Association Between Use of Marijuana and Male Reproductive Hormones and Semen Quality

A Study Among 1,215 Healthy Young Men

Tina Djernis Gundersen; Niels Jørgensen; Anna-Maria Andersson; Anne Kirstine Bang; Loa Nordkap; Niels E. Skakkebæk; Lærke Priskorn; Anders Juul; Tina Kold Jensen

Disclosures

Am J Epidemiol. 2015;182(6):473-481. 

In This Article

Discussion

In this study on more than 1,200 healthy young men, of whom 45% had smoked marijuana during the past 3 months, we found associations between regular use of marijuana more than once per week during the past 3 months and reduced semen quality, whereas no adverse association was found for irregular use. The combined use of marijuana and other recreational drugs decreased semen quality further. In addition, marijuana use was associated with increased serum testosterone to the same level as cigarette smoking. We cannot exclude the possibility that the men who used marijuana generally have an unhealthier lifestyle and health behavior, which may also affect their semen quality and hormone levels. We, however, adjusted for known lifestyle factors.

A study[6] investigated chronic marijuana users who, after 4 weeks of abstinence from marijuana, smoked between 8 and 20 marijuana-containing joints per week for 4 weeks. An association between marijuana use and decreased sperm count was detected, which persisted in the following 4-week recovery period. This is in accordance with our findings. On the contrary, a study of 159 men attending an infertility clinic found a positive correlation between marijuana use and percentage of motile sperm.[18] The tendencies remained unchanged after adjusting for other substance use and history of sexually transmitted diseases. The discrepancies may be due to the fact that we studied healthy young men with a higher marijuana intake than infertile men, who may have changed their intake because of fertility problems. Only 2 previous studies have assessed the combined effects of marijuana and recreational drug use on semen quality. A case study[19] on a multidrug addict, investigated before and 2 years after cessation of the abuse, showed long-lasting semen abnormalities. Another study of 6 male multidrug addicts showed semen abnormalities.[8] All subjects were underweight and malnourished, making it impossible to compare them with our healthy, young men.

The biological mechanisms by which marijuana affects semen quality and hormone levels are not fully known. The active component of cannabis, Δ9-tetrahydrocannabinol (THC), binds to the human cannabinoid receptors CB1 and CB2. CB1 receptors are found in the anterior pituitary but have also been identified in the testis, vas deferens, and human sperm cells,[20] leading to a dose-dependent decreased sperm motility and decreased mitochondrial activity in spermatozoa when activated.[21] This makes it possible for marijuana to affect hormone levels and spermatogenesis, as well as the mature sperm cells. In vitro studies have shown that low doses of THC hyperactivated the spermatozoa and that high doses of THC had an inactivating effect,[5] mimicking the human cannabinoid anandamide.[22] THC could affect the normal balance of anandamide leading to impaired semen quality.

The hypophyseal hormones are known to affect spermatogenesis, and marijuana may affect semen quality by influencing both this axis and the testis. Marijuana has been found to reduce testosterone and luteinizing hormone.[23,24] However, previous studies did not take into account cigarette smoking and other possible confounders. In this study, we found a significant increase in testosterone correlated to the use of marijuana, contrary to the other studies. However, this increase could not be separated from the effect of tobacco smoking alone, found in other studies to raise testosterone levels,[25,26] making it impossible to separate the adverse effects of marijuana and cigarette smoking in this study.

Our study has several strengths, as it was large and included unselected young men of whom many used marijuana. A total of 45% of our men reported having tried marijuana during the past 3 months, and 33% used marijuana less than once per week, which is comparable to Danish population studies of men aged 16–34 years in which 46% reported ever having tried marijuana[1] and 17% during the past year. Only 6% of young Danes aged 16–34 years reported having used marijuana during the last month, which is lower than in our study. However, our men are younger, and the response categories are not directly comparable.

Our participation-rate was 30%, which is higher than participation rates in other population-based studies on semen quality.[9,27] Most of the men were unaware of their own fertility potential (8% had been responsible for a pregnancy), making this unlikely to have affected their motivation to participate. Approximately 15% of the men had a sperm concentration at a level that would indicate a high risk of needing future fertility treatment if they want to father a child.[10] However, we believe that they represent the general population of young Danish men as we conducted a study where reproductive hormones among participants and nonparticipants were compared.[28] We found no significant difference with regard to reproductive hormones in the 2 groups, indicating that our participants represented the general population with respect to reproductive health. In addition, this study compared semen quality and reproductive hormones in groups of men with different marijuana use, and it is therefore of less importance whether the groups of men in fact represented the general population.

Participants were asked to evaluate their use of marijuana in the last 3 months and, though the study was anonymous, there may have been a tendency to underestimate the consumption. However, this seems unlikely, as 45% of the young men reported marijuana use during the past 3 months, which may even indicate overreporting. The potential sources of exposure misclassification are unlikely to be related to the semen parameters or hormone levels, because the men responded to the questionnaire before knowing the results of their semen and serum analysis. Such nondifferential misclassifications would underestimate the results and can therefore not explain our findings. It would have been preferable to measure the carboxy THC metabolite levels in urine samples from the men in order to confirm the results from the questionnaire. However, studies suggest that urine-, blood-, and oral-fluid tests designed to measure marijuana use are unlikely to detect use further back than 1 month, whereas in this study we assessed use during the past 3 months. Furthermore, research has shown large intersubject differences in measurable levels in urine, making urine-sample testing less useful in this study.[29]

Doses and time of abstinence from marijuana and other recreational drugs can vary individually and occasionally. We did not obtain information on these factors, but previous studies have suggested a dose and time dependence.[6,22,30–32] In addition, spermatozoa mature within 3 months, and estimated marijuana intake over the past 3 months is therefore a good study design for assessing the association between semen quality and marijuana and recreational drug use.

Men who used marijuana had an unhealthier lifestyle and health behavior, were often smokers, consumed more alcohol, had a higher caffeine intake, were more likely to have had a sexually transmitted disease, and were more likely to have used recreational drugs other than marijuana. The adverse association between marijuana use and semen quality tended to be larger among men with low alcohol intake, although the results were not statistically significant. The negative association between marijuana use and semen quality and hormone levels may be attributed to differences in lifestyle, health behavior, and diet found among users, and even though we adjusted for many lifestyle factors, residual confounding is still possible.

In conclusion, to the best of our knowledge, this is the first study showing adverse associations between regular marijuana use more than once weekly and semen quality among healthy young men, the association being even more pronounced among men taking other recreational drugs as well. We found an increase in testosterone levels among marijuana smokers within the same range as for tobacco smokers. As the study was cross-sectional, it was not possible to test whether semen quality and hormone levels are restored after cessation of the use, but until further studies have been conducted, men should be informed of the possibility that habitual marijuana use might be detrimental to their semen parameters. Our findings are potentially of great public interest, as almost half of the young Danish men use marijuana, which may contribute to the etiology for the recently reported high frequency of subnormal human sperm counts.

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