Impact of Duloxetine on Male Fertility

Antidepressant medications are commonly prescribed in the USA not only for depression, but
also for anxiety disorders such as generalized anxiety disorder and obsessive-compulsive
disorder, premature ejaculation, post-traumatic stress disorder, and neuropathic pain.
Despite being widely prescribed in the United States in men of reproductive age, the impact
of antidepressants on fertility has not been extensively studied.

After noticing worsened semen parameters in men on anti-depressants, the investigators
performed the first prospective study to demonstrate a deleterious impact of selective
serotonin reuptake inhibitors (SSRI) on sperm DNA integrity, which has been linked to
reproductive outcomes. Further small studies have corroborated the negative impact of SSRIs
on male fertility, as assessed by semen parameters and/or sperm DNA integrity.

No studies have examined the impact of a newer, but similar, class of antidepressant - the
serotonin-norepinephrine reuptake inhibitor (SNRI). Like SSRIs, SNRIs inhibit the reuptake of
serotonin, but also act on norepinephrine. The use of SNRIs has increased recently due to
their slightly improved efficacy profile when compared to SSRIs. Duloxetine is an SNRI and is
one of the most commonly prescribed anti-depressants in the United States.

The investigators are conducting this trial to determine whether or not the administration of
duloxetine will result in a deterioration in sperm DNA fragmentation in healthy, fertile men.

Inclusion Criteria:

- Healthy men aged 18-65 years old;

- normal or borderline semen analysis (sperm concentration > 10 million/mL, sperm
motility > 30%, sperm morphology > 3%);

- willing to engage in sexual activity (alone or with a partner) at least once per week
for the duration of the study;

- capable of providing semen sample.

Exclusion Criteria:

- Clinically detected varicocele;

- oligoasthenoteratospermia or azoospermia on semen analysis;

- ongoing attempts to initiate pregnancy;

- current sexual dysfunction (classified as moderate or worse on IIEF);

- history of seizure disorder;

- history of previous chemotherapy or radiation therapy;

- current psychiatric history or history of bipolar disorder;

- family history of bipolar disorder, depression, or suicide;

- use of any psychotropic medications or anticonvulsants;

- use of sleeping pills more than once per week;

- use of any hormonal medications on a daily or intermittent basis during the preceding
3 months;

- use of medications which may affect hormone measures and/or sexual function;

- inability to read, follow instructions, or complete questionnaires in English;

- consumption of tobacco or illicit drugs;

- consumption of >2oz of alcohol daily.