The Longevity Dilemma: Metformin’s Impact on Aging and Testosterone

Metformin, a drug for lowering blood sugar levels, is one of the most popular medications in the world. Furthermore, promising studies indicate that this medication can help combat aging. However, at the same time, metformin has a negative impact on testosterone levels. How and why?

A drop in testosterone levels, decreased libido, and erectile dysfunction are typical complications of type 2 diabetes in men over 40 years old. Studies suggest that nearly all diabetics experience potency disorders—years earlier than their peers.

Although obesity and low physical activity, which often lead to the development of diabetes, are serious risk factors in and of themselves, testosterone levels are also affected by the use of the sugar-lowering drug metformin. However, this side effect is often not mentioned in the instructions.

Diabetes and Testosterone Levels

Diabetes is a group of diseases related to disruptions in glucose and insulin metabolism in the body. Diabetes occurs when the body loses the ability to properly use the hormone insulin—either producing insufficient amounts or losing sensitivity to its action.

In type 2 diabetes, body tissues lose sensitivity to insulin. Despite the hormone being present in the blood, it does not have the proper effect on glucose—resulting in elevated blood sugar levels that pose health risks, including vascular complications affecting erections.

Additionally, studies suggest that men with low testosterone levels have a higher risk of developing diabetes, obesity, and metabolic syndrome—factors that further disrupt metabolic functions and provoke potency problems.

Metformin for Lowering Sugar Levels

Metformin is the most commonly prescribed medication for type 2 diabetes. In many countries, it is among the top five best-selling drugs—for example, in the United States, more than 80 million metformin prescriptions are issued annually.

Its use suppresses the formation of glucose in the liver, simultaneously lowering the percentage of its absorption by altering gut microbiota and increasing tissue sensitivity to insulin.

However, in addition to its primary function, metformin lowers testosterone levels—in both men and women, for instance, those with polycystic ovary syndrome.

Metformin and Testosterone

Testosterone is a key male hormone. It not only regulates potency but also normalizes blood pressure, improves glucose utilization, and supports strength and muscle mass. A higher level of testosterone helps both avoid diabetes and control it better.

On the other hand, reducing insulin resistance, while it improves diabetes control and reduces the risk of complications, can in itself negatively affect testosterone synthesis.

Traditionally, the negative consequences of diabetes are considered a more dangerous factor for male sexual health than lowering testosterone levels.

What is the reason for metformin’s effect on testosterone levels?

The lowering of testosterone levels with the use of metformin, especially in women with polycystic ovary syndrome (PCOS), is explained by a number of mechanisms, including:

Inhibition of Cytochrome P450-C17a: This is a key enzyme in the biosynthesis of steroid hormones, including testosterone. Metformin may inhibit this enzyme, thereby reducing the production of testosterone.

Modulation of Leptin Secretion: Leptin is a hormone that plays a critical role in regulating appetite and metabolism. Leptin levels may be linked to testosterone levels, and metformin can help modulate leptin secretion, affecting testosterone levels.

Improvement of Insulin Resistance: Insulin and testosterone levels can be linked, and metformin, by improving insulin sensitivity, can also affect testosterone levels.

In other words, this drug has a similar effect on both testosterone and leptin (produced in visceral fat and regulates the mechanisms of satiety from food). By influencing leptin, metformin helps combat excess weight and reduce fasting glucose (which, again, is associated with appetite).

Studies

There was a study aimed to examine the impact of the diabetes drug metformin on testosterone levels, sex drive, and erectile function in men with type 2 diabetes. The participants in the study were divided into three groups: group A consisted of 34 patients treated with metformin, group B included 30 patients treated with sulfonylurea (another type of diabetes drug), and group C comprised 27 healthy, non-diabetic men.

The results showed that total testosterone levels and Sex Hormone Binding Globulin (SHBG) levels were significantly higher in the sulfonylurea-treated patients compared to those treated with metformin. Free Testosterone (FT) and Free Androgenic Index (FAI) were also higher in the sulfonylurea group compared to the metformin group.

Metformin-treated patients had lower bioavailable testosterone levels and scored lower on the Sexual Health Inventory for Men (SHIM), indicating more significant erectile dysfunction.

Thus, metformin was associated with a significant reduction in testosterone levels, sex drive, and an increase in low testosterone-induced erectile dysfunction. Conversely, sulfonylurea was linked to a significant increase in testosterone levels, sex drive, and improved erectile function.

In managing diabetes, men need to take into account not only diet, physical activity, BMI, glucose levels, and glycated hemoglobin levels – but also the levels of male sex hormones. Unfortunately, it is often simply impossible to replace metformin with another drug.

Taking metformin to increase longevity, a practice by renowned researcher David Sinclair, is also a double-edged sword. It turns out that either we live long but like vegetables, or brightly, but not as long as we would like 🙂 Hence, although I managed to get this prescription drug, I’ve put it aside for now, choosing to take NMN, resveratrol, quercetin, and CoQ10 from David’s arsenal (not counting various vitamins, minerals, and trace elements).