ENHANCED TRANSDERMAL DELIVERY OF TESTOSTERONE - A NEW PHYSIOLOGICAL APPROACH FOR ANDROGEN REPLACEMENT IN HYPOGONADAL MEN

This report describes the rationale, development and initial clinical testing of a new modality for the treatment of hypogonadal men - an en hanced transdermal delivery system (TDS) for administering native test osterone. In contrast to the experimental trans-scrotal testosterone p atches, the enhanced testosterone TDS can be applied to non-scrotal sk in sites, such as the back, chest, arms, etc. A one-month pilot study in six hypogonadal men shows that the nightly application of two patch es (for 24 h) delivers approximately 4 to 7 mg of testosterone per day , and produces testosterone plasma levels that closely mimic the magni tude and time course of the normal circadian rhythm seen in healthy yo ung men. Moreover, the enhanced delivery of testosterone across non-sc rotal skin, is not associated with any appreciable degree of transderm al first-pass metabolism, and therefore produces physiological levels and patterns of dihydrotestosterone (DHT) and estradiol (E2). In all b ut one subject, skin tolerability has been acceptable. During 7 months of treatment in two patients, hormone levels have remained within the normal range, tolerability has been good, and subjective improvements in sexual function and well being have been reported. In comparison t o other available methods of androgen replacement therapy (i.e. testos terone-ester injections, synthetic oral agents and testosterone pellet implants), we believe that the enhanced transdermal delivery of nativ e testosterone promises to be a more physiological and patient-friendl y approach for the treatment of hypogonadal men.