Department of Women's and Children's Health, and Center of Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
Deparment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Andrology. 2022 Oct;10(7):1376-1386. doi: 10.1111/andr.13229. Epub 2022 Jul 29.
Hypospadias is a common congenital malformation often related to the effect of androgens in utero. While hypogonadism is associated with many potential health risks including metabolic and cardiovascular disease, the risk of clinical hypogonadism and comorbidities in men with hypospadias later in life has not been studied.
Investigate the risk of hypogonadism and somatic comorbidities in adolescents and men born with hypospadias.
We conducted a population-based cohort study using Swedish registers. Associations between hypospadias and hypogonadism, delayed puberty, metabolic, and cardiovascular disease respectively were estimated using Cox proportional hazards regression. Body measurements from military conscription were analysed in a subpopulation as indicators of growth and cardiometabolic risk. We used sibling comparison analyses to control for familial confounding.
Using register data, a total of 2,165,255 men including 9,714 men born with hypospadias were followed from the age of 10 to a maximum of 60 years. We found an association between hypospadias and hypogonadism (Hazard ratio (HR) 3.27, 95% confidence interval (CI) 2.33-4.59) which was more pronounced in proximal hypospadias. Men with hypospadias had shorter average height than their brothers and the general population. We further found an increased risk of delayed puberty (HR 1.49, 95% CI 1.08-2.07), diabetes mellitus type 2 (HR 1.57, 95% CI 1.18-2.09) and cardiovascular disease (HR 1.47, 95% CI 1.27-1.71).
We found an increased risk of hypogonadism, metabolic and cardiovascular disease in men born with hypospadias, increasing with severity of phenotype, as well as impacted growth. These results indicate discruptions in androgen function past childhood, although some of the associations may be due to other underlying aetiologies.
Hypospadias is associated with an increased risk of androgen-related comorbidity in adolescence and adulthood. We suggest that this can be considered clinically, while further research is needed, especially in older populations.
尿道下裂是一种常见的先天性畸形，通常与子宫内雄激素的作用有关。虽然低促性腺激素血症与许多潜在的健康风险有关，包括代谢和心血管疾病，但尿道下裂患者成年后发生临床性腺功能减退症和合并症的风险尚未得到研究。
研究男性尿道下裂患者在青少年和成年时发生性腺功能减退症和躯体合并症的风险。
我们使用瑞典登记册进行了一项基于人群的队列研究。使用 Cox 比例风险回归估计尿道下裂与性腺功能减退症、青春期延迟、代谢和心血管疾病之间的关联。在亚人群中，使用兵役身体测量结果作为生长和心脏代谢风险的指标进行分析。我们使用同胞比较分析来控制家族性混杂。
使用登记数据，共对 2165255 名男性（包括 9714 名男性尿道下裂患者）进行了随访，随访年龄从 10 岁到最大 60 岁。我们发现尿道下裂与性腺功能减退症（危险比[HR]3.27，95%置信区间[CI]2.33-4.59）之间存在关联，近端尿道下裂更为明显。尿道下裂患者的平均身高低于其兄弟和一般人群。我们还发现青春期延迟（HR 1.49，95%CI 1.08-2.07）、2 型糖尿病（HR 1.57，95%CI 1.18-2.09）和心血管疾病（HR 1.47，95%CI 1.27-1.71）的风险增加。
我们发现男性尿道下裂患者发生性腺功能减退症、代谢和心血管疾病的风险增加，且随着表型严重程度的增加而增加，同时也影响了生长。这些结果表明，雄激素功能在儿童期后出现紊乱，尽管一些关联可能是由于其他潜在病因所致。
尿道下裂与青少年和成年期雄激素相关合并症的风险增加有关。我们建议在临床上考虑这一点，同时需要进一步研究，特别是在老年人群中。
