Clinical Hypogonadism and Androgen Replacement Therapy: An Overview

Dana A. Ohl; Susanne A. Quallich

Disclosures

Urol Nurs. 2006;26(4):253-259,269. 

In This Article

Physiology of Testosterone

Testosterone is a cholesterol-based steroid hormone (Griffen & Wilson, 2003). This hormone exerts effects on the male body throughout the life cycle. The initial influence of testosterone is seen during the 7th week of fetal development when it leads to differentiation of the fetal genitourinary tract. The male fetus develops Leydig cells, which begin to produce testosterone. The testosterone then drives the development of the vas deferens, epididymis, and seminal vesicles. Beginning at 8 weeks, the testosterone masculinizes the external genitalia.

At puberty, testosterone begins to exert influence over the development of secondary sexual characteristics and anabolic processes (see Table 1 ). The pulsatile secretion of gonatropin-releasing hormone (GnRH) from the hypothalamus causes both luteinizing hormone (LH) and follicle-stimulating hormone (FSH) to be released from the anterior pituitary. The release of LH signals the Leydig cells to produce testosterone, resulting in the development of male secondary sex characteristics. The hypothalamic-pituitary axis (HPA) is controlled by a negative feedback loop. As the level of testosterone rises in the blood, GnRH and LH/FSH secretion decline.

The anabolic effects are manifest as overt physical changes in the male. Virilization of the individual becomes evident, as there are changes to body musculature and fat distribution. Bone growth and epiphysial closure are promoted. There is laryngeal enlargement and subsequent vocal cord thickening, as well as testicular growth and the initiation of spermatogenesis.

Once physical maturity has been achieved, testosterone has a more homeostatic function. It sustains spermatogenesis, maintains muscle bulk, maintains secondary sex characteristics, and aids in erectile function.

Endogenous testosterone in the circulation can be free (unbound), weakly bound to albumin, or tightly bound to sex hormone binding globulin (SHBG). The free and albumin-bound testosterone is available for use by the body. The largest percentage, however, is bound to SHBG and is unavailable for use in the body. Any condition that increases SHBG will decrease the amount of available testosterone. This includes conditions that elevate estrogens, elevated thyroid hormone, and aging.

Testosterone in circulation can also be converted into other hormones. It can be converted peripherally to dihydrotestosterone (DHT) by 5-alpha reductase. DHT has a role in the growth of prostatic tissue and therefore can influence lower urinary tract symptoms. Testos terone is aromatized to form estradiol (E2) in fatty tissue. In obese men, the increased amount of fat leads to increased aromatase activity, resulting in increased levels of estradiol. High circulating levels of estradiol down-regulates the hypothalamic-pituitary axis and decreases the amount of circulating testosterone.

As the male body ages, gonadal function slowly declines with a resulting drop in serum testosterone of approximately 1% per year after age 30, a phenomenon that occurs in both males and females (Morales, Heaton, & Carson, 2000). This can lead to multiple clinical manifestations (see Table 2 ). However, andropause is not analogous to the sudden cessation of reproductive capability seen with women during menopause. Despite a decline in testosterone, men retain their reproductive capacity. It has been suggested that the term andropause be reserved for those men who have lost their reproductive capabilities (such as after a bilateral orchiectomy for hormonal control of prostate cancer).

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