Exemestane (FCE 24304), a new steroidal aromatase inhibitor

J Steroid Biochem Mol Biol. 1992 Sep;43(1-3):137-43. doi: 10.1016/0960-0760(92)90198-r.


Exemestane (FCE 24304; 6-methylenandrosta-1,4-diene-3,17-dione) is a novel orally active irreversible aromatase inhibitor. Its in vitro and in vivo pharmacological properties have been compared to 4-hydroxyandrostenedione (4-OHA). In preincubation studies with human placental aromatase, exemestane, like 4-OHA, showed enzyme inactivating properties with a similar affinity (Ki 26 vs 29 nM) and a lower rate of inactivation (t1/2 13.9 vs 2.1 min). Conversely, when tested in pregnant mares' serum gonadotropin-treated rats, exemestane was more potent in reducing microsomal ovarian aromatase activity than 4-OHA, after both subcutaneous (ED50 1.8 vs 3.1 mg/kg) and oral dosing (ED50 3.7 vs greater than 100 mg/kg). No interference of exemestane on desmolase or 5 alpha-reductase activity was found. The compound did not show any relevant binding affinity to steroidal receptors, but slight binding to the androgen receptor (approximately 0.2% of dihydrotestosterone), like 4-OHA. In the first phase I trial, healthy postmenopausal volunteers were given single oral doses of exemestane, ranging from 0.5 to 800 mg, and plasma [estrone (E1), estradiol (E2) and estrone sulphate (E1S)] and urinary estrogens (E1 and E2) were measured up to 5-8 days. The minimal effective dose in decreasing estrogens was 5 mg. At 25 mg the maximal suppression was observed at day 3: plasma estrogens fell to 35 (E1), 39 (E2) and 28% (E1S), and urinary estrogens fell to 20 (E1) and 25% (E2) of basal values, these effects still persisting on day 5. No effects on plasma levels of cortisol, aldosterone, 17-hydroxyprogesterone, DHEAS, LH and FSH, and no significant adverse events were observed up to the highest tested dose of 800 mg exemestane.

Publication types

  • Clinical Trial
  • Review

MeSH terms

  • 5-alpha Reductase Inhibitors
  • Androgens / pharmacology
  • Androstadienes / metabolism
  • Androstadienes / pharmacology*
  • Androstenedione / analogs & derivatives
  • Androstenedione / metabolism
  • Androstenedione / pharmacology
  • Animals
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology*
  • Aromatase Inhibitors*
  • Humans
  • Lyases / antagonists & inhibitors
  • Receptors, Steroid / metabolism


  • 5-alpha Reductase Inhibitors
  • Androgens
  • Androstadienes
  • Antineoplastic Agents
  • Aromatase Inhibitors
  • Receptors, Steroid
  • Androstenedione
  • Lyases
  • exemestane
  • formestane