everolimus to exemestane therapy against advanced breast cancer can significantly improve progression-free survival compared with exemestane therapy alone. A Phase III trial was reported in 2011, concluding that the use of exemestane in postmenopausal women at an increased risk for breast cancer reduced the incidence of invasive breast cancer. In 4,560 women, after 35 months, the administration of exemestane at a dose of 25 mg/day resulted in a 65% reduction in the risk of breast cancer compared with placebo; annual incidence rates were 0.19% and 0.55%, respectively (hazard ratio: 0.35; 95% CI [0.18-0.70]; p