Steady serum testosterone levels in the low normal range mimicking circadian variation are attained after testosterone transdermal patch application (Fig. 2). The scrotal testosterone patch was the first to become available in the early 1990s, but this patch has been superseded by other transdermals. The scrotal testosterone patch is 60 cm in diameter and requires shaving or clipping of scrotal skin hair (86,87). There are two nonscrotal skin patches available in the United States. The smaller permeation-enhanced patch (Androderm) delivers 5 mg testosterone per day and produces serum testosterone in the low normal range (86-90). This smaller testosterone patch has a major side effect of causing skin irritation in up to 60% of subjects, leading to discontinuation in up to 10 to 15% of subjects (86-90). Preapplication of corticosteroid cream may reduce the skin irritation. The larger non-scrotal testosterone patches (Testoderm TTS) produce much less skin irritation but may not adhere well to the skin.
The most recent development in transdermal delivery are testosterone gels. Andro-gel and Testim are 1% testosterone hydroalcoholic gels that dry in a few minutes after application. The daily dose varies between 5 and 10 g, delivering 5 to 10 mg testosterone per day (~10 to 14% is bioavailable). Application of testosterone gels result in dose-dependent increase in serum testosterone levels. With gels, the levels of serum testosterone are relatively steady after a few days of application (91,92a). As with other testosterone preparations, positive effects on libido, mood, muscle size and strength and body fat have been demonstrated in hypogonadal men with testosterone gels. In addition, positive effects on BMD have been shown (93) and the effects persist for at least 3 yr. Because of the ease of application and flexibility of dosing, this method of testosterone replacement is acceptable to many hypogonadal men. A potential problem is the possibility of transfer of testosterone to women and children during close contact of skin surfaces. This can be avoided by wearing clothing or removing the residual testosterone on the skin with showering. Several other testosterone gels and creams are being developed.
In addition to testosterone gels, the potent androgen DHT gel has been studied as a treatment for hypogonadal younger (94) and older men (95-98). DHT improved sexual dysfunction in older partially androgen-deficient men but had minimal effect on muscle mass and strength (95,96). It is controversial whether DHT has significant benefits over testosterone as an androgen replacement therapy. DHT is not converted to estradiol (nonaromatizable androgen). Because some of the beneficial (and adverse effects) of testosterone have been attributed, at least in part, to its metabolite estradiol, it is not clear whether DHT will have a positive effect on bone mass, cognitive function, and fat mass (99) or be free from the problem of testosterone-induced gynecomastia.
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