Actions of Testosterone and signs of testosterone deficiency

The actions of testosterone in peripheral tissues are mediated by the action of DHT on androgen receptors. Testosterone accounts for sexual differentiation and maturation and the development of secondary sex characteristics at puberty. In addition to its action on the hypothalamic-pituitary axis, testosterone acts on the cerebral cortex. Many of the behavioral characteristics that we associate with maleness are, to some extent, the result of the action of either testosterone or DHT on the brain. For example, in the limbic system, testosterone and DHT stimulate libido. These hormones also increase skeletal muscle mass, cardiac muscle mass, and the formation and mineralization of bone, and they stimulate erythropoiesis. In short, testosterone and DHT have far-reaching effects, which extend beyond sexual differentiation and fertility.

It follows, then, that the symptoms and signs of testosterone deficiency, whether associated with AIDS or with other chronic diseases, include decreases in:
- Energy.
- Sense of well-being.
- Libido
- Muscle strength.
- Muscle mass.
- Erythropoiesis.
- Bone mineralization.

Early in the course of the AIDS epidemic, these symptoms were considered to be manifestations of AIDS, but some astute investigators recognized that they could be associated with a deficiency of testosterone.

About 60% of testosterone in the circulation is bound to sex hormone-binding globulin (SHBG); 38% is bound to albumin; and only 2% is unbound, or free. Testosterone that is bound to SHBG does not easily dissociate, but that bound to albumin can dissociate.

The laboratory assay for free testosterone is more expensive than that for total testosterone. Thus, many laboratories determine only the latter unless they are specifically requested to assay the former. The normal serum value for total testosterone in males is 280 to 1100 ng/dL (9.7 to 38.2 nmol/L); the normal serum level of free testosterone is 50 to 210 pg/mL (174 to 729 pmol/L).

Hypogonadism in HIV-Infected Patients:
Male hypogonadism is defined as the failure of spermatogenesis and the failure of synthesis of normal levels of testosterone by the testes. Two principal types of man hypogonadism -- primary (testicular failure) and secondary (failure of the hypothalamic-pituitary axis, also called central hypogonadism) exist. The differentiation between primary and secondary hypogonadism is relatively simple but is not made on the basis of the level of testosterone. In both conditions, the serum levels of testosterone will be low. Instead, measurement of the levels of the gonadotropins FSH and LH can help differentiate between primary and secondary hypogonadism. Serum levels of both FSH and LH will be normal or reduced in secondary hypogonadism but increased in primary testicular failure.
The early studies of HIV-infected patients indicated that most patients who had hypogonadism had secondary, or central, hypogonadism. Only rarely found to be a result of prime testicular failure, hypogonadism usually occurred because of opportunistic infection. In a study of 70 HIV-sure men seen at a Johns Hopkins University clinic, 19 were asymptomatic, 42 had AIDS, and 9 had what used to be called AIDS-related complex. Of the 42 patients who had AIDS, 66% reported decreased libido, 33% had erectile dysfunction, and 50% were found to have low serum levels of testosterone. Even asymptomatic, HIV-positive patients were establish to have decreased serum levels of testosterone. Seventy-five percent of the hypogonadal men had hypogonadotropic hypogonadism.