Article

Testosterone exposure in childhood: Discerning pathology from physiology

Children's Hospital of Wisconsin, Medical College of Wisconsin, Division of Endocrinology, Department of Pediatrics , 9000 W. Wisconsin Ave PO Box 1997, MS C520, Milwaukee, WI 53201 , USA +1 414 266 6750
Expert Opinion on Drug Safety (Impact Factor: 2.91). 03/2013; 12(3). DOI: 10.1517/14740338.2013.782000
Source: PubMed

ABSTRACT

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.

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    • "Testosterone esters have highly variable pharmacokinetics and are associated with injection site pain and polycythemia. Skin adhesion problems, skin or mucosal irritation , or unintentional testosterone transference to women and children are examples of undesired properties of existing TRT preparations (Steidle et al., 2003; Korbonits et al., 2004; Wang et al., 2004; Merhi & Santoro, 2007; Basaria, 2010; Cabrera & Rogol, 2013). These limitations and adverse reactions have encouraged the investigation of other modes of delivery for TRT including the intranasal route of administration. "
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    ABSTRACT: Advantages of testosterone nasal gel include ease of administration, low dose, and no risk of secondary transference. The efficacy and safety of testosterone nasal gel was evaluated in hypogonadal males. The ninety-day, randomized, open-label, dose-ranging study, included potential dose titration and sequential safety extensions to 1 year. At 39 US outpatient sites, 306 men (mean age 54.4 years) with two fasting morning total serum testosterone levels <300 ng/dL were randomized (n = 228, b.i.d. dosing; n = 78, t.i.d. dosing). Natesto(™) Testosterone Nasal Gel was self-administered, using a multiple-dose dispenser, as two or three daily doses (5.5 mg per nostril, 11.0 mg single dose). Total daily doses were 22 mg or 33 mg. The primary endpoint was the Percentage of patients with Day-90 serum total testosterone average concentration (Cavg ) value within the eugonadal range (≥300 ng/dL, ≤1050 ng/dL). At Day 90, 200/273 subjects (73%; 95% CI 68, 79) in the intent-to-treat (ITT) population and 180/237 subjects (76%; 71, 81) in the per-protocol (PP) population were in the normal range. Also, in the normal range were 68% (61, 74) of ITT subjects and 70% (63, 77) of PP subjects in the titration arm, as well as, 90% (83, 97) of ITT subjects and 91% (84, 98) of PP subjects in the fixed-dose arm. Natesto(™) 11 mg b.i.d. or 11 mg t.i.d. restores normal serum total testosterone levels in most hypogonadal men. Erectile function, mood, body composition, and bone mineral density improved from baseline. Treatment was well tolerated; adverse event rates were low. Adverse event discontinuation rates were 2.1% (b.i.d.) and 3.7% (t.i.d.). This study lacked a placebo or an active comparator control which limited the ability to adequately assess some measures.
    Full-text · Article · Dec 2015 · Andrology

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May 27, 2014