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Evaluation of the Impact of Marijuana Use on Semen Quality
By: Caleb A. Cooper, MD; Matthew J. Sloan, MD; Tristan Nicholson, MD; Marah C. Hehemann, MD; Omer A. Raheem, MD; Thomas Walsh, MD | Posted on: 01 Jan 2022
Consumption of marijuana (Cannabis sativa) for medical and recreational purposes is rising both domestically and globally. In the United States, medical use of marijuana is legal in 33 states, and recreational use has been legalized in 11 states. Cannabinoids have 2 major categories: exogenous, which are plant-based and include THC (Δ9-tetrahydrocannabinol), the psychoactive component of marijuana, and endogenous, which are synthesized by various tissues of the human body. THC can alter the signaling system within spermatozoa by competing with endogenous cannabinoids at cannabinoid-binding receptors, potentially resulting in negative effects on spermatogenesis, sperm function and male fertility.1 Given the unclear impact of marijuana on male infertility, there is an increasing demand to better understand its potential impacts on reproductive health.
We designed a prospective, cross-sectional study to characterize differences in semen quality between men who reported consumption of marijuana (either current or past use) compared to never-users.2 Reproductive age men seeking infertility evaluation and without discrete identifiable cause for their infertility were included. A total of 409 men completed a semen analysis (SA) and a reproductive health questionnaire with questions regarding age, marijuana use history, including frequency and duration, and tobacco smoking history. Questions regarding current and past marijuana consumption were used to classify patients as never, current or past users. Past use was defined as any marijuana use and a ≥3-month period of abstinence from marijuana consumption at time of SA. A single laboratory performed SA in accordance with WHO 2010, 5th edition guidelines.3
Of the men included in our study, 174 (43%) reported marijuana use. Among marijuana users, current and past users comprised 71 (17%) and 103 (25%) individuals, respectively (see figure). The majority of patients had a body mass index (BMI) ≥25 in all groups; however, never-users were more likely to have a healthy BMI (20–24.99, p <0.02; see table). Current users were more likely to have below WHO reference semen volume (p=0.04), and a higher proportion were found to have abnormal strict morphology (p <0.001). Marijuana never-users were more likely to have below WHO reference sperm motility when compared with ever-users (p <0.001).
Table. Participant characteristics and semen analysis results
Variables | WHO Reference Ranges | Current (71 pts, 17%) | Past (103 pts, 25%) | Never (235 pts, 57%) | p Value |
---|---|---|---|---|---|
Mean yrs age (SD) | 34.8 (5.2) | 35.0 (5.3) | 36.3 (7.4) | 0.39 | |
No. mean kg/m2 BMI (%): | <0.02 | ||||
<20 | 2 (2.8) | 5 (4.8) | 1 (0.4) | ||
20-24.99 | 16 (22.5) | 18 (17.5) | 67 (28.5) | ||
≥25 | 53 (74.7) | 80 (77.7) | 167 (71.1) | ||
No. current tobacco use (%): | <0.01 | ||||
No | 44 (62.0) | 78 (75.7) | 167 (71.1) | ||
Yes | 26 (36.6) | 25 (24.3) | 28 (11.9) | ||
Unknown | 1 (1.4) | 0 (0.0) | 40 (17.0) | ||
Mean vol (SD) | 1.5-7.6 ml | 3.2 (1.47) | 3.13 (1.48) | 3.03 (1.55) | 0.68 |
Mean concentration (SD) | 15-259 million/ml | 98.36 (98.08) | 100.15 (92.76) | 79.22 (75.07) | 0.26 |
Mean % motility (SD) | 40-81 | 46.04 (21.66) | 48.74 (15.91) | 49.99 (18.69) | 0.25 |
Mean % progress motility (SD) | 31-75 | 40.83 (19.73) | 40.06 (16.67) | 41.7 (18.66) | 0.85 |
Mean % strict morphology (SD) | 4-48 | 5.48 (4.19) | 3.94 (3.65) | 4.79 (4.71) | 0.007 |
Mean TMC (SD) | >20 million | 145.48 (174.97) | 146.3 (150.29) | 139 (169.51) | 0.95 |
Mean total progressive motile count (SD) | >12.5 million | 128.15 (150.51) | 123.59 (134.37) | 121.48 (158.67) | 0.93 |
In multivariate logistic regression analysis, both current and past users demonstrated significantly increased odds of having abnormal strict morphology (OR 2.15, 95% CI 1.21–3.79 and OR 2.26, 95% CI 1.37–3.73, respectively). Current users had significantly increased odds of having below WHO reference value semen volume (OR 2.76, 95% CI 1.19–6.42). There was a trend toward current users having a greater odds of below WHO reference value total progressively motile count (OR 1.71, 95% CI 0.85–3.47); however, the significance threshold was not met. Current users had significantly reduced odds of having below WHO reference value total motility (OR 0.47, 95% CI 0.25–0.91). However, a significant difference was not found in regard to progressive motility.
