Management Of Delayed Puberty

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For induction of puberty in boys with constitutional delay of puberty, the indication for treatment is usually psychosocial: boys with delayed puberty may suffer because of short stature and lack of pubertal progression. This distress may affect their school performance and their social relationships. Testosterone esters, given intramuscularly, remain the most commonly used treatment approach; therapy can be started with 50 mg of a mixture of testosterone propionate and testosterone enanthate every 4 wk. Often, a treatment course of 6 to 12 mo will accelerate growth and sexual maturation, and such a short treatment course is usually sufficient to alleviate psychosocial problems related to pubertal delay. Other treatment options are testosterone undecanoate by mouth, transdermal testosterone patches or gels, or oxandrolone. Compared with other treatment regimens, a short-course of low-dose depot testosterone intramuscularly is an effective, practical, safe, well-tolerated, and inexpensive regimen.

In boys with short parents, consideration should be given to delaying testosterone therapy to avoid compromising final height. On the other hand, a significant delay in pubertal development may also decrease final adult height, because in boys with delayed puberty, estrogen concentrations are low for chronological age (but not for bone age), and, consequently, GH secretion is functionally and temporally impaired for age. If this functional GH deficiency persists for a long time, adult height may be reduced.

In hypogonadal boys when testosterone therapy is required to induce pubertal development, the dosing and timing should be aimed at mimicking normal pubertal development, accounting for the individual's desire to begin puberty and also the family history of age at onset of puberty. Doses should be adjusted to the response of the individual patient, which may be monitored in terms of the development of secondary sex characteristics and bone maturation. In boys with hypopituitarism, testosterone therapy should be coordinated with the use of GH. This should be individualized for each patient to optimize growth and pubertal development.

For boys who are hypogonadal, testosterone substitution therapy should be initiated at a low dose, because too large a dose may advance skeletal maturation disproportionately and, thus, compromise final adult height. Furthermore, large doses may cause acne, gynecomastia, or too-rapid change in libido. Doses are adjusted according to the clinical response (Tanner stage and bone age). Most commonly, long-acting testosterone preparations, which are administered intramuscularly, are used for this purpose. Esterification of testosterone with either propionic or enanthic acid at position 17 prolongs the metabolite's activity (69). Testosterone propionate is not a suitable testosterone preparation for substitution therapy, because plasma concentration show wide fluctuations, and the maximal between-injection interval is only 3 d with a 50 mg dose (70). Testosterone enanthate at a dose of 250 mg intramuscularly has a half-life of 4.5 d. Based on multiple-dose pharmacokinetics, an injection interval of every 2 wk, with a dose of 250 mg, leads to supraphysiological serum testosterone concentrations of up to 51 nmol/L and nadir level in the low normal range (12 nmol/L) before the next injection (70). In male hypogonadism, a mixture of testosterone propionate and testosterone enanthate is widely used for substitution therapy (see Chapter 18).

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