Treatment of delayed puberty in boys

Androgen replacement therapy in male adolescents with constitutional delay of growth and adolescence has been shown to be beneficial psychologically as well as physiologically, and should be initiated promptly on diagnosis (Albanese and Stanhope 1995; de Lange etal. 1979; Kaplan et al. 1973; Rosenfeld et al. 1982). Boys with delayed puberty are at risk for not obtaining adequate peak bone mass and for having deficiencies in developing social skills, an impaired body image, and low self-esteem. Younger boys with short stature, delayed bone age (at least 10.5 years), and delayed pubertal development in the absence of other endocrinological abnormalities can be treated with 50-100 mg of testosterone enanthate or cypionate im, every four weeks for three months, whereas boys > 13 years old maybe treated with 250 mg (im, every four weeks for three months). After a three-month "wait and see" period, another course of treatment may be offered if pubertal development does not continue. An increase in testes size is the most important indicator of spontaneous pubertal development (testes volume >3 ml). Overtreat-ment with testosterone may result in premature closure of the epiphyses of long bones, resulting in reduced adult height. Therefore, treatment of patients who have not yet reached full adult height has to be undertaken carefully.

Low-dose oral testosterone undecanoate has been tested for the treatment of constitutional delay of puberty (Albanese etal. 1994; Brown etal. 1995; Butler etal. 1992). For example, treatment of 11-14 year old prepubertal boys with 20 mg testosterone undecanoate per day for six months resulted in an increase in growth velocity without advancing bone age and pubertal development (Brown et al. 1995). Such

"mild" treatment appears to be suited for an early phase when virilization is not yet requested. Transdermal testosterone should also be a useful method to induce puberty. However, experience in a larger series of patients has not yet been reported. At the beginning of therapy it is often difficult to distinguish between boys with constitutional delay of growth and puberty, who require only temporary androgen replacement, and boys with idiopathic hypogonadotropic hypogonadism, who require lifelong androgen therapy to stimulate puberty and to maintain adult sexual function. However, boys with permanent hypogonadotropic hypogonadism will not have testicular growth induced by androgen therapy. Because pubertal growth is a product of the interaction of growth hormone (GH) and insulin-like growth factor I (IGF-I) and the hypothalamic-pituitary-gonadal axis, boys with concomitant GH deficiency will require the simultaneous administration of GH and androgens for the treatment of delayed puberty. In boys with secondary causes of delayed puberty, development can also be induced by pulsatile GnRH or hCG/hMG respectively. This therapy has the advantage that testicular development is induced simultaneously. However, we prefer to induce initial virilization by testosterone and to stimulate spermatogenesis at a later stage with the more demanding GnRH or gonadotropin therapy.

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