Testosterone therapy in boys with constitutional delay of growth and puberty: a PubMed-based systematic review and exploratory meta-analysis

Constitutional delay of growth and puberty (CDGP), the most common cause of delayed puberty in boys, accounts for the majority of pediatric endocrinology referrals. Although traditionally viewed as a variant of normal development, affected adolescents frequently experience short stature relative to their peers, delayed secondary sexual characteristics, and clinically meaningful psychosocial distress. Short-course low-dose testosterone has been used for more than 5 decades to accelerate pubertal progression and linear growth; however, the evidence base is heterogeneous and has not been synthesized in a PubMed-indexed review anchored in original testosterone studies. To systematically review PubMed-indexed studies from the last 40 years evaluating testosterone therapy in boys with CDGP or closely related self-limited delayed puberty and perform an exploratory meta-analysis of outcomes for which directly extractable comparative data are available. PubMed was searched from January 1, 1986, to March 10, 2026, for relevant original studies, systematic reviews, and meta-analyses. Eligible reports enrolled boys with CDGP or self-limiting delayed puberty treated with testosterone and reported growth, pubertal progression, bone age, predicted or near-adult height, or safety outcomes. Randomized studies were appraised by the Cochrane revised tool for risk of bias in randomized trials, while nonrandomized studies were appraised using the Risk of Bias in Non-randomized Studies - of Interventions. Random-effects mean differences (MDs) for height velocity were calculated when comparative means and dispersions were extractable. Twenty original studies involving 1,329 boys met the qualitative inclusion criteria, together with 2 supporting evidence syntheses. Across formulations (intramuscular testosterone enanthate or cypionate, depot ester mixtures, oral testosterone undecanoate, and transdermal gel), the literature consistently showed greater short-term height velocity and more rapid pubertal progression in treated boys without a clinically meaningful adverse effect on near-adult height when conservative regimens were used. Only 2 controlled studies (46 boys) directly provided pooled height velocity data. Random-effects pooling showed a statistically significant increase in short-term height velocity with testosterone versus placebo or no treatment (MD, 2.40 cm/yr; 95% confidence interval, 1.49-3.32; I²=0%). Narrative evidence from long-term studies does not support the detrimental effects of brief low-dose testosterone administration on near-adult or adult height. Testosterone therapy in boys with CDGP was associated with faster short-term growth and pubertal maturation, and long-term data did not show a detrimental effect on near-adult height when conservative time-limited regimens were used. The quantitative evidence base is small and methodologically heterogeneous, and modern multicenter randomized trials incorporating validated patient-reported outcomes and long-term follow-ups are necessary.