Department of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
Hum Reprod. 2019 Apr 1;34(4):715-723. doi: 10.1093/humrep/dez002.
Is marijuana smoking associated with semen quality, sperm DNA integrity or serum concentrations of reproductive hormones among subfertile men?
Men who had ever smoked marijuana had higher sperm concentration and count and lower serum FSH concentrations than men who had never smoked marijuana; no differences were observed between current and past marijuana smokers.
Studies of marijuana abuse in humans and animal models of exposure to marijuana suggest that marijuana smoking adversely impacts spermatogenesis. Data is less clear for moderate consumption levels and multiple studies have found higher serum testosterone concentrations among marijuana consumers.
STUDY DESIGN, SIZE, DURATION: This longitudinal study included 662 subfertile men enroled at the Massachusetts General Hospital Fertility Center between 2000 and 2017. The men provided a total of 1143 semen samples; 317 men also provided blood samples in which we measured reproductive hormones.
PARTICIPANTS/MATERIALS, SETTING, METHODS: Use of marijuana and other drugs was self-reported at baseline. Standard protocols were followed for measuring semen quality, sex hormones and DNA integrity. We used linear mixed effect models with a random intercept to evaluate the associations of self-reported marijuana smoking at enrolment with semen parameters from subsequently collected samples, and linear regression models for sperm DNA integrity and serum reproductive hormones, while adjusting for confounders including smoking and cocaine use.
Men who had ever smoked marijuana (N = 365) had significantly higher sperm concentration (62.7 (95% confidence interval: 56.0, 70.3) million/mL) than men who had never smoked marijuana (N = 297) (45.4 (38.6, 53.3) million/mL) after adjusting for potential confounders (P = 0.0003). There were no significant differences in sperm concentration between current (N = 74) (59.5 (47.3, 74.8) million/mL) and past marijuana smokers (N = 291) (63.5 (56.1, 72.0) million/mL; P = 0.60). A similar pattern was observed for total sperm count. Furthermore, the adjusted prevalence of sperm concentration and total sperm motility below WHO reference values among marijuana smokers was less than half that of never marijuana smokers. Marijuana smokers had significantly lower follicle stimulating hormone (FSH) concentrations than never marijuana smokers (-16% (-27%, -4%)) and there were no significant differences between current and past marijuana smokers (P = 0.53). Marijuana smoking was not associated with other semen parameters, with markers of sperm DNA integrity or with reproductive hormones other than FSH. Chance findings cannot be excluded due to the multiple comparisons.
LIMITATIONS, REASONS FOR CAUTION: Our results may not be generalisable to men from the general population. Marijuana smoking was self-reported and there may be misclassification of the exposure.
These findings are not consistent with a deleterious effect of marijuana on testicular function. Whether these findings are reflective of the previously described role of the endocannabinoid system in spermatogenesis or a spurious association requires confirmation in further studies.
STUDY FUNDING/COMPETING INTEREST(S): The project was funded by grants R01ES009718 and P30ES000002 from the National Institute of Environmental Health Sciences (NIEHS). None of the authors has any conflicts of interest to declare.
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在不育男性中，吸食大麻与精液质量、精子 DNA 完整性或血清生殖激素浓度有关吗？
与从未吸食过大麻的男性相比，曾经吸食过大麻的男性的精子浓度和数量更高，血清 FSH 浓度更低；而当前和过去吸食大麻的男性之间没有差异。
人类滥用大麻和动物接触大麻模型的研究表明，大麻吸食会对精子发生产生不利影响。对于适度消费水平的数据则不太清楚，并且多项研究发现大麻消费者的血清睾酮浓度更高。
研究设计、规模、持续时间：这项纵向研究包括 2000 年至 2017 年间在马萨诸塞州综合医院生育中心招募的 662 名不育男性。这些男性共提供了 1143 份精液样本；317 名男性还提供了血液样本，我们在其中测量了生殖激素。
参与者/材料、设置、方法：大麻和其他药物的使用情况在基线时进行自我报告。我们遵循标准协议测量精液质量、性激素和 DNA 完整性。我们使用具有随机截距的线性混合效应模型来评估自我报告的在入组时吸食大麻与随后采集的样本中的精液参数之间的关联，并使用线性回归模型来评估精子 DNA 完整性和血清生殖激素，同时调整包括吸烟和可卡因使用在内的混杂因素。
与从未吸食过大麻的男性（N=297）相比，曾经吸食过大麻的男性（N=365）的精子浓度（62.7（95%置信区间：56.0，70.3）百万/mL）显著更高（P=0.0003）。在调整了潜在混杂因素后，当前（N=74）（59.5（47.3，74.8）百万/mL）和过去吸食大麻的男性（N=291）（63.5（56.1，72.0）百万/mL）之间的精子浓度没有显著差异（P=0.60）。总精子计数也出现了类似的模式。此外，吸食大麻者的精子浓度和总精子活力低于世卫组织参考值的比例显著低于从未吸食过大麻者（分别为 50%和 30%）。与从未吸食过大麻者相比，大麻吸食者的卵泡刺激素（FSH）浓度显著降低（-16%（-27%，-4%）），且当前和过去吸食大麻者之间没有显著差异（P=0.53）。大麻吸食与其他精液参数、精子 DNA 完整性标志物或除 FSH 以外的生殖激素无关。由于多次比较，可能存在偶然发现。
局限性、谨慎的原因：我们的结果可能不适用于来自一般人群的男性。大麻吸食情况是自我报告的，可能存在暴露情况的错误分类。
这些发现与大麻对睾丸功能的有害影响不一致。这些发现是否反映了先前描述的内源性大麻素系统在精子发生中的作用，或者只是一种偶然的关联，需要在进一步的研究中得到证实。
研究资金/利益冲突：该项目由美国国立环境卫生科学研究所（NIEHS）的 R01ES009718 和 P30ES000002 资助。作者均无任何利益冲突。
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