Reproductive hormones, bone mineral content, body composition, and testosterone therapy in boys and adolescents with Klinefelter syndrome

Krabbe, Hans Valdemar López; Petersen, Jørgen; Asserhøj, L L; Johannsen, Trine Holm; Christiansen, Peter Munk; Jensen, Rikke Beck; Cleemann, Line; Hagen, Casper P; Priskorn, Lærke; Jørgensen, Niels O. G.; Main, Katharina M.; Juul, Anders; Aksglæde, Lise

doi:10.1530/ec-23-0031

Cited by 2 publications

References 57 publications

(89 reference statements)

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Serum Concentrations of Inhibin B in Healthy Females and Males Throughout Life

Borelli-Kjær,

Aksglaede,

Jensen

et al. 2024

The Journal of Clinical Endocrinology &Amp; Metabolism

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Objective To describe the natural history of inhibin B throughout life according to sex, age, and pubertal development. Methods Based on serum samples from 2707 healthy controls aged 0 to 80 years, sex- and age-specific reference ranges of inhibin B concentrations were constructed. Concentrations were evaluated according to pubertal development and use of oral contraceptives (OCs). Also, measurements from 42 patients with Klinefelter syndrome were included. Results In both sexes, inhibin B concentrations were high during minipuberty, decreased in childhood, and increased significantly from Tanner stages B1 to B3 (peak: B4) in females and from G1 to G3 (peak: G3) in males. Despite variations in menstruating females, inhibin B concentrations remained relatively constant after puberty, until becoming unmeasurable at menopause. Despite a modest decrease, the inhibin B concentration in males remained relatively high from puberty onwards. At any age, males had highest concentrations. Inhibin B standard deviation (SD) scores were lower in OC-users (median SD score = -0.88) than in non-users (SD score = 0.35), p < 0.001. In patients with Klinefelter syndrome, inhibin B concentrations spanned the reference range until around 15 years of age, where they decreased to subnormal or unmeasurable levels. Conclusion Valuable sex- and age-specific reference data for inhibin B concentrations were provided. In OC-users, decreased concentrations of inhibin B underlined the ovaries as the only place of inhibin B production. In patients with Klinefelter syndrome, the decline in inhibin B concentrations at puberty underlined the shift in regulation of inhibin B production at pubertal onset.

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Serum Concentrations of Inhibin B in Healthy Females and Males Throughout Life

Borelli-Kjær,

Aksglaede,

Jensen

et al. 2024

The Journal of Clinical Endocrinology &Amp; Metabolism

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Causal association of sex hormones with osteoporosis: a two-sample Mendelian randomization study

zhang,

Lian,

Nie

et al. 2023

Preprint

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Background Epidemiologic studies have identified a correlation between sex hormones and osteoporosis(OP), yet the presence of a causal effect remains unverified. Confounding factors and reverse causal associations mean observational studies merely reflect this correlation, without clarifying the intricate causal relationships at play. This study, therefore, employed Mendelian randomization to thoroughly examine the causal link between sex hormones and osteoporosis. Methods Exposure variables for sex hormones, encompassing total testosterone (TT), bioavailable testosterone (BAT), sex hormone binding globulin (SHBG), and estradiol (E2), were derived from the IEU Open GWAS aggregated data. The outcome variable, osteoporosis, was sourced from the UK Biobank database. The Mendelian randomization analysis was conducted using the inverse variance weighted analysis (IVW) method, MR-Egger, and weighted median (WM) method to assess the causal relationship between sex hormones and osteoporosis. Outliers were identified via MR-PRESSO, the effect of individual SNPs on IVW analysis outcomes was investigated through leave-one-out sensitivity analysis, horizontal pleiotropy was detected using MR-Egger-intercept, heterogeneity among instrumental variables was evaluated with Cochran's Q-test, potential biases in findings were examined through funnel plots, and MR Steiger analysis was employed to explore any reverse causal associations. Results Mendelian randomization revealed that genetically predicted TT levels were inversely correlated with osteoporosis risk [IVW: OR (95% CI): 0.997 (0.995, 0.999), P = 0.004], while BAT exhibited a negative causal association with osteoporosis [IVW: OR (95% CI): 0.990 (0.987, 0.994), P = 4.83E-07]. Conversely, SHBG was positively correlated with osteoporosis [IVW: OR (95% CI): 1.008 (1.003, 1.012), P = 0.0004], and E2 demonstrated no causal effect [IVW: OR (95% CI): 0.981 (0.960, 1.002), P = 0.07129]. Cochran's Q-test indicated no heterogeneity in the instrumental variables (IVs) for BAT and E2(P > 0.05) and detected heterogeneity in the IVs for TT and SHBG (P < 0.05), thereby underscoring the relevance of the random-effects IVW model. Neither MR-Egger intercept nor MR- PRESSO analyses detected any level pleiotropy (P > 0.05). The IVW results remained robust after sequential omission of SNPs via the leave-one-out method.MR Steiger analysis confirmed the absence of reverse causality. Conclusion Our results indicate a causal relationship between sex hormones and osteoporosis, wherein TT and BAT decrease osteoporosis risk, whereas SHBG increases it. These findings suggest that sex hormones levels are significant in osteoporosis prevention and treatment strategies

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Reproductive hormones, bone mineral content, body composition, and testosterone therapy in boys and adolescents with Klinefelter syndrome

Cited by 2 publications

References 57 publications

Serum Concentrations of Inhibin B in Healthy Females and Males Throughout Life

Serum Concentrations of Inhibin B in Healthy Females and Males Throughout Life

Causal association of sex hormones with osteoporosis: a two-sample Mendelian randomization study

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