241monitored and maintained in the eugonadal range. After 6–12 months of ini-
tiation of hCG therapy with serum testosterone in eugonadal range, absence of
spermatozoa in ejaculate mandates the addition of FSH (hMG/ rFSH). The
combination therapy should be continued for at least next 1–2 years. However,
in patients with a testicular volume <4 ml, therapy may be initiated with hCG
and FSH simultaneously to improve the fertility outcome. Assisted reproduc-
tive technologies may be considered in those who fail to achieve spermatogen-
esis despite optimal therapy.- How to induce puberty in girls with congenital IHH?
Puberty should be initiated at the age of 12–13 years in girls. Treatment
modalities to induce puberty in girls with congenital IHH include pulsatile
GnRH and estrogen therapy. Pubertal induction with estrogen is preferred
because of oral route of administration and once-daily dosing. Many prepara-
tions of estrogen are commercially available; however, preparations contain-
ing 17β-estradiol are preferred, because it is the predominant estrogen in
premenopausal women. 17β estradiol (e.g., estradiol valerate, micronized
estradiol) is initiated at a dose of 0.25 mg/day and titrated upward every six
months to an adult replacement dose of 2 mg/day. Progesterone should be
added once breakthrough bleed occurs or after at least 2 years of estrogen
therapy. Later, the treatment should be maintained with estrogen and proges-
terone cyclically.- How to clinically differentiate between congenital IHH and Klinefelter’s syn-
drome in a boy with delayed puberty?
The presence of anosmia/hyposmia, synkinesia, craniofacial midline defects,
micropenis, cryptorchidism, and eunuchoidal proportions (arm span > height
and lower segment > upper segment) favors a diagnosis of congenital IHH in a
boy with delayed puberty, whereas the presence of long-leggedness, gyneco-
mastia, small firm testis, and learning disabilities suggests hypergonadotropic
hypogonadism, especially Klinefelter’s syndrome. - Does the presence of gynecomastia differentiate between hypogonadotropic
hypogonadism and hypergonadotropic hypogonadism during adolescence?
No. Although gynecomastia is considered as a typical feature of hypergo-
nadotropic hypogonadism (particularly Klinefelter’s syndrome), 30–40 % of
patients with hypogonadotropic hypogonadism can also have gynecomastia.
Elevated LH levels in patients with Klinefelter’s syndrome induce the activity
of aromatase in Leydig cells, leading to altered testosterone/estradiol ratio in
favor of estradiol, and consequent gynecomastia. Gynecomastia in patients
with hypogonadotropic hypogonadism is possibly due to partially preserved
LH secretion.
7 Delayed Puberty