Aging and declining testosterone: past, present, and hopes for the future

Abstract

As men age, serum testosterone (T) levels decline, whereas serum luteinizing hormone (LH) levels increase somewhat or remain unchanged. Age-related reductions in T levels may be associated with alterations in body composition; energy level; muscle strength; physical, sexual, and cognitive functions; and mood. The predominant contributor to the decline in serum T levels is the decreased ability of the aging testes to make T. As in humans, the Brown Norway rat demonstrates age-related reductions in serum T levels in the setting of unchanged or modestly increased serum LH levels. In this rat model, the ability of aged Leydig cells, the terminally differentiated T-producing cells of the testis, to produce T in response to LH stimulation is significantly diminished. This review begins with a discussion of what is known of the molecular mechanisms by which T synthesis declines with Leydig cell aging. It concludes with a brief history of T replacement therapy, current guidelines, controversies related to T replacement therapy in older men, and proposed future clinical directions.

Figure

(A) Total testosterone (TT, ng/mL), bioavailable testosterone (Bio T, ng/mL), and free testosterone (FT; ng/mL ×10), by age group, from either the Baltimore Longitudinal Study of Aging (BLSA; Harman et al, 2001) or the Massachusetts Male Aging Study (MMAS; Mohr et al, 2005). Data adapted. (B) Percentage of men, by age group, with levels of serum TT, FT, or a free testosterone index (FTI = TT/SHBG) that met the hormonal definition of androgen deficiency as defined by either the BLSA (Harman et al, 2001) or Boston Area Community Health survey (BACH; Araujo et al, 2007) and the percentage of men, by age group, with symptoms of androgen deficiency from the BACH (Sx AD BACH; Araujo et al, 2007) or the MMAS (Sx AD MMAS; Araujo et al, 2004). Data adapted. SHBG indicates sex hormone–binding globulin.