Jensen Tina Kold, Finne Katrine Folmann, Skakkebæk Niels E, Andersson Anna-Maria, Olesen Inge Ahlmann, Joensen Ulla Nordström, Bang Anne Kirstine, Nordkap Loa, Priskorn Lærke, Krause Marianna, Jørgensen Niels, Juul Anders
Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, Copenhagen, Denmark Department of Environmental Medicine, University of Southern Denmark, Odense, Denmark
Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, Copenhagen, Denmark.
Hum Reprod. 2016 Aug;31(8):1886-94. doi: 10.1093/humrep/dew122. Epub 2016 Jun 6.
Is there an association between pubertal onset and subsequent reproductive health in young men?
Self-reported later onset of puberty was associated with reduced semen quality and altered serum levels of reproductive hormones among 1068 healthy, young Danish men.
The long-term effects of variations in the onset of male puberty on subsequent reproduction remain largely unstudied.
STUDY DESIGN, SIZE, DURATION: In a cross-sectional study, young healthy Danish men were approached when they attended a compulsory medical examination to determine their fitness for military service from 2008 to 2012.
PARTICIPANTS/MATERIALS, SETTINGS, METHODS: A total of 1068 healthy, young Danish men (mean age 19 years) participated. They were asked to assess whether onset of penile and testicular growth, development of pubic hair and voice break occurred earlier, at the same time as or later than their peers. Their semen quality (semen volume, sperm concentration, total sperm count and percentages of motile and morphologically normal spermatozoa) and serum concentrations of sex hormones (LH, FSH, total testosterone, SHBG, inhibin B) and testicular size were determined.
The response rate was 29%. Of the 1068 men who then participated, 652 answered the questions about penile growth and pubic hair development and were therefore included in the analysis. Self-reported later onset of puberty was associated with a 25% reduction in sperm concentration (95% CI -41%; -4%), a 40% reduction in total sperm count (-55%; -21%), a 1.6% age point reduction in morphological normal spermatozoa (-2.9; -0.3) and a 1.6 ml reduction in testicular size (-2.4 and -0.8 ml), after adjustment for confounders. Self-reported later onset of puberty was also associated with a 9% (3%; 15%) reduction in free testosterone and a 16% (2%; 31%) increase in FSH, after adjustment for confounders.
LIMITATIONS, REASON FOR CAUTION: Our study was cross-sectional and reverse causality cannot be ruled out. In addition, we cannot rule out the possibility that the men with late puberty onset had not yet fully matured although most were in Tanner stage 5.
Approximately 15% of young Danish men have self-reported later onset of puberty than their peers. We found poorer testicular function in young men with a history of later pubertal development, suggesting that timing of pubertal onset may be a fundamental marker of male reproductive health. However, we cannot exclude the possibility that these men had not fully matured at the time of examination and therefore their semen quality may yet improve, which makes follow-up important.
STUDY FUNDING/COMPETING INTERESTS: This work was supported by the Danish Council for Strategic Research, Program Commission on Health, Food and Welfare (project number 2101-08-0058), Rigshospitalet (grants 961506336 and R42-A1326), European Union, DEER (grant agreement no 212844), the Danish Ministry of Health and the Danish Environmental Protection Agency and Kirsten and Freddy Johansens Foundation (grant 95-103-72087). There are no competing interests.
年轻男性青春期启动与随后的生殖健康之间是否存在关联？
在1068名健康的丹麦年轻男性中，自我报告的青春期启动较晚与精液质量下降及生殖激素血清水平改变有关。
男性青春期启动时间变化对随后生殖的长期影响在很大程度上仍未得到研究。
研究设计、规模、持续时间：在一项横断面研究中，2008年至2012年期间，当年轻健康的丹麦男性参加义务体检以确定其是否适合服兵役时，对他们进行了研究。
参与者/材料、环境、方法：共有1068名健康的丹麦年轻男性（平均年龄19岁）参与。他们被要求评估阴茎和睾丸生长开始、阴毛发育及变声的时间早于、与同龄人同时还是晚于同龄人。测定了他们的精液质量（精液量、精子浓度、总精子数以及活动精子和形态正常精子的百分比）、性激素血清浓度（促黄体生成素、促卵泡生成素、总睾酮、性激素结合球蛋白、抑制素B）以及睾丸大小。
应答率为29%。在随后参与的1068名男性中，652人回答了关于阴茎生长和阴毛发育的问题，因此被纳入分析。在对混杂因素进行调整后，自我报告的青春期启动较晚与精子浓度降低25%（95%可信区间 -41%；-4%）、总精子数降低40%（-55%；-21%）、形态正常精子的百分比降低1.6个年龄点（-2.9；-0.3）以及睾丸大小减小1.6毫升（-2.4和 -0.8毫升）有关。在对混杂因素进行调整后，自我报告的青春期启动较晚还与游离睾酮降低9%（3%；15%）以及促卵泡生成素升高16%（2%；31%）有关。
局限性、谨慎的理由：我们的研究是横断面研究，无法排除反向因果关系。此外，尽管大多数男性处于坦纳5期，但我们不能排除青春期启动较晚的男性尚未完全成熟的可能性。
约15%的丹麦年轻男性自我报告青春期启动比同龄人晚。我们发现有青春期发育较晚病史的年轻男性睾丸功能较差，这表明青春期启动时间可能是男性生殖健康的一个基本标志。然而，我们不能排除这些男性在检查时尚未完全成熟的可能性，因此他们的精液质量可能仍会改善，这使得随访很重要。
研究资金/利益冲突：这项工作得到了丹麦战略研究理事会、健康、食品和福利项目委员会（项目编号2101 - 08 - 0058）、哥本哈根大学医院（拨款961506336和R42 - A1326）、欧盟、DEER（拨款协议编号212844）、丹麦卫生部和丹麦环境保护局以及柯尔斯滕和弗雷迪·约翰森基金会（拨款95 - 103 - 72087）的支持。不存在利益冲突。
