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Most people want to grow old gracefully. For men, this can mean maintaining overall health, appearance, sex drive and "brain power."
Most men consider themselves "old" after age 55 to 60, and many perceive the physical and mental changes that gradually occur at this stage as a normal consequence of aging. Therefore, men may not seek help for the indolent decline in energy, sexual function disturbances, loss of lean muscle mass, or occasional lapses in memory or sleep disturbances.
When men do seek help for any one or a combination of these symptoms, we should perform a thorough workup to exclude nonage-related causes of hormonal decline, or to treat true age-related androgenic decline.
Defining the Problem
Many labels have been suggested for the age-related, gradual decline in androgen levels in menmale menopause, male climacteric, andropause and, perhaps most correctly, androgen decline in the aging male.1
Male menopause certainly is a misnomer when applied to the androgenic hormonal decline in aging men. The term menopause is associated with women's hormonal decline and represents a symptomatic, predictable and rapid decline of ovarian function that culminates in infertility.
The decrease of androgenic hormone in men is gradual, unpredictable and often symptomatically subtle. Fertility is not universally lost. The term climacteric is appropriate only insofar as it refers to a period of change in men, but it's rather nonspecific when applied to androgen decline.
Andropause comes closer to labeling the physiological and psychological sequelae of androgen decline, but it too is a biologically incorrect and inappropriate term. As such, I will use androgen decline in the aging male (ADAM) for accuracy and simplicity's sake.1,2
Epidemiology of ADAM
Many confounding factors stand in the way of delineating the numbers of men who are affected by ADAM symptoms. Some authors have stated that approximately 50 percent of men 50 and older will experience some symptoms of ADAM. This, however, remains unsubstantiated, since no longitudinal studies have examined the numbers of U.S. men affected with the sequelae of age-related androgen decline.
What is known is that serum testosterone levels begin a slow decline around age 25. By age 75, as much as a 50 percent decrease in testosterone levels may occur. By age 80, testosterone levels can fall as much as 75 percent.3,4 Other researchers have estimated that testosterone levels decrease from 0.8 percent to 1.0 percent per year after age 50.5,6
ADAM-related symptoms, such as lethargy, depression, increased irritability, mood swings, difficulty attaining and maintaining an erection, decreased muscle mass and memory loss were experienced by 50 percent of 1,700 men aged 40 to 70 who participated in the Massachusetts Male Aging Study.7
But the men in the study merely acknowledged these symptoms in a questionnaire. It's not completely clear whether most symptoms were severe enough to motivate them to seek help. Whether men are symptomatically aware of the gradual but measurable decline in serum testosterone levels remains to be answered.
Other confounding factors interfere with assessing the number of men affected by ADAM. These include the variability of decline in testosterone levels among men; the variability in laboratory measurement techniques of the male hormone; the decline of other hormones, such as growth hormone (GH), insulin-like growth factor-1 (IGF-1), dehydroepiandrosterone (DHEA) and melatonin; and the lack of any consistent, unambiguous symptom complex pathognomonic for age-related androgen decline.1,8 Many, if not most, ADAM-related symptoms can be caused by one or a combination of nonage-related disorders, such as depression, substance abuse, endocrine disease and cancer.
Physiologic Changes
Testosterone levels are regulated through negative feedback with the anterior pituitary and hypothalamus. Increases or decreases in serum testosterone levels signal the hypothalamus to inhibit or stimulate the secretion of gonadotropin-releasing hormone (GnRH).
GnRH levels, along with testosterone levels, signal the anterior pituitary to either release or inhibit the secretion of luteinizing hormone (LH). Levels of LH can stimulate or inhibit the Leydig's cells in the testes to increase or decrease testosterone production. Approximately 95 percent of testosterone is produced by the Leydig's cells in the testes; the remaining 5 percent is produced in the adrenal cortex using the androgenic steroid androstenedione as the source of testosterone.9,10
The physiologic changes in male androgen levels that occur with aging can be explained by several well established factors. A decrease in the number of Leydig's cells occurs in the testes of older men. Additionally, impaired secretion of GnRH from the hypothalamus results in decreased stimulation of the anterior pituitary to secrete LH. This is thought to be a result of a "flattening" of the normal hypothalamus-driven circadian rhythm in older men.1,8
In addition, obesity plays a role in the decrease of measurable levels of testosterone in young and old men. The decline in testosterone levels may be related to an increase in sex hormone binding globulin (SHBG).1,8 SHBG levels increase in older men, independent of obesity. SHBG has a high binding affinity with testosterone and lowers the amount of "free" testosterone that's measurable and available to act on end organs and tissues. Together, these changes produce the decline in testosterone in men diagnosed with ADAM.8
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