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Background: Differentiation between isolated hypogonadotropic hypogonadism (IHH) and constitutional delay in puberty (CDP) throughout adolescence can be challenging for doctors. This study examines the withdrawal effects of short-term, low-dose testosterone treatment (testosterone priming) on the ability of dynamic testing to distinguish between CDP and IHH based on activation of the hypothalamo-pituitary–testicular axis. Methods: A case–control study included 20 boys with delayed puberty (group A) and 20 patients with IHH (group B). Both groups underwent Triptorelin and human chorionic gonadotropin (hCG) stimulation tests before and 2 months after testosterone injections (100 mg) intramuscularly every 4 weekly for 3 months. Results: The triptorelin-stimulated 4-h LH with a cutoff of 2.4 IU/L and the hCG-stimulated testosterone with a cutoff of 1.160 ng/mL had sensitivities of 65% each, and specificities of 90% and 95%, respectively, to diagnose CDP. After testosterone withdrawal, the cut-off values for 4-h LH were 8.850 IU/L and 3.190 ng/mL for hCG-stimulated testosterone. Basal inhibin B > 88.25 pg/ml was found to be a differentiating factor in diagnosing CDP after testosterone withdrawal. Conclusions: following the withdrawal of testosterone therapy, Inhibin B levels or 4-h stimulated LH are the most effective discriminant assays to distinguish CDP from IHH. [ABSTRACT FROM AUTHOR]

BACKGROUND: U.S. Special Operations Forces (SOF) are at increased risk of multiple mild traumatic brain injury (mmTBI). Testosterone was prescribed for several participants in a VA program designed to address sequelae of mmTBI for SOF. OBJECTIVE: To determine testosterone prevalence in the Palo Alto VA Intensive Evaluation and Treatment Program (IETP) and observe for association between testosterone and neurobehavioral outcomes. METHODS: A retrospective cohort study included patients in the Palo Alto VA IETP. Sociodemographic data, testosterone blood levels, and neurobehavioral outcomes were collected from medical records. RESULTS: 55 IETP participants were included: six were testosterone users; the rest were classified as non-users. Testosterone use in this population is 11%, higher than reported national averages in the U.S. Of the 6 testosterone users, 2 (33%) had a formal diagnosis of hypogonadism prior to initiation of testosterone. Neurobehavioral outcome scores between testosterone users and non-users failed to show statistically significant differences, except for the PROMIS pain score, which was higher in the testosterone user population. CONCLUSION: The current study did not find an association between mmTBI, testosterone use, or testosterone level and neurobehavioral outcomes. This study highlights a need to further examine the relationship between hypogonadism, mmTBI, SOF culture around testosterone, and the effects of testosterone use in this population. [ABSTRACT FROM AUTHOR]

Background and objective: The longitudinal efficacy and clinical utility of Testosterone Therapy (TTh) in ameliorating functional hypogonadism (FH) remain contentious, with long‐term data being scarce. To address this lacuna, a comprehensive long‐term registry study, stratifying patients across a spectrum of hypogonadal etiologies, offers a robust investigative paradigm. Materials and methods: This 9‐year registry, encompassing 650 patients (equivalent to 4,362 cumulative years of treatment), included 188 patients diagnosed with FH (mean age 42.3 ± 11.3 years) and 462 individuals with classical hypogonadism (CH). The cohort segregated into 266 men with primary hypogonadism (PH, mean age 34.0 ± 11.7 years) and 196 with secondary hypogonadism (SH, mean age 31.9 ± 12.0 years). Uniform treatment across the cohort involved intramuscular administration of testosterone undecanoate (1,000 mg). A comparative analysis was conducted focusing on anthropometric, metabolic, and safety parameters. Results: Serum testosterone levels increased from 6.6 ± 2.4 to 19.3 ± 2.9 nmol/L (p < 0.001). TTh was linked with weight reduction and decreased waist circumference (WC) in both CH and FH cohorts (both p < 0.001). Cox regression and Kaplan–Meier analyses delineated disparities: men with FH demonstrated a higher propensity for losing > 10% body weight and > 5% WC compared to CH (hazard ratio [HR] 1.3 [1.1–1.4], p = 0.008 and HR 1.4 [1.3–1.5], p = 0.001). Increases in hematocrit > 50% were uniform across groups, albeit amelioration of anemia was more pronounced in FH versus CH (p = 0.002). Increments of prostate‐specific antigen (PSA) levels were more likely to occur in FH (HR 1.3 [1.1–1.6], p = 0.003). FH patients exhibited pronounced improvements in metabolic parameters and in aging male symptom score (AMS) and IIEF‐EF questionnaire scores. These effects were markedly modulated by age and initial weight. Subgroup analysis of age‐matched obese patients revealed an accentuated impact of TTh in CH compared to FH. Discussion and conclusion: The therapeutic outcomes of TTh across distinct hypogonadal populations demonstrate heterogeneous responses, significantly influenced by diagnostic categorization, age, and baseline risk factor profiles. [ABSTRACT FROM AUTHOR]

