Women With PCOS May Reduce T2D Risk With Contraceptive Pill

Excessive levels of androgens in women with polycystic ovary syndrome (PCOS), which increases their risk of developing type 2 diabetes (T2D) by decreasing the body’s ability to effectively process insulin and thereby elevating their blood glucose levels, may have a potential remedy in the contraceptive pill.

In research published today in Diabetes Care, University of Birmingham investigators point to a lower risk of developing T2D from potential benefits via reduced unbound active androgens. Low levels of these unbound hormones, which augment the body’s response to insulin, can be spurred by the estrogens in a combination contraceptive pill increasing the body’s production of sex hormone-binding globin (SHBG), which binds to androgens, rendering them inactive and unable to interfere with insulin processing. An additional potential benefit is a lessened chance of developing hirsutism, which is a symptom of PCOS.

“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,” the authors wrote, adding that “combined oral contraceptive pills (COCPs) are used in PCOS both for cycle regulation and to reduce the biologically active androgen fraction.” They also noted that a tell-tale sign of PCOS is excessive androgen.

Their retrospective population-based cohort study (January 1, 2000-January 31, 2017) matched women (based on age + 2 years and body mass index [BMI]) from the United Kingdom’s The Health Improvement Network, a primary care database, 1:2 to women with PCOS (n = 64,051) or without PCOS (n = 123,545) and investigated their dysglycemia (prediabetes and T2D) risk and COCP use. They were followed for a median (interquartile range) 3.5 (1.4-7.2) years.

An overall 28% lessened risk of dysglycemia (adjusted odds ratio [aOR], 0.72; 95% CI, 0.59-0.87) was seen in women with PCOS who were taking a COCP, after the authors used conditional logistic regression, whereas with higher rates of dysglycemia in all subgroups of BMI evaluated, there was an 87% greater risk of mortality (HR, 1.87; 95% CI, 1.78-1.97; P < .001).

Diabetes status was determined by measuring glycated hemoglobin, fasting blood glucose, random blood glucose, and response to 2-hour oral glucose tolerance test, and a nested case-control study of 4814 women matched 1:1 based on PCOS status evaluated the impact of COCPs on their dysglycemia risk.

The authors’ analyses also found:

• Women with PCOS were more likely to be of South Asian descent vs the non-PCOS cohort (4.8% vs 2.9%), to have hypothyroidism (3.4% vs 2.1%) and to be hypertensive (2.2% vs 1.6%)
• 43.4% of the women with PCOS had prescriptions for COCPs
• The incidence of T2D per 10,000 person-years among women with PCOS was more than twice that of the non-PCOS cohort, 48.7 vs 22.8, for a doubled risk (HR, 2.13; 95% CI, 1.98-2.29; P < .001) that remained after adjusting for age, BMI, ethnicity, smoking status, hypothyroidism, and deprivation quintile
• Dysglycemia rate was almost twice as high in the PCOS cohort than it was in the non-PCOS cohort, per 10,000 person-years: 96.3 vs 49.4
• Variables linked to PCOS that carried the highest risk of T2D were anovulation (adjusted HR [aHR], 1.21; 95% CI, 1.08-1.35; P = .001) and hirsutism (aHR, 1.20; 95% CI, 1.05-1.36; P = .007)
• COCPs that contained antiandrogenic progestin reduced the risk of T2D by 16% (aHR, 0.84; 95% CI, 0.73-0.97; P = .020) and those that lacked this had a 17% lower T2D risk (aHR, 0.83; 95% CI, 0.72-0.94; P = .005)
• For every COCP prescription within the study exposure window, the risk of dysglycemia dropped 2% (aHR, 0.98; 95% CI, 0.96-0.99; P = .004)
• COCPs that contained antiandrogenic progestin reduced the odds of dysglycemia by 24% (aOR, 0.76; 95% CI; 0.63-0.91; P = .003) and those that lacked this had 28% reduced odds of dysglycemia (aOR, 0.72; 95% CI, 0.59-0.87; P < .001)

Noting that their study is the largest to date to report on glycemic outcomes among women with PCOS, the authors highlight that their findings mirror results from previous studies on women with PCOS from Denmark and Finland that demonstrate greater diabetes risk in these patients and that “PCOS-specific factors, including androgen excess, underpin the increased metabolic risk.”

“We demonstrated that women with PCOS have a significantly increased risk of dysglycemia that persisted after adjustment for BMI,” they concluded, after which they recommended routine T2D screening for women with PCOS “irrespective of body weight category.”

Reference

Kumarendran B, O'Reilly MW, Subramanian A, et al. Polycystic ovary syndrome, combined oral contraceptives, and the risk of dysglycemia: a population-based cohort study with a nested pharmacoepidemiological case-control study. Diabetes Care. 2021;44:1-9. doi:10.2337/dc21-0437