title: Demonstration of progesterone receptor-mediated gonadotrophin suppression in the human male.
abstract: OBJECTIVE
  Synthetic gestogens in combination with testosterone have potential as a male hormonal contraceptive, predominantly acting by augmenting suppression of gonadotrophin secretion. Little is known, however, of the effects of gestogens in the male. Gestogens have affinity for both androgen and progesterone receptors but the relative contribution of action at these two receptors in gonadotrophin suppression remains unclear. In this study the effects of progesterone, with no significant androgen-receptor affinity are compared to desogestrel, a synthetic gestogen with relatively low affinity for the androgen receptor, on gonadotrophin secretion in normal men.
  
  
  METHODS
  Subjects received either 50 mg progesterone intramuscularly (i.m.) or 300 micro g desogestrel orally daily for 7 days. Frequent blood sampling over 12 h was undertaken before and after drug administration. GnRH [100 micro g intravenously (i.v.)] was administered 2 h before the end of the frequent sampling period.
  
  
  METHODS
  Twenty healthy men were randomly allocated to the two treatment groups.
  
  
  RESULTS
  Both progesterone and desogestrel administration resulted in decreases in the concentration of both LH and FSH secretion, as well as testosterone. Analysis of the pulsatile nature of LH secretion indicated that both treatments reduced LH pulse amplitude, and that progesterone reduced LH pulse frequency. Progesterone, but not desogestrel, treatment also reduced the increase in LH secretion in response to GnRH.
  
  
  CONCLUSIONS
  The effects of progesterone were at least as marked as those of a maximally effective dose of desogestrel. As progesterone has negligible affinity for the androgen receptor, these results are compatible with the suppressive effects of synthetic 19-norgestogens on gonadotrophin secretion in the male being mediated via the progesterone receptor, with its androgenicity contributing minimally to gonadotrophin suppression.
authors.affiliation: Contraceptive Development Network and MRC Human Reproductive Science Unit, Centre for Reproductive Biology, University of Edinburgh, Edinburgh, UK.
authors.forename: B M
authors.initials: BM
authors.lastname: Brady
authors.forename: R A
authors.initials: RA
authors.lastname: Anderson
authors.forename: D
authors.initials: D
authors.lastname: Kinniburgh
authors.forename: D T
authors.initials: DT
authors.lastname: Baird
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D003272:Contraceptive Agents, Male / Q000494:pharmacology; D003864:Depression, Chemical; D017135:Desogestrel; D005640:Follicle Stimulating Hormone / Q000097:blood; D007987:Gonadotropin-Releasing Hormone; D006065:Gonadotropins, Pituitary / Q000097:blood*; D006728:Hormones; D006801:Humans; D007265:Inhibins / Q000097:blood; D007273:Injections, Intramuscular; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D011374:Progesterone; D011980:Receptors, Progesterone / Q000187:drug effects*; D013739:Testosterone / Q000097:blood
chemical_list: D003272:Contraceptive Agents, Male; D006065:Gonadotropins, Pituitary; D006728:Hormones; D011980:Receptors, Progesterone; C422364:inhibin B; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D011374:Progesterone; D007265:Inhibins; D017135:Desogestrel; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone