237spermatogenesis at puberty, and this effect of LH is mediated by increase in
intratesticular testosterone. However, once initiated, spermatogenesis can be
maintained by LH alone. Therapy with hCG results in testicular growth along
with virilization and spermatogenesis, particularly in those who have evidence
of endogenous FSH secretion (e.g., testicular volume ≥4 ml). Further, hCG
therapy leads to stable levels of serum testosterone without peaks and troughs
as compared to exogenous testosterone therapy because of regulated produc-
tion of testosterone by Leydig cells. The recommended dose of hCG is 500–
2,000 IU subcutaneously/intramuscularly thrice a week, with an aim to maintain
serum testosterone in mid-normal adult reference range. However, hCG therapy
is expensive, requires frequent injections, and is associated with development
of gynecomastia and anti-hCG antibodies.- Why is gynecomastia more common with hCG therapy than with testosterone?
Gynecomastia is more common with hCG as compared to testosterone therapy.
This is because hCG directly stimulates aromatase activity in Leydig cells,
resulting in increased testicular production of estradiol, in addition to periph-
eral aromatization of testosterone. Exogenous testosterone therapy leads to
gynecomastia due to aromatization of testosterone to estradiol in adipose tis-
sues. Testosterone-mediated gynecomastia is more common in obese subjects
and possibly in those with increased sensitivity to estradiol and/or FSH (as FSH
increases aromatase activity). Circulating estradiol levels may not necessarily
be elevated in all patients because local aromatase activity in the breast tissue
also contributes to gynecomastia.- A 16-year-old boy presented with delayed puberty and was diagnosed to have
congenital IHH. He was initiated on intramuscular testosterone 50 mg every
month. After 6 months, the dose was increased to 100 mg every month. Three
months later, he presented with painful gynecomastia. How to proceed
further?
The index patient developed gynecomastia after initiation of testosterone
therapy. Testosterone-mediated gynecomastia is frequently painful because
of rapid enlargement of breast. Treatment strategies include reduction in
either dose and/or frequency of testosterone administration or use of selec-
tive estrogen receptor modulators/aromatase inhibitors. Selective estrogen
receptor modulators like tamoxifen have been widely used in the treatment of
peripubertal gynecomastia and are most effective in those with recent-onset
gynecomastia. There are anecdotal case reports regarding use of aromatase
inhibitors like anastrozole for the treatment of testosterone-mediated gyne-
comastia. In the index patient, dose of testosterone was reduced to 50 mg
every month.
7 Delayed Puberty