What clinical evidence supports testosterone treatment for micropenis in childhood, and what are the long‑term outcomes?
Executive summary
Short courses of testosterone in infancy or childhood reliably increase stretched penile length (SPL) in the short term across multiple case series and reviews, with many patients reaching age‑appropriate ranges after treatment [1] [2] [3]. Long‑term outcomes are more heterogeneous: several longitudinal series report adult penile size within or close to population norms when childhood testosterone was given for hypogonadotropic conditions, but animal data and some human reports raise concerns about timing, durability, and gaps in high‑quality long‑term evidence [4] [5] [6] [7].
1. Evidence that testosterone increases penile size in childhood: consistent short‑term gains
Multiple clinical reports and reviews describe reproducible, clinically meaningful increases in SPL following short courses of testosterone or hCG in boys with micropenis, with studies reporting increases from roughly 15–26 mm pre‑treatment to 37–64 mm post‑treatment depending on age and protocol [1] [2] [3]. Low‑dose intramuscular testosterone given intermittently (typical regimens: 25–50 mg IM every 3–4 weeks for three doses) or hCG protocols for older prepubertal boys are the most commonly reported approaches and are uniformly linked to short‑term phallic enlargement in these series [1] [3] [8].
2. Long‑term adult outcomes: encouraging but not definitive
Longitudinal follow‑ups in carefully characterized cohorts—especially boys with congenital hypogonadotropic hypogonadism—show that one or two short courses of testosterone in infancy/childhood can augment penile size into the normal range for age and that appropriate pubertal replacement at adolescence often yields adult penile size within about 2 standard deviations of the mean [4] [5] [9]. These reports argue against radical interventions such as sex‑rearing changes for many etiologies of micropenis [4] [9]. However, reviews highlight mixed long‑term results across heterogeneous diagnoses and study designs, and note that some patients with normal gonadal function will gain penile length with spontaneous puberty regardless of early therapy [7].
3. Risks, timing and biological plausibility: why timing matters
Animal experiments show that very early androgen exposure can produce premature penile growth but later redevelopment of micropenis in adulthood, suggesting a window effect and raising caution about timing of treatment [6] [10]. Human observational data also question whether aligning therapy with “mini‑puberty” in infancy necessarily improves long‑term outcomes; recent retrospective studies suggest that initiation during mini‑puberty does not always predict better responses [11]. Transient side effects reported include temporary acceleration of linear growth and skeletal maturation, which generally normalize after stopping therapy in the small series available [3].
4. Limitations of the evidence base: small samples, heterogeneous causes, and few RCTs
The literature is dominated by case series, retrospective cohorts, and disorder‑specific follow‑ups (e.g., hypogonadotropic hypogonadism), with little randomized controlled trial data and substantial heterogeneity in dose, route, duration, and outcome measures, which complicates broad generalization [7] [8]. Protocols vary from topical DHT to systemic testosterone and hCG, and studies frequently mix etiologies (primary vs central hypogonadism, androgen insensitivity spectrum), limiting head‑to‑head comparisons [2] [7].
5. Clinical interpretation and controversies: balance of benefit versus uncertainty
For boys with documented fetal or early testosterone deficiency, short, monitored courses of testosterone are a widely accepted and evidence‑supported option to produce age‑appropriate penile growth and to avoid radical measures, but clinicians acknowledge persistent uncertainty about optimal timing and the durability of benefit into adulthood for all causes of micropenis [4] [5] [7]. Guidelines caution that hormonal attempts to increase penile size after puberty are ineffective and that long‑term evidence—especially randomized or multicenter prospective data—is lacking [2].
6. What remains unanswered and the research agenda
Key gaps include randomized trials comparing androgen types and timing, systematic long‑term follow‑up into adult sexual function and psychosocial outcomes, and condition‑specific outcome registries to resolve heterogeneity; ongoing protocolized trials and multicenter collaboration are needed to move from consistent short‑term gains to robust, generalizable long‑term recommendations [8] [7].