Andropause: clinical implications of the decline in serum testosterone levels with aging in men.

T is now well accepted that serum testosterone (T) levels decline progressively with aging in men (1–5). This decline is associated with alterations in body composition; diminished energy, muscle strength, and physical function; reduced sexual function; depressed mood; and decreased cognitive function. Similar changes occur in young men with androgen deficiency and are improved with T replacement therapy. However, the physiological and clinical significance of the aging-associated decline in serum T levels in men is unclear, particularly because T levels may remain within the normal range for young men. From a practical clinical standpoint, it is most appropriate to define “andropause” as an age-related decline in serum T levels in older men to below the normal range in young men that is associated with a clinical syndrome (i.e., symptoms and signs) consistent with androgen deficiency. The decline in T levels is a consequence both of aging per se and age-associated comorbid illnesses and medications that are used to treat them (6–13). However, regardless of the etiology, androgen deficiency may contribute, at least in part, to age-related decrements in physiological function and may be associated with a clinical syndrome. Andropause has also been referred to by some as “androgen deficiency in the aging male (ADAM),” “partial androgen deficiency in the aging male (PADAM),” or “aging-associated androgen deficiency (AAAD).” The term “male menopause” is inappropriate because there is no interruption or cessation of menses, and “viropause” is inaccurate because there is no loss of virilization. “Male climacteric” refers to the syndrome of endocrine, somatic, and psychic changes that occur in normal men with aging. This term emphasizes the multidimensional nature of age-related changes, including decreases in other hormones such as growth hormone (GH), insulin-like growth factor-1 (IGF-1), dehydroepiandrosterone (DHEA), and melatonin (1,14–17), but it does not relate aspects of the male aging syndrome specifically with androgen levels. The term “andropause” is not completely accurate because androgen secretion does not cease altogether. However, because it is the only term that relates the syndrome of age-related physiological changes with the gradual and progressive decline in T levels that occurs with aging, andropause will be used in this review. Andropause is a term also used commonly by experts in the field and by lay persons because it retains some analogy to menopause in women. P HYSIOLOGICAL B ASIS OF A NDROPAUSE