Impact of Duloxetine on Male Fertility

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.

Study Overview

• Status: Completed
• Conditions: Depression; Infertility, Male
• Intervention / Treatment: Drug: Duloxetine; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 69
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10065
      • Weill Cornell Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Weill Medical College of Cornell University
• Investigators: Study Chair: Peter Schlegel, MD, Weill Medical College of Cornell University; Principal Investigator: Nahid Punjani, MD, Weill Medical College of Cornell University

Study record dates

Study Major Dates

• Study Start (Actual): December 12, 2016
• Primary Completion (Actual): August 31, 2018
• Study Completion (Actual): August 31, 2018

Study Registration Dates

• First Submitted: January 27, 2017
• First Submitted That Met QC Criteria: January 30, 2017
• First Posted (Estimate): February 1, 2017

Study Record Updates

• Last Update Posted (Actual): March 12, 2020
• Last Update Submitted That Met QC Criteria: February 26, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infertility; Infertility, Male; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Antidepressive Agents; Dopamine Agents; Serotonin and Noradrenaline Reuptake Inhibitors; Duloxetine Hydrochloride
• Other Study ID Numbers: 1603017099

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No