Androgens in Health and Disease.pdf - E Library

Chapter 17/Androgens and Puberty 341
Recent investigations have suggested that peak bone mass may be attained as early as
late adolescence in the hip and spine (53). In healthy adolescents, bone mass increases
throughout childhood, with maximal bone mass accrual occurring in early to midpuberty
and slowing in late puberty. Longitudinal data from healthy girls demonstrate that the
rate of accrual in bone mass is most pronounced between 11 and 14 yr of age and falls
significantly after 16 yr of age and/or 2 yr after menarche (54). These data suggest that
there is a critical window in time to maximize bone mass in early and midpuberty; the
majority of bone mass will have accumulated by late puberty.
The presence of osteopenia in subjects with abnormal pubertal development demonstrates
the critical impact of pubertal hormone changes on normal bone mineral acquisition.
Adult patients with hypogonadotropic hypogonadism commonly have osteopenia,
resulting from inadequate bone mineral accrual during puberty and/or abnormal bone
remodeling after puberty (55). Some adult men with a history of CDGP have decreased
bone mass (56). Androgen receptors are located in growth-plate osteoblasts in males and
females and are thought to mediate the anabolic effects of testosterone on bone (57).
However, estrogen appears to be the more important sex steroid involved in skeletal
maturation and mineralization, although it is unknown whether estradiol acts directly on
bone or indirectly by stimulating other mediators of bone growth.
Patients with aromatase deficiency or estrogen-receptor defects have a phenotype that
includes tall stature and normal secondary sexual characteristics, however, they have
osteopenia and skeletal immaturity in adulthood, despite normal androgen levels (58).
Treatment of a male with aromatase deficiency with estrogen resulted in dramatic increase
in bone density and completion of skeletal maturation, indicating the critical role of estrogen
in skeletal mineralization and maturation (59).
COMMON USES OF EXOGENOUS TESTOSTERONE IN CHILDREN
The most common conditions in children where treatment with testosterone may be
beneficial are those associated with permanent hypogonadism (hypergonadotropic
and hypogonadotropic hypogonadism) and CDGP, a physiologic form of hypogonadotropic
hypogonadism.
Constitutional Delay of Growth and Puberty
Constitutional delay of growth and puberty is a frequent variant of normal pubertal
maturation. It is characterized by a slowing of the growth rate as well as by a delay in the
timing and tempo (rate of progression of the various stages) of puberty (60). Typically,
these boys seek medical evaluation in the early teens as they become aware of the
discrepancy in sexual development and height between themselves and their peers.
Clinically, they have a height age (the age corresponding to the height at which the
patient’s height is at the 50% percentile) that is delayed with respect to the chronological
age, but it is concordant with their bone age. Sexual development is prepubertal or early
pubertal and is again appropriate for the bone age, but delayed for chronological age.
There is often a family history of one parent or a sibling of either sex having also been
a “late bloomer.”
Height velocity continues at a prepubertal rate or slows slightly as a prepubertal dip,
in contrast to peers of the same chronological age, whose height velocity begins to
accelerate at the age of 12–13 yr. When the height is plotted on the standard growth