Androgens in Health and Disease.pdf - E Library

Chapter 18/Androgens in Older Men 351
cross-sectional and longitudinal studies have shown that even healthy older men lose
bone mass with age (44). Hypogonadism is one cause of male osteoporosis, and low T
levels are a risk factor for minimal trauma hip fracture in older men (47). Men who are
physically or chemically castrated in adult life demonstrate a significant decline in BMD
(48,49). Young adult men with acquired androgen deficiency have lower BMD than agematched
controls (50), and T replacement in this group is associated with significant
increases in both vertebral and hip BMD (51). Bioavailable T levels have been shown to
correlate positively with BMD in older men (25), as have bioavailable estradiol levels (27).
Sexual Function
Numerous measures of sexual function change as men age, including a decline in
orgasmic frequency, an increase in erectile dysfunction (ED), and a decline in quality and
quantity of sexual thoughts and enjoyment (52). Data to support a relationship between T
levels and the decline in many aspects of sexual function with age are scarce, however.
Especially with ED, the correlation data would suggest low T levels have only a minimal
role in the etiology of this condition in the older man. Although T may have some effect
on optimal penile rigidity, through its effect in regulating nitric oxide synthase activity in
the smooth muscle of the corpora cavernosa, the prevalence of low T is not significantly
different between older men with and without impotence (53). In young hypogonadal men,
T replacement improves a variety of sexual behaviors, including sexual thoughts, sexual
desire, spontaneous erections, and frequency of sexual activity (54). The threshold level
of serum T needed for optimal sexual function, however, has not been determined, but it
may be relatively low. T administration does not seem to improve ED in men with normal
T levels (55).
Mood and Cognitive Function
Androgens may improve aspects of mood, such as irritability and depressive affect,
when given to hypogonadal young adult men (56). Compared to nondepressed men,
elderly men who are depressed have been reported to have lower total T levels (57) and,
similarly, lower bioavailable T levels have been associated with depressed mood in a
large cross-sectional study of older men (58).
The relationship between T and cognitive function in men is not clear because of a
lack of data, the many different cognitive processes that can and have been assessed,
and the timing of the androgen exposure in relation to the subject age. The effects of
androgens seem to be specific to certain domains, with some studies showing a positive
correlation with spatial performance and others reporting improvement in verbal fluency
(59). One epidemiological study of older men reported a positive association
between total and bioavailable T levels and better performance on tests of verbal
memory and mental control (60).
Erythropoiesis
Androgens are known to stimulate red blood stem cells and the production of erythropoietin
(61); androgen receptors are found in cultured erythroblasts (62). Adult men
have higher hemoglobin levels, hematocrits, and red blood cell mass than do adult
women, and these sex differences are not present before puberty (63). Young
hypogonadal men have lower red blood cells counts and hemoglobin levels than do their
age-matched controls, and these parameters increase when T is replaced (64). Likewise,