Taken together, these findings support the hypothesis that marijuana has detrimental effects on semen quality, with marijuana ever-users having greater odds of below WHO reference values for strict morphology and semen volume when compared to never-users. However, contrary to our prediction, the odds of sperm motility being within WHO reference values were higher among marijuana ever-users compared to never-users.
Two recent European studies similarly describe negative effects of marijuana use on semen quality, including increased risk of poor morphology, as well as a reduction in median sperm concentration and total sperm count.4,5 In contrast, Nassan et al published a conflicting report that found marijuana users had higher mean sperm concentration and total sperm count compared to nonusers.6 These findings are less clinically meaningful given that both means are well within the range of normal as defined by WHO 2010. Notably, this study did not demonstrate an appreciable difference between never-smokers and ever-smokers with respect to odds of abnormal strict morphology.
The prevalence of marijuana use among men presenting for infertility in our cohort was comparable to use within the general population in Washington state.7 Past use was more common than current use (25% vs 17%). Current users were found to have a twofold increased risk of abnormal strict morphology. Surprisingly, past users had the highest odds of deficits in strict morphology, suggesting a possible delayed negative effect of marijuana.
Marijuana ever-users demonstrated a significantly greater chance of sperm motility being within WHO reference ranges and trended toward improved odds of normal progressive motility. Specifically, current-users demonstrated a twofold increased likelihood of sperm motility surpassing WHO reference range compared to nonusers. This finding suggests a possible partially pro-spermatogenic effect, the mechanism of which is unclear.
Among past users of marijuana, we found a trend toward below WHO reference ranges for sperm concentration, and an almost threefold increased risk of low semen volume. These reduced parameters can result in a relative decline in total motile count (TMC), and we did find a trend toward abnormal TMC in our cohort of marijuana users. Given that TMC has been suggested to be one of the most important indicators for severity of infertility, we recommend against marijuana use in men trying to conceive or with infertility, especially in those found to have reduced TMC.8
Our study is a single-center study in a state where marijuana is legal, potentially limiting the generalizability of our findings. However, a growing number of states have legalized marijuana for both medicinal and recreational use, possibly expanding the generalizability of our results. Another limitation is that exposures such as diet, control of sleep apnea, exercise frequency and duration could not be controlled. Lastly, we did not evaluate subjects’ usage of other recreational drugs, which may impact semen quality and warrants additional investigation.
Our investigation builds on literature supporting the complex interactions between marijuana and the male reproductive system. We found that marijuana consumption had a mixed impact on sperm quality in men presenting for infertility evaluation. Further large-scale randomized studies will be important to fully understand the association between marijuana use and male reproductive health.
- Whan LB, West MCL, McClure N et al: Effects of delta-9-tetrahydrocannabinol, the primary psychoactive cannabinoid in marijuana, on human sperm function in vitro. Fertil Steril 2006; 85: 653.
- Hehemann MC, Raheem OA, Rajanahally S et al: Evaluation of the impact of marijuana use on semen quality: a prospective analysis. Ther Adv Urol 2021; 13: 1.
- World Health Organization: WHO Laboratory Manual for the Examination and Processing of Human Semen. Geneva, Switzerland: World Health Organization 2010.
- Pacey AA, Povey AC, Clyma JA et al: Modifiable and non-modifiable risk factors for poor sperm morphology. Hum Reprod 2014; 29: 1629.
- Gundersen TD, JØrgensen N, Andersson A-M et al: Association between use of marijuana and male reproductive hormones and semen quality: a study among 1,215 healthy young men. Am J Epidemiol 2015; 182: 473.
- Nassan FL, Arvizu M, Mínguez-Alarcón L et al: Marijuana smoking and markers of testicular function among men from a fertility centre. Hum Reprod 2019; 34: 715.
- Lapham GT, Lee AK, Caldeiro RM et al: Frequency of cannabis use among primary care patients in washington state. J Am Board Fam Med 2017; 30: 795.
- Hamilton JAM, Cissen M, Brandes M et al: Total motile sperm count: a better indicator for the severity of male factor infertility than the WHO sperm classification system. Hum Reprod 2015; 30: 1110.