title: Estrogen suppression in premenopausal women following 8 weeks of treatment with exemestane and triptorelin versus triptorelin alone.
abstract: BACKGROUND
  Luteinizing hormone-releasing hormone (LHRH) agonists (e.g., triptorelin) reduce ovarian estrogen production in premenopausal women with hormone-sensitive breast cancer. Aromatase inhibitors (e.g., exemestane) inhibit extraovarian production of estrogen and may further reduce circulating estrogens when combined with an LHRH agonist.
  
  
  METHODS
  Healthy premenopausal women were randomized to receive 3.75 mg triptorelin (T) on days 1 and 29 with 25 mg exemestane (EX) or matched placebo once daily for 8 weeks, from day 1 to day 56. The primary objective was to evaluate the effect of T +/- EX on estradiol (E(2)) suppression by comparing the AUC(day 36-57 )for the 2 treatments. Secondary objectives included evaluation of estrone (E(1)), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) suppression; effects of EX on the T-induced gonadotrophin and estrogen flare; pharmacokinetics (PK); and safety.
  
  
  RESULTS
  Twenty-eight (14 in each arm) were evaluable for efficacy and PK. Mean plasma estrogen levels (AUC(day 36-57)) were significantly lower for subjects who received T + EX than for subjects who received T alone (20.6 vs. 54.0 pg d/ml [-62%; P < 0.05], and 38.9 vs. 198.0 pg d/ml [-80%; P < 0.01] for E(2) and E(1), respectively). Coadministration of EX did not affect the initial flare or subsequent suppression of LH and FSH following the first dose of T, or the PK of T. Both treatments were well tolerated.
  
  
  CONCLUSIONS
  Coadministration of T and EX resulted in greater estrogen suppression than when T was given alone. These findings could translate into improved clinical outcomes for premenopausal breast cancer patients receiving LHRH agonists.
authors.affiliation: Nerviano Medical Sciences, Nerviano, Italy.
authors.forename: Maria Gabriella
authors.initials: MG
authors.lastname: Jannuzzo
authors.forename: Enrico
authors.initials: E
authors.lastname: Di Salle
authors.forename: Riccardo
authors.initials: R
authors.lastname: Spinelli
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Pirotta
authors.forename: Peter
authors.initials: P
authors.lastname: Buchan
authors.forename: Akintunde
authors.initials: A
authors.lastname: Bello
mesh_terms: D000328:Adult; D000730:Androstadienes / Q000494:pharmacology* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D004311:Double-Blind Method; D004958:Estradiol / Q000096:biosynthesis*; D004970:Estrone / Q000096:biosynthesis; D005260:Female; D006062:Gonadotropins / Q000096:biosynthesis; D006801:Humans; D010053:Ovary / Q000187:drug effects; D017697:Premenopause; D017329:Triptorelin Pamoate / Q000494:pharmacology* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000730:Androstadienes; D000970:Antineoplastic Agents; D006062:Gonadotropins; D017329:Triptorelin Pamoate; D004970:Estrone; D004958:Estradiol; C056516:exemestane