Does metformin affect sexual dysfunction?

At the European Association for the Study of Diabetes’ meeting in September 2016, I was privileged to attend a wonderful session titled “Metformin: Oldie but goodie”, during which metformin’s mechanism of action, benefits and potential side effects were discussed. The likely cardiovascular benefits were summarised. These included potentially reduced cardiovascular events in type 2 diabetes (conflicting reports), reductions in blood pressure unrelated to weight loss, improvements in lipid profile and endothelial function, reductions in fibrinogen and possible increases in fibrinolysis (Sreekumaran Nair, 2016).

We also heard about the potential for anti-oncogenic effects. Observational studies have shown benefits for breast, colon, prostate and hepatocellular cancers, with evidence suggesting that metformin reduces proliferation of cancer cells in vitro. Metformin may even have anti-ageing effects, as evidenced by its ability to increase longevity in microbes, worms and some mammals.

There was no reference, however, to the potential impact of metformin upon sexual function. Two recent publications raise the question whether metformin may indeed be associated with sexual health, each with contrasting findings. In the first (summarised alongside), Al-Kuraishy and colleagues report that metformin is associated with a significant reduction in testosterone levels and sex drive, and the induction of low-testosterone-induced erectile dysfunction. By contrast, sulfonylureas were associated with significant improvement in these parameters.

These findings are consistent with previous evidence showing that metformin inhibits cytochrome P450 c17a, a key enzyme in testosterone synthesis that reduces luteinising hormone secretion (Valsamakis et al, 2013) and modulates leptin secretion (Ozata et al, 2001), which affects testosterone production.

In the second study (also summarised), Krysiak and colleagues report that metformin treatment normalised low sexual desire and sexual satisfaction in women with type 2 diabetes and prediabetes. The drug also normalised or improved some domains of the Female Sexual Function Index in women with diabetes; this effect was correlated with an improvement in insulin resistance. The authors cite a number of postulated mechanisms, which include the favourable effect on the hormonal milieu and insulin sensitivity.

So the findings of these studies are somewhat contrasting, and their interpretation suffers from a number of confounding factors and small sample sizes (less than 100). However, they serve to remind us that the effects upon sexual function (perhaps the most common complication in diabetes) of one of the most widely used glucose-lowering therapies are not well studied. How often have you asked your patients with diabetes about the impact of metformin on their sex life?

To read the article summaries, please download the PDF