title: The effects of 1-month administration of asoprisnil (J867), a selective progesterone receptor modulator, in healthy premenopausal women.
abstract: BACKGROUND
  Asoprisnil (J867) is a novel selective progesterone receptor modulator (SPRM) that exhibits partial agonist and antagonist activities and tissue selective effects. This double-blind, dose-escalation study was conducted to evaluate the effects of asoprisnil in 60 regularly cycling premenopausal women.
  
  
  METHODS
  Asoprisnil or placebo was administered orally for 28 days starting at the beginning of the menstrual cycle in doses of 5 mg once daily (QD), 5 mg twice daily (BID), 10 mg QD, 25 mg QD, 25 mg BID and 50 mg BID. Within each dose group, two women were randomized to placebo and eight to asoprisnil. Progesterone concentrations indicative of luteinization were defined as at least one progesterone measurement during the luteal phase exceeding 3.5 ng/ml.
  
  
  RESULTS
  Asoprisnil consistently prolonged the menstrual cycle at doses > or = 10 mg QD. However, the effects on luteal phase progesterone indicative of luteinization were inconsistent and lacked dose dependency. Asoprisnil suppressed periovulatory estradiol but not below follicular phase levels. No significant changes were observed in cortisol and prolactin. Asoprisnil was well tolerated.
  
  
  CONCLUSIONS
  Asoprisnil reversibly suppressed menstruation at doses > or = 10 mg QD irrespective of the effect on luteal phase progesterone concentrations indicative of luteinization. It induces amenorrhea primarily by targeting the endometrium in the absence of estrogen deprivation.
authors.affiliation: TAP Pharmaceutical Products Inc., Lake Forest, IL 60045, USA. Kristof.Chwalisz@TAP.com
authors.forename: Kristof
authors.initials: K
authors.lastname: Chwalisz
authors.forename: Walter
authors.initials: W
authors.lastname: Elger
authors.forename: Therese
authors.initials: T
authors.lastname: Stickler
authors.forename: Cynthia
authors.initials: C
authors.lastname: Mattia-Goldberg
authors.forename: Lois
authors.initials: L
authors.lastname: Larsen
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood; D004311:Double-Blind Method; D004717:Endometrium / Q000166:cytology / Q000187:drug effects; D004958:Estradiol / Q000097:blood; D004963:Estrenes; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008183:Luteal Phase / Q000187:drug effects*; D034461:Luteinization / Q000187:drug effects; D007986:Luteinizing Hormone / Q000097:blood; D008875:Middle Aged; D009842:Oligopeptides; D010091:Oximes / Q000008:administration & dosage* / Q000009:adverse effects; D010120:Oxytocics / Q000008:administration & dosage* / Q000009:adverse effects; D017697:Premenopause; D011374:Progesterone / Q000097:blood; D011980:Receptors, Progesterone / Q000378:metabolism*; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism
chemical_list: D004963:Estrenes; D009842:Oligopeptides; D010091:Oximes; D010120:Oxytocics; D011980:Receptors, Progesterone; D012738:Sex Hormone-Binding Globulin; D011374:Progesterone; D004958:Estradiol; D019314:Dehydroepiandrosterone Sulfate; C118154:BIO 1211; C488516:asoprisnil; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D006854:Hydrocortisone