Testosterone exposure in childhood: discerning pathology from physiology

Introduction: Testosterone (T) drives normal male sexual development both in utero and at puberty. Aberrant T exposure manifests as virilization of a female fetus, contrasexual precocity in girls, and isosexual precocity in boys. Evidence of pathologic T exposure warrants a prompt evaluation. Areas covered: The authors introduce the topic of T exposure in children by reviewing its physiology in the fetus and during childhood and adolescence. Pathologic conditions leading to virilization of a female fetus as well as androgen-mediated gonadotropin-independent precocious puberty in both genders are then discussed. The authors finish by noting exogenous T exposure in children and adolescents, focusing specifically on secondary exposure to topical T preparations. Expert opinion: Contrasexual precocity in a girl or sexual precocity in a boy should prompt evaluation for causes of gonadotropin-independent pubertal changes. Initial biochemical evaluation includes a bone age, T, 17-hydroxyprogesterone, androstenedione, dehydroepiandrosterone sulfate (DHEA-S) and high sensitivity gonadotropin levels. The provider must query exposure to topical androgen-containing preparations as unintentional secondary exposure to topical T must be considered. Hyperandrogenism is temporally related to exposure of topical T and removal of exposure results in a marked decrease in serum T as well as resolution or stabilization of the signs and symptoms.