{"paper_id":"9a691c74-53f7-4c17-915c-79a852d85261","body_text":"Abstract\nObjective: To determine the minimal oral dose of dienogest that will reliably and safely inhibit ovulation in healthy women with normal menstrual cycles.\nDesign 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.\nParticipants: 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.\nMain 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.\nResults: 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.\nConclusions: 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.\nSimilar content being viewed by others\nReferences\nPauerstein CJ, Eddy CA, Croxatto HD, et al. Temporal relationships of estrogen, progesterone, and luteinizing hormone levels to ovulation in women and infrahuman primates. Am J Obstet Gynecol 1978; 130: 876–86\nSpona J, Schneider WHF, Bieglmayer C, et al. Ovulation inhibition with different doses of levonorgestrel and other progestogens: clinical and experimental investigations. Acta Obstet Gynecol Scand Suppl 1979; 88: 8–15\nLippert TH, Mück AO. Der klinische Steinwert von Dienogest. In: Teichman AT, editor. Dienogest-präklinik und klinik eines neues gestagens. New York: Walter de Gruyter, 1995: 261–74\nEverett JW. Ovulation inhibition by progestins. In: Young WC, editor. Sex and internal secretions. Baltimore: Williams and Wilkins, 1961: 497\nPincus G. The control of fertility. New York: Academic Press, 1965\nSchürenkämper P, Lisse K. Effects of the new prostestagen STS 557 on the biosynthesis of steroids in tissue slices of the human ovary. Exp Clin Endocrinol 1985; 86: 185–9\nOettel M, Bervoas-Martin S, Elger W, et al. A 19-nor-progestogen without a 17β-ethinyl group I: dienogest from a pharmacokinetic point of view. Drugs Today 1995; 31: 499–516\nOettel M, Carol W, Elger W, et al. A 19-norprogestogen without 17β-ethinyl group II: dienogest from a pharmacodynamic point of view. Drugs Today 1995; 31: 517–36\nPonsold K, Teichmüller G. Konzeption und Chemie der 17β-CH2X-Gonadiene. In: Teichman AT, editor. Dienogest-präklinik und klinik eines neues gestagens. New York: Walter de Gruyter, 1995: 3–10\nJuchem M, Schaffrath M, Pollow K, et al. Dienogest: bindungsstudien an verschiedenen rezeptor- und serum-proteinen. In: Teichman AT, editor. Dienogest-präklinik und klinik eines neues gestagens. New York: Walter de Gruyter, 1995: 119–34\nOettel M, Elger W, Ernst M, et al. Experimentelle endo-krinpharmakologie von dienogest. In: Teichman AT, editor. Dienogest-präklinik und klinik eines neues gestagens. New York: Walter de Gruyter, 1995: 11–22\nSchleussner E, Michels W, Bethge S, et al. Die Wirkung von Dienogest auf die hypothalamisch-hypophysäre Achse: Ergebnisse einer Pilotstudie. In: Teichman AT, editor. Dienogest-präklinik und klinik eines neues gestagens. New York: Walter de Gruyter, 1995: 171–9\nBöcker R, Kleingeist B. Der einfluss von dienogest auf das humane cytochrom P-450-enzymsystem in vitro. In: Teichman AT, editor. Dienogest-präklinik und klinik eines neues gestagens. New York: Walter de Gruyter, 1995: 141–8\nHoffman H, Zimmermann H, Hillesheim H, et al. Pharma-kologisch-toxicologisches wirkprofil von dienogest. In: Teichman AT, editor. Dienogest-präklinik und klinik eines neues gestagens. New York: Walter de Gruyter, 1995: 59–72\nMoore C, Klinger G, Walter F, et al. Pilot-studie an gesunden probandinnen über 6 Zyklen zum einfluss von MP 2000 auf kontrazeptive Sicherheit, Zyklusstabilität and Verträglichkeit. In: Teichman AT, editor. Dienogest-präklinik und klinik eines neues gestagens. New York: Walter de Gruyter, 1995: 181–90\nWilks JW, Spilman CH, Campbell JA. Arrest of folliculogenesis and inhibition of ovulation in the monkey following weekly administration of progestogens. Fertil Steril 1983; 40: 688–92\nHobe G, Klinger G, Reddersen G, et al. Radioimmunologische bestimmung des prostagens dienogest im plasma und Speichel. Pharmazie 1986; 41: 772–4\nDericks-Tan JSE, Gudacker V, Taubert HD. Influence of oral contraceptives on integrated secretion of gonadoptropins. Contraception 1992; 46: 369–77\nKöhler G, Wodrig W. Endokrinologische befunde und die reaktivität der hypophyse gegenüber GnRh unter gestagen-monotherapie der endometriose mit dienogest. In: Teichman AT, editor. Dienogest-präklinik und klinik eines neues gestagens. New York: Walter de Gruyter, 1995: 253–61\nMoore C, Walter F, Klinger G, et al. Der einfluss von dienogest auf die ovulation junger Frauen und auf weitere ausgewCählte endokronologische Parameter. In: Teichman AT, editor. Dienogest-präklinik und klinik eines neues gestagens. New York: Walter de Gruyter, 1995: 161–70\nZahradnik HP, Moore C. Clinical experiences with an oral contraceptive containing ethinyloestradiol and dienogest. In: Elstein M, editor. Extragenital effects of oral contraceptives. New York: Parthenon, 1997; 53–61\nAuthor information\nAuthors and Affiliations\nRights and permissions\nAbout this article\nCite this article\nMoore, C., Carol, W., Gräser, T. et al. Influence of Dienogest on Ovulation in Young Fertile Women. Clin. Drug Investig. 18, 271–278 (1999). https://doi.org/10.2165/00044011-199918040-00003\nPublished:\nIssue date:\nDOI: https://doi.org/10.2165/00044011-199918040-00003","source_license":"CC0","license_restricted":false}