Endocrine Abstracts

Study question: Does the combination of estradiol valerate (EV) and dienogest (DNG) have favorable effects on inflammation and lipids compared with ethinyl estradiol (EE) + DNG?

What is known already: Use of combined oral contraceptives (COCs) increases HDL-cholesterol and triglycerides and promotes low-grade inflammation. The metabolic effects of COCs depend on both estrogen and progestin components. To our knowledge this is the first study comparing COCs containing EE and EV combined with the same progestin.

Study design: Randomized, controlled, open-label clinical trial. Power calculation was based on primary outcomes of glucose metabolism. Sixty volunteers were recruited and randomized to use either EE+DNG, EV+DNG or DNG-only continuously for 9 weeks.

Materials & methods: Participants were healthy, young, non-smoking women with regular menstrual cycles. Wash-out period for hormonal medication was a minimum of two months. Mean age, BMI and WHR were comparable in all study groups at the beginning of the study. 56 women completed the study (EV+DNG n=20, EE+DNG n=19 and DNG-only n=17).

Main results and the role of chance: Serum hs-CRP increased during the use of EE+DNG (mean change±S.D. 1.10±2.11 mg/l) compared with EV+DNG (−0.06±0.97 mg/l) or DNG-only (0.13±0.68 mg/l) (P=0.001 and P=0.021 respectively). Pentraxin, another marker of low-grade inflammation, was also increased in the EE+DNG group compared with EV+DNG and DNG-only groups (P=0.017 and P=0.003). EE+DNG group displayed higher HDL cholesterol and triglyceride levels (HDL: EE+DNG 0.20±0.24 mmol/l vs EV+DNG −0.02±0.20 mmol/l, P=0.002, vs. DGN −0.02±0.18 mmol/l, P=0.002; Triglycerides: EE+DNG 0.45±0.21 mmol/l, vs EV+DNG 0.18±0.36 mmol/l, P=0.003, DNG 0.06±0.18 mmol/l, P<0.001). To conclude, the EV+DNG and DNG-only preparations seem to have better metabolic profile compared with EE preparation.

Limitations: The study period of 9 weeks is too short for conclusions about the possible long-term effects of the studied preparations. As the power calculation was based on glucose metabolism, there is a chance of type II error for statistically non-significant findings.

Implications of the findings: According to the present data, COCs containing EV and DNG-only have neutral effects on the markers of inflammation and lipids compared with EE containing preparations. As contraceptives often are used for decades, these results may have clinical significance when choosing preparation for patients with increased metabolic risk.

Trial registration number: NCT02352090