Paroxetine Linked to Sperm DNA Fragmentation

SAN FRANCISCO — Treatment with paroxetine (Paxil) appears to put healthy men at greater risk of sperm DNA fragmentation, according to data from a small study presented at the annual meeting of the American Society for Reproductive Medicine.

In 35 healthy male volunteers, SSRI treatment was significantly correlated with increased DNA fragmentation (odds ratio 11.12, P = .0003) on multivariate logistic regression, after correcting for age and body mass index.

“Healthy volunteers demonstrated a dramatic increase in DNA fragmentation within just a few weeks of paroxetine treatment, without an apparent impact on standard semen parameters. This negative impact on sperm DNA fragmentation may affect reproductive outcomes,” even with intracytoplasmic sperm injection, study investigator Dr. Cigdem Tanrikut said in an interview.

“Certainly, one should query male patients about SSRI use. However, based on these preliminary findings, it would be premature to suggest a patient come off of SSRIs altogether or change to an alternate therapy given the lack of data regarding other newer antidepressants,” said Dr. Tanrikut, director of male reproductive medicine at Massachusetts General Hospital's fertility center in Boston.

Men in the study ranged in age from 18 to 65 years. Intake assessment included physical exam, semen analysis, and the Brief Sexual Function Inventory (BSFI). Repeat semen analysis was obtained before SSRI initiation.

Paroxetine was given for 5 weeks: 10 mg daily during week 1; 20 mg daily during week 2; 30 mg daily during weeks 3–4; and 20 mg daily during week 5. Semen analysis was performed at weeks 2 and 4. One month after cessation of the SSRI, a final semen analysis was then performed. The BSFI was completed at week 4 and at the final semen collection.

Standard World Health Organization evaluation of semen parameters was performed in a certified laboratory. TUNEL (terminal dUTP nick-end labeling) assays were performed at baseline and at week 4 to evaluate the percentage of sperm DNA fragmentation. Semen parameters and TUNEL assays for each participant were compared at each time point.

Semen parameters—including volume, concentration, motility, and morphology—were not significantly altered during SSRI treatment. However, the mean DNA fragmentation TUNEL score was significantly higher with SSRI use, compared with baseline measurements (30.3% vs. 13.8%, P = .0002). The unadjusted odds ratio of having abnormal DNA fragmentation while on paroxetine was 9.33.

In addition, the BSFI revealed significant sexual dysfunction on paroxetine as compared with baseline. Up to 35% of men noted significant changes in erectile function, and up to 47% of subjects reported ejaculatory difficulties while on paroxetine. At least partial recovery of sexual function was noted within 1 month after stopping treatment.

The study was supported by the Frederick J. and Theresa Dow Wallace Fund of the New York Community Trust and Brady Urology Foundation.

Based on these preliminary findings, it would be premature to suggest changing to an alternate therapy. DR. TANRIKUT

SAN FRANCISCO — Treatment with paroxetine (Paxil) appears to put healthy men at greater risk of sperm DNA fragmentation, according to data from a small study presented at the annual meeting of the American Society for Reproductive Medicine.

In 35 healthy male volunteers, SSRI treatment was significantly correlated with increased DNA fragmentation (odds ratio 11.12, P = .0003) on multivariate logistic regression, after correcting for age and body mass index.

“Healthy volunteers demonstrated a dramatic increase in DNA fragmentation within just a few weeks of paroxetine treatment, without an apparent impact on standard semen parameters. This negative impact on sperm DNA fragmentation may affect reproductive outcomes,” even with intracytoplasmic sperm injection, study investigator Dr. Cigdem Tanrikut said in an interview.

“Certainly, one should query male patients about SSRI use. However, based on these preliminary findings, it would be premature to suggest a patient come off of SSRIs altogether or change to an alternate therapy given the lack of data regarding other newer antidepressants,” said Dr. Tanrikut, director of male reproductive medicine at Massachusetts General Hospital's fertility center in Boston.

Men in the study ranged in age from 18 to 65 years. Intake assessment included physical exam, semen analysis, and the Brief Sexual Function Inventory (BSFI). Repeat semen analysis was obtained before SSRI initiation.

