PCOS: It affects about 5-15% of postmenopausal women worldwide, with no racial or ethnic difference in prevalence. The relationship between PCOS and diabetes is still being investigated. We know that there is insulin resistance in the majority of women with PCOS. Why does this lead to diabetes in PCOS?
Despite how common PCOS is, there is frequent failure to diagnose it. Women with PCOS see an average of four doctors and it takes up to two years to get an accurate diagnosis.
I think the main message for healthcare providers is that, in fact, PCOS is very easy to diagnose. About 80-90% of young women who chronically skip menstrual cycles — usually having fewer than 8-10 menstruation per year — will have PCOS.
It is a syndrome, so it is classified according to its features, which are
Reproductive anomaly that often leads to chronic anovulation, characterized by the absence of regular menstruation.
Increased production of male hormone. A symptom of this is usually increased abnormal hair growth in women. It could be acne. It could be hair loss.
In about the 1980s, it was noted that PCOS was associated with insulin resistance and an increased risk of type 2 diabetes. Therefore, it has a complete metabolic aspect. And the big research question since then has been, why are metabolic abnormalities associated with reproductive abnormalities?
Research on the relationship between insulin resistance and PCOS has led to some very important insights that insulin itself is a reproductive hormone and can directly stimulate the ovaries, in synergy with LH, to produce more androgens and that insulin resistance in the brain can lead to ovulation disruption – on Least of animal models that we know. So, it is a very intimate relationship.
The incidence of type 2 diabetes in women with PCOS has not been studied. However, we do know that the prevalence is about 10% and that another 30%, at least in the United States, have prediabetes or impaired glucose tolerance.
In women with PCOS, there are several risk factors that have been identified for developing type 2 diabetes. Obesity is certainly obese, so the prevalence is actually higher in women with a BMI of 30 or more. However, it is important to note that we continue to see type 2 diabetes and an increased risk of type 2 diabetes in thin women with PCOS. Another risk factor for type 2 diabetes and PCOS is a family history of type 2 diabetes.
There are racial disparities in the prevalence of metabolic complications of PCOS, so we are seeing more metabolic syndrome and prediabetes in African American women with PCOS.
However, as with many metabolic issues in PCOS, the studies are not where we would like. We really need large, population-based studies to better define the risks in PCOS for type 2 diabetes, cardiovascular disease, and other metabolic problems.
We treat type 2 diabetes in women with PCOS very similarly to recommendations for individuals with type 2 diabetes in general, which is to lose weight and exercise in moderation. And if women with PCOS have prediabetes, we usually prescribe metformin. In fact, metformin is really one of the medications we use because it has additional reproductive benefits in women with PCOS.
I think the most exciting research being done with PCOS revolves around its genetic susceptibility. We know that PCOS runs in families and that sisters of women with PCOS have an increased risk of PCOS. So far, about 20 susceptibility genes have been discovered.
Some additional and very interesting findings in PCOS are the identification of PCOS subtypes that appear to have distinct genetic causes. So, this is research that my group has been doing for the past several years. And we found, using machine learning techniques such as cluster analysis, that we can identify subgroups of women with PCOS who have different hormonal profiles. And then when we do genetic analysis with these subgroups, we discover new genes. And our most recent work is that these subgroups are found in several ethnic groups.
Another area of increasing focus is the idea that there are disease subtypes within these common syndromes, such as type 2 diabetes, which are also beginning to appear in obesity. And in PCOS, the subtypes are clearly defined, and there appears to be a subtype with more metabolic features and unique genes associated with it. Therefore, PCOS may be a special phenotype of type 2 diabetes, in which it may be possible to discover new diabetes genes and new pathways that could be targets for treatment. Therefore, PCOS should really be a condition of cross-cutting interest to researchers in diabetes, obesity, and metabolism, as well as to reproductive scientists.