Combined Contraceptive Pills Could Reduce Diabetes Risk in Polycystic Ovary Syndrome

Wiebke Arlt, MD, DSc

New research from the University of Birmingham suggests use of combined oral contraceptive pills (COCPs) could lower the risk of prediabetes and type 2 diabetes among women with polycystic ovary syndrome (PCOS).

A pair of studies leveraging primary care data from more than 17 million patients in the United Kingdom, results provide insight into the increased risk for prediabetes and type 2 diabetes observed among women with PCOS and suggest women with PCOS and COCP use reduced their odds of developing either by 26%.

“We knew from previous, smaller studies, that women with PCOS have an increased 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 show for the very first time that we have a potential treatment option – combined oral contraceptives – to prevent this very serious health risk,” said senior investigator Wiebke Arlt, MD, DSc, Director of the University of Birmingham’s Institute of Metabolism and Systems Research, in a statement.

With an interest in exploring the association of PCOS with increased risk of dysglycemia, Arlt and a team of colleagues designed a pair of studies to, first, investigate the dysglycemia risk among women with PCOS compared to matched controls and, next, to determine whether COCP use influenced risk of dysglycemia.

The first study was designed as a retrospective population-based cohort study using data from the UK-based The Health Improvement Network (THIN) database, which contains primary care information from more than 17 million patients across 787 general practices. With a study period ranging from January 1, 2000, to January 31, 2017, investigators identified 64,051 women with PCOS aged 18-50 years and 123,545 matched controls for inclusion in their analyses.

For the purpose of analyses, dysglycemia was defined as a composite of prediabetes and type 2 diabetes. Investigators defined type 2 diabetes as an HbA1c at or greater than 6.5% or a fasting blood glucose at or above 7 mmol/L and dysglycemia was defined as an HbA1c at or greater than 6.0%, a fasting blood glucose at or greater than 6 mmol/L, and a random blood glucose at or greater than 11.1 mmol/L.

The second study was designed as a nested pharmacoepidemiological case-control study using women with dysglycemia from the first study as case subjects matched with controls selected from the remaining population. Of the 64,051 women included in the first study, 2885 developed dysglycemia during the follow-up. However, 478 case subjects could not be matched to controls and the final analyses included 2407 case subjects and 2407 matched controls.

Based on incidence rate of type 2 diabetes observed in the primary analysis of the first study, investigators determined the risk of type 2 diabetes among women with PCOS was more than double than the risk observed among women without PCOS (HR, 2.13 [95% CI, 1.98-2.29]; P <.001). Further analysis adjusting for age, deprivation quintiles, BMI, ethnicity, smoking status, and hypothyroidism provided similar results (aHR, 2.04 [95% CI, 1.89-2.20]; P <.001). When assessing the effects of PCOS on dysglycemia, results indicated PCOS was associated with an 87% increase in risk in adjusted analysis (aHR, 1.87 [95% CI, 1.78-1.97]; P <.001).

In the second study, results of an analysis adjusted for age, smoking status, BMI category, ethnicity, Townsend score, baseline hypothyroidism, hypertension, and prescription of isolated antiandrogen drugs, metformin, and lipid-lowering medication at baseline suggested women with PCOS and exposure to COCP appeared to have a 26% reduction in odds of developing dysglycemia compared to their counterparts without exposure to COCP (aOR, 0.74 [95% CI, 0.65-0.85]; P <.001). Further analysis suggested every COCP prescription recorded in the study period was associated with a 2% reduction in odds of dysglycemia (aOR, 0.98 [95% CI, 0.96-0.99]; P=.004).

“We hypothesize that the pill reduces the risk of diabetes by dampening the action of androgens. How does this work? The pill contains estrogens which increase a protein in the blood called sex hormone-binding globin (SHBG). SHBG binds androgens and, thereby, renders them inactive. Thus, if the pill is taken, SHBG increases. This decreases the amount of unbound, active androgens, lowering their impact on insulin and diabetes risk,” added Michael O’Reilly, MBBCh, PhD, a health research board emerging clinician-scientist and clinical associate professor at RCSI University of Medicine and Health Sciences, in the aforementioned statement.

This statement, “Polycystic Ovary Syndrome, Combined Oral Contraceptives, and the Risk of Dysglycemia: A Population-Based Cohort Study With a Nested Pharmacoepidemiological Case-Control Study,” was published Diabetes Care.