Testosterone Replacement Therapy

Abstract

The benefits conferred by testosterone replacement therapy are substantial, both in the short term for the eradication of symptoms of androgen deficiency, and in the long term for the prevention of osteoporosis. As with any long-term treatment there are risks that must be considered, but overall the benefits achieved far outweigh potential risk. Ideally, androgen replacement therapy should provide physiological serum testosterone levels, as well as DHT and estradiol levels, and correct the clinical symptoms of androgen deficiency in hypogonadal men. This goal is difficult to achieve because the dose dependency of androgen-dependent physiological processes is not known. Androgen preparations that are currently available do not fulfill all criteria for an ideal androgen replacement therapy. Parenteral testosterone esters are effective, safe, practical, and inexpensive. The transdermal testosterone systems provide an alternative to testosterone esters in selected patients but these preparations are expensive. Ongoing studies are showing the benefits of testosterone replacement therapy in aging men, but there is concern about side effects on cardiovascular system and prostate. Thus, clinical decision regarding testosterone therapy in older men should be better defined.

Pharmacokinetics ofS-3-(4-acetylamino-phenoxy)-2-hydroxy-2-methyl-N-(4-nitro- 3-trifluoromethyl-phenyl)-propionamide in rats, a non-steroidal selective androgen receptor modulator

“…17-Alkylated testosterone derivatives (e.g. methyltestosterone and oxandrolone) are orally bioavailable, but they cause unacceptable hepatic toxicity, are less efficacious and are, therefore, not recommended for long-term administration (Heywood et al 1977,Ishak and Zimmerman 1987,Velazquez and Bellabarba Arata 1998. Another drawback of testosterone administration is the crossreactivity of both testosterone and its metabolites with other steroid hormone receptors (Wilson et al 1980,Bhasin andBremner 1997).…”

Pharmacodynamics of Selective Androgen Receptor Modulators

“…Unmodified testosterone is impractical for oral administration due to its low systematic bioavailability (Handelsman et al, 1990). Testosterone esters (e.g., testosterone propionate and testosterone enanthate) are presently the most widely used testosterone preparations, usually administered by intramuscular injection in oil vehicles (Snyder and Lawrence, 1980;Velazquez and Bellabarba Arata, 1998). A prolonged duration of action is achievable with these esters.…”

“…17␣-Alkylated testosterones (e.g., methyltestosterone and oxandrolone) can be given orally. Nevertheless, they often cause unacceptable hepatotoxicity and are less efficacious; hence, they are not recommended for long-term androgen therapy (Heywood et al, 1977;Ishak and Zimmerman, 1987;Velazquez and Bellabarba Arata, 1998). Another common concern about steroidal androgens is the undesirable effects resulting from the cross-reactivity of the androgens or their in vivo metabolites with steroid receptors other than the androgen receptor (AR) (Wilson et al, 1980;Bhasin and Bremner, 1997).…”

Evolution of delivery systems for testosterone administration

“…Testosterone plays an essential role in normal male development and in the maintenance of many male characteristics, including muscle mass and strength, bone density, and sexual function [1][2][3][4]. Androgen replacement therapy (ART) is indicated for androgen deficiency caused by testicular or pituitary disorders, which may be hereditary or acquired.…”