Research Article| Volume 102, ISSUE 4, P237-242, October 2020

Ovulation inhibition with a new vaginal ring containing trimegestone



      The primary objective was to determine the lowest trimegestone (TMG) dose, administered via a vaginal ring, that effectively inhibited ovulation.

      Study design

      Single-centre, open-label, single-dose, parallel-group clinical trial with adaptive design. Eighty healthy female volunteers with proven ovulatory cycles were allocated to treatment with a vaginal ring during 28 days, with an average daily release rate of either 46 µg, 94 µg, 147 µg, or 184 µg TMG (20 women/group). Ultrasound measurements of follicular growth and endometrial thickness, and blood sampling for follicle-stimulating hormone, luteinizing hormone, estradiol and progesterone determinations were performed every 3rd (±1) day from treatment day 4 (±1) until day 28 (±1), and in a follow-up phase after ring removal, until study day 39 (±1). Trimegestone concentrations were measured at each visit in the treatment phase.


      Mean age and body mass index were 28.8 years and 23.15 kg/m2. One subject in the lowest dose group (46 µg/day) ovulated, no ovulations were seen in the higher dose groups. The degree of ovarian suppression increased with the dose. Median estradiol levels were 119, 36.5, 33.2 and 27.2 pg/mL in the 46, 94, 147 and 184 µg/day groups, respectively. Ovarian activity was resumed in the follow-up phase. Plasma TMG levels gradually declined over the treatment period and showed dose proportionality. The study treatment was safe and well tolerated.


      The release rate of 94 µg TMG per day was the lowest effective dose for ovulation inhibition. The study results justify further development of the TMG-ring as progestogen-only contraceptive.


      The vaginal ring releasing TMG seems to be an effective new progestogen-only contraceptive preparation, having the advantage of once-a-month vaginal insertion.


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        • World Health Organization
        Medical eligibility criteria for contraceptive use: a WHO family planning cornerstone.
        4th ed. World Health Organization, Geneva2010
      1. World Health Organization Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. Cardiovascular disease and use of oral and injectable progestogen-only contraceptives and combined injectable contraceptives. Contraception 1998;57:315-324.

        • Heinemann L.A.
        • Assmann A.
        • DoMinh T.
        • Garbe E.
        Oral progestogen-only contraceptives and cardiovascular risk: results from the Transnational Study on Oral Contraceptives and the health of Young Women.
        Eur J Contracept Reprod Health Care. 1999; 4: 67-73
        • Vasilakis C.
        • Jick H.
        • Mar Melero-Montes M.
        Risk of idiopathic venous thromboembolism in users of progestogens alone.
        Lancet. 1999; 354: 1610-1611
        • McCann M.F.
        • Potter L.S.
        Progestin-only oral contraception: a comprehensive review.
        Contraception. 1994; 50: S9-195
        • Rice C.F.
        • Killick S.R.
        • Dieben T.
        • Coelingh Bennink H.
        A comparison of the inhibition of ovulation achieved by desogestrel 75 µg and levonorgestrel 30 µg daily.
        Hum Reprod. 1999; 14: 982-985
      2. Collaborative Study Group on the Desogestrel-containing Progestogen-only Pill. A double-blind study comparing the contraceptive efficacy, acceptability and safety of two progestogen-only pills containing desogestrel 75 µg/day or levonorgestrel 30 µg/day. Eur J Contracept Reprod Health Care 1998;3:169-178.

        • Porter C.
        • Rees M.
        Bleeding problems and progestogen-only contraception.
        J Fam Plann Reprod Health Care. 2002; 28: 178-181
      3. Grimes DA, Lopez LM, O’Brien PA, Raymond EG. Progestin-only pills for contraception. Cochrane Database Syst Rev 2013;11:CD007541.

        • Duijkers I.J.M.
        • Heger-Mahn D.
        • Drouin D.
        • Skouby S.
        A randomised study comparing the effect on ovarian activity of a progestogen-only pill (POP) containing desogestrel and a new POP containing drospirenone in a 24/4 regimen.
        Eur J Contracept Reprod Health Care. 2015; 20: 419-427
        • Archer D.F.
        • Ahrendt H.-J.
        • Drouin D.
        Drospirenone-only contraceptive: results from a multicentre comparative trial of efficacy, safety and tolerability.
        Contraception. 2015; 92: 439-444
        • Wenneker R.C.
        • Bitran D.
        • Zhang Z.
        The preclinical biology of a new potent and selective progestin: trimegestone.
        Steroids. 2003; 68: 915-920
        • Sitruk-Ware R.
        • Bossemeyer R.
        • Bouchard P.
        Preclinical and clinical properties of trimegestone: a potent and selective progestin.
        Gynecol Endocrinol. 2007; 23: 310-319
        • Hoogland H.J.
        • Skouby S.O.
        Ultrasound evaluation of ovarian activity under oral contraceptives.
        Contraception. 1993; 47: 583-590
        • Landgren B.-M.
        • Diczfalusy E.
        Hormonal effects of the 300 µg norethisterone (NET) minipill. 1. Daily steroid levels in 43 subjects during a pretreatment cycle and during the second month of NET administration.
        Contraception. 1980; 21: 87-113
        • Barbieri R.L.
        Hormone treatment of endometriosis: the estrogen threshold hypothesis.
        Am J Obstet Gynecol. 1992; 166: 740-745
        • Riggs M.M.
        • Bennetts M.
        • van der Graaf P.H.
        • Martin S.W.
        Integrated pharmacometrics and systems pharmacology model-based analysis to guide GnRH receptor modulator development for management of endometriosis.
        CPT Pharmacometrics Syst Pharmacol. 2012 Oct; 17e11
      4. Hadji P, Colli E, Regidor P-A. Bone health in estrogen-free contraception. Osteoporos Int 2019. Published online: