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; I[2]=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.

The optimal approach to hormonal treatment aimed at increasing penis size has been established for infant males with micropenis; however, data are limited in partial androgen insensitivity syndrome (PAIS). We report a 6-month-old male patient treated with intramuscular testosterone for micropenis. At birth, he presented with atypical genitalia, including a microphallus, hypospadias, and a bifid scrotum. His karyotype was 46,XY, and endocrine evaluation revealed normal testicular function. A novel missense variant of the AR gene (p.G578E) was identified. Intramuscular testosterone enanthate 62.5 mg/dose was administered every 4 weeks for 3 doses (6-8 months). Stretched penile length increased from 18 to 30 mm (+67%) without adverse events. During treatment, luteinizing hormone secretion was suppressed, with trough levels falling below the limit of detection, consistent with androgen-mediated negative feedback. Luteinizing hormone levels during mini-puberty in response to testosterone treatment, supporting testosterone therapy in patients with PAIS.

Benign prostatic hyperplasia (BPH), the leading cause of lower urinary tract symptoms (LUTS), is commonly treated with conventional therapies that often have undesirable side effects. Safer alternatives such as bone marrow mesenchymal stem cells (BM-MSCs)-derived exosomes (MSCs-Exo) could represent a novel strategy for attenuation of disease progression. The objective of this study was to evaluate MSCs-Exo as a cell-free therapy for BPH and explore its protective effect. Eighteen acclimatized male adult rats were allocated randomly into three groups: normal control group, BPH group, and BPH group treated with MSCs-Exo. BPH was established by s.c. injection of testosterone enanthate (3 mg/ Kg) five days per week over a two-week period. The MSCs-Exo were isolated and identified by transmission electron microscopy and flowcytometric detection of the exosome-specific surface markers: CD9 and CD63. MSCs-Exo were administered by i.p. injection (100 µg protein) once per week for two weeks. MSCs-Exo significantly decreased the prostate index and prostate-specific antigen-like protein (PSA-like protein) compared to the BPH group. Immunohistochemical staining showed decreased expression of NF-κB p65, TNF-α, and β-catenin but increased expression of SIRT1 in MSCs-Exo group. Gene expression of β-catenin-related proteins, LRP6 and c-Myc, was measured by RT-qPCR and exhibited decreased expression in MSCs-Exo group. These observations were linked with the downregulation of miR-133-3p. MSCs-Exo exerted a potential prophylactic effect in BPH; it attenuated prostatic enlargement and showed anti-inflammatory and anti-proliferative activities, which could be through modulation of two pathogenic mechanisms mediated by miR-133-3p and β-catenin.

Severe diet- and exercise-induced energy deficit (SED) suppresses androgen production in healthy men, altering metabolism and driving muscle loss. The gut microbiota modulates host metabolism, yet the community's response to SED and any role of androgen hormones are unclear. Herein, healthy, physically active men were randomized to receive 200 mg/wk testosterone enanthate (n = 24) or placebo (n = 26) during a 28-day residential intervention that restricted energy intake and increased energy expenditure inducing a ∼2,000 kcal/day SED. Multiomic analyses revealed altered gut microbiota composition, reduced fecal short-chain fatty acids (SCFA), and shifts in bacterial metabolic pathways toward lipid utilization and mucin degradation during SED, suggesting adverse effects of SED on gut microbiota metabolic functions. Testosterone administration preserved certain SCFA-producing taxa and bioenergetic pathways without fully counteracting the effects of SED indicating a limited but potentially important interplay between androgen status and the gut microbiota under conditions of SED.NEW & NOTEWORTHY This study is the first to demonstrate that testosterone administration partially preserves gut microbiota composition and metabolic function during severe energy deficit in healthy men. Using a multiomic approach, we show that testosterone modulates short-chain fatty acid-producing taxa and microbial pathways linked to host energy metabolism. These findings reveal a novel role for androgens in shaping host-microbiome interactions during catabolic stress and may inform strategies to maintain metabolic resilience.

