Gonadotrophin and testosterone suppression by 7alpha-methyl-19-nortestosterone acetate administered by subdermal implant to healthy men.
The synthetic androgen 7alpha-methyl-19-nortestosterone (MENT) is a potent suppressor of gonadotrophin that has several advantages for long term administration to normal or hypoandrogenic men. The aim of this study was to examine MENT serum concentrations following subdermal insertion of MENT acetate (MENT Ac) implants and their effects on gonadotrophins, testosterone, dihydrotestosterone (DHT), sex hormone-binding globulin, prostate specific antigen and insulin-like growth factor-1 serum concentrations in normal men. 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 daily dose delivered in vivo by one implant was approximately 500 microg. One, two or four MENT Ac implants produced dose dependent and sustained serum MENT concentrations for the entire duration of treatment of 0.7 +/- 0.1, 1.2 +/- 0.1 and 2.0 +/- 0.1 nmol/l respectively. This treatment induced a dose dependent decrease in gonadotrophin and androgen serum levels. Two and four implants induced maximal suppression that was maintained throughout treatment and was completely reversed after removal of the implants. The mean 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 reactions were reported by the volunteers and no consistent changes in clinical chemistry and haematology were found. These results indicate that MENT Ac implants are an efficient way of MENT administration and confirm the potent gonadotrophin and androgen suppressive effect of this drug.
Noé
G
G
Instituto Chileno de Medicina Reproductiva, Santiago, Chile.
Suvisaari
J
J
Martin
C
C
Moo-Young
A J
AJ
Sundaram
K
K
Saleh
S I
SI
Quintero
E
E
Croxatto
H B
HB
Lähteenmäki
P
P
D000328:Adult; D013196:Dihydrotestosterone / Q000097:blood; D004343:Drug Implants; D004963:Estrenes / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D005640:Follicle Stimulating Hormone / Q000097:blood*; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood*; D008297:Male; D008875:Middle Aged; D045167:Progesterone Congeners / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D017430:Prostate-Specific Antigen / Q000097:blood; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D013739:Testosterone / Q000097:blood*
D004343:Drug Implants; D004963:Estrenes; D045167:Progesterone Congeners; D012738:Sex Hormone-Binding Globulin; D013196:Dihydrotestosterone; D013739:Testosterone; C073330:methylestrenolone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D017430:Prostate-Specific Antigen