Influence of Dienogest on Ovulation in Young Fertile Women

Abstract

Objective: To determine the minimal oral dose of dienogest that will reliably and safely inhibit ovulation in healthy women with normal menstrual cycles. Design and Setting: Randomised, open, four-arm, phase II study involving one control cycle followed by one treatment cycle. Over 21 days patients received one of four oral doses of dienogest 0.5, 1.0, 1.5 or 2.0mg daily. Blood sampling for several hormones was performed on 13 days of each cycle. Participants: Forty-two healthy women were enrolled in the study. Because of an anovulatory control cycle and other reasons, nine of these volunteers did not start the treatment. 33 participants (mean age 24 ± 2 years) completed the study according to the protocol. Main Outcome Measures: Inhibition of ovulation was assessed by serum levels of progesterone, oestradiol, luteinising hormone and follicle-stimulating hormone. Safety and tolerability was measured by pre- and post-study medical examinations, cycle control, laboratory (blood and urine) tests, and incidence and severity of adverse events. Results: Dienogest 0.5mg inhibited ovulation in two-thirds of the participants. Doses of dienogest ranging from 1.0 to 2.0mg inhibited ovulation in all patients who completed the study. No serious adverse events were observed at any dose. The frequency of dysmenorrhoea was lower during the treatment cycle than during the control cycle. Increases in cycle duration and reductions in the duration of menstrual flow and serum dienogest levels were dose dependent. Conclusions: Dienogest 1.0mg is the minimal daily dose needed to inhibit ovulation in healthy individuals with normal ovulatory cycles. Dienogest was well tolerated at doses of up to 2.0mg and showed good control of withdrawal bleeding and dysmenorrhoea. Dienogest is suitable for use as the progestin compound in oral contraceptives.