What medical conditions can impact penile development in children and adolescents?
Executive summary
A range of congenital, endocrine, genetic and acquired conditions can alter penile growth in children and adolescents; the most commonly documented causes include fetal androgen insufficiency, pituitary–gonadal disorders (eg, congenital gonadotropin deficiency), enzyme defects such as 5α‑reductase deficiency, androgen receptor abnormalities and structural anomalies like hypospadias, while lifestyle and systemic factors (notably obesity and delayed puberty) also influence growth and final size [1] [2] [3] [4]. Early endocrine evaluation and, where indicated, time-sensitive hormonal therapy in infancy or around puberty are repeatedly emphasized in the literature as interventions that often increase penile length and reduce later psychological morbidity [5] [2] [6].
1. Congenital hormonal insufficiency and micropenis: the pituitary–testis axis
When fetal or postnatal testosterone production is insufficient because of absent or reduced luteinizing hormone (LH) or other pituitary gonadotropins—conditions grouped as hypogonadotropic hypogonadism or isolated gonadotropin deficiency—penile growth can be stunted, producing micropenis; multiple longitudinal studies link congenital lack of LH/testicular androgen activation to small penile size even before puberty and show penile growth with androgen therapy [2] [7] [1].
2. Disorders of androgen synthesis and metabolism: 5α‑reductase and related enzyme defects
Enzymatic defects that impair conversion of testosterone to the more potent dihydrotestosterone (DHT), most notably 5α‑reductase type 2 deficiency, produce undervirilized external genitalia and micropenis at birth but may show substantial spontaneous penile enlargement at puberty when testosterone rises—hence the condition’s distinctive clinical course and management implications [3] [8].
3. Androgen receptor defects and androgen resistance
When target tissues cannot respond to androgens because of androgen receptor abnormalities, penile development may remain inadequate despite normal or elevated circulating androgens; such cases are less likely to respond to conventional testosterone therapy and require genetic and endocrinologic evaluation as part of disorders of sex development (DSD) workup [1] [8].
4. Structural and congenital anomalies: hypospadias, chordee, and related conditions
Anomalies in urethral development (eg, hypospadias) and severe congenital penile malformations are sometimes part of broader disorders of penile development and can be associated with smaller post‑pubertal penile length; surgical history and the severity of the anomaly are independent factors affecting eventual size and function, and multidisciplinary care (urology, endocrinology, genetics) is recommended [9] [10] [11].
5. Acquired, systemic and modifiable factors: obesity, timing of puberty, and iatrogenic effects
Beyond congenital and genetic causes, systemic factors shape penile growth: obesity in childhood and adolescence is strongly associated with lower testosterone and reduced penile growth, and delayed or early pubertal timing and overall somatic growth patterns predict adult penile length; iatrogenic or surgical procedures (eg, corrective operations for curvature) can also alter post‑pubertal measurements [4] [12] [9].
6. Diagnosis, treatment windows and outcomes
Micropenis is defined anthropometrically (stretched penile length ≤ −2.5 SD for age) and mandates a focused history, karyotype and hormonal assessment because early endocrine therapy—hCG or testosterone in infancy or androgens around early puberty—can increase penile size in many cases, although response varies (better with hormone‑deficiency etiologies, limited with receptor defects); surgical options exist but are typically deferred until adolescence or adulthood except in selected circumstances [1] [5] [6] [13].
7. Caveats, debate and gaps in evidence
Available studies show consistent associations and treatment responses for many causes, but long‑term outcomes (eg, whether early penile growth gains persist into adulthood for all etiologies) remain incompletely characterized in some cohorts, and individual prognosis depends on the specific diagnosis (eg, enzyme defect vs receptor defect) and timing of intervention; the literature therefore supports multidisciplinary evaluation and individualized counseling rather than one‑size‑fits‑all declarations [1] [14] [6].