Impact of Duloxetine on Male Fertility

Study Overview
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Brief Summary
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The investigators are conducting a placebo-controlled, randomized control trial with duloxetine in healthy, fertile men not previously on any antidepressants. Participants will be randomized to either the duloxetine or placebo groups for 6 weeks. The investigators will assess changes in sperm DNA fragmentation at 0, 2, 6, 8, and 10 weeks. Other outcomes measured will include semen parameters (sperm concentration, motility, morphology), hormone levels (testosterone, estrogen, prolactin, LH, FSH), and sexual function (IIEF and MSHQ) surveys.

Detailed Description
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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.

Official Title
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Impact of Duloxetine on Male Fertility

Conditions
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Infertility, Male, Depression

Intervention / Treatment
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* Drug: Duloxetine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Blinded, placebo-controlled, randomized controlled trial
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Duloxetine<br>Duloxetine orally 60mg daily for 5 weeks, then taper to 30mg daily for 1 week | Drug: Duloxetine<br>* Duloxetine orally 60mg daily for 5 weeks, then taper to 30mg daily for 1 week<br>|
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo<br>* Placebo orally 2 tabs daily for 5 weeks, then taper to 1 tab daily for 1 week<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Abnormal Sperm DNA Fragmentation at 6 Weeks | Number of participants with TUNEL values > 25% at 6 weeks in each treatment group | 6 Weeks (primary time point of interest) | 
| Number of Participants With Abnormal Sperm DNA Fragmentation at 0 Weeks | Number of participants with Tunel Values > 25% at 0 Weeks (baseline) in each treatment group | 0 weeks | 
| Number of Participants With Abnormal Sperm DNA Fragmentation at 2 Weeks | Number of participants with Tunel values > 25% at 2 weeks in each treatment group | 2 weeks | 
| Number of Participants With Abnormal Sperm DNA Fragmentation at 8 Weeks | Number of participants with Tunel values > 25% at 8 weeks in each treatment group | 8 weeks | 
| Number of Participants With Abnormal Sperm DNA Fragmentation at 10 Weeks | Number of participants with Tunel values > 25% at 10 weeks in each treatment group | 10 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sperm Concentration at 0 Weeks | Sperm concentration (number of sperm/mL) in semen analysis at 0 weeks | 0 weeks | 
| Sperm Concentration at 2 Weeks | Sperm concentration (number of sperm/mL) in semen analysis at 2 weeks | 2 weeks | 
| Sperm Concentration at 6 Weeks | Sperm concentration (number of sperm/mL) in semen analysis at 6 weeks | 6 weeks | 
| Sperm Concentration at 8 Weeks | Sperm concentration (number of sperm/mL) in semen analysis at 8 weeks | 8 weeks | 
| Sperm Concentration at 10 Weeks | Sperm concentration (number of sperm/mL) in semen analysis at 10 weeks | 10 Weeks | 
| Sperm Motility at 0 Weeks | Sperm motility (mean percent) at 0 weeks | 0 weeks | 
| Sperm Motility at 2 Weeks | Sperm motility (mean percent) at 2 weeks | 2 weeks | 
| Sperm Motility at 6 Weeks | Sperm motility (mean percent) at 6 weeks | 6 weeks | 
| Sperm Motility at 8 Weeks | Sperm motility (mean percent) at 8 weeks | 8 weeks | 
| Sperm Motility at 10 Weeks | Sperm motility (mean percent) at 10 weeks | 10 Weeks | 
