Androgens in Health and Disease.pdf - E Library

340 Richmond and Rogol
increase linear growth velocity without a disproportionate advancement of skeletal
maturation, decrease in adult height, or excessive virilization (46). Rosenfeld and coworkers
(47) have the longest and most extensive study of oxandrolone and GH treatment
in girls with Turner syndrome. They demonstrated the benefits of this combination
therapy on growth velocity and adult height. More recently, Nilsson and colleagues (48)
treated a group of 17 girls with Turner syndrome with oxandrolone and GH. The mean
adult height was 154.2 cm, which is equivalent to a mean net gain of 8.5 cm over the
projected adult height. Fewer studies have been done to evaluate the effect of this synthetic
androgen on GH release. Results of GH secretory activity and IGF-1 levels,
however, are conflicting, but most of the evidence indicates that there is no stimulatory
effect of oxandrolone on GH secretion despite its ability to increase the growth rate.
Androgen and Estrogen Receptor Blockade
Studies utilizing selective androgen-receptor or estrogen-receptor blockade have been
more helpful in elucidating the differential effects of androgens and estrogens on the GH/
IGF-1 axis. Flutamide, a nonsteroidal antagonist of the androgen receptor, administered
to normal, late pubertal boys in an amount large enough to increase serum LH, freetestosterone,
and estradiol level, has been associated with an increase in GH secretion
(49). The increase in GH secretion was the result of an increase of both the maximal GH
secretory rate and the mass of GH secreted per burst. A smaller increase in the frequency
of GH secretory episodes was noted, but no changes in GH half-life were detected.
Interruption of the negative feedback loop as a result of androgen blockade resulted in
the above-noted elevations in LH, total estradiol, and free-testosterone concentrations.
The observed rise in GH secretion and estradiol concentrations secondary to flutamideinduced
blockade of the androgen receptor may reflect either enhanced estrogen-mediated
effects or a reduced effect of androgen-mediated inhibition of the GH/IGF-1 axis.
Tamoxifen is a nonsteroidal antagonist of the estrogen receptor. When administered
to adolescent boys, it has been associated with a significant decrease in GH secretion and
IGF-1 levels (50). Diminished GH secretion results from the decrease in the maximal
secretory rate and number of secretory bursts, with a trend toward a lower GH mass
secreted per burst. No changes in the GH half-life or metabolic clearance rate or in the
concentrations of testosterone, estradiol, or LH were observed.
These observations indicate that endogenous estrogens have a facilitatory role in the
neuroendocrine control of the GH/IGF-1 axis in adolescent boys. It is possible that any
stimulatory role of androgens on GH secretion is exerted through the estrogen receptor.
Effects of Sex Steroids on Bone Mineralization During Puberty
Puberty is a critical period to increase the rate of bone formation and to maximize bone
mineral content and bone strength. More than 90% of peak skeletal mass is present by
age 18 yr. It is the bone mass at this time that accounts for at least one-half of the
variability in bone mass in the elderly (51).
Increases in height and weight are the strongest correlates of skeletal mineralization
during childhood and adolescence (52). There are gender differences in bone density
during childhood and adolescence because of differences in the timing of growth and
puberty, resulting in females reaching peak bone mass earlier than males, although bone
density values at peak bone mass are similar between the sexes.