Testicular function in a birth cohort of young men
Testicular function in a birth cohort of young men
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DOI：
10.1093/humrep/dev244
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发表时间：
2015-12-01
影响因子：
6.1
通讯作者：
Handelsman, D. J.
中科院分区：
文献类型：
--
作者：
Hart, R. J.;Doherty, D. A.;Handelsman, D. J.
研究问题：通过调查持续参与率较高的出生队列来得出公正的人群，对于未根据生育能力选择的人群，参数和对睾丸功能的影响是什么？总结答案：虽然精索静脉曲张、隐睾和肥胖可能会影响人类睾丸功能，但最常见的药物暴露和附睾囊肿的存在似乎没有或很少有不利影响。 已知的情况：大多数以前的研究为精子发生建立有效参考人群的尝试依赖于可能存在偏见的来源，例如来自不孕不育诊所的招募人员、自行选择的自愿精子捐献者用于研究或人工授精或曾经有生育能力的男性寻求输精管结扎术。众所周知，需要精液分析的研究招募率较低，因此对其有效性提出质疑。然而，有人担心，令人惊讶的高比例的年轻男性的精液变量可能不符合世界卫生组织对生育男性的所有参考范围标准，一些研究报告称，多达一半的参与者没有达到生育男性的参考范围。报道的精子浓度中值范围为 40 至 6000 万个精子/ml。 研究设计、规模和持续时间：西澳大利亚怀孕队列 (Raine) 成立于 1989 年。在 20-22 岁时，队列成员被联系参加一般随访，其中 913 名可联系的男性中有 753 人参与。其中，423 名男性（20-22 年队列研究参与者的 56%，可接触男性的 46%）参与了睾丸功能研究。在 423 名男性中，404 人接受了睾丸超声检查，365 人提供了至少一份精液样本，287 人提供了第二份精液样本，384 人提供了血液样本。 参与者/材料、地点、方法：在珀斯苏比亚科爱德华国王纪念医院进行睾丸超声检查，检查睾丸体积以及是否存在附睾囊肿和精索静脉曲张。精液样本由位于珀斯克莱蒙特的西澳大利亚生育专家通过标准精液评估和精子染色质结构测定 (SCSA) 提供和分析。血清血样由珀斯克劳利西澳大利亚大学提供，并分析血清黄体生成素 (LH)、卵泡刺激素 (FSH)、抑制素 B、睾酮、二氢睾酮 (DHT)、脱氢表雄酮 (DHEA)、雌二醇、雌酮和 DHT 的主要代谢物：5 α-雄甾烷-3 α、17 β-二醇 (3 α-二醇）和5-α雄甾烷-3-β-17-β-二醇（3β-二醇）。通过液相色谱法、质谱法测量血清类固醇，通过 ELISA 测定法测量 LH、FSH 和抑制素 B。 主要结果和机会的作用：隐睾与睾丸 (P = 0.047) 和精液 (P = 0.027) 体积、精子浓度 (P = 0.007) 和精子输出 (P = 0.003) 显着减少有关。精索静脉曲张与较小的睾丸体积 (P < 0.001)、较低的精子浓度 (P = 0.012) 和总精子输出量 (P = 0.030) 以及较低的血清抑制素 B 水平 (P = 0.046) 相关。吸烟、饮酒、疝气修补术、附睾囊肿、药物和非法药物与任何显着的精液变量、睾丸体积或循环生殖激素无关。 BMI与精液量（r = -0.12，P = 0.048）、精子产量（r = -0.13，P = 0.02）、血清LH（r = -0.16，P = 0.002）、抑制素B（r = -0.16，P < 0.001）、睾酮（r = -0.23，P < 0.001）和DHT (r = -0.22，P < 0.001) 与 3 alpha D (r = 0.13，P = 0.041) 和 DHEA (r = 0.11，P = 0.03) 呈正相关。在提供两个样本的 287 名参与者中，第二个精液样本与第一个精液样本进行了比较，Bland-Altman 分析没有显着偏差。睾丸体积与精子浓度（r = 0.25，P < 0.001）、精子输出量（r = 0.29，P < 0.001）和抑制素B（r = 0.42，P < 0.001）呈显着正相关，与血清LH（r = -0.24，P < 0.001）和FSH（r = -0.32，P < 0.001）呈负相关。 0.001）。 SCSA 与精子活力（r = -0.20，P < 0.001）和形态（r = -0.16，P = 0.005）呈负相关。只有 52 名男性 (14.4%) 全部符合 WHO 精液参考标准。 15-20% 的男性在首次分析时未满足一些标准，包括精液量（
STUDY QUESTION: By investigating a birth cohort with a high ongoing participation rate to derive an unbiased population, what are the parameters and influences upon testicular function for a population not selected with regard to fertility?SUMMARY ANSWER: While varicocele, cryptorchidism and obesity may impact on human testicular function, most common drug exposures and the presence of epididymal cysts appear to have no or minimal adverse impact.WHAT IS KNOWN ALREADY: The majority of previous attempts to develop valid reference populations for spermatogenesis have relied on potentially biased sources such as recruits from infertility clinics, self-selected volunteer sperm donors for research or artificial insemination or once-fertile men seeking vasectomy. It is well known that studies requiring semen analysis have low recruitment rates which consequently question their validity. However, there has been some concern that a surprisingly high proportion of young men may have semen variables that do not meet all the WHO reference range criteria for fertile men, with some studies reporting that up to one half of participants have not meet the reference range for fertile