Lotti F, Corona G, Vitale P, Maseroli E, Rossi M, Fino M G, Maggi M
Sexual Medicine and Andrology Unit, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy.
Sexual Medicine and Andrology Unit, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy Endocrinology Unit, Maggiore-Bellaria Hospital, Bologna, Italy.
Hum Reprod. 2015 Mar;30(3):590-602. doi: 10.1093/humrep/deu347. Epub 2015 Jan 6.
What is the impact of smoking behaviour on seminal, hormonal and male genital tract ultrasound parameters in subjects seeking medical care for couple infertility?
In males of infertile couples, current smokers (CS), when compared with non-smokers, show lower ejaculate and ultrasound-derived seminal vesicles (SV) volume, despite higher testosterone levels.
Data on the effects of smoking on male fertility are conflicting. A correlation between smoking and reduced semen parameters has been reported, however, with a high heterogeneity among studies. An association between smoking behaviour and higher testosterone levels in men has been described in several, but not all, the previous studies. No study has systematically evaluated the impact of smoking on the male genital tract ultrasound characteristics.
STUDY DESIGN, SIZE AND DURATION: Retrospective cross-sectional analysis of a consecutive series of 426 subjects seeking medical care for couple infertility from January 2010 to July 2013.
PARTICIPANTS/MATERIALS, SETTING, METHODS: From the entire cohort, 394 men (age 36.0 ± 8.0 years) free of genetic abnormalities were selected. All subjects underwent a complete andrological and physical examination, biochemical and hormonal assessment, scrotal and transrectal colour-Doppler ultrasound and semen analysis (including seminal interleukin-8 levels, sIL-8) within the same day.
Among the patients evaluated, 229 were never smokers (NS), 56 past smokers (PS) and 109 CS. When CS were compared with the rest of the sample (non-smokers, NS + PS), in a multivariate model (analysis of covariance, ANCOVA) adjusted for age, lifestyle (including alcohol, cannabis and physical activity), BMI and sex hormone-binding globulin, significantly higher androgen (total testosterone, P = 0.001; calculated free testosterone, P < 0.005) and lower FSH (P < 0.05) levels were observed in CS. However, when total testosterone was also included in the multivariate model as a further covariate, the difference in FSH levels was not confirmed. In a similar model, a lower ejaculate volume (P < 0.01) and a higher prevalence of normal sperm morphology (P < 0.02) were also detected in CS in comparison with the rest of the sample. However, when total testosterone was also included in the multivariate model as a further covariate, only the difference in ejaculate volume between CS and non-smokers was confirmed (-0.61 ± 0.23 ml, P < 0.01). Finally, CS showed lower total SV volume, before and after ejaculation, even after adjusting for confounders (P = 0.02 and <0.01, respectively). Similar results were observed when the reported number of cigarettes smoked or the number of pack-years was considered separately.
LIMITATIONS, REASONS FOR CAUTION: The present results are derived from patients consulting an Andrology Clinic for couple infertility, who could have different characteristics from the general male population or males consulting general practitioners for reasons other than couple infertility. In addition, we did not have a true control group composed of age-matched, apparently healthy, fertile men, and therefore true normative data of sonographic parameters cannot be inferred. Due to the cross-sectional nature of our study, neither a causality hypothesis nor mechanistic models can be drawn. Finally, this is a retrospective study, and further prospective studies are required.
We report an apparent paradox in CS: lower SV volume despite higher testosterone levels. Our data suggest that smoking may negatively affect SV volume in an independent manner, as the difference between CS and non-smokers retained significance after adjusting for confounders including testosterone. This is the first study reporting such ultrasound evidence. How this new smoking-related alteration, along with low semen volume, impacts male fertility needs to be addressed by further studies.
STUDY FUNDING/COMPETING INTERESTS: No funding was received for the study. None of the authors have any conflict of interest to declare.
在因夫妻不育而寻求医疗护理的人群中，吸烟行为对精液、激素及男性生殖道超声参数有何影响？
在不育夫妻的男性中，与非吸烟者相比，当前吸烟者（CS）的射精量及超声测量的精囊（SV）体积较低，尽管其睾酮水平较高。
关于吸烟对男性生育能力影响的数据存在矛盾。有报道称吸烟与精液参数降低之间存在关联，但各研究之间存在高度异质性。在之前的一些（但并非全部）研究中描述了吸烟行为与男性较高睾酮水平之间的关联。尚无研究系统评估吸烟对男性生殖道超声特征的影响。
研究设计、规模及持续时间：对2010年1月至2013年7月期间因夫妻不育而寻求医疗护理的426例连续病例进行回顾性横断面分析。
参与者/材料、设置、方法：从整个队列中，选取394名无遗传异常的男性（年龄36.0±8.0岁）。所有受试者在同一天接受了完整的男科及体格检查、生化及激素评估、阴囊及经直肠彩色多普勒超声检查以及精液分析（包括精液白细胞介素-8水平，sIL-8）。
在评估的患者中，229例从不吸烟（NS），56例既往吸烟者（PS），109例当前吸烟者（CS）。当将CS与样本中的其他人群（非吸烟者，NS + PS）进行比较时，在多变量模型（协方差分析，ANCOVA）中，对年龄、生活方式（包括饮酒、吸食大麻和体育活动）、BMI及性激素结合球蛋白进行校正后，CS中雄激素（总睾酮，P = 0.001；计算得出的游离睾酮，P < 0.005）水平显著较高，而卵泡刺激素（FSH）水平较低（P < 0.05）。然而，当将总睾酮也作为进一步的协变量纳入多变量模型时，FSH水平的差异未得到证实。在类似模型中，与样本中的其他人群相比，CS中的射精量也较低（P < 0.01），正常精子形态的患病率较高（P < 0.02）。然而，当将总睾酮也作为进一步的协变量纳入多变量模型时，仅证实了CS与非吸烟者之间射精量的差异（-0.61±0.23 ml，P < 0.01）。最后，即使在对混杂因素进行校正后，CS在射精前后的总SV体积也较低（分别为P = 0.02和<0.01）。当分别考虑报告的吸烟支数或吸烟包年数时，观察到了类似结果。
局限性、注意事项：本研究结果来自因夫妻不育而咨询男科门诊的患者，他们可能具有与一般男性人群不同的特征，或者是因夫妻不育以外的原因咨询全科医生的男性。此外，我们没有由年龄匹配、明显健康、有生育能力的男性组成的真正对照组，因此无法推断超声参数的真正正常数据。由于我们研究的横断面性质，既不能得出因果假设，也不能得出机制模型。最后，这是一项回顾性研究，需要进一步的前瞻性研究。
我们报告了当前吸烟者中一个明显的矛盾现象：尽管睾酮水平较高，但SV体积较低。我们的数据表明，吸烟可能以独立的方式对SV体积产生负面影响，因为在对包括睾酮在内的混杂因素进行校正后，CS与非吸烟者之间的差异仍然显著。这是第一项报告此类超声证据的研究。这种与吸烟相关的新变化以及低精液量如何影响男性生育能力，需要通过进一步研究来解决。
研究资金/利益冲突：本研究未获得资金支持。所有作者均无利益冲突需要声明。
