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Pharmacodynamic study of four oral dosages of dienogest

2010; Elsevier BV; Volume: 94; Issue: 4 Linguagem: Inglês

10.1016/j.fertnstert.2010.07.708

1556-5653

Christine Klipping, Ingrid Duijkers, Thomas Faustmann, S.F. Klein, Barbara Schuett,

Ovarian function and disorders

OBJECTIVE: Dienogest (DNG), a selective progestin, is approved in Japan and Europe for treatment of endometriosis at a dosage of 2 mg/day. This study evaluated the dose-dependency of pharmacodynamic parameters of DNG in healthy women, with a focus on ovulation suppression. DESIGN: A double-blind, randomized, parallel-arm study of DNG (0.5, 1, 2, or 3 mg/day), administered for a maximum of 72 days. MATERIALS AND METHODS: Eligible women were allocated to one of the four treatment arms. Ovarian activity was assessed every third day (according to Hoogland) based on follicle size measured by transvaginal ultrasound, and serum estradiol (E2) and progesterone levels. The primary end-point was the Hoogland score for the first (days 1-36) and second (days 37-72) observational periods. RESULTS: 102 volunteers were included and data for 87 women evaluated according to protocol (n=21, 23, 20 and 23 for dosage arms 0.5, 1, 2 and 3 mg DNG, respectively). Ovulation (Hoogland score 6) occurred in 5% and 4% of women receiving 0.5 and 1 mg DNG, respectively, during the first observational period and in 10% and 4% during the second. No ovulation was seen in the 2 and 3 mg DNG groups. Ovarian activity (Hoogland score 4: follicle size >13 mm, serum E2 levels >27 pg/ml, low progesterone) was recorded in >50% of women receiving 0.5 and 1 mg DNG, but in 30 mm at several assessments), while E2 levels were higher versus the 2 and 3 mg dosage groups. Mean (and median) E2 concentrations for the whole treatment period were in the range of 20-50 pg/ml with 2 or 3 mg DNG, versus 40-140 pg/ml pretreatment. CONCLUSION: These pharmacodynamic data, in agreement with clinical studies in endometriosis, show that 2 mg DNG daily inhibits ovulation while only moderately suppressing estrogen production.