Background: Testosterone plays a vital role in maintaining tissue homeostasis, and testosterone deficiency may potentially influence the likelihood of urethral stricture recurrence. Objectives: To evaluate the prognostic value of testosterone levels in the recurrence after direct visual internal urethrotomy in primary short segment bulbar urethral strictures and its clinical reflections. Materials and methods: A total of 723 patients who underwent direct vision internal urethrotomy between January 2000 and October 2022 were retrospectively analyzed. After implying exclusion criteria, 116 patients with available data were enrolled. Patients were divided into two groups as recurrence and no recurrence. Age, stricture length, etiology, time of recurrence, diagnosis of previous diabetes mellitus, hypertension, smoking, body mass index, and total testosterone levels were recorded. Free testosterone and bioavailable testosterone values were calculated using total testosterone, albumin, and sex hormone binding globulin values. Hypogonadism was considered as a total testosterone level less than 300 ng/dL. Demographic characteristics and total testosterone, free testosterone, and bioavailable testosterone levels were compared between the two groups for statistical significance. The recurrence rates of patients with and without hypogonadism were compared. Results: Recurrence was observed in 41.4% of the cases (n = 48). There was no statistically significant difference between the groups in terms of age, body mass index values, diabetes mellitus, hypertension, smoking status, presence of hypogonadism, and etiology (p = 0.745, 0.863, 0.621, 0.622, 0.168, 0.051, and 0.232). In terms of total testosterone levels and bioavailable testosterone levels, the recurrence group had significantly lower values (p = 0.018 and 0.04). There was no significant difference between the two groups in terms of stricture length (p = 0.071). Sixteen of 28 patients with hypogonadism had recurrence, whereas 32 of 88 patients without hypogonadism had recurrence (p = 0.051). Discussion: Testosterone levels have potential to predict recurrence in primary short‐segment bulbar urethral strictures. This study represents the inaugural analysis of the impact of testosterone deficiency on recurrence within the cohort of patients with primary short‐segment bulbar urethral strictures. Conclusion: Testosterone levels and ratios may serve as predictive factors for identifying recurrent cases in primary short‐segment bulbar strictures. For patients at a higher risk of recurrence, urethroplasty may be considered as an initial treatment option, even in cases of primary and short‐segment strictures. [ABSTRACT FROM AUTHOR]

Female hypogonadism (FH) is a relatively common endocrine disorder in women of premenopausal age, but there are significant uncertainties and wide variation in its management. Most current guidelines are monospecialty and only address premature ovarian insufficiency (POI); some allude to management in very brief and general terms, and most rely upon the extrapolation of evidence from the studies relating to physiological estrogen deficiency in postmenopausal women. The Society for Endocrinology commissioned new guidance to provide all care providers with a multidisciplinary perspective on managing patients with all forms of FH. It has been compiled using expertise from Endocrinology, Primary Care, Gynaecology and Reproductive Health practices, with contributions from expert patients and a patient support group, to help clinicians best manage FH resulting from both POI and hypothalamo‐pituitary disorders, whether organic or functional. [ABSTRACT FROM AUTHOR]

