Does fluoxetine (Prozac) affect male fertility?

From the Guidelines

Fluoxetine may potentially affect male fertility, and men taking this medication who are concerned about fertility should discuss this with their healthcare provider. The evidence regarding the impact of fluoxetine on male fertility is mixed, with some studies suggesting that this selective serotonin reuptake inhibitor (SSRI) can impact sperm parameters, including count, motility, and morphology, as well as increase DNA fragmentation in sperm cells 1. The medication may also cause sexual side effects like delayed ejaculation or erectile dysfunction that could indirectly affect fertility, as noted in guidelines for disorders of ejaculation 1. These effects appear to be reversible after discontinuation of the medication. However, the benefits of treating depression or anxiety often outweigh potential fertility concerns, and alternative antidepressants with potentially fewer reproductive effects might be considered if fertility is a priority, though individual responses vary 1. The mechanism behind these effects likely involves serotonin's role in sexual function and sperm production, as well as potential hormonal changes. Any decisions about medication changes should always be made in consultation with a healthcare provider, taking into account the most recent and highest quality evidence available, such as the updates to male infertility guidelines 1. Key considerations include the potential for fluoxetine to affect sperm quality and the importance of discussing fertility concerns with a healthcare provider, as emphasized in guidelines for the diagnosis and treatment of infertility in men 1. Ultimately, the decision to use fluoxetine or alternative treatments should be based on a careful weighing of the potential benefits and risks, with a focus on minimizing harm and optimizing outcomes for morbidity, mortality, and quality of life.

From the FDA Drug Label

Impairment of Fertility — Two fertility studies conducted in adult rats at doses of up to 7.5 and 12. 5 mg/kg/day (approximately 0.9 and 1.5 times the MRHD on a mg/m2 basis) indicated that fluoxetine had no adverse effects on fertility.

The FDA drug label does not provide direct information on the effects of fluoxetine on male fertility in humans. However, based on the available animal studies, it can be inferred that fluoxetine may not have adverse effects on fertility in adult males, as the studies in adult rats showed no adverse effects on fertility. Key points:

• Two fertility studies in adult rats showed no adverse effects on fertility
• The studies were conducted at doses of up to 7.5 and 12.5 mg/kg/day
• The results may not be directly applicable to humans 2

From the Research

Effects of Fluoxetine on Male Fertility

• Fluoxetine, also known as Prozac, has been studied for its potential effects on male fertility in various research studies 3, 4, 5, 6.
• A study published in 2007 found that long-term ingestion of fluoxetine in adult male rats caused a significant decrease in spermatogenesis, sperm motility, and density, as well as a decrease in testosterone levels and weights of reproductive organs 3.
• Another study published in 2021 found that fluoxetine decreased serum testosterone, diminished epithelial height and diameter of seminiferous tubules, and increased collagen fiber deposition in testicular tissue in adult male albino rats 4.
• A literature review published in 2022 found that selective serotonin reuptake inhibitors (SSRIs), including fluoxetine, can decrease the number and viability of sperm and cause disruption of their morphological structure, and recommended that SSRIs be avoided in male patients of reproductive age who wish to conceive 5.
• A study published in 2020 found that fluoxetine has been associated with gonadotoxic effects, including decreased sperm concentration and motility, increased deoxyribonucleic acid fragmentation, and decreased reproductive organ weights, but noted that this effect is reversible 6.

Mechanisms and Reversibility

• The exact mechanisms by which fluoxetine affects male fertility are not fully understood, but may involve changes in hormone levels, sperm quality, and testicular function 3, 4, 6.
• The effects of fluoxetine on male fertility appear to be reversible, with studies suggesting that discontinuation of the medication can lead to improvements in sperm quality and fertility parameters 5, 6.

Clinical Implications

• The available evidence suggests that fluoxetine may have negative effects on male fertility, particularly with long-term use or at high doses 3, 4, 5, 6.
• Clinicians should be aware of these potential effects when prescribing fluoxetine to male patients of reproductive age, and consider alternative treatments or monitoring of fertility parameters as needed 5, 6.