Gonadotrophin and testosterone suppression by 7a-methyl-19-nortestosterone acetate administered by subdermal implant to healthy men
Noe,Gabriela; Suvisaari,J.; Martin,C.W.; Moo-Young,Alfred J.; Sundaram,Kalyan; Saleh,Saleh I.; Quintero,E.; Croxatto,Horacio B.; Lahteenmaki,Pekka
Human Reproduction 14(9): 2200-2206
Publication date: 1999
The synthetic androgen 7-methyl-19-nortestosterone (MENT) isa potent suppressor of gonadotrophin that has several advantagesfor long term administration to normal or hypoandrogenic men.The aim of this study was to examine MENT serum concentrationsfollowing subdermal insertion of MENT acetate (MENT Ac) implantsand their effects on gonadotrophins, testosterone, dihydrotestosterone(DHT), sex hormone-binding globulin, prostate specific antigenand insulin-like growth factor-1 serum concentrations in normalmen. A total of 45 healthy men were recruited at three clinics.Each subject received one, two or four implants for 28 days.Serum samples were obtained before insertion and on days 8,15, 22, 29, 36 and 43 after implant insertion. The average dailydose delivered in vivo by one implant was ~500 µg. One,two or four MENT Ac implants produced dose dependent and sustainedserum MENT concentrations for the entire duration of treatmentof 0.7 ± 0.1, 1.2 ± 0.1 and 2.0 ± 0.1 nmol/lrespectively. This treatment induced a dose dependent decreasein gonadotrophin and androgen serum levels. Two and four implantsinduced maximal suppression that was maintained throughout treatmentand was completely reversed after removal of the implants. Themean decreases were 93 ± 1% for testosterone, 80 ±3% for DHT, 97 ± 1% for luteinizing hormone and 95 ±1% for follicle stimulating hormone. No serious adverse reactionswere reported by the volunteers and no consistent changes inclinical chemistry and haematology were found. These resultsindicate that MENT Ac implants are an efficient way of MENTadministration and confirm the potent gonadotrophin and androgensuppressive effect of this drug.