Deterioration in cardiometabolic risk markers in obese women during depot medroxyprogesterone acetate use

Background Highly effective contraception is essential in obese women, but it should not increase their risk of developing or worsening obesity-related cardiometabolic illness. The purpose of this 18-week prospective experimental study was to compare the impact of subcutaneous depot medroxyprogesterone acetate (DMPA-SC) on cardiometabolic markers in obese and normal-weight women. Methods Normal-weight [body mass index (BMI) 18.5–24.9 kg/m2] and obese (BMI≥30 kg/m2) women received injections of 104 mg DMPA-SC at baseline and 12 weeks later. Markers of cardiometabolic risk measured at baseline and 18 weeks after the first injection included body morphometry, fasting blood tests, and oral and frequently sampled intravenous glucose tolerance tests (FSIGT). Results At baseline, median gravidity, BMI, abdominal circumference, and acute insulin response to intravenous glucose were higher and high-density lipoprotein (HDL) cholesterol and insulin sensitivity (SI from FSIGTs) were lower in the 10 obese participants than the five normal-weight women (p≤.05 for each). While there was no significant difference between median baseline and follow-up values among normal-weight women, the difference between median baseline and follow-up among the obese cohort was significantly higher for BMI and lower for HDL cholesterol and insulin sensitivity (SI) (p≤.05 for each). The absolute changes for routinely measured clinical laboratory values of metabolic decline were no different among the normal-weight vs. obese women. The difference in absolute change in β-cell compensation for insulin resistance [disposition index (DI)] was significant between the two groups at follow-up, with the normal-weight group experiencing an increase in DI while the obese group experienced a decline in DI (188.5 vs. −286, p=.04). Conclusions Obese women have an increased baseline cardiometabolic risk when compared with normal-weight women at baseline. There was a significantly greater decline in β-cell compensation for insulin resistance in obese women on DMPA. Our data suggest potential deleterious effects of DMPA on glucose regulation in obese women. Further studies should elucidate the long-term cardiometabolic consequences of DMPA use in obese women.