Metformin and Fertility

Metformin and Fertility

Quick overview of what you’ll learn from this blog post:

  • Quick intro to what Metformin is
  • Quick overview of how Metformin works
  • Highlights from key studies supporting Metformin’s use and safety
  • Considerations for Metformin’s potential impact on fertility

Today, we are going to be taking a look at Metformin and its potential impact on fertility.

Let’s get started!

The Basics of Metformin

Metformin is a prescription drug and is a frequently used medication for the treatment of type 2 diabetes. It belongs to a class of drugs known as biguanides which are a family of drugs that work in a similar way.

It is used to help control blood sugar levels. Metformin is often combined with diet and exercise to improve blood sugar control in adults with type 2 diabetes.

Metformin was first identified from the natural compounds present in the plant Galega officinalis, commonly known as French lilac in 1922. However, it did not get approved for medical use until decades later.

French Doctor Jean Sterne did the first human study with Metformin in the 1950s and it was approved in France in 1957. Perhaps most surprisingly, the United States only approved it in 1995!

A Quick Synopsis of How Metformin Works

Metformin works by reducing the level of glucose production in the liver, the amount of glucose the body absorbs, and by increasing the effect of insulin on our cells. Insulin is a hormone which helps us to remove excessive amounts of sugar from our bloodstream.

In this way, Metformin can help to lower elevated blood sugar levels, a risk factor in developing type 2 diabetes. Metformin also reduces the amount of insulin the body makes, since insulin is used more efficiently. This is why it is often the first choice to help people with diabetes manage their blood sugar levels and keep their condition under control.

Metformin has a long track record for its safety and a well established beneficial impact on insulin resistance and its consequences such as metabolic syndrome, pre-diabetes and diabetes.

Metformin and Fertility

There has been a lot of interest and enthusiasm for the potential of Metformin to slow down aging, but there is little discussion about its impact on fertility. Afterall, conditions including diabetes, pre-diabetes and metabolic syndrome are associated with impaired fertility, which might mean that Metformin could improve fertility in those suffering these conditions.

So, with that out of the way, let’s take a look at some of the key research for Metformin in the context of fertility.

Metformin and Polycystic Ovary Syndrome (PCOS)

Metformin is frequently prescribed off-label to treat symptoms of polycystic ovary syndrome (PCOS). The US Department of Health and Human Services Office on Women’s Health has the following to say about PCOS and the use of Metformin:

“Polycystic ovary syndrome (PCOS) is a health problem that affects 1 in 10 women of childbearing age. Women with PCOS have a hormonal imbalance and metabolism problems that may affect their overall health and appearance.”

Excess insulin is thought to drive an increase in testosterone in women, and also decrease sex hormone binding globulin (SHGB). These cause an imbalance in other hormones such as estrogen and progesterone.

In fact, Metformin is often used for PCOS because not only does it improve insulin’s ability to reduce blood sugar, but it appears to reduce insulin and androgen levels too. Women with PCOS may experience ovulation restarting after taking Metformin for a few months.

A 2014 meta-analysis of nine controlled studies involving women suffering from PCOS treated with Metformin suggests that there was no increase in major birth defects in the treatment group versus the control group.

Metformin and Male Reproduction

When it comes to the topic of male fertility, there have not been many clinical trials that focused on the impact of Metformin.

In one study, a total of 45 men suffering from metabolic syndrome were given Metformin for a 6 month period. Blood data was taken and semen samples both before and after the study were also collected.

The results suggest that in men experiencing metabolic syndrome, Metformin use was associated with a significant reduction in insulin resistance. There was also a drop in the level of sex hormone binding globulin, an increase in androgen levels in the blood, and an improved quality of semen.

This is supported by the animal data. According to a review published in the journal Frontiers in Endocrinology, it stated:

“Collectively, these studies suggested that obesity (or the metabolic changes associated with this condition) or a high fat diet may set the basis of an increased susceptibility to infertility issues. Metformin (in a dose, biological sample, and species-specific manner) treatment has the potential to activate targets resulting in an overall improvement of fertility.”

The review concluded that Metformin modifies ovary and testis function via AMPK-dependent and independent mechanisms. AMPK is a central regulator of energy homeostasis and balances nutrient supply with energy demand. The results of this modification are improved sperm and egg quality, higher fertilization rates and a reduction in miscarriage incidence.

A Recent 2022 Study is Making Headlines

A more recent 2022 study suggested there was an association between Metformin use and the rate of birth defects in their children. It focused on 4 groups of people:

  • Non-diabetics
  • People on Insulin
  • People on Metformin
  • People on Sulfonylureas

The researchers examined the occurrence of birth defects in each of the groups. The data they presented suggested that there was a link between men taking Metformin and birth defects in their offspring.

However, our medical experts have reviewed the study in detail and believe the results are misleading and could lead to misinterpretation. Why? The study failed to take into account that the men who were in the Metformin group were older than the non-diabetic group with an average age of 40 vs 33.

What makes this problematic–and may lead to misinterpretation–is that this is not a direct and fair comparison. An argument can be made that men in their 40s are more likely to have other ailments, as indicated in the other treatments they were currently taking, such as:

  • 34% of men on Metformin were also on lipid-modifying agent, vs 0.3% of non-diabetics, and 7% of people on insulin
  • 6.7% of men on Metformin were also on antidepressant, vs 1.5% of non-diabetics, and 2.8% of people on insulin
  • 6.7% of men on Metformin were also on angiotensin-converting enzyme, vs 0.5% of non-diabetics, and 11.8% of people on insulin

This suggests that the Metformin group in this particular study often had other underlying health issues that the other groups did not. This serves as a confounding factor as these other medications could have influenced the results and impacted fertility.

Also, it is worth noting that Metformin is often used off-label for its weight loss benefits. There is a good chance that the Metformin group was more overweight than the other groups. Unfortunately, no weight data for group participants was published.

Furthermore, it is known that being overweight is linked to lower sperm quality especially in men with a BMI over 25 kg/m. The potential of the Metformin group to have contained men who were overweight and likely experiencing lower sperm quality as a result cannot be discounted.

Because of these issues, the results of the study should be taken with a pinch of salt and a further and better designed study is needed before conclusions can be made.

The Bottom Line

Metformin has a well established safety profile and the weight of evidence currently favors that it improves fertility, particularly in those with diabetes.

Note: The above statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.