Objective: The hypothalamic‐pituitary‐testicular axis is characterised by the existence of major functional changes from its establishment in fetal life until the end of puberty. The assessment of serum testosterone and gonadotrophins and semen analysis, typically used in the adult male, is not applicable during most of infancy and childhood. On the other hand, the disorders of gonadal axis have different clinical consequences depending on the developmental stage at which the dysfunction is established. This review addresses the approaches to evaluate the hypothalamic‐pituitary‐testicular axis in the newborn, during childhood and at pubertal age. Design: We focused on the hormonal laboratory and genetic studies as well as on the clinical signs and imaging studies that guide the aetiological diagnosis and the functional status of the gonads. Results: Serum gonadotrophin and testosterone determination is useful in the first 3–6 months after birth and at pubertal age, whereas AMH and inhibin B are useful biomarkers of testis function from birth until the end of puberty. Clinical and imaging signs are helpful to appraise testicular hormone actions during fetal and postnatal life. Conclusions: The interpretation of results derived from the assessment of hypothalamic‐pituitary‐testicular in paediatric patients requires a comprehensive knowledge of the developmental physiology of the axis to understand its pathophysiology and reach an accurate diagnosis of its disorders. [ABSTRACT FROM AUTHOR]

Background: Inter‐assay variation between different immunoassays and different mass spectrometry methods hampers the biochemical confirmation of male hypogonadism. Furthermore, some laboratories utilise assay manufacturer reference ranges that do not necessarily mirror assay performance characteristics, with the lower limit of normality ranging from 4.9 nmol/L to 11 nmol/L. The quality of the normative data underlying commercial immunoassay reference ranges is uncertain. Design: A working group reviewed published evidence and agreed upon standardised reporting guidance to augment total testosterone reports. Results: Evidence‐based guidance on appropriate blood sampling, clinical action limits, and other major factors likely to affect the interpretation of results are provided. Conclusions: This article aims to improve the quality of the interpretation of testosterone results by non‐specialist clinicians. It also discusses approaches for assay harmonisation which have been successful in some but not all healthcare systems. [ABSTRACT FROM AUTHOR]

Background: Androgen deprivation therapy (ADT) in prostate cancer (PCa) has been associated with development of insulin resistance. However, the predominant site of insulin resistance remains unclear. Methods: The ADT & Metabolism Study was a single‐center, 24‐week, prospective observational study that enrolled ADT‐naive men without diabetes who were starting ADT for at least 24 weeks (ADT group, n = 42). The control group comprised men without diabetes with prior history of PCa who were in remission after prostatectomy (non‐ADT group, n = 23). Prevalent diabetes mellitus was excluded in both groups using all three laboratory criteria defined in the American Diabetes Association guidelines. All participants were eugonadal at enrollment. The primary outcome was to elucidate the predominant site of insulin resistance (liver or skeletal muscle). Secondary outcomes included assessments of body composition, and hepatic and intramyocellular fat. Outcomes were assessed at baseline, 12, and 24 weeks. Results: At 24 weeks, there was no change in hepatic (1.2; 95% confidence interval [CI], −2.10 to 4.43; p =.47) or skeletal muscle (−3.2; 95% CI, −7.07 to 0.66; p =.10) insulin resistance in the ADT group. No increase in hepatic or intramyocellular fat deposition or worsening of glucose was seen. These changes were mirrored by those observed in the non‐ADT group. Men undergoing ADT gained 3.7 kg of fat mass. Conclusions: In men with PCa and no diabetes, 24 weeks of ADT did not change insulin resistance despite adverse body composition changes. These findings should be reassuring for treating physicians and for patients who are being considered for short‐term ADT. In this prospective study of hormone‐naive men who were eugonadal and did not have diabetes, 24 weeks of androgen deprivation therapy (ADT) for prostate cancer (PCa) was not associated with worsening of hepatic or skeletal muscle insulin resistance despite a substantial increase in fat mass. These findings have relevance for both physicians and patients when determining treatment for PCa and suggest that a short course of ADT may not worsen metabolic risk in patients without pre‐existing diabetes. [ABSTRACT FROM AUTHOR]