men. Reported median sperm concentrations have ranged from 40 to 60 million sperm/ml.STUDY DESIGN, SIZE AND DURATION: The Western Australian Pregnancy Cohort (Raine) was established in 1989. At 20-22 years of age, members of the cohort were contacted to attend for a general follow-up, with 753 participating out of the 913 contactable men. Of these, 423 men(56% of participants in the 20-22 years cohort study, 46% of contactable men) participated in a testicular function study. Of the 423 men, 404 had a testicular ultrasound, 365 provided at least one semen sample, 287 provided a second semen sample and 384 provided a blood sample.PARTICIPANTS/MATERIALS, SETTING, METHODS: Testicular ultrasound examinations were performed at King Edward Memorial Hospital, Subiaco, Perth, for testicular volume and presence of epididymal cysts and varicoceles. Semen samples were provided and analysed by standard semen assessment and a sperm chromatin structural assay (SCSA) at Fertility Specialists of Western Australia, Claremont, Perth. Serum blood samples were provided at the University of Western Australia, Crawley, Perth and were analysed for serum luteinizing hormone (LH), follicular stimulating hormone (FSH), inhibin B, testosterone, dihydrotestosterone (DHT), dehydroepiandrosterone (DHEA), estradiol, estrone and the primary metabolites of DHT: 5 alpha-androstane-3 alpha, 17 beta-diol (3 alpha-diol) and 5-alpha androstane-3-beta-17-beta-diol (3 beta-diol). Serum steroids were measured by liquid chromatography, mass spectrometry and LH, FSH and inhibin B were measured by ELISA assays.MAIN RESULTS AND THE ROLE OF CHANCE: Cryptorchidism was associated with a significant reduction in testicular (P = 0.047) and semen (P = 0.027) volume, sperm concentration (P = 0.007) and sperm output (P = 0.003). Varicocele was associated with smaller testis volume (P < 0.001), lower sperm concentration (P = 0.012) and total sperm output (P = 0.030) and lower serum inhibin B levels (P = 0.046). Smoking, alcohol intake, herniorrhaphy, an epididymal cyst, medication and illicit drugs were not associated with any significant semen variables, testicular volume or circulating reproductive hormones. BMI had a significantly negative correlation with semen volume (r = -0.12, P = 0.048), sperm output (r = -0.13, P = 0.02), serum LH (r = -0.16, P = 0.002), inhibin B (r = -0.16, P < 0.001), testosterone (r = -0.23, P < 0.001) and DHT (r = -0.22, P < 0.001) and a positive correlation with 3 alpha D (r = 0.13, P = 0.041) and DHEA (r = 0.11, P = 0.03). Second semen samples compared with the first semen samples in the 287 participants who provided two samples, with no significant bias by Bland-Altman analysis. Testis volume was significantly correlated positively with sperm concentration (r = 0.25, P < 0.001) and sperm output (r = 0.29, P < 0.001) and inhibin B (r = 0.42, P < 0.001), and negatively correlated with serum LH (r = -0.24, P < 0.001) and FSH (r = -0.32, P < 0.001). SCSA was inversely correlated with sperm motility (r = -0.20, P < 0.001) and morphology (r = -0.16, P = 0.005). WHO semen reference criteria were all met by only 52 men (14.4%). Some criteria were not met at first analysis in 15-20% of men, including semen volume (