Effect of a single vaginal administration of levonorgestrel in Carraguard�� gel on the ovulatory process: a potential candidate for ���dual protection��� emergency contraception



      The study was conducted to evaluate the effect of Carraguard vaginal gel containing 0.75 mg of levonorgestrel (CARRA/LNG gel) administered in a single dose at different stages of follicle development over subsequent follicle rupture and hormonal levels.


      Randomized, blinded, cross-over study comparing the effects of a single administration of CARRA/LNG gel or Carraguard (CARRA) gel. Twenty-four healthy women were enrolled in two centers. The gels were administered when the follicle had reached diameters of 12���14, 15���17 and ���18 mm in eight women each. Volunteers were followed for one treatment, one washout cycle and a second treatment cycle. Follicle rupture or nonrupture was assessed by transvaginal ultrasound. Luteinizing hormone, estradiol and progesterone levels were measured daily for 5 days following treatment, and three times per week until menses.


      No follicular rupture within the 5-day period following administration was observed in 74% and 30% of the CARRA/LNG and CARRA gel treatment cycles, respectively, while ovulation was documented in 4% and 61%, respectively. The overall proportion of cycles with lack of follicular rupture or ovulatory dysfunction (follicle rupture preceded by an inadequate LH surge) was 96% for CARRA/LNG and 39% in the CARRA gel cycles.


      Single vaginal administration of 0.75 mg LNG in CARRA gel in the late follicular phase is effective for interfering with the ovulatory process.


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        • Baba M.
        • Nakajima M.
        • Schols D.
        • Pauwels R.
        • Balzarini J.
        • De Clercq E.
        Pentosan polysulfate, a sulfated oligosaccharide, is a potent and selective anti-HIV agent in vitro.
        Antiviral Res. 1988; 9: 335-343
        • Pearce-Pratt R.
        • Phillips D.M.
        Sulfated polysaccharides inhibit lymphocyte-to-epithelial transmission of HIV-1.
        Biol Reprod. 1996; 54: 173-182
        • Zacharopoulos V.R.
        • Phillips D.M.
        Vaginal formulations of carrageenan protect mice from herpes simplex virus infection.
        Clin Diagn Lab Immunol. 1997; 4: 465-468
        • Jerse A.E.
        Experimental gonococcal genital tract infection and opacity protein expression in estradiol-treated mice.
        Infect Immun. 1999; 67: 5699-5708
        • Maguire R.
        • Bergman N.
        • Phillips D.M.
        Comparison of microbicides for efficacy in protecting mice against vaginal challenge with herpes simplex virus type 2, cytotoxicity, antibacterial properties, and sperm immobilization.
        Sex Transm Dis. 2001; 28: 259-265
        • Spencer S.E.
        • Valentin-Bon I.E.
        • Whaley K.
        • Jerse A.E.
        Inhibition of Neisseria gonorrhoeae genital tract infection by leading-candidate topical microbicides in a mouse model.
        J Infect Dis. 2004; 189: 410-419
        • Elias C.J.
        • Coggins C.
        • Alvarez F.
        • et al.
        Colposcopic evaluation of a vaginal gel formulation of iota-carrageenan.
        Contraception. 1997; 56: 387-389
        • Coggins C.
        • Blanchard K.
        • Alvarez F.
        • et al.
        Preliminary safety and acceptability of a carrageenan gel for possible use as a vaginal microbicide.
        Sex Transm Infect. 2000; 76: 480-483
        • Kilmarx P.H.
        • van de Wilgert J.H.
        • Chaikummao S.
        • et al.
        Safety and acceptability of the candidate microbicide Carraguard in Thai women: findings from a Phase II clinical trial.
        J Acquir Immune Defic Syndr. 2006; 43: 327-334
      1. Sitruk-Ware R, Brache V, Maguire R, et al. Pharmacokinetic study to compare the absorption and tolerability of two doses of levonorgestrel following single vaginal administration of levonorgestrel in Carraguard�� gel: a new formulation for ���dual protection��� contraception. Contraception 2007;75:454���60.

