Androgens in Health and Disease.pdf - E Library

Chapter 17/Androgens and Puberty 337
during sleep, resulting in elevations of early-morning gonadal steroid hormone levels,
which then wane throughout the day. With maturity, this release occurs regularly throughout
the day (16). The intermittent release of gonadotropins is reflective of the episodic
release of gonadotropin-releasing hormone (GnRH) (17). The increased sex hormone
production by the testes results from increased LH stimulation; FSH stimulates primarily
maturation of the tubules and spermatogonia.
Testosterone, Estrogen, and Adrenal Steroids
In human neonates, the levels of circulating growth hormone (GH) are higher in the
male. This is most likely related to higher levels of gonadal steroid hormones in the male
during the first months of life. Female neonates have circulating testosterone levels that
fall to childhood values by the second week of life. In contrast, male infants have a rise
in testosterone concentrations to midpubertal levels beginning at about 2 wk of age,
which peak at 1–2 mo and then slowly decline to prepubertal values by 6 mo of age (18).
Nighttime elevations of serum testosterone are detectable in the male before the onset
of physical signs of puberty and during early puberty after the development of sleepentrained
secretion of LH (19). In the daytime, testosterone levels begin to increase at
approx 11 yr when the testis volume is at least 4 mL, and continue to rise throughout puberty
(20). The steepest increment in testosterone levels occurs between pubertal stages 2 and
3; mean testosterone levels can rise from 0.7 to 8 nmol/L (from 0.2 to 2.4 ng/mL) within
10 mo (21).
Although the measurement of the ratio of testosterone to its metabolites has been
advocated as a means of detecting the use of illicit androgen preparations by athletes, the
ratio of testosterone to epitestosterone in the urine may be elevated normally during the
progression through puberty. Consequently, the validity of this procedure during puberty
is questionable (22). Testosterone and other steroids can be measured in saliva for screening
purposes and for monitoring therapy (23).
Several recent studies have evaluated the effects of testosterone on body composition
and strength. Bhasin and colleagues (24) administered 100 mg testosterone enanthate
weekly for 10 wk to seven hypogonadal men with very low serum testosterone levels.
Serum testosterone increased sevenfold, body weight increased by 4.5 kg (mean), fatfree
mass increased by 5.0 kg (mean), and body fat did not change. Thus, almost all of
the weight gain was explained by the increase in fat-free mass. Arm and leg muscle crosssectional
areas, assessed by magnetic resonance imaging (MRI), increased significantly.
Substantial increases in muscle strength were also noted after testosterone treatment.
The mechanisms underlying the effects of androgens on bone are probably multifactorial.
Androgen receptors have been found on the osteoblast, suggesting that androgens
have direct, local effects on bone metabolism (25). In addition, in vitro studies
have shown that androgens may stimulate osteoblast differentiation, suggesting that
testosterone stimulates osteoblast function and bone formation directly (26). Testosterone
may affect bone resorption by modulating either the local production of osteoclastregulatory
interleukins and other cytokines, or the osteoclast response to circulating
calcium-regulatory hormones. In testosterone deficiency, an enhanced production of
interleukin-6 (IL-6) by osteoblasts leads to osteoclastogenesis and increased bone
resorption (27). Accelerated bone resorption may contribute to the osteopenia in
hypogonadal men. The administration of gonadal steroids, including androgens, leads
to a decreased production of IL-6 by osteoblasts and, consequently, reduced osteoclast