PCOS, Insulin and Obesity: Everything You Need to Known
Global obesity is on the rise. Over the last 40 years, the worldwide rate of obesity in women has more than doubled, increasing from 6% to 15% [source]. Along with more than 50 other obesity-related illnesses, the rate of PCOS has also increased in this time [source]. PCOS and obesity are very closely linked, with between 38% and 88% of all women with PCOS being either overweight or obese [source] . Very large studies have shown that overweight women of all ages are far more likely to develop PCOS symptoms [source]. By worsening insulin resistance, weight gain and obesity leads to nearly all of the major PCOS symptoms, such as heightened testosterone levels (acne, hair growth), menstrual disruption and infertility. In this article we explore the latest understandings of how and why obesity is such an extreme risk factor for PCOS and what can be done about it.
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Obesity causes insulin resistance
Insulin is an important hormone that is usually released by the body in response to rising blood sugar levels. Insulin communicates with insulin receptors all over the body, stimulating them to cause changes such as absorbing sugar from the blood and storing it cells. When insulin activates an insulin receptor, two different pathways are activated. These pathways are the PI3-K pathway and MAPK pathway.
For people who are obese, or who suffer from Type II Diabetes, the PI3-K pathway does not work properly. For women with PCOS, the PI3K pathway is also defective, although the exact reason for this is still not understood [source]. It is thought that inflammation contributes to the pathway breaking [source]. It is well known that as weight gain increases, so does the degree of insulin resistance of the PI3-K pathway [source]. When insulin cannot properly activate this PI3-K pathway, it sends signals to the body to produce even more insulin, in an unsuccessful attempt to get the pathway to work. It is important to note that while all of this is happening, the second MAPK pathway is working perfectly normally, except it is being overstimulated because the body is now producing too much insulin [source].
The link between weight gain and insulin resistance is thought to be due to the increases in visceral fat (fat around the organs) and hepatic fat (fat around the liver) [source]. It has also been shown that increased amounts of fat tissue release higher levels of chemicals (called adipokines) into the blood. Some of these chemicals, such as Visfatin, regulate insulin sensitivity, inflammation and metabolism, so it is likely that changing their levels may also contribute to insulin resistance [source].
Does obesity cause PCOS?
While obesity may not be the very root cause of PCOS, for many women who suffer from the disease it is the most important contributing factor. Some women are genetically predisposed to PCOS development. For these women, obesity can be the final straw that tips their body over the edge into PCOS and its symptoms [source]. This has been supported by research that shows that the genetic changes that make someone more likely to gain weight and become obese are the same genetic changes that make them more likely to develop PCOS [source].
As previously stated, between 38% to 88% of women with PCOS will also be overweight or obese [source]. Similarly, obese women of all ages are far more likely to develop PCOS compared to their lean counterparts [source].
Insulin resistance is a feature common to nearly all women with PCOS [source]. As we discussed above, insulin resistance comes from one of the two insulin pathways, PI3-K, not working properly. This leads to the body producing more insulin. Excess insulin results in over-stimulation of the second, fully functioning insulin pathway, the MAPK pathway. It is now understood that it is the over-stimulation of MAPK due to excess insulin that causes many of the problems associated with PCOS, such as excess testosterone and reproductive issues [source].
“Weight gain is one of the most serious contributing factors to PCOS development”
Although weight gain is one of the most serious contributing factors to PCOS development, it is important to remember that it is not the only factor. PCOS is complex disease, which means that is caused by a wide range of factors that all combine together, such as genetics, diet, body fat, smoking, sleep, and more. Many women with PCOS will not be overweight at all yet will still exhibit PCOS symptoms, including insulin resistance. Despite this, it is certain that obesity seriously worsens PCOS symptoms and avoiding excess body fat should be a goal for all women suffering from PCOS [source].
How does obesity affect PCOS?
We’ve already seen that obesity leads to insulin resistance, which leads to excess insulin and over-stimulation of the MAPK pathway, but how does this change PCOS symptoms?
