Use of Testosterone and Anabolic Steroids in Patients Who Have HIV

Decreases in energy, sense of well-being, libido, muscle strength and muscle mass occur often in patients who have persistent diseases, such as HIV infection. When these symptoms were first recognized in HIV-positive patients, they were thought to be manifestations of HIV infection but may possibly be associated with hypothyroidism. Most HIV-infected patients who have hypogonadism have secondary or central hypogonadism, not prime testicular failure. In HIV-infected hypogonadal men, administration of testosterone appears to increase overweight-free mass, muscle mass, and quality of living (increased libido, erectile role, and sense of well-being). Similarly, anabolic steroid hormones appear to increase lean body weight and decrease fat content. Although androgens have been used for the treatment of HIV-related wasting and for hypogonadism, many questions remain unanswered, including those regarding the large-term effects, if any, of suppression of luteinizing hormone and follicle-stimulating hormone, as well as the long-term possibilities of malignancy of the prostate and of hepatocellular cancer. Appropriate doses of the various preparations of testosterone and anabolic steroids have not been determined. For several years, androgens particularly testosterone have been used for the treatment of HIV-related wasting. Despite a substantial cadaver of literature on the topic, there remain a big number of unanswered questions. Perhaps the best place to begin a review of the role of androgens in counteracting wasting is to recall the standard physiology of testosterone.

The testes have 2 principal functions - spermatogenesis and the secretion of testosterone. Spermatogenesis is a function of the Sertoli cells and is stimulated by follicle-stimulating hormone (FSH), which is secreted by the pituitary gland. Negative feedback on the pituitary gland to command the release of FSH is provided by the hormone inhibin, which is thought to be secreted by either the Sertoli cells or the cells of the spermatogenic tubules.
The compound of testosterone begins with the mobilization of cholesterol by the steroid acute regulator protein. The dominant steps implicated in synthesizing testosterone from cholesterol are the development of pregnenolone, 17- -hydroxypregnenolone, dehydroepiandrosterone (DHEA), androstenedione, and testosterone. A less dominant pathway involves the formation of progesterone from pregnenolone, followed by 17-hydroxyprogesterone, androstenedione, and testosterone.

Regardless of the pathway, the rate-limiting step in the synthesis of testosterone is the primary formation of pregnenolone from cholesterol. This movement is catalyzed by the enzyme P-450scc (cholesterol side-chain cleavage enzyme) and is inducible by luteinizing hormone (LH) secreted by the pituitary gland. Once released from the testes, testosterone may be converted to dihydrotestosterone (DHT) in various target cells by the enzyme 5 -reductase. Testosterone may also be converted to estradiol by the enzyme P-450arom (aromatase). Testosterone regulates the secreting of LH through a negative feedback structure. Under normal circumstances, the pituitary gland is very sensitive to the feedback provided by testosterone. In patients who have low blood levels of testosterone, blood levels of LH are increased. Testosterone also acts on the hypothalamic-pituitary axis to suppress the stimulating action of gonadotropin-releasing hormone on the pituitary release of LH.