Inhibition of ovulation by NOMAC/E₂, a novel monophasic oral contraceptive combining nomegestrol acetate and 17β-oestradiol: A double-blind, randomised, dose-finding pilot study

Abstract

Objective To explore the optimal dose of the progestogen, nomegestrol acetate (NOMAC), required in a monophasic oral contraceptive, in combination with 1.5 mg 17β-oestradiol (E₂), to inhibit ovulation.

Methods A double-blind, randomised study assessing 41 normally cycling women (aged 18–35 years) over two screening cycles, one control cycle and one consecutive treatment cycle; 38 women completed the treatment period. Subjects received 0.625 mg NOMAC/1.5 mg E₂ (n = 9), 1.25 mg NOMAC/1.5 mg E₂ (n = 10), 2.5 mg NOMAC/1.5 mg E₂ (n = 10) or 2.5 mg NOMAC alone (n = 9) for 21 days.

Results During the treatment cycle, ovulation was suppressed in all treatment groups. The lowest plasma E₂ levels were observed with 2.5 mg NOMAC given alone. Addition of 1.5 mg E₂ to 2.5 mg NOMAC resulted in statistically significant increases in E₂ levels and decreases in mean follicle-stimulating hormone and luteinising hormone levels. In the three NOMAC/E₂ combination groups, a statistically significant inverse correlation was found between E₂ plasma levels and NOMAC dose.

Conclusion The dose of 2.5 mg NOMAC was confirmed to be optimal to inhibit both ovulation and follicular maturation. The antigonadotropic effect of 2.5 mg NOMAC was reinforced when combined with 1.5 mg E₂.

Keywords:

• 19-Norprogesterone
• Oestradiol
• Oral contraception
• Progestogen
• Antigonadotropic
• Ovarian function
• Nomegestrol acetate

Acknowledgements

The authors acknowledge Helen Varley, PhD (Envision Scientific Solutions, Horsham, UK) for writing and editorial assistance, contracted by Théramex for these services.

Declaration of interest: This report presents data generated from study 96-ESC/NOM-1-RD, which was funded by Théramex, part of the Merck-Serono division. Dr Nathalie Chabbert-Buffet has received consultancy fees from Servier, Aventis and Orion Pharma, and has acted as a clinical investigator in trials funded by Théramex, HRA Pharma and Organon. Didier Chassard has no conflicts of interest to declare. Prof. Sophie Christin-Maitre has received consultancy fees from Schering-Plough, Pierre Fabre, Procter & Gamble and Théramex, and has acted as a clinical investigator in trials funded by Théramex and Organon. Edith Ochsenbein is a previous employee of Théramex. Jean-Louis Thomas was an employee of Théramex at the time of the study and manuscript writing.