Metformin Effects on Male Reproductive Health

Metformin, a first‐line therapy for type II diabetes and insulin resistance, has emerged as a compound of interest in male reproductive biology. Beyond its glycaemic‐control properties, metformin modulates cellular energy sensors, mitigates oxidative stress and influences hormonal axes that underpin spermatogenesis. Preclinical models indicate that metformin restores integrity of the blood–testis barrier, enhances antioxidant enzyme activity and ameliorates lipid‐induced testicular damage. In clinical contexts, metformin appears to improve semen parameters in men with metabolic syndrome, partly by normalising testosterone levels and reducing intra-testicular lipid deposition. However, concerns have been raised regarding paternal and prenatal exposure: epigenetic alterations in male germ cells may carry long-term consequences for offspring fertility. Moreover, isolated reports of sexual dysfunction in patients on metformin underscore the need to balance benefits and potential adverse effects. Globally, with over 150 million users, understanding metformin’s dual roles in metabolic and reproductive health has practical implications for fertility management, drug safety surveillance and environmental monitoring, given its persistence in water systems. Integrating mechanistic insights with clinical observations is essential to optimise therapeutic strategies for men at the intersection of metabolic disease and reproductive impairment.

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Metformin Effects on Male Reproductive Health publication trend

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Technical terms

Oxidative stress: Imbalance between reactive oxygen species production and antioxidant defence, leading to cellular damage.

Blood–testis barrier: A tight junction system between Sertoli cells that protects developing sperm from toxins and immune attack.

Epigenetic regulation: Modification of gene expression through DNA methylation and histone changes without altering the DNA sequence.

Sertoli cell: A somatic cell in the testis that supports and nourishes developing spermatozoa.

AMP-activated protein kinase (AMPK): A cellular energy sensor activated by low ATP levels, regulating metabolism and stress responses.

References

1. Metformin Improves Fertility in Obese Males by Alleviating Oxidative Stress‐Induced Blood‐Testis Barrier Damage. Oxidative Medicine and Cellular Longevity (2019).
2. Metformin in Reproductive Biology. Frontiers in Endocrinology (2018).
3. Metformin Ameliorates Testicular Function and Spermatogenesis in Male Mice with High-Fat and High-Cholesterol Diet-Induced Obesity. Nutrients (2020).
4. In Utero Exposure to Metformin Reduces the Fertility of Male Offspring in Adulthood. Frontiers in Endocrinology (2021).
5. Hypothesis: Metformin is a potential reproductive toxicant. Frontiers in Endocrinology (2022).
6. Erectile dysfunction as a possible important side effect of metformin: A case report. Malaysian Family Physician (2023).