Can Fluoxetine Cause Azoospermia?
Fluoxetine does not typically cause complete azoospermia (absence of sperm), but it can significantly impair sperm quality, reduce sperm count, and negatively affect multiple fertility parameters. While guidelines recommend SSRIs including fluoxetine for premature ejaculation, the evidence shows these medications can have substantial reproductive effects that fall short of complete azoospermia.
Evidence from Guidelines on SSRI Effects
Exogenous testosterone—not SSRIs—is the medication class that causes true azoospermia through suppression of gonadotropin secretion, with spermatogenesis decreasing or ceasing altogether 1.
Guidelines recommend fluoxetine 20-40 mg daily as a first-line treatment for premature ejaculation, but they do not list azoospermia as a recognized adverse effect 1, 2.
The AUA/SMSNA guidelines focus on sexual side effects of SSRIs (reduced libido, erectile dysfunction) rather than complete absence of sperm production 1.
What Fluoxetine Actually Does to Sperm
The most recent high-quality research demonstrates that fluoxetine impairs sperm quality through multiple mechanisms, but does not eliminate sperm production entirely:
Fluoxetine significantly reduces sperm motility, viability, mitochondrial membrane potential, and chromatin integrity while increasing DNA fragmentation and oxidative stress 3.
Long-term fluoxetine exposure (60 days in animal models) causes decreased spermatogenesis, significantly reduced sperm motility and density, decreased testosterone and FSH levels, and reduced fertility—but not complete azoospermia 4.
Fluoxetine administered during juvenile-peripubertal development uniformly diminishes LH, FSH, progesterone, and testosterone levels, with a subpopulation showing greatly affected sperm quality parameters 5.
Clinical Implications
If a patient on fluoxetine presents with azoospermia, look for alternative explanations:
Screen for concurrent testosterone therapy or anabolic steroid use, which are the primary pharmacologic causes of azoospermia 1.
Evaluate for hypogonadotropic hypogonadism, gonadotoxic therapies, or anatomic obstruction 1.
Consider that fluoxetine may be contributing to oligospermia (low sperm count) rather than complete azoospermia 4.
Mechanism of Reproductive Effects
Fluoxetine disrupts the hypothalamic-pituitary-testicular axis by altering gonadotropin and sex steroid concentrations 5.
The medication increases oxidative stress (elevated ROS and MDA levels) while decreasing total antioxidant capacity in sperm 3.
Fluoxetine upregulates apoptotic pathways in sperm by increasing expression of CASPASE8, CASPASE9, and BAX genes while decreasing anti-apoptotic BCL2 expression 3.
Practical Recommendations
For men of reproductive age taking fluoxetine who are concerned about fertility:
Counsel that fluoxetine can impair sperm quality and reduce fertility potential, but complete azoospermia is not an expected outcome 5, 3, 4.
If azoospermia is documented, pursue a complete infertility workup rather than attributing it solely to fluoxetine 1.
Consider alternative treatments for premature ejaculation if fertility is a priority, such as topical anesthetics or on-demand clomipramine 1.
Document baseline semen analysis before starting fluoxetine in men planning future fertility 4.