How continuous glucose monitoring (CGM) can help with infertility and PCOS

What is PCOS?

Polycystic ovary syndrome (PCOS) is the leading cause of infertility and, according to the CDC, affects 6-12% of women of reproductive age in the United States. Worldwide, the reported incidence is as high as 26%! While the name of this condition might lead you to believe that it’s all about the ovaries, it’s actually considered to be a “multisystem reproductive metabolic disorder” and is intimately related to the body’s ability to manage glucose and insulin effectively, with up to 70% of women with PCOS having insulin resistance.

PCOS is an imbalance in a woman’s hormone levels and frequently includes symptoms of menstrual irregularity, obesity (80% prevalence in PCOS), increased body hair, infertility, increased levels of male hormones (hyperandrogenism), high levels of insulin (hyperinsulinemia), and multiple small follicles on the ovaries. The exact cause of PCOS is not well understood, but a combination of genetic and lifestyle factors is the likely culprit.

Having PCOS puts women at major risk for developing type 2 diabetes, with more than half of women with PCOS developing type 2 diabetes by the time they reach 40 years of age. PCOS is so tied in with metabolic health that a 2012 NIH panel proposed that the name of the disease be changed from PCOS to “metabolic reproductive syndrome” to more accurately characterize it, but this has not yet come to fruition.

Given that insulin and glucose regulation are directly influenced by diet and lifestyle, much research has been done to ascertain whether optimizing diet and lifestyle can impact PCOS as part of a treatment approach, and the results are very promising.‍

Dietary changes that reduce exposure to glucose and insulin seem to improve PCOS symptoms and fertility for many. This article describes this research, as well as opportunities to use new metabolic tracking tools like continuous glucose monitoring (CGM) to guide daily choices that can optimize metabolic health in an effort to improve PCOS.

PCOS and insulin resistance: the two-way street between androgens and insulin

Insulin is a hormone vital to keeping blood glucose levels under control. While it is not entirely clear why insulin resistance affects the majority of women with PCOS, it is likely due to a combination of genetic factors (such as alterations in the insulin receptor which make women with PCOS less sensitive to insulin’s effects), and dietary and lifestyle factors (which can exacerbate chronic insulin secretion and promote insulin resistance).

When carbohydrates (and, to a lesser extent, proteins) are consumed, insulin is released from the pancreas to move glucose out of the bloodstream and into the body’s cells. Excess sugar intake, poor sleep, chronic stress, lack of physical activity, environmental toxins, and genetic factors can all lead to conditions of high glucose and insulin which, over time, render cells “numb” to the effects of insulin, a process referred to as insulin resistance. When this happens, glucose is less able to get into cells, thus more insulin is produced to help drive the excess glucose out of the bloodstream. When this process goes on for long periods of time, it can develop into prediabetes and then ultimately into type 2 diabetes. Women with PCOS have a three to ten times greater risk of developing type 2 diabetes than women without PCOS.

The question is, how are these high insulin levels affecting PCOS and infertility? The answer is multifaceted:

• First, there are insulin receptors on specific hormone-producing ovarian cells called theca cells. When theca cells are stimulated, they produce higher levels of androgens (i.e. hormones like testosterone that are responsible for the development and maintenance of masculine characteristics) than they normally do. One study showed that women with PCOS and high androgen levels have higher blood glucose levels and greater blood glucose fluctuations than women with PCOS who do not have elevated androgen levels, supporting the relationship between insulin, glucose and high androgen levels. High androgen levels are responsible for many of the most common PCOS symptoms like excess hair growth and menstrual irregularity.
• Insulin can also cause an increase in the actual number of theca cells within the ovary, thereby increasing the capacity of the ovaries to produce androgens.
• Elevated insulin levels decrease the production of sex hormone-binding globulin (SHBG), a protein produced in the liver that works by binding to testosterone and other androgens in circulation. By reducing SHBG production, insulin further contributes to elevated androgen activity by leaving higher levels of circulating free testosterone.
• High levels of insulin may increase appetite and make sweet foods taste better, potentially causing women to eat more and gain weight.
• High levels of insulin impair fatty acid oxidation (“fat burn”) in cellular mitochondria (the “powerhouse” of cells), which may contribute to weight gain. Excess body weight, particularly in the abdominal area, is associated with worsening insulin resistance.

The story doesn’t stop there: While insulin promotes higher levels of androgens and increased androgen activity, these elevated androgen levels simultaneously cycle back to worsen insulin resistance. Androgens may:

• Contribute to obesity and worsen insulin resistance by redistributing fat from the extremities to the abdominal area.
• Worsen insulin resistance by direct effects on insulin activity in skeletal muscle and fat tissue.
• Promote non-alcoholic fatty liver disease (NAFLD), which is associated with metabolic dysfunction.
• Lower the levels of the insulin-sensitizing adiponectin, an anti-diabetic hormone secreted by fat cells that is generally higher in women than in men.

The following figure illustrates the complex, self-perpetuating relationship between insulin and androgens, as well as their downstream effects.

Figure 1: Root-causes and clinical features of PCOS, including reproductive, metabolic and psychosocial features

How do diet and lifestyle fit in?

If this sounds complicated… it is! However, there are various ways for women with PCOS to improve their symptoms. Research has shown that lifestyle and dietary factors can play a significant role in improving PCOS symptoms by not only contributing to weight loss, but also by directly increasing insulin sensitivity. There is no single diet for PCOS that will cure the condition, but research suggests that low glycemic index (LGI) and ketogenic diets, both of which minimize intake of refined carbohydrates (e.g. white bread, pasta, white rice, cereals), may be effective.

