Pharmacokinetics of a new transdermal testosterone gel in gonadotrophin-suppressed normal men.
OBJECTIVE
In a phase I single-centre, open, randomized study, the pharmacokinetics of two doses of a transdermal testosterone gel containing 2.5% testosterone were evaluated in 26 healthy male volunteers.


METHODS
To eliminate the influence of endogenous serum testosterone, gonadotrophins and endogenous testosterone secretion were suppressed by a single intramuscular injection of 400 mg norethisterone enanthate. Fourteen men applied 5.0 g and 12 men applied 2.5 g testosterone gel daily for 10 days. Half the men in each group washed the gel off 10 min after it had been applied.


RESULTS
In all the men, a marked suppression of LH, FSH, testosterone, dihydrotestosterone (DHT) and oestradiol was observed after norethisterone treatment. Physiological serum concentrations of testosterone were restored during the 10-day treatment period in the group of men applying 5.0 g testosterone gel. Increasing serum concentrations of testosterone from day 1 to day 10 were observed. Oestradiol and DHT concentrations did not exceed normal values. Washing 10 min after gel application did not influence the resorption of testosterone. A dose of 2.5 g testosterone gel was insufficient to achieve physiological serum concentrations of testosterone.


CONCLUSIONS
Testosterone replacement treatment with 5.0 g of this 2.5% testosterone gel is able to achieve constant physiological testosterone concentrations in gonadotrophin-suppressed men. Washing the skin after 10 min does not influence the pharmacokinetic profile and thus significantly reduces the risk of contamination of female partners or infants.
Rolf
C
C
Institute of Reproductive Medicine of the University, Domagkstr. 11, D-48129 Munster, Germany.
Kemper
S
S
Lemmnitz
G
G
Eickenberg
U
U
Nieschlag
E
E
D000328:Adult; D004305:Dose-Response Relationship, Drug; D005782:Gels; D006062:Gonadotropins / Q000037:antagonists & inhibitors*; D020249:Hormone Replacement Therapy; D006801:Humans; D007273:Injections, Intramuscular; D008297:Male; D009640:Norethindrone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D013739:Testosterone / Q000008:administration & dosage* / Q000009:adverse effects / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics*
D005782:Gels; D006062:Gonadotropins; D013739:Testosterone; C024319:norethindrone enanthate; D009640:Norethindrone