Pharmacokinetics of a new transdermal testosterone gel in gonadotrophin-suppressed normal men

Abstract

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. Design: 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. Conclusion: 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.

Transdermal Estradiol and Testosterone Transfer in Man: Existence, Models, and Strategies for Prevention

“…Transdermal hormone transfer from dosed individual to naïve interpersonal contact can occur [36,39,42,[45][46][47] and may cause clinically significant hormone imbalance and adverse events [21][22][23][24][25][26][27][28] . Transfer from parent to young child, as has been previously described [29][30][31][32][33][34][35] , is concerning.…”

“…While transdermal delivery of estradiol and testosterone may be clinically relevant for the treated individual, unintentional transfer to a close contact can cause hormone imbalance and adverse effects. These imbalances may increase the risk of adverse cardiac events in men; cause hyperandrogenism, hirsutism, acne, coarsening of the voice, clitoris hypertrophy, and male-pattern baldness in women; and can lead to early puberty changes, virilization, and premature epiphyseal closure of the bones in children [21][22][23][24][25][26][27][28] . Cases of skin-to-skin transfer of transdermal testosterone products from father to son have caused precocious puberty and/or pronounced virilization [29][30][31][32][33][34][35] .…”

Testosterone substitution with a new transdermal, hydroalcoholic gel applied to scrotal or non-scrotal skin: a multicentre trial

“…After 10 min, the alcohol, a gel ingredient serving as enhancer for transdermal permeation, evaporates. Preliminary studies had demonstrated that the removal of TGW 10 min after application resulted in sufficient testosterone serum levels in gonadotrophin-suppressed normal men after scrotal or non-scrotal application (6).…”

“…We have compared this new gel (TGW , Testocur w ) with a non-scrotal patch (Androderm w 2.5, AstraZeneca, Wedel, Germany), the only transdermal application available when the study started in 2002, in a three-arm, parallel-group, open, randomised, controlled, multicentre, clinical trial over a period of 24 weeks. In preliminary studies, we have analysed the pharmacokinetics and interpersonal transfer of TGW in healthy, gonadotropin-suppressed men (5,6), whereas this study evaluates efficacy, safety, tolerability and pharmacokinetic properties of TGW in hypogonadal patients during long-term treatment. Most of the patients suffered from primary or secondary hypogonadism; some had late-onset hypogonadism.…”

Der Altershypogonadismus des Mannes

“…In den USA, wo das Präparat seit 2 Jahren erhältlich ist, konnten recht positive Erfahrung hinsichtlich Wirksamkeit,Verträglichkeit und Akzeptanz gemacht werden [35].Da ein relativ großer Hautbereich für die Applikation benötigt wird,ist eine Übertragung auf Kontaktpersonen nicht grundsätzlich auszuschließen. Eine Kontamination durch ein Gel auf Alkoholbasis ist aufgrund der raschen Resorption jedoch unwahrscheinlich [25,26]. Solche Übertragungen werden jedoch von nicht zugelassenen Testosteroncremes und -gelen, die nach diversen Rezepten individuell angefertigt werden, berichtet.…”