Obesity in women with PCOS severely increases the risk of Type II Diabetes [source], Obstructive Sleep Apnoea [source], non-alcoholic fatty liver disease and dyslipidaemia [source], which all increase the overall risk of experiencing a cardiovascular event. Research shows that these increased risks are due to the lack of activity of the PI3-K due to insulin resistance. Therefore, these risks increase with more weight gain [source].
It is well understood that the excess testosterone and reproductive symptoms of PCOS are driven primarily by the effects of excess insulin on the MAPK pathway, particularly in the ovary [source]. This theory is supported by the fact that if women with PCOS are separated into groups based on their symptoms, the group that has both excess testosterone and infertility symptoms will also be the group that shows high insulin resistance, as well as a higher BMI (Body Mass Index) [source].
Obesity increases testosterone levels in PCOS
In PCOS, excess androgens (mostly testosterone), are produced and released from the ovary and part of the brain (the adrenal gland). Raising total levels of testosterone around the body leads to many of the most recognisable symptoms of PCOS, such as acne, excess hair growth in a male pattern, menstrual disruption, and ovulation disruption. What exactly causes the body to produce too much androgen though?
In the ovaries, insulin acts a sex hormone. It activates the MAPK pathway in certain parts of the ovary, which drives the ovaries to produce and release testosterone. Additionally, there appears to be a connection between insulin levels and Luteinising Hormone levels. Luteinising Hormone is another key driver of testosterone production. A similar process happens in the adrenal cortex of the brain, also resulting in excess testosterone release [source].
Normally, the liver should produce and release something called Sex Hormone Binding Globulin (SHBG). The job of SHBG is to collect excess testosterone that is circulating around the body, lowering overall levels. Excess insulin prevents the liver from producing enough SHBG, which means that there is nothing to collect all of the excess testosterone being produced by the brain and ovaries. This leaves the testosterone free to activate sensors in hair follicles and the skin, leading to hair growth and acne [source]. In fact, recent research suggests that monitoring SHBG levels is one of the best ways to monitor PCOS intensity and check if treatments are working [source].
Obesity and weight gain can also increase testosterone in other, non-insulin ways. Research has shown that certain enzymes produced by fat tissue are connected to PCOS symptoms. In particular, an enzyme called 5-alpha Reductase is responsible for converting testosterone into a more powerful androgen, 5-DHT, which may make PCOS symptoms even worse. The more body fat present, the more 5-alpha Reductase will be released, resulting in higher levels of 5-DHT [source].
Obesity causes infertility in PCOS
During normal ovulation, a follicle inside the ovary is slowly developed with an egg inside it, before it ruptures and releases the egg so that it can be fertilised. This process is incredibly complex and closely linked to the menstrual cycle
See: Ovulation, Menstruation and PCOS: What goes wrong?
Excess insulin caused by obesity and PCOS cause premature changes to happen in the developing follicle. Excess insulin causes the follicle to become overly sensitive to Luteinising Hormone, which contributes to ovulation stopping [source]. Excess insulin causes higher levels of testosterone in the ovaries, which sends signals to the follicle to stop growing, contributing to ovulation stopping [source]. Lastly, excess insulin sends signals to the follicle to start producing the hormone progesterone too early. Progesterone is responsible for stopping growth at the end ovulation, so contributes to ovulation stopping [source]
“Excess insulin and testosterone cause infertility in PCOS”
Excess insulin and testosterone levels caused by obesity are often the root cause of infertility in women with PCOS, and seriously worsen the situation even if it is not the root cause. Although it is not the case for everybody, if a PCOS sufferer is overweight or obese, weight loss with the goal of healthy levels of insulin sensitivity is the single best solution for restoring normal ovulation and fertility.
