Testosterone Use in Adolescent Males

Current Practice and Unmet Needs

Maria Vogiatzi; James P. Tursi; Jonathan S. Jaffe; Sue Hobson; Alan D. Rogol

Disclosures

J Endo Soc. 2021;5(1) 

In This Article

Abstract and Introduction

Abstract

Testosterone replacement therapy (TRT) is routinely prescribed in adolescent males with constitutional delay of growth and puberty (CDGP) or hypogonadism. With many new testosterone (T) formulations entering the market targeted for adults, we review current evidence and TRT options for adolescents and identify areas of unmet needs. We searched PubMed for articles (in English) on testosterone therapy, androgens, adolescence, and puberty in humans. The results indicate that short-term use of T enanthate (TE) or oral T undecanoate is safe and effective in inducing puberty and increasing growth in males with CDGP. Reassuring evidence is emerging on the use of transdermal T to induce and maintain puberty. The long-term safety and efficacy of TRT for puberty completion and maintenance have not been established. Current TRT regimens are based on consensus and expert opinion, but evidence-based guidelines are lacking. Limited guidance exists on when and how T should be administered and optimal strategies for monitoring therapy once it is initiated. Only TE and T pellets are US Food and Drug Administration approved for use in adolescent males in the United States. Despite the introduction of a wide variety of new T formulations, they are designed for adults, and their metered doses are difficult to titrate in adolescents. In conclusion, TRT in adolescent males is hindered by lack of long-term safety and efficacy data and limited options approved for use in this population. Additional research is needed to identify the route, dose, duration, and optimal timing for TRT in adolescents requiring androgen therapy.

Introduction

Testosterone (T) therapy is routinely prescribed in adolescent males with constitutional delay of growth and puberty (CDGP) or hypogonadism. T plays a critical role in male sexual development and function, beginning in utero and continuing through infancy, adolescence, and beyond.[1] In addition, T has numerous effects on various tissues and systems. These include the acceleration of linear growth during adolescence, a positive effect on bone mass and accretion,[1–3] and changes in body composition associated with an increase in lean mass and a reduction and redistribution of fat mass.[1,4] Recent evidence indicates that T and other androgens are involved in sexually dimorphic differences in certain brain regions, such as the amygdale,[1,5,6] while their effects on neurocognition and behaviors are being actively investigated.[7,8]

T therapy in boys with CDGP is applied for a limited time, typically 3 to 6 months.[1,9] The goals are to initiate sexual changes, increase growth, and ameliorate the negative psychosocial aspects associated with CDGP.[1,10–21] Testosterone replacement in adolescents with primary or secondary hypogonadism is a long-term therapy. By using escalating T doses, such therapy induces progressive pubertal changes that mimic the physiologic course of puberty in healthy males.[1,22] Despite the importance and routine administration of T to these populations, there has been marked variation in its use and little consensus on proper procedures.[1,22] To add to the complexity, T therapy in boys and adolescent males is largely given "off label".[23] T enanthate (TE) and T pellets are the only formulations approved by the US Food and Drug Administration (FDA) for the treatment of males with delayed puberty.[23–25] No preparation is FDA approved for long-term use in adolescents. Additional pediatric uses of exogenous T, which are not FDA approved, but have been suggested, include the treatment of microphallus in infants and the management of diminished or absent minipuberty, as well as its rapidly emerging use as cross-sex hormone therapy for transgender males.[1,26–30]

T replacement therapy (TRT) has recently expanded in adults because of its increased use among men with functional hypogonadism.[31] A number of new T preparations have entered the market, with improved pharmacokinetics, ease of administration, and likely increased adherence.[22,32] However, all focus on adult males, and dose formulations are frequently not metered for pediatric use. The Endocrine Society and multiple other medical societies have developed practice guidelines for the care of adult patients, with little or no reference to adolescents.[32–35] This review summarizes the T options available to adolescent males and the evidence that supports current TRT practice in this population. We will use the results of this analysis to address the unmet needs and challenges related to TRT in adolescents and highlight areas for investigation likely to lead to improved care in these patients.

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