Hormone withdrawal-associated symptoms: Comparison of oestradiol valerate/dienogest versus ethinylestradiol/norgestimate

Abstract

Objectives To determine the effect of oestradiol valerate/dienogest (E₂V/DNG) versus ethinylestradiol/norgestimate (EE/NGM) on hormone-withdrawal associated symptoms (HWAS) in otherwise healthy women who had experienced at least one of these symptoms when using 21/7-day combined oral contraceptives (COCs).

Methods This phase III, parallel-group study randomised 409 women aged 18 to 50 years to E₂V/DNG or EE/NGM. The primary efficacy variable was the change from baseline to cycle 6 in the average of the three highest visual analogue scale values for headache and/or pelvic pain during cycle days 22 to 28.

Results In total, 395 were included in the full analysis set (E₂V/DNG, n = 191; EE/NGM, n = 204). E₂V/DNG reduced the symptoms of headache or pelvic pain during cycle days 22 to 28 from baseline to cycle 6 to a significantly greater extent than EE/NGM (mean decrease 43.6 vs. 35.5 mm; p = 0.0024). Both treatments were well tolerated with a similar proportion of women experiencing adverse events that were considered at least possibly related to treatment (35% E₂V/DNG vs. 34% EE/NGM).

Conclusions E₂V/DNG reduces the frequency and intensity of headache and pelvic pain to a greater extent than EE/NGM, and may be a good option for women susceptible to HWAS with conventional 21/7-day COCs.

Keywords:

• Dienogest
• Headache
• Hormone withdrawal-associated symptoms
• Oestradiol valerate
• Oral contraception

ACKNOWLEDGEMENTS

This study was funded by Bayer HealthCare Pharmaceuticals, Berlin, Germany, the manufacturer of Qlaira^®/Natazia™. The authors would like to thank Clare Wheatcroft and Amy Evans of inScience Communications, Springer Healthcare, who provided medical writing assistance. This work was funded by Bayer HealthCare Pharmaceuticals.

Declaration of interest: R. Garn Mabey received payment from Affiliated Clinical Research for participating in this clinical study. Jeffrey T. Jensen has received payments for consulting and giving talks for Bayer HealthCare Pharmaceuticals, a company that may have a commercial interest in the results of this research and technology. This potential conflict of interest has been reviewed and managed by Oregon Health & Science University. He is also a consultant for Merck, HRA Pharma and Agile Pharmaceuticals, and has received research funding from Bayer HealthCare Pharmaceuticals, Wyeth Pharmaceuticals, Warner Chilcott, Medicines 360, the Population Council, and the NIH. Susanne Parke, Uwe Mellinger and Marco Serrani are employees of Bayer HealthCare Pharmaceuticals, Berlin, Germany.