Another topic of increasing interest is the functional interlink between the hypothalamic-pituitary-gonadal and the hypothalamic-pituitary-adrenal axis. Manipulation of one hormonal system is not without effect on the other. In humans, the underlying mechanisms and modalities are affected by stress. This dual systems approach holds promise in establishing further links between the neuroendocrinology of stress and the central bases of sex-dependent disorders, including psychiatric, cardiovascular and metabolic disease.1
Nevertheless, a brief review of the biologic effects of androgens2 indicates that the consequences of testosterone deficiency are severe and in some cases dangerous and debilitating and may be influenced beneficially by testosterone therapy.
| Target tissue | Biologic effect |
| Reproductive tissues | Stimulation of prenatal differentiation and pubertal devel- opment of the testes, penis, epididymis, seminal vesicles, and prostate. In adults: Maintenance of these tissues, central and peripheral modulation of erectile function,3 initiation and maintenance of spermatogenesis. |
| Sexual function and behavior | Key role in stimulating and maintaining sexual function in men. Hypogonadal men: Testosterone induces greater interest in sexual activity, while suppression of testosterone levels to the range of astrates in normal young men reduces sexual desire, sexual fantasies, and spontaneous erections. In non-human primates, aggression is directly correlated with serum testosterone levels, while in humans self-assessed aggression is less clearly correlated. |
| Muscle | Androgens increase nitrogen balance, lean body mass, and body weight. Testosterone increases the size of the muscle cells with little effect on their number. |
| Skin and hair | Increase in sebum production with acne as a possible consequence. Male hair pattern. |
| Liver | Increased synthesis of clotting factors, hepatic triglyc-eride lipase, sialic acid, α1-antitrypsin and haptoglobin. Decreased production of SHBG, other hormone-binding proteins, transferrin and fibrinogen. |
| Lipids | Androgens decrease HDL cholesterol plasma concentrations in adolescent boys with delayed puberty and in hypogonadal men. |
| Bone | Hypogonadism is a risk factor for osteoporosis in men.4 Androgens stimulate the proliferation of bone cells in vitro. |
| Hematology, immunology | Stimulation of the erythropoietin production in the kidneys, Androgens exert suppressive effects on both humoral and cellular immune responses and seem to represent natural anti-inflammatory hormones.5.6 |
Table 1. Biologic effects of androgens.
References:
1.Viau V: Functional cross-talk between the hypothalamic-pituitary-gonadal and -adrenal axes. J Neuroendocrinol 2002; 14: 506–513.
2. Bagatell CJ, Bremner WJ: Androgens in men-uses and abuses. Drug Ther 1996; 334 (11): 707–714.
3. Foresta C, Caretta N, Rossato M, Garolla A, Ferlin A: Role of androgens in erectile function. J Urol 2004; 171: 2358–2362.
4. Hansen KA, Tho SPT: Androgens and bone health. Semin Reprod Endocrinol 1998;16 (2): 129–134.
5. Cutolo M, Seriolo B, Villaggio B, Pizzorni C, Craviotto C, Sulli A: Androgens and estrogens modulate the immune and inflammatory responses in rheumatoid arthritis. Ann. N.Y. Acad. Sci. 2002; 966: 131–142.
6. Wilder RL: Neuroimmunoendocrinology of the rheumatic diseases. Ann. N.Y. Acad. Sci. 2002; 966: 13–19.