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Testosterone Therapy in Boys with Delayed Puberty

Am Fam Physician. 1999 Apr 1;59(7):1956-1959.

While boys with a constitutional delay of puberty eventually have normal activation of the hypothalamic-pituitary-gonadal axis, their sexual immaturity and relative short stature may contribute to psychosocial problems. Androgen therapy, commonly given as a four-month course of testosterone injections, provides a boost in physical growth and maturity. In addition to constitutional delay of puberty, obesity and growth hormone deficiency may cause delayed puberty. Kaplowitz conducted a retrospective study to compare responses to testosterone therapy in boys with delayed puberty from constitutional delay, obesity and possible gonadotropin deficiency.

All of the boys were 14 years of age or older when they received testosterone injections. Twenty-three had constitutional delay of puberty and were of short stature, six had obesity and were of normal stature, five had hypopituitarism and growth hormone deficiency and two had isolated gonadotropin deficiency. They were prepubertal or in early puberty according to both physical characteristics and serum testosterone levels, which were less than 40 ng per dL (1.4 nmol per L). All received a course of testosterone enanthate injections, 100 mg intramuscularly, once a month for four months.

Testosterone therapy resulted in an increase in height and weight velocity in the 23 boys with constitutional pubertal delay. Penis and testicular size also increased during treatment. The six obese boys also had an increase in penis and testicular growth. The five boys with growth hormone deficiency received growth hormone replacement in addition to testosterone injections. Two of these boys had severe gonadotropin deficiency and did not demonstrate increased maturation rates. In two boys, testicular size increased, although not as rapidly as in boys with constitutional delay of puberty.

The author concludes that monitoring the response to testosterone injections in boys with delayed puberty helps to differentiate constitutional delay of puberty from gonadotropin deficiency in boys with delayed puberty. Since a rapid growth rate requires increased androgen and growth hormone production, the response to testosterone augmentation in the boys with constitutional delayed puberty excluded the possibility of growth hormone deficiency. In the obese boys, progression of maturation may have occurred after testosterone injections because of the inhibitory effects of androgens on leptin levels, which are presumed to be inceased in obese adolescent boys. After age 10, as testosterone and gonadotropin levels increase, serum leptin levels normally decline to levels found in boys five to six years of age, suggesting that increasing testosterone levels may inhibit leptin production. The author also believes that a lack of response to four testosterone injections may be useful in identifying boys who require long-term therapy because of gonadotropin deficiency.

In an accompanying editorial, Saenger and Sandberg note that testosterone therapy in boys with delayed maturation may help increase the velocity of maturation, but there is insufficient documentation to show that the psychosocial stress from delayed maturation is severe enough to warrant intervention with testosterone injections. Most of these children have a healthy adaptation, and treatment decisions should be weighed carefully. The authors believe the psychosocial benefit of treating constitutional delay of puberty may be overstated.

Kaplowitz P. Delayed puberty in obese boys: comparison with constitutional delayed puberty and response to testosterone therapy. J Pediatr December 1998; 133:745–9, and Saenger P, Sandberg DE. Delayed puberty: when to wake the bugler [Editorial]. J Pediatr. December 1998;133:724–5.


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