Treatment with paroxetine (Paxil), which belongs to the selective serotonin reuptake inhibitor (SSRI) class of antidepressant drugs, increases DNA fragmentation in sperm, according to research presented today at the 64th annual meeting of the American Society for Reproductive Medicine in San Francisco.
Although the study did not directly evaluate male fertility, the five-fold increase in the number of men who developed abnormal sperm DNA while being treated with paroxetine is "troubling" and "suggests an adverse effect on fertility," co-investigator Dr. Cigdem Tanrikut, from Harvard Medical School in Boston, told Reuters Health.
In a clinical trial she described as "the first study to assess the impact of an SSRI on semen parameters in healthy men," 35 men took paroxetine for 5 weeks. The drug was administered in once-daily doses of 10 mg the first week, 20 mg in the second week, 30 mg the third and fourth week, and 20 mg in the fifth week.
Tests were conducted on semen samples obtained prior to starting paroxetine and after 4 weeks of treatment. The average DNA fragmentation score increased from 13.8 percent before paroxetine was begun to 30.3 percent at week 4, a statistically significant amount.
The percentage of men who had a fragmentation score of 30 percent or higher before treatment rose from 10 percent to 50 percent.
Semen analyses conducted throughout the study, however, showed normal volume, concentration, movement and appearance.
Paroxetine was also associated with significant sexual dysfunction, with one third of men reporting problems with erectile function and nearly half reporting ejaculatory difficulties.
"DNA integrity is crucial to normal fertility," Tanrikut said. For example, increased DNA fragmentation of sperm increases the risk of failure of intrauterine insemination.
"Abnormal sperm DNA integrity even affects pregnancy outcomes of the most advanced assisted reproductive technologies, such as in vitro fertilization (IVF)," she added. "In fact, it is the only male factor finding that has been shown to affect intracytoplasmic sperm injection (ICSI) results."
"A large proportion of patients on (SSRIs) may have their fertility affected," co-investigator Dr. Peter N. Schlegel, at Weill Medical College of Cornell University in New York, observed in correspondence with Reuters Health.
Among infertile men taking an SSRI, "a standard semen analysis won't measure this effect," Schlegel pointed out, and "a special test for DNA fragmentation...should be considered."
The sperm appears to be damaged by a slowing down of their transport through the body, "a novel mechanism of damage," he said. "Most agents affect fertility by knocking down sperm production. Slowing down sperm transport can allow sperm to be damaged (by higher temperatures, or just 'getting too old' — being ejaculated after they should have been)."
"We have seen severe cases where the sperm are slowed down so much that almost no sperm appear in the ejaculate."
Based on these findings, the research team is planning larger studies using other SSRI antidepressants.