Gonadotropins for pubertal induction in males with hypogonadotropic hypogonadism: systematic review and meta-analysis.

OBJECTIVE: Hypogonadotropic hypogonadism is characterized by inadequate secretion of pituitary gonadotropins, leading to absent, partial, or arrested puberty. In males, classical treatment with testosterone promotes virilization but not testicular growth or spermatogenesis. To quantify treatment practices and efficacy, we systematically reviewed all studies investigating gonadotropins for the achievement of pubertal outcomes in males with hypogonadotropic hypogonadism. DESIGN: Systematic review and meta-analysis. METHODS: A systematic review of Medline, Embase, Global Health, and PsycINFO databases in December 2022. Risk of Bias 2.0/Risk Of Bias In Non-randomized Studies of Interventions/National Heart, Lung, and Blood Institute tools for quality appraisal. Protocol registered on PROSPERO (CRD42022381713). RESULTS: After screening 3925 abstracts, 103 studies were identified including 5328 patients from 21 countries. The average age of participants was <25 years in 45.6% (n = 47) of studies. Studies utilized human chorionic gonadotropin (hCG) (n = 93, 90.3% of studies), human menopausal gonadotropin (n = 42, 40.8%), follicle-stimulating hormone (FSH) (n = 37, 35.9%), and gonadotropin-releasing hormone (28.2% n = 29). The median reported duration of treatment/follow-up was 18 months (interquartile range 10.5-24 months). Gonadotropins induced significant increases in testicular volume, penile size, and testosterone in over 98% of analyses. Spermatogenesis rates were higher with hCG + FSH (86%, 95% confidence interval [CI] 82%-91%) as compared with hCG alone (40%, 95% CI 25%-56%). However, study heterogeneity and treatment variability were high. CONCLUSIONS: This systematic review provides convincing evidence of the efficacy of gonadotropins for pubertal induction. However, there remains substantial heterogeneity in treatment choice, dose, duration, and outcomes assessed. Formal guidelines and randomized studies are needed.

Serum periostin levels following small bone fractures, long bone fractures and joint replacements: an observational study.

BACKGROUND: In asthma, serum periostin may potentially be used as a biomarker in the management of patients with Type-2 eosinophilic airway inflammation. However, serum periostin may be influenced by factors other than Type 2 inflammation, potentially confounding its interpretation. We aimed to measure change in periostin following bone injury. METHODS: 102 adults without asthma were recruited into three groups: joint replacement surgery, long bone fracture, short bone fracture. Participants underwent seven measurements of serum periostin over 26 weeks after bone injury, and prior to surgery in the joint replacement group. Differences in periostin were measured using a ratio of geometric mean (RGM), with comparison made with pre-surgery (joint replacement) or 26 week (long and short fracture) reference measurements. RESULTS: In the joint replacement group, periostin fell within 48 h (RGM 0.80, 95% CI 0.75-0.86), then increased to a maximum at 8 weeks (RGM 1.89, 1.77-2.02) and by 26 weeks remained above the reference measurement (RGM 1.27, 1.19-1.36). In the long bone fracture group, periostin was reduced at 48 h (RGM 0.76, 0.71-0.83) and then progressively increased to a maximum at 8 weeks (RGM 1.15, 1.06-1.23) compared with the reference measurement. In the short bone fracture group, periostin was reduced at 48 h (RGM 0.9, 0.85-0.95) but was not different from after week 1 compared with the reference measurement. CONCLUSIONS: Serum periostin levels are influenced by bone injury. The timing and extent of bone injury needs consideration if periostin is used as a biomarker in the management of eosinophilic asthma.Trial registration This trial was prospectively registered with the Australia New Zealand Trials Registry on Feb 7 2014, (ACTRN12614000151639: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=363881).