Major depressive disorder (MDD) under treatment may be accompanied by residual sexual dysfunction and fatigue. This broadens the differential diagnosis and destabilizes symptom attribution. A 54-year-old Japanese man with MDD formed a late-onset hypogonadism (LOH) hypothesis from online information and self-referred to urology. He was receiving long-term polypharmacy and presented with fatigue, insomnia, arthralgia, and reduced libido. Total testosterone was 2.82 ng/mL, and free testosterone was 5.3 pg/mL. After counseling and informed consent, testosterone replacement therapy (TRT) was initiated with testosterone enanthate 250 mg intramuscularly once monthly. During eight injections, perceived benefit was limited and transient. Erectile difficulty and irritability recurred, and TRT was discontinued. Depressive symptoms persisted, and ongoing medication adjustments were required during TRT. This limited causal interpretation of symptom changes and TRT responsiveness. This case shows that reducing diagnostic reasoning to a binary choice of LOH or MDD can fragment hypothesis updating. From the outset, depressive pathophysiology, medication effects, and the LOH hypothesis should be evaluated in parallel. A shared diagnostic plan with prespecified indicators and discontinuation criteria can preserve diagnostic convergence even under fragmented care.

Late-onset hypogonadism (LOH) is a clinical concept that integrates symptoms with decreased testosterone and affects sexual function, physical vitality, and psychological or behavioral domains. In patients whose complaints traverse multiple specialties, symptom nonspecificity can constrain hypothesis updating. Variation in biochemical assessment, including measurement timing and thresholds, can amplify reliance on treatment response. A 52-year-old Japanese man presented with fatigue, awakening after sleep onset, flushing, palpitations, and erectile dysfunction despite internal medicine evaluations. Vital signs, electrocardiography, blood tests, CT, and MRI suggested no organic disease, and he was referred to urology for suspected LOH. Blood tests showed total testosterone 3.79 ng/mL (not ≤2.5 ng/mL) and free testosterone 7.5 pg/mL (at the threshold). At the patient's request, a trial course of testosterone replacement therapy with testosterone enanthate was initiated, with tadalafil. Sexual function improved, and flushing and edema decreased after several days, followed by recurrence of edema, sweating, and fluctuating fatigue by three weeks. Symptoms persisted, and attribution remained unsettled. Psychiatric consultation was added. This case visualizes how entry-point framing, biochemical borderline results, and symptom overlap can prevent diagnostic convergence. It supports a parallel-evaluation diagnostic design that prespecifies competing hypotheses and interprets treatment response as supportive but non-decisive evidence.

The present study tested the effects of chronic testosterone enanthate (TE) or estradiol benzoate (EB) on sexual behavior and motivation in female or male Long-Evans rats, respectively. Sexually experienced gonadally intact female rats were treated with TE (4.5 mg/0.1 ml) or oil twice per week for five weeks, whereas sexually experienced gonadally intact male rats were treated with EB (10 μg/0.1 ml) or oil daily for 28 days. On the last day of treatment, subjects were tested for partner preference, whereby subjects could choose to spend time near (no-contact phase) or with (contact phase) either a male or female stimulus. TE-treated females spent less time with the male stimulus during the no-contact phase, but less time with the female stimulus during the contact phase, compared to hormone-primed controls. TE-treated females displayed fewer solicitation behaviors than controls. TE treatment continued for 2 weeks after mating to monitor vaginal estrus. TE-females entered estrus, albeit less frequently than controls. At the end of exposure, body weight was greater, but ovarian weight was lower in TE-treated females than in controls. Conversely, EB-treated males spent more time with the male stimulus and less time with the female stimulus than controls during the contact phase. EB-treated males displayed fewer mounts and took longer to display their first mount. Testes and body weight were lower in EB-treated males than in controls at the end of the treatment period. These results add to our understanding of the effects of opposite-sex hormones on sexual behavior and reproductive physiology using an animal model.