Clinical features and prevalence of Klinefelter syndrome in transgender individuals: A systematic review.

OBJECTIVE: Previous studies have suggested a higher prevalence of Klinefelter syndrome amongst transgender individuals. We undertook a systematic review to determine the prevalence of Klinefelter syndrome amongst transgender individuals presumed male at birth and summarize the clinical features and potential treatment implications for individuals with Klinefelter syndrome commencing gender-affirming hormone therapy. DESIGN: Using preferred reporting items for systematic review and meta-analysis guidelines, we searched EMBASE, MEDLINE and the Cochrane Central Register of Controlled Trials (CENTRAL) up to 31 December 2021. All studies reporting on the prevalence or clinical features of transgender individuals with Klinefelter syndrome were included. This study is registered with the International Prospective Register of Systematic Reviews, number CRD42021227916. RESULTS: Our search strategy retrieved 11 cohort studies comprising 1376 transgender individuals. In all, 14 of 1376 (1.02%) individuals were diagnosed with Klinefelter syndrome. Based on the seven studies in which karyotype was undertaken in all individuals, the prevalence is 9/1013 (0.88%; 95% CI, 0.41%-1.68%). Case reports highlight unique treatment considerations in this population, including azoospermia, venous thromboembolism, and monitoring of breast cancer and bone health. CONCLUSIONS: Compared to the general population, observational studies document a higher prevalence of Klinefelter syndrome amongst transgender individuals, though underdiagnosis in the general population limits conclusions. Routine karyotype in transgender people initiating gender-affirming hormone therapy is not supported unless clinical features of Klinefelter syndrome, such as small testicular volume, or hypergonadotropic hypogonadism are present. Transgender individuals with Klinefelter syndrome need to manage a unique risk profile if they desire feminizing gender-affirming hormone therapy.

Efficacy of Flash Glucose Monitoring in Type 1 and Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

Objective: Flash glucose monitoring (FlashGM) is a sensor-based technology that displays glucose readings and trends to people with diabetes. In this meta-analysis, we assessed the effect of FlashGM on glycaemic outcomes including HbA1c, time in range, frequency of hypoglycaemic episodes and time in hypo/hyperglycaemia compared to self-monitoring of blood glucose, using data from randomised controlled trials. Methods: A systematic search was conducted on MEDLINE, EMBASE and CENTRAL for articles published between 2014 and 2021. We selected randomised controlled trials comparing flash glucose monitoring to self-monitoring of blood glucose that reported change in HbA1c and at least one other glycaemic outcome in adults with type 1 or type 2 diabetes. Two independent reviewers extracted data from each study using a piloted form. Meta-analyses using a random-effects model was conducted to obtain a pooled estimate of the treatment effect. Heterogeneity was assessed using forest plots and the I2 statistic. Results: We identified 5 randomised controlled trials lasting 10 - 24 weeks and involving 719 participants. Flash glucose monitoring did not lead to a significant reduction in HbA1c. However, it resulted in increased time in range (mean difference 1.16 hr, 95% CI 0.13 to 2.19, I2 = 71.7%) and decreased frequency of hypoglycaemic episodes (mean difference -0.28 episodes per 24 hours, 95% CI -0.53 to -0.04, I2 = 71.4%). Conclusions: Flash glucose monitoring did not lead to a significant reduction in HbA1c compared to self-monitoring of blood glucose, however, it improved glycaemic management through increased time in range and decreased frequency of hypoglycaemic episodes. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier PROSPERO (CRD42020165688).

Efficacy of Micronized Progesterone for Sleep: A Systematic Review and Meta-analysis of Randomized Controlled Trial Data.

CONTEXT: Preclinical data has shown progesterone metabolites improve sleep parameters through positive allosteric modulation of the γ-aminobutyric acid type A receptor. We undertook a systematic review and meta-analysis of randomized controlled trials to assess micronized progesterone treatment on sleep outcomes. EVIDENCE ACQUISITION: Using preferred reporting items for systematic review and meta-analysis guidelines, we searched MEDLINE, Embase, PsycInfo, and the Cochrane Central Register of Controlled Trials for randomized controlled trials of micronized progesterone treatment on sleep outcomes up to March 31, 2020. This study is registered with the International Prospective Register of Systematic Reviews, number CRD42020165981. A random effects model was used for quantitative analysis. EVIDENCE SYNTHESIS: Our search strategy retrieved 9 randomized controlled trials comprising 388 participants. One additional unpublished trial was found. Eight trials enrolled postmenopausal women. Compared with placebo, micronized progesterone improved various sleep parameters as measured by polysomnography, including total sleep time and sleep onset latency, though studies were inconsistent. Meta-analysis of 4 trials favored micronized progesterone for sleep onset latency (effect size, 7.10; confidence interval [CI] 1.30, 12.91) but not total sleep time (effect size, 20.72; CI -0.16, 41.59) or sleep efficiency (effect size, 1.31; CI -2.09, 4.70). Self-reported sleep outcomes improved in most trials. Concomitant estradiol administration and improvement in vasomotor symptoms limit conclusions in some studies. CONCLUSIONS: Micronized progesterone improves various sleep outcomes in randomized controlled trials, predominantly in studies enrolling postmenopausal women. Further research could evaluate the efficacy of micronized progesterone monotherapy using polysomnography or validated questionnaires in larger cohorts.