Clinical Geriatrics

Significant alterations in the hormonal milieu occur in the aging population.1,2 In women, these changes are predictable and well recognized, and include a constellation of somatic and psychological symptoms due to a decline in circulating estrogenic hormones, called menopause. In contradistinction to menopause, the changes in the hypothalamic-pituitary-gonadal (HPG) axis in men are highly variable and are not seen in all men. These manifestations often may go unrecognized. These changes in the hormonal milieu in men are known by a collective term, male climacteric, or andropause. Andropause is given many names, such as male climacteric and viropause. This symptom complex in the aging male is better known as “androgen deficiency in the aging male.”3,4 In andropause, changes in the male sex hormones as well as other hormones in the body occur. Simply defined, andropause is an indefinite syndrome in middle-aged and elderly men consisting of several physical, sexual, and emotional symptoms resulting from a complex interaction of hormonal, psychological, situational, and physical factors.

The physical findings of andropause include weakness, fatigue, reduced muscle and bone mass, and impaired hematopoiesis. The sexual dysfunction can take the form of oligospermia, diminished libido, and impotence. The psychological and emotional component can involve depression, anxiety, irritability, insomnia, memory impairment, and reduced cognitive function.

FACTS AND STATISTICS
In 1950, less than 5% of the population was older than 65 years of age. In contrast, by 2025, more than 15% of the world population will be older than 65 years, and prevalence is likely to proportionately increase in accordance with these projected population statistics.2,3 With this increasing age, it is more likely that the obstructive uropathies, cancers of bladder, prostate, and kidney, and erectile dysfunction will be more often diagnosed and treated.

The number of men in the United States who are 65 years of age is projected to increase from 14,452,000 in 2000 to 31,343,000 in 2030.3 Approximately 30% of men 60-70 years of age and 70% of men 70-80 years of age have low bioavailable or free testosterone levels.3,4 At present, it is controversial whether to treat all aging men with symptoms of andropause. The urologist is, however, the best person to identify, assess, and monitor the problems associated with hormonal supplementation on the prostate gland.

PATHOPHYSIOLOGY
The production of testosterone in men is controlled by the HPG axis. Gonadotropin-releasing hormone (GnRH) is secreted from the hypothalamus and stimulates the pituitary gland to release luteinizing hormone (LH), which, in turn, acts on testicular Leydig’s cells to produce testosterone.5,6 Testosterone is metabolized by 5-alpha-reductase enzyme to dihydrotestosterone (DHT) in the prostate, and then metabolized to estradiol by the enzyme aromatase.

Testosterone is bound (80%) to sex hormone-binding globulin (SHBG) and, to a lesser extent, to other serum proteins, such as albumin. It is estimated that 2% of testosterone exists free in the serum. The non–SHBG-bound form of testosterone, along with free testosterone, constitutes the biologically active fraction of testosterone.

The HPG axis is complex and interacts with a number of other endocrine systems, whose production of hormones is also affected by aging. Of these other hormones affected by aging, the most important are the weak androgenic hormones (ie, dehydroepiandrosterone and its sulfate) released from the adrenal gland. These hormones decline with aging.

The pineal hormone melatonin also is elaborated in reducing amounts with aging. A reduction in the serum levels of melatonin is responsible for the disturbances of sleep and biorhythms associated with aging.2 These phenomena are attributed to some extent to the declining levels of serum testosterone with aging.