        • Wilcox A.J.
        • Weinberg C.R.
        • Baird D.D.
        Timing of sexual intercourse in relation to ovulation. Effects on the probability of conception, survival of the pregnancy and sex of the baby.
        N Engl J Med. 1995; 333: 1517-1521
        • Croxatto H.B.
        • Brache V.
        • Pavez M.
        • et al.
        Pituitary���ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 0.75 mg dose given on the days preceding ovulation.
        Contraception. 2004; 70: 442-450
        • Massai R.
        • Forcelledo M.L.
        • Brache V.
        • et al.
        Does meloxicam increase the incidence of anovulation induced by single administration of levonorgestrel in emergency contraception? A pilot study.
        Hum Reprod. 2007; 22: 434-439
        • Johansson E.
        • Brache V.
        • Alvarez F.
        • et al.
        Pharmacokinetic study of different dosing regimens of levonorgestrel for emergency contraception in healthy women.
        Hum Reprod. 2002; 17: 1472-1476
        • Tremblay D.
        • Gainer E.
        • Ulmann A.
        The pharmacokinetics of 750 ��g levonorgestrel after administration of one single dose or two doses at 12- or 24-h interval.
        Contraception. 2001; 64: 327-331
        • Kook K.
        • Gabelnick H.
        • Duncan G.
        Pharmacokinetics of levonorgestrel 0.75 mg tablets.
        Contraception. 2002; 66: 73-76
        • Alvarez F.
        • Faundes A.
        • Johansson E.
        • Coutinho E.
        Blood levels of levonorgestrel in women following vaginal placement of contraceptive pills.
        Fertil Steril. 1983; 40: 120-123
        • Kives S.
        • Hahn P.
        • White E.
        • Stanczyk F.Z.
        • Reid R.
        Bioavailability of the Yuzpe and levonorgestrel regimens of emergency contraception: vaginal vs. oral administration.
        Contraception. 2005; 71: 197-201
        • Devoto L.
        • Fuentes A.
        • Palomino A.
        • et al.
        Pharmacokinetics and endometrial tissue levels of levonorgestrel alter administration of a single 1.5-mg dose by the oral and vaginal route.
        Fertil Steril. 2005; 84: 46-51
        • De Ziegler D.
        • Bulletti C.
        • De Monstier B.
        • Jaaskelainen A.S.
        The first uterine pass effect.
        Ann N Y Acad Sci. 1997; 828: 291-299
        • Roumen F.J.M.E.
        • Dieben T.O.M.
        Comparison of uterine concentrations of ethinyl estradiol and etonogestrel after use of a contraceptive vaginal ring and an oral contraceptive.
        Fertil Steril. 2006; 85: 57-62
        • Alexander N.J.
        • Baker E.
        • Kaptein M.
        • Karck U.
        • Miller L.
        • Zampaglione E.
        Why consider vaginal drug administration?.
        Fertil Steril. 2004; 82: 1-12
        • Von Hertzen H.
        • Piaggio G.
        • Ding J.
        • et al.
        Low dose mifepristone and two regimens of levonorgestrel for emergency contraception: a WHO multicentre randomised trial.
        Lancet. 2002; 360: 1803-1810
        • WHO Task Force on Postovulatory Methods of Fertility Regulation
        Efficacy and side effects of immediate postcoital levonorgestrel used repeatedly for contraception.
        Contraception. 2000; 61: 303-308
        • Dupont S.
        • Webber J.
        • Dass K.
        • Thornton S.
        Emergency contraceptive pill (ECP) and sexual risk behaviour.
        Int J STD AIDS. 2002; 13: 482-485
        • Fairhurst K.
        • Ziebland S.
        • Wyke S.
        • Seaman P.
        • Glasier A.
        Emergency contraception: why can't you give it away? Qualitative findings from an evaluation of advanced provision of emergency contraception.
        Contraception. 2004; 70: 25-29