Paroxetine was given for 5 weeks: 10 mg daily during week 1; 20 mg daily during week 2; 30 mg daily during weeks 3–4; and 20 mg daily during week 5. Semen analysis was performed at weeks 2 and 4. One month after cessation of the SSRI, a final semen analysis was then performed. The BSFI was completed at week 4 and at the final semen collection.

Standard World Health Organization evaluation of semen parameters was performed in a certified laboratory. TUNEL (terminal dUTP nick-end labeling) assays were performed at baseline and at week 4 to evaluate the percentage of sperm DNA fragmentation. Semen parameters and TUNEL assays for each participant were compared at each time point.

Semen parameters—including volume, concentration, motility, and morphology—were not significantly altered during SSRI treatment. However, the mean DNA fragmentation TUNEL score was significantly higher with SSRI use, compared with baseline measurements (30.3% vs. 13.8%, P = .0002). The unadjusted odds ratio of having abnormal DNA fragmentation while on paroxetine was 9.33.

In addition, the BSFI revealed significant sexual dysfunction on paroxetine as compared with baseline. Up to 35% of men noted significant changes in erectile function, and up to 47% of subjects reported ejaculatory difficulties while on paroxetine. At least partial recovery of sexual function was noted within 1 month after stopping treatment.

The study was supported by the Frederick J. and Theresa Dow Wallace Fund of the New York Community Trust and Brady Urology Foundation.

Based on these preliminary findings, it would be premature to suggest changing to an alternate therapy. DR. TANRIKUT

SAN FRANCISCO — Treatment with paroxetine (Paxil) appears to put healthy men at greater risk of sperm DNA fragmentation, according to data from a small study presented at the annual meeting of the American Society for Reproductive Medicine.

In 35 healthy male volunteers, SSRI treatment was significantly correlated with increased DNA fragmentation (odds ratio 11.12, P = .0003) on multivariate logistic regression, after correcting for age and body mass index.

“Healthy volunteers demonstrated a dramatic increase in DNA fragmentation within just a few weeks of paroxetine treatment, without an apparent impact on standard semen parameters. This negative impact on sperm DNA fragmentation may affect reproductive outcomes,” even with intracytoplasmic sperm injection, study investigator Dr. Cigdem Tanrikut said in an interview.

“Certainly, one should query male patients about SSRI use. However, based on these preliminary findings, it would be premature to suggest a patient come off of SSRIs altogether or change to an alternate therapy given the lack of data regarding other newer antidepressants,” said Dr. Tanrikut, director of male reproductive medicine at Massachusetts General Hospital's fertility center in Boston.

Men in the study ranged in age from 18 to 65 years. Intake assessment included physical exam, semen analysis, and the Brief Sexual Function Inventory (BSFI). Repeat semen analysis was obtained before SSRI initiation.

Paroxetine was given for 5 weeks: 10 mg daily during week 1; 20 mg daily during week 2; 30 mg daily during weeks 3–4; and 20 mg daily during week 5. Semen analysis was performed at weeks 2 and 4. One month after cessation of the SSRI, a final semen analysis was then performed. The BSFI was completed at week 4 and at the final semen collection.

Standard World Health Organization evaluation of semen parameters was performed in a certified laboratory. TUNEL (terminal dUTP nick-end labeling) assays were performed at baseline and at week 4 to evaluate the percentage of sperm DNA fragmentation. Semen parameters and TUNEL assays for each participant were compared at each time point.

Semen parameters—including volume, concentration, motility, and morphology—were not significantly altered during SSRI treatment. However, the mean DNA fragmentation TUNEL score was significantly higher with SSRI use, compared with baseline measurements (30.3% vs. 13.8%, P = .0002). The unadjusted odds ratio of having abnormal DNA fragmentation while on paroxetine was 9.33.

In addition, the BSFI revealed significant sexual dysfunction on paroxetine as compared with baseline. Up to 35% of men noted significant changes in erectile function, and up to 47% of subjects reported ejaculatory difficulties while on paroxetine. At least partial recovery of sexual function was noted within 1 month after stopping treatment.

The study was supported by the Frederick J. and Theresa Dow Wallace Fund of the New York Community Trust and Brady Urology Foundation.

Based on these preliminary findings, it would be premature to suggest changing to an alternate therapy. DR. TANRIKUT