Aim Irregular menstrual cycles are associated with increased cardiovascular mortality. Polycystic ovary syndrome (PCOS) is characterized by excess androgens and irregular menstruations; Androgens are drivers of increased metabolic risk in women with PCOS. Combined oral contraceptive pills (COCs) are used in PCOS both for cycle regulation and to reduce the biologically active androgen fraction. We examined COC use and risk of dysglycemia (prediabetes and type 2 diabetes) in women with PCOS. Methodology Using a large UK primary care database (The Health Improvement Network [THIN]; 3.7 million patients from 787 practices), we conducted a retrospective population-based cohort study to determine the risk of dysglycaemia (64,051 women with PCOS and 123,545 control subjects), as well as a nested pharmacoepidemiological case-control study to investigate the use of COCs in relation to the risk of dysglycemia (2,407 women with PCOS with [case subjects] and without [control subjects] a diagnosis of dysglycemia during follow-up). Cox models were used to estimate unadjusted and adjusted hazard ratios, and conditional logistic regression was used to obtain adjusted odds ratios (aOR). Results The adjusted hazard ratio for dysglycemia in women with PCOS was 1.87 (95% CI 1.78 to 1.97; P < 0.001; adjustment for age, social deprivation, BMI, ethnicity, and smoking), with higher rates of dysglycemia in all BMI subgroups. Women with PCOS and COCP had a reduced risk of dysglycemia (aOR 0.72, 95% CI 0.59 to 0.87). Conclusions In this study, limited by its retrospective nature and the use of data from routinely collected electronic general practice records, which does not allow us to exclude the impact of prescription bias by indication, women with PCOS exposed to COCs had a reduced risk of dysglycemia in all BMI subgroups. Future prospective studies should be considered to better understand these observations and possible causality. |
Comments
A study led by the University of Birmingham has revealed for the first time that the contraceptive pill can reduce the risk of type 2 diabetes by more than a quarter in women with polycystic ovary syndrome (PCOS).
Research findings also show that women with PCOS have twice the risk of developing type 2 diabetes or prediabetes (dysglycemia), highlighting the urgent need to find treatments to reduce this risk.
In addition to the risk of type 2 diabetes, PCOS, which affects 10% of women worldwide, is also associated with other long-term conditions, such as endometrial cancer, cardiovascular disease, and fatty liver disease ( NAFLD).
Symptoms of PCOS include irregular periods or no periods at all, which can lead to fertility problems, and many suffer from unwanted hair growth (known as ’hirsutism’) on the face or body, hair loss on the scalp and oily skin or acne. These symptoms are caused by high levels of hormones called androgens in the blood of women with PCOS.
Women with PCOS often also struggle with weight gain and their body’s cells are often less responsive to insulin , the hormone that allows the body to absorb glucose (blood sugar) into cells for energy. This reduced insulin response can lead to elevated blood glucose levels and can cause the body to produce more insulin, which in turn causes the body to produce more androgens. Androgens further increase insulin levels, creating a vicious cycle.
The team of scientists led by the University of Birmingham carried out two studies to, firstly, identify the risk of developing type 2 diabetes and prediabetes in women with PCOS and, secondly, to investigate the impact of oral contraceptive use combinations, often called ’the pill’, on the risk of type 2 diabetes and prediabetes in women with PCOS. The pill is often given to women with PCOS to improve the regularity of menstrual bleeding.
Using UK patient GP records of 64,051 women with PCOS and 123,545 matched control women without PCOS, they first carried out a large population-based cohort study to analyze the risk of type 2 diabetes and prediabetes.
They found that women with PCOS had twice the risk of type 2 diabetes or prediabetes compared to those without PCOS. They also identified hirsutism (excessive hair growth), a clinical sign of high androgen levels, as a significant risk factor for type 2 diabetes and prediabetes among women with PCOS.
To investigate the impact of the pill on type 2 diabetes or prediabetes, researchers, including experts from the RCSI University of Medicine and Health Sciences, carried out an additional nested case-control study of 4,814 women with PCOS. The scientists found that the use of combined oral contraceptives reduced the odds of developing type 2 diabetes and prediabetes in women with PCOS by 26%.
The researchers behind the study, published in Diabetes Care , now plan to conduct a clinical trial to further evidence their findings in the hope that it will lead to changes in global healthcare policy.
Co-senior author Professor Wiebke Arlt, director of the Metabolism and Systems Research Institute at the University of Birmingham, said: “We knew from previous smaller studies that women with PCOS have a higher risk of type 2 diabetes. However, what is important about our research is that we have been able to provide new evidence from a very large population-based study to demonstrate for the first time that we have a potential treatment option - combined oral contraceptives - to prevent this very serious situation. health risk."
Joint first author Dr Michael O’Reilly, Emerging Clinical Scientist at the Health Research Board and Clinical Associate Professor at the RCSI University of Medicine and Health Sciences, added: "We hypothesize that the pill reduces the risk of diabetes by attenuating the action of androgens . How does this work? The pill contains estrogens that increase a protein in the blood called sex hormone-binding globin (SHBG). SHBG binds to androgens and therefore renders them inactive. Therefore, if you take the pill, it increases SHBG. "This decreases the amount of unbound active androgens, reducing their impact on insulin and the risk of diabetes."
Joint first author Anuradhaa Subramanian, also from the University of Birmingham, added: "With one in 10 women living with PCOS, which is a lifelong metabolic disorder, it is incredibly important that we find ways to reduce the risks for associated health".
Co-senior author Krish Nirantharakumar, professor of health data science and public health at the Institute of Applied Health Research at the University of Birmingham, added: “Importantly, our data highlight that normal-weight women with ovarian syndrome polycystic patients also had a higher risk of type 2 diabetes and prediabetes.
This parallels our previous finding of an increased risk of NAFLD in normal-weight women with PCOS, further challenging the notion that PCOS-related metabolic complications are only relevant in the context of obesity. . "These data suggest that, rather than isolated obesity, PCOS-specific factors, including androgen excess, underlie the increased metabolic risk."
