SSRI Antidepressant Treatment May Reduce Male Fertility

By Karla Gale

NEW YORK (Reuters Health) Nov 10 - Treatment with the selective serotonin reuptake inhibitor (SSRI) paroxetine (Paxil) increases sperm DNA fragmentation, according to research presented today at the 64th annual meeting of the American Society for Reproductive Medicine in San Francisco.

"Although fertility was not directly assessed in this study, the five-fold increase in the number of patients who developed abnormal sperm DNA integrity while on 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 trial that 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. Paroxetine was administered in once-daily doses of 10 mg the first week, 20 mg the second week, 30 mg the third and fourth week, and 20 mg the fifth week.

Assays were performed on semen samples obtained prior to starting paroxetine and at week 4. The mean DNA fragmentation score increased from 13.8% at baseline to 30.3% at week 4 (p = 0.002), while the proportion of subjects with a fragmentation score of 30% or higher rose from 10% to 50% (p = 0.001).

Semen analyses conducted throughout the study, however, showed normal volume, concentration, motility, and morphology.

Paroxetine was 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," Dr. Tanrikut said. For example, increased DNA fragmentation is considered a negative predictor of intrauterine insemination success.

"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. "For men on these drugs with infertility, a standard semen analysis won't measure this effect -- a special test for DNA fragmentation (e.g., TUNEL or SCSA) should be considered."

"Interestingly," he continued, "the effect appears to be damage to sperm by slowing down their transport through the body. This is a novel mechanism of damage. 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 adverse findings, the research team is now planning larger scale, randomized, double-blinded, placebo-controlled studies using other SSRI antidepressants.