| Sperm Head Defects at 0 Weeks | Sperm head defects (mean number) at 0 weeks | 0 weeks | 
| Sperm Head Defects at 2 Weeks | Sperm head defects (mean number) at 2 weeks | 2 weeks | 
| Sperm Head Defects at 6 Weeks | Sperm head defects (mean number) at 6 weeks | 6 weeks | 
| Sperm Head Defects at 8 Weeks | Sperm head defects (mean number) at 8 weeks | 8 weeks | 
| Sperm Head Defects at 10 Weeks | Sperm head defects (mean number) at 10 weeks | 10 Weeks | 
| Sperm Neck Defects at 0 Weeks | Sperm neck defects (mean number) at 0 weeks | 0 weeks | 
| Sperm Neck Defects at 2 Weeks | Sperm neck defects (mean number) at 2 weeks | 2 weeks | 
| Sperm Neck Defects at 6 Weeks | Sperm neck defects (mean number) at 6 weeks | 6 weeks | 
| Sperm Neck Defects at 8 Weeks | Sperm neck defects (mean number) at 8 weeks | 8 weeks | 
| Sperm Neck Defects at 10 Weeks | Sperm neck defects (mean number) at 10 weeks | 10 Weeks | 
| Sperm Tail Defects at 0 Weeks | Sperm tail defects (mean number) at 0 weeks | 0 weeks | 
| Sperm Tail Defects at 2 Weeks | Sperm tail defects (mean number) at 2 weeks | 2 weeks | 
| Sperm Tail Defects at 6 Weeks | Sperm tail defects (mean number) at 6 weeks | 6 weeks | 
| Sperm Tail Defects at 8 Weeks | Sperm tail defects (mean number) at 8 weeks | 8 weeks | 
| Sperm Tail Defects at 10 Weeks | Sperm tail defects (mean number) at 10 weeks | 10 Weeks | 
| Testosterone Level at 0 Weeks | Testosterone level (ng/dL) at 0 weeks | 0 weeks | 
| Testosterone Level at 2 Weeks | Testosterone level (ng/dL) at 2 weeks | 2 weeks | 
| Testosterone Level at 6 Weeks | Testosterone level (ng/dL) at 6 weeks | 6 weeks | 
| Testosterone Level at 8 Weeks | Testosterone level (ng/dL) at 8 weeks | 8 weeks | 
| Testosterone Level at 10 Weeks | Testosterone level (ng/dL) at 10 weeks | 10 Weeks | 
| Estrogen Level at 0 Weeks | Estrogen level (pg/mL) at 0 weeks | 0 weeks | 
| Estrogen Level at 2 Weeks | Estrogen level (pg/mL) at 2 weeks | 2 weeks | 
| Estrogen Level at 6 Weeks | Estrogen level (pg/mL) at 6 weeks | 6 weeks | 
| Estrogen Level at 8 Weeks | Estrogen level (pg/mL) at 8 weeks | 8 weeks | 
| Estrogen Level at 10 Weeks | Estrogen level (pg/mL) at 10 weeks | 10 Weeks | 
| Prolactin Level at 0 Weeks | Prolactin level (ng/mL) at 0 weeks | 0 weeks | 
| Prolactin Level at 2 Weeks | Prolactin level (ng/mL) at 2 weeks | 2 weeks | 
| Prolactin Level at 6 Weeks | Prolactin level (ng/mL) at 6 weeks | 6 weeks | 
| Prolactin Level at 8 Weeks | Prolactin level (ng/mL) at 8 weeks | 8 weeks | 
| Prolactin Level at 10 Weeks | Prolactin level (ng/mL) at 10 weeks | 10 Weeks | 
| Luteinizing Hormone Level at 0 Weeks | Luteinizing hormone level (mIU/mL) at 0 weeks | 0 weeks | 
| Luteinizing Hormone Level at 2 Weeks | Luteinizing hormone level (mIU/mL) at 2 weeks | 2 weeks | 
| Luteinizing Hormone Level at 6 Weeks | Luteinizing hormone level (mIU/mL) at 6 weeks | 6 weeks | 
| Luteinizing Hormone Level at 8 Weeks | Luteinizing hormone level (mIU/mL) at 8 weeks | 8 weeks | 
| Luteinizing Hormone Level at 10 Weeks | Luteinizing hormone level (mIU/mL) at 10 weeks | 10 Weeks | 
| Follicle Stimulating Hormone Level at 0 Weeks | Follicle stimulating hormone level (mIU/mL) at 0 weeks | 0 weeks | 
| Follicle Stimulating Hormone Level at 2 Weeks | Follicle stimulating hormone level (mIU/mL) at 2 weeks | 2 weeks | 
| Follicle Stimulating Hormone Level at 6 Weeks | Follicle stimulating hormone level (mIU/mL) at 6 weeks | 6 weeks | 
| Follicle Stimulating Hormone Level at 8 Weeks | Follicle stimulating hormone level (mIU/mL) at 8 weeks | 8 weeks | 
| Follicle Stimulating Hormone Level at 10 Weeks | Follicle stimulating hormone level (mIU/mL) at 10 weeks | 10 Weeks |