Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy.
Department of Endocrine and Metabolic Medicine, IRCCS Istituto Auxologico Italiano, Milan, Italy.
Front Endocrinol (Lausanne). 2022 Aug 5;13:939897. doi: 10.3389/fendo.2022.939897. eCollection 2022.
Experimental studies proposed a direct effect of follicle-stimulating hormone (FSH) on the skeletal metabolism, but results of human studies mainly conducted in females are controversial. The present study aims to investigate the possible role of FSH excess in male bone health, by comparing for the first time primary and central hypogonadism.
119 men were enrolled in this cross-sectional observational study at the time of the first diagnosis of hypogonadism. All participants had spontaneous pubertal development. Regarding patients with hypergonadotropic hypogonadism (Hyper-H), Klinefelter syndrome (KS) patients were distinguished from the other forms (non-KS-Hyper-H) based on the onset of FSH elevation. Bone mineral density (BMD) at both lumbar spine (LS) and femoral neck (FN), as well as the prevalence of morphometric vertebral fractures (VFx), were assessed.
Across the whole cohort, higher LS and FN BMD were associated with older age at diagnosis and higher body mass index (BMI), respectively. After adjusting for potential confounders (age at diagnosis, BMI, smoking habits, degree of hypogonadism defined by calculated free testosterone, and 25OH vitamin D levels), non-KS-Hyper-H patients showed significantly lower LS BMD and tended to show lower FN BMD values, as compared to those with hypogonadotropic hypogonadism (Hypo-H). In KS men, LS BMD was significantly lower than in those with non-KS-Hyper-H. No significant differences in the prevalence of VFx were found between the groups.
These findings suggest a potential negative effect of FSH excess on the male bone mass, especially at spine. The duration of high FSH levels may also contribute to these findings.
实验研究提出卵泡刺激素(FSH)对骨骼代谢有直接影响,但主要在女性中进行的人体研究结果存在争议。本研究旨在通过首次比较原发性和中枢性性腺功能减退症来研究 FSH 过多对男性骨骼健康的可能作用。
在性腺功能减退症首次诊断时,共纳入 119 名男性进行这项横断面观察性研究。所有参与者均有自发的青春期发育。对于高促性腺激素性性腺功能减退症(Hyper-H)患者,根据 FSH 升高的起始时间将 Klinefelter 综合征(KS)患者与其他形式(非-KS-Hyper-H)区分开来。评估腰椎(LS)和股骨颈(FN)的骨矿物质密度(BMD),以及形态计量椎体骨折(VFx)的患病率。
在整个队列中,LS 和 FN 的 BMD 较高与诊断时年龄较大和体重指数(BMI)较高相关。在校正了潜在混杂因素(诊断时年龄、BMI、吸烟习惯、根据计算的游离睾酮定义的性腺功能减退程度以及 25OH 维生素 D 水平)后,非-KS-Hyper-H 患者的 LS BMD 明显较低,且 FN BMD 值有较低的趋势,与促性腺激素性性腺功能减退症(Hypo-H)患者相比。KS 男性的 LS BMD 明显低于非-KS-Hyper-H 患者。各组之间 VFx 的患病率无显著差异。
这些发现表明 FSH 过多可能对男性骨量产生负面影响,尤其是在脊柱。高 FSH 水平的持续时间也可能导致这些发现。