Background: Oxandrolone is a synthetic testosterone analogue that is widely used among bodybuilders and
athletes. However, oxandrolone causes male infertility. Recently, it was found that metformin reduces the risk of infertility
associated with diabetes mellitus.
Aim: This study aimed to investigate the protective effects of metformin against oxandrolone-induced infertility in male
Methods: Rats continuously received one of four treatments (n=7) over 14 days: control DMSO administration, oxandrolone
administration, metformin administration, or co-administration of oxandrolone and metformin. Doses were equivalent to
those used for human treatment. Subsequently, testicular and blood samples were collected for morphological, biochemical,
and histological examination. In addition, gene expression of the testosterone synthesizing enzyme CYP11A1 was analyzed
in the testes using RT-PCR.
Results: Oxandrolone administration induced male infertility by significantly reducing relative weights of testes by 48%,
sperm count by 82%, and serum testosterone levels by 96% (ANOVA, P value < 0.05). In addition, histological examination
determined that oxandrolone caused spermatogenic arrest which was associated with 2-fold downregulation of testicular
CYP11A1 gene expression. However, co-administration of metformin with oxandrolone significantly ameliorated
toxicological alterations induced by oxandrolone exposure (ANOVA, P value < 0.05).
Conclusion: Metformin administration protected against oxandrolone-induced infertility in male rats. Further clinical
studies are needed to confirm the protective effect of metformin against oxandrolone-induced infertility among athletes.