The glycemic index of a food refers to how much it raises blood glucose levels after consumption. A meal with a low glycemic index should not increase blood glucose and insulin levels as much as a high glycemic index meal. Low glycemic index foods include beans, legumes, non-starchy vegetables, certain fruits, nuts, seeds, tofu, and animal protein. In general, foods with higher fiber have a lower glycemic index since fiber slows digestion and makes some carbohydrates less digestible.

Several studies report that a LGI diet may be beneficial for women with PCOS.

• One study looked at 21 women with PCOS over a 24 week period. For the first 12 weeks, they were allowed to eat their usual diet. At week 12, they started an LGI diet that was calorically equivalent to the diet they consumed during the first 12 weeks of the study. After 12 weeks on the LGI diet, researchers found that insulin resistance had decreased significantly.
• Another study involving 49 women with PCOS found that, independent of weight loss, women adopting an LGI diet over a period of 12 months had increased insulin sensitivity and improved menstrual symptoms compared to those using a conventional healthy diet. In fact, 95% of women in the LGI group who completed the intervention showed an increase in menstrual regularity. The women in this study on the LGI diet also reported a significant improvement in their emotional well-being based on a quality-of-life questionnaire, as compared to women on a conventional diet. Research suggests there may be an association between insulin resistance and depression.
• More recently, researchers looked at how a low calorie, LGI diet affected women with and without PCOS. They found that after 24 weeks on the LGI diet, the 28 women with PCOS lost weight, had lower fasting insulin levels, and decreased their insulin resistance. Menstrual regularity improved in 80% of women with PCOS, and over 30% of women with PCOS experienced a decrease in the occurrence of acne!
• A study from 2020 of 14 overweight women with PCOS showed that adoption of a ketogenic Mediterranean diet for 12 weeks led to significant improvement in PCOS-associated biomarkers. The women lost an average of 20 pounds, had significantly reduced abdominal fat, and had significantly lower levels of insulin, insulin resistance, triglycerides, total cholesterol, and LDL cholesterol. Their reproductive hormone levels (namely testosterone and SHBG) also became more normalized.
• A review from 2017 that included seven research papers investigating the impact of low carb diets (i.e. diet with less than 45% of total energy coming from carbohydrates) on fertility outcomes demonstrated improvement in fertility with low carb diets. The authors concluded that “there is convincing evidence that reducing carbohydrate load can reduce circulating insulin levels, improve hormonal imbalance and result in a resumption of ovulation to improve pregnancy rates. Numerous studies have shown that low carbohydrate diets not only elicit fast and significant weight loss but also reduce serum insulin, consequently improving insulin sensitivity.”

How can continuous glucose monitoring (CGM) help in PCOS?

While evidence is continuing to emerge that supports a benefit of ketogenic, low-carbohydrate, and low glycemic diets in women with PCOS, these diets can be difficult to implement and maintain. Furthermore, generalized dietary modifications may not be particularly helpful for all women, particularly in light of emerging data to suggest that the same food can have very different effects on the glucose levels in different individuals. For instance, as illustrated in the figure below, a banana can cause a huge blood glucose spike in person #1, while simultaneously producing very little glucose response in person #2. Consequently, eliminating bananas may very well have a positive impact on insulin levels and PCOS symptoms in person #1, but may have no effect at all in person #2.

Continuous glucose monitoring (CGM) may provide a more precise and individualized approach to constructing a diet that helps keep blood glucose levels stable and insulin levels low in women with PCOS. CGM allows for the measurement of blood glucose levels in real-time, offering instant and personalized feedback on dietary and lifestyle choices and whether these choices are having a positive or negative effect on processes that drive PCOS symptoms. Given this, CGM is uniquely positioned to help optimize diet and empower patients to take control over the modifiable aspects of PCOS.

CGM may also identify women with PCOS who are developing insulin resistance earlier than the other testing methods, as it provides a more detailed account of daily glucose patterns. One study showed that women with PCOS with normal glucose tolerance (i.e. they do not have a diagnosis of diabetes or prediabetes) still show differences in how their blood sugar fluctuates compared to women without PCOS.

Sum it up for me!

The short answer with PCOS is that the condition is complicated, but it involves hormonal imbalances that involve both the reproductive and metabolic systems. While the exact causes are likely diverse and multifaceted, dietary and lifestyle factors play an important role in disease severity, and new tools can likely help mitigate these symptoms. Here’s the breakdown:

• Women with PCOS often have insulin resistance.
• Insulin resistance stimulates the ovaries to produce more androgen hormones, which leads to menstrual irregularity, infertility, and other common PCOS symptoms.
• Elevated androgen levels worsen abdominal fat deposition and insulin resistance.
• Insulin resistance can be modified by dietary and lifestyle changes, and these changes can also improve PCOS parameters, including menstrual regularity.
• CGM can guide personalized dietary and lifestyle choices to minimize and prevent glucose fluctuations that promote insulin secretion.

One way to interrupt the vicious cycle of elevated androgens and insulin resistance in PCOS is to maintain stable blood glucose and insulin levels to minimize the development of insulin resistance and its associated negative health consequences. CGM helps accomplish this by providing individuals with the necessary tools to track the foods they eat and see which ones have a low glycemic index for them. By having this personalized information, smart food choices and lifestyle changes can be made that will have long-lasting, positive effects on both PCOS symptoms and overall health.