During the American Urological Association (AUA) annual meeting, Dr. Jorge Hallak, MD, of the University of Sao Paulo, presented marijuana's deleterious effects on the male reproductive system.

Dr. Hallak's long-term study shows that men who smoked marijuana had significantly degraded sperm quality and testicular function, worse than tobacco users and comparable to men with diagnosed infertility.

"Overall, the marijuana group had semen quality equivalent to the infertile group, with the exception of higher ROS and DNA damage than infertile men," Hallak said during an AUA press briefing. "DNA damage is higher in all groups (marijuana users, smokers, and infertile men) as compared to controls, but higher levels were found in the marijuana group and infertile men. Basic semen parameters are not sufficient to identify changes of magnitude in sperm cell function."

Over the past 2 decades, technologic advances allowed more detailed examination of sperm and it has shown that sperm is highly vulnerable to oxidative stress, which has been implicated in a multitude of major human diseases and disorders. Subfertility and infertility almost always arise as a consequence of oxidative stress, said Hallak.

The rationale for evaluating marijuana's effect on male fertility parameters included a lack of information on the topic and the worldwide use of the drug. With an estimated 200 million users worldwide, marijuana is the most widely used psychoactive drug, including more than 20 million regular users in the U.S.

Since 2000, Hallak and colleagues have studied the effects of marijuana and tobacco on spermatozoa and testicular function and relationships with male infertility, hypogonadism, and sexual dysfunction. Each study participant has two comprehensive semen analyses that go well beyond usual lab assessments and include ROS, sperm DNA integrity, creatinine kinase activity, and antisperm antibodies.

Unlike many prior studies, enrollment was limited to users of cannabis and excluded use of cannabinoid-containing products. The study population comprised 125 men with diagnosed infertility, 144 tobacco smokers, 74 marijuana users, and a control group of 279 men (prevasectomy with no clinical factors for testicular dysfunction).

Current marijuana use was ascertained by self-report at the time of enrollment. Median age at first use of marijuana was 18.6, and the median duration of marijuana use was 8 years.

Clinical characteristics of the infertile men included increased levels of prolactin; decreased sperm concentration, motility, and morphology; and increased seminal pH and ROS. Tobacco smokers had decreased follicle-stimulating hormone, luteinizing hormone, and prolactin; decreased testicular volume, and decreased seminal volume.

Marijuana users had a significantly lower median estradiol level (10.04 ng/dL) as compared with all the other groups (P<0.001). Marijuana use was associated with the highest median seminal ROS: 14.31 x 104 cpm/20 x 106 versus 5.66 for infertile men, 0.70 for smokers, and 0.68 for the fertile control group. Hallak noted that marijuana induces production of intracellular ROS whereas tobacco smoke creates extracellular oxidative stress.

In the same study, Hallak reported the first reported evidence of an association between marijuana use and development of benign prostatic hyperplasia/lower urinary tract symptoms (BPH/LUTS).