Influence of dienogest on ovulation in young fertile women

Objective: To determine the minimal oral dose of dienogest that will reliab ly and safely inhibit ovulation in healthy women with normal menstrual cycl es. Design and Setting: Randomised, open, four-arm, phase II study involving on e control cycle followed by one treatment cycle. Over 21 days patients rece ived one of four oral doses of dienogest 0.5, 1.0, 1.5 or 2.0mg daily. Bloo d sampling for several hormones was performed on 13 days of each cycle. Participants: Forty-two healthy women were enrolled in the study. Because o f an anovulatory control cycle and other reasons, nine of these volunteers did not start the treatment. 33 participants (mean age 24 +/- 2 years) comp leted 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 medica l examinations, cycle control, laboratory (blood and urine) tests, and inci dence and severity of adverse events. Results: Dienogest 0.5mg inhibited ovulation in two-thirds of the participa nts. Doses of dienogest ranging from 1.0 to 2.0mg inhibited ovulation in al l 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 reduc tions in the duration of menstrual flow and serum dienogest levels were dos e dependent. Conclusions: Dienogest 1.0mg is the minimal daily dose needed to inhibit ov ulation in healthy individuals with normal ovulatory cycles. Dienogest was well tolerated at doses of up to 2.0mg and showed good control of withdrawa l bleeding and dysmenorrhoea. Dienogest is suitable for use as the progesti n compound in oral contraceptives.