PCOS, obesity and sleep apnoea
Recent discoveries have uncovered a significant link between obesity, sleep apnoea and PCOS. Obstructive Sleep Apnoea (OSA) is an illness that occurs when the upper airways are briefly obstructed during sleep, resulting in low blood oxygen levels and reduced sleep quality [source]. Recently, OSA has been closely linked to insulin resistance. In fact, studies have shown that women with OSA have worse insulin resistance than women of the same age and weight who sleep normally [source]. It is thought that this is related to levels or cortisol and other chemicals released by fat tissue [62].
Although OSA is typically more common in men, women with PCOS have almost double the risk of developing OSA compared to other women of the same age and BMI [64]. It is possible that the increased risk of sleep apnoea in PCOS women is due to hormonal changes. It is known that high testosterone levels can influence breathing stability during sleep [source]. It is also possible that low levels of hormones in the blood such as progesterone due to disrupted ovulation can cause the muscles in the upper airway to relax too much [source]. Obesity seriously increases the risk of developing obstructive sleep apnoea for women with PCOS [source].
Obese women with PCOS and obstructive sleep apnoea will nearly always demonstrate high levels of insulin resistance, making them very high risk individuals for developing Type II Diabetes [source]. For this reason, it is important that doctors proactively screen for obstructive sleep apnoea every year for obese patients with PCOS [source].
Can weight loss help with PCOS?
In short, for overweight women with PCOS, weight loss is one of the single best methods for managing the disease and restoring normal body function. The combination of weight loss and exercise is proven to improve insulin sensitivity and reduce excess insulin levels. Given how central insulin resistance is to the symptoms of PCOS, it is no surprise that improving insulin sensitivity improves PCOS symptoms. This is most effectively achieved by lifestyle management that results in weight loss. It is proven that calorie restriction and weight loss of just 5% results in reduced insulin levels, improved testosterone levels and normalised ovulation [source].
Not all women with PCOS and insulin resistance will be overweight or obese. For all women with insulin resistance, physical exercise is also proven to improve insulin sensitivity, even without any weight loss [source]. Physical exercise additionally helps to reduce the risk of developing cardiovascular problems, a common risk with PCOS. Studies have shown that regular aerobic exercise can restore reproductive function and ovulation in women with PCOS [source]. It is important to note however, that over-exercising can be harmful for PCOS symptoms. It is recommended that between 30-60 minutes per day of exercise should be the maximum. More than 60 minutes per day may actually increase the risk of ovulation interruption [source].
Does PCOS cause obesity?
We understand now that weight gain and obesity is strongly associated with PCOS and definitely worsens the symptoms of PCOS, but does PCOS itself make an individual more likely to gain wait and become obese? We know that obesity contributes to PCOS, but does PCOS contribute to obesity? Most research in this area has been unable to conclude with any certainty if PCOS contributes to obesity.
Some studies have found that young women with PCOS were more likely to become obese later in life, however these studies were too small to truly say that this is the case for the entire population [source]. Additionally, research has suggested that the higher testosterone levels in women with PCOS may contribute to an increased appetite for high-fat and carbohydrate rich foods, which could lead to easier weight gain. It was also noted that increased insulin resistance may also increase weight gain, suggesting a negative cycle of weight gain, leading to insulin resistance, leading to more weight gain [source]. Genetic studies have also found that the same genetic changes in women that increase the likelihood of obesity are the ones that increase the likelihood of PCOS, however this does not necessarily mean that PCOS causes obesity [source].
On the other hand, many women who have PCOS and insulin resistance have a perfectly normal body weight and body fat percentage and the most recent reviews of the current research in the area have found no conclusive evidence that PCOS can cause weight gain [source]. Just like PCOS itself, obesity is a complex condition, meaning that there are many factors that contribute to it. Things like genetics, lifestyle and possibly diseases like PCOS may increase the likelihood of weight gain, but over-eating and under-exercising are still the root cause of weight gain. Similarly, even if an individual has a higher genetic likelihood of weight gain, this will not stop them losing weight via calorie deficit.
