title: Dose-finding study of oral desogestrel with testosterone pellets for suppression of the pituitary-testicular axis in normal men.
abstract: Prototype hormonal male contraceptive regimens generally achieve only incomplete suppression to azoospermia with potentially adverse metabolic effects. We have carried out a short-term dose-finding study to investigate the potential of an oral gestogen, desogestrel, with testosterone pellets. Normal men received a single dose of 300 mg testosterone with 75 microg, 150 microg or 300 microg desogestrel daily for 8 weeks (n = 10 per group). LH and FSH were rapidly suppressed, with little difference between groups. Testosterone concentrations fell slightly during treatment with evidence of a linear dosage effect. Plasma inhibin B showed minor changes, but in seminal plasma it was suppressed, becoming undetectable in all men in the 300 microg desogestrel group. There were no significant changes in lipoproteins, fibrinogen or sexual behaviour during treatment, and minor falls in haematocrit and haemoglobin concentration. Sperm concentration fell in a dose-dependent manner, with three men, one man and seven men in the three groups respectively achieving severe oligozoospermia (<3 x 10(6)/ml), and three men achieving azoospermia in the 300 microg group despite the short duration of the study. The combination of oral desogestrel with depot testosterone thus results in profound suppression of gonadotrophin secretion without adverse metabolic or behavioural effects. Desogestrel with a long-acting testosterone preparation is a promising approach to hormonal male contraception.
authors.affiliation: Department of Obstetrics and Gynaecology, Centre for Reproductive Biology, University of Edinburgh, UK.
authors.forename: C W
authors.initials: CW
authors.lastname: Martin
authors.forename: S C
authors.initials: SC
authors.lastname: Riley
authors.forename: D
authors.initials: D
authors.lastname: Everington
authors.forename: N P
authors.initials: NP
authors.lastname: Groome
authors.forename: R A
authors.initials: RA
authors.lastname: Riemersma
authors.forename: D T
authors.initials: DT
authors.lastname: Baird
authors.forename: R A
authors.initials: RA
authors.lastname: Anderson
mesh_terms: D000284:Administration, Oral; D000328:Adult; D003280:Contraceptives, Oral, Synthetic / Q000008:administration & dosage / Q000494:pharmacology; D003692:Delayed-Action Preparations; D017135:Desogestrel / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000097:blood; D005640:Follicle Stimulating Hormone / Q000037:antagonists & inhibitors / Q000097:blood; D006801:Humans; D007265:Inhibins / Q000037:antagonists & inhibitors / Q000097:blood; D007986:Luteinizing Hormone / Q000037:antagonists & inhibitors / Q000097:blood; D008297:Male; D009845:Oligospermia / Q000139:chemically induced; D010902:Pituitary Gland / Q000187:drug effects*; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000097:blood; D012661:Semen / Q000378:metabolism; D012738:Sex Hormone-Binding Globulin / Q000032:analysis; D012725:Sexual Behavior / Q000187:drug effects; D013076:Sperm Count / Q000187:drug effects; D013737:Testis / Q000187:drug effects*; D013739:Testosterone / Q000008:administration & dosage* / Q000097:blood / Q000494:pharmacology
chemical_list: D003280:Contraceptives, Oral, Synthetic; D003692:Delayed-Action Preparations; D020033:Protein Isoforms; D012738:Sex Hormone-Binding Globulin; D013739:Testosterone; D004958:Estradiol; D007265:Inhibins; D017135:Desogestrel; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone