Androgens in Health and Disease.pdf - E Library

324 Matsumoto
Androgel 5 g (50 mg of T) and 10 g (100 mg of T) daily produced serum T concentrations
in the mid- and high-normal range, respectively, compared to Androderm 5 mg daily that
produced serum T levels in the low- to mid-normal range (Fig. 1B) (23). After 2 wk of
daily use, morning serum T levels are measured in order to assess the adequacy of T
delivery. AndroGel may also produce serum DHT levels above the normal range, probably
as a result of the large surface area of skin covered. However, local skin irritation
occurs in ≤ 5% of patients. The major limiting factor to the use of AndroGel for androgen-replacement
therapy is cost. It is the most expensive T formulation that is available,
and if more than one packet (e.g., 5 g) of AndroGel is required for adequate replacement,
the cost is prohibitive for most patients. There is also concern with this formulation
regarding transfer of T from application sites on the skin of patients to women (especially
pregnant women) and children. Precautions to minimize potential transfer of T to others
include thorough washing of hands immediately after application of AndroGel, covering
application sites with clothing, and thorough washing of areas that come into contact
with application sites. Also, 5–6 h (and occasionally as soon as 1–2 h) after application,
showering is permitted that washes off residual T on the surface of the skin with minimal
effect on the absorption of T from subcutaneous sites.
Subcutaneous T Pellets
Testosterone pellets (Testopel Pellets, Bartor Pharmacal, Rye, NY), 225—450 mg,
(three to six 75-mg pellets) implanted subcutaneously every 3–4 mo are available for
long-term androgen-replacement therapy in hypogonadal men, but is very seldom used
in the United States. Outside of the United States, subcutaneous implantation of T pellets
has been used more commonly for androgen replacement. Using a different formulation,
subcutaneous implantation of 600–1200 mg (three to six 200-mg pellets) is accomplished
using a trocar that is introduced through a small skin incision (57–59). These T
implants produce sustained, nearly zero-order release of T into circulation, and maintain
steady-state physiological serum T levels for 4–6 mo. Because a minor surgical procedure
is required two to three times yearly to implant a large number pellets and there is
a potential for extrusion and other local side effects and difficulty in removing pellets if
necessary, this method of T replacement is not acceptable to many hypogonadal men.
ANDROGEN FORMULATIONS UNDER DEVELOPMENT
Recently, there has been an eruption of interest by pharmaceutical companies in
developing new and possibly more selective androgen formulations or compounds. This
interest has been ignited in part by the realization that male hypogonadism is a common
clinical disorder, but also by the potential for expanded indications for androgen treatments
(e.g., chronic illnesses and wasting syndromes, age-related androgen deficiency
[andropause] and hormonal male contraception).
There is considerable interest in developing new short-acting T formulations—in
particular, orally active preparations—both for androgen-replacement therapy of
hypogonadal men and low-dose androgen supplementation. In countries outside the
United States, an oral, 17β-hydroxyl ester, T undecanoate has been available for many
years and used to provide safe and effective androgen replacement in hypogonadal men
(24,60). Unlike oral 17α-alkylated androgens, T undecanoate formulated in oleic acid
is absorbed from the gastrointestinal tract directly into the lymphatic system, bypassing