Pharmaceutical Impacts on Male Fertility

Pharmaceutical agents, while essential for treating a broad range of conditions, can exert unintended effects on male reproductive health. Male fertility relies on the coordinated actions of germ cells, Sertoli cells and Leydig cells within the testes to ensure proper spermatogenesis, hormonal balance and sperm maturation. Several drug classes—including antipsychotics, antidepressants and gastric acid-suppressing agents—have been identified as potential disruptors of these processes. Mechanisms of toxicity range from endocrine interference and oxidative stress to direct damage of germinal epithelium and alterations in neurotransmitter pathways critical for sperm function. Growing evidence highlights the importance of evaluating gonadal safety during drug development and post-marketing surveillance. Clinically, such findings inform guidelines for fertility preservation and risk–benefit assessment, while regulatory agencies are urged to incorporate reproductive endpoints in preclinical and clinical studies. The global significance of declining sperm quality underscores the need for heightened awareness among prescribers and patients, as well as interdisciplinary collaboration between reproductive biologists, pharmacologists and clinicians.

Research from Nature Portfolio

Recent studies have demonstrated that the atypical antipsychotic olanzapine can induce reproductive toxicity in male rodents. Oral administration of olanzapine was associated with reduced sperm concentration and altered morphology, accompanied by histopathological changes in testicular tissue. Alterations in serum levels of follicle-stimulating hormone, luteinising hormone and testosterone were observed, and markers of oxidative stress in the testis indicated disrupted redox homeostasis. These findings implicate hormonal imbalance and oxidative damage as key mediators of drug-induced fertility impairment.

Pharmaceutical Impacts on Male Fertility publication trend

The graph below shows the total number of articles in pharmaceutical impacts on male fertility across all publications each year (not limited to Nature Index journals).

Technical terms

Endocrine-disrupting chemical (EDC): A compound that interferes with hormonal signalling.

Spermatogenesis: The process of sperm cell development in the testes.

Oxidative stress: An imbalance between reactive oxygen species production and antioxidant defence.

Choline acetyltransferase (ChAT): An enzyme that synthesises the neurotransmitter acetylcholine, important for sperm motility regulation.

Gonadotrophins: Hormones, including FSH and LH, that regulate testicular function.

References

1. FDA-approved medications that impair human spermatogenesis. Oncotarget (2016).
2. Olanzapine induced reproductive toxicity in male rats. Scientific Reports (2021).
3. Esomeprazole reduces sperm motility index by targeting the spermic cholinergic machinery: A mechanistic study for the association between use of proton pump inhibitors and reduced sperm motility index. Biochemical Pharmacology (2020).
4. Harmful Consequences of Proton Pump Inhibitors on Male Fertility: An Evidence from Subchronic Toxicity Study of Esomeprazole and Lansoprazole in Wistar Rats. International Journal of Endocrinology (2022).