Late follicular phase administration of levonorgestrel as an emergency contraceptive changes the secretory pattern of glycodelin in serum and endometrium during the luteal phase of the menstrual cycle


      This study examined serum glycodelin concentrations and endometrial expression during the luteal phase following oral administration of levonorgestrel (LNG) at different stages of the ovarian cycle. Thirty women were recruited and allocated into three groups. All groups were studied during two consecutive cycles, a control cycle and the treatment cycle. In the treatment cycle, each woman received two doses of 0.75 mg LNG taken 12 h apart on days 3���4 before the luteinizing hormone (LH) surge (Group 1), at the time of LH rise (Group 2) and 48 h after the rise in LH was detected (Group 3). Serum progesterone (P) and glycodelin were measured daily during the luteal phase, and an endometrial biopsy was taken at day LH +9 for immunohistochemical glycodelin-A staining. In Group 1, serum P levels were significantly lower, serum glycodelin levels rose earlier and endometrial glycodelin-A expression was weaker than in Groups 2 and 3, in which no differences were found between control and treatment cycles. Levonorgestrel taken for emergency contraception (EC) prior to the LH surge alters the luteal phase secretory pattern of glycodelin in serum and endometrium. Based on the potent gamete adhesion inhibitory activity of glycodelin-A, the results may account for the action of LNG in EC in those women who take LNG before the LH surge.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Contraception
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Segal S.J.
        • Nordberg O.S.
        Fertility regulation technology: status and prospects.
        Popul Bull. 1977; 31: 1-25
        • WHO
        Task Force on Postovulatory Methods of Fertility Regulation. Randomized controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception.
        Lancet. 1998; 352: 428-433
        • Yuzpe A.A.
        • Thurlow H.J.
        • Ramzy I.
        • Leyshon J.L.
        Post coital contraception: pilot study.
        J Reprod Med. 1974; 13: 53-58
        • Glasier A.
        Emergency postcoital contraception.
        N Engl J Med. 1997; 337: 1058-1064
        • Durand M.
        • Cravioto M.C.
        • Raymond E.G.
        • et al.
        On the mechanism of action of short-term levonorgestrel administration in emergency contraception.
        Contraception. 2001; 64: 227-234
        • Trussell J.
        • Raymond E.G.
        Statistical evidence about the mechanism of action of the Yuzpe regimen of emergency contraception.
        Obstet Gynecol. 1999; 93: 872-876
        • Hapangama D.
        • Glasier A.F.
        • Baird D.T.
        The effects of peri-ovulatory administration of levonorgestrel on the menstrual cycle.
        Contraception. 2001; 63: 123-129
        • Marions L.
        • Hultenby K.
        • Lindell I.
        • Sun X.
        • Stabi B.
        • Gemzell Danielsson K.
        Emergency contraception with mifepristone and levonorgestrel: mechanism of action.
        Obstet Gynecol. 2002; 100: 65-71
        • Swahn M.L.
        • Westlund P.
        • Johannisson E.
        • Bygdeman M.
        Effect of post-coital contraceptive methods on the endometrium and the menstrual cycle.
        Acta Obstet Gynecol Scand. 1996; 75: 738-744
        • Gemzell-Danielsson K.
        • Marions L.
        Mechanisms of action of mifepristone and levonorgestrel when used for emergency contraception.
        Hum Reprod Update. 2004; 10: 341-348
        • Croxatto H.B.
        • Devoto L.
        • Durand M.
        • et al.
        Mechanism of action of hormonal preparations used for emergency contraception: a review of the literature.
        Contraception. 2001; 63: 111-121
        • Seppala M.
        • Taylor R.N.
        • Koistinen H.
        • Koistinen R.
        • Milgrom E.
        Glycodelin: a major lipocalin protein of the reproductive axis with diverse actions in cell recognition and differentiation.
        Endocr Rev. 2002; 23: 401-430
        • Julkunen M.
        • Koistinen R.
        • Sjoberg J.
        • Rutanen E.M.
        • Wahlstrom T.
        • Seppala M.
        Secretory endometrium synthesized placental protein 14.
        Endocrinology. 1986; 118: 1782-1786
        • Brown S.E.
        • Mandelin E.
        • Oehninger S.
        • Torner J.P.
        • Seppala M.
        • Jones Jr., H.W.
        Endometrial glycodelin-A expression in the luteal phase of stimulated ovarian cycles.
        Fertil Steril. 2000; 74: 130-133
        • Oehninger S.
        • Coddington C.C.
        • Hodgen G.D.
        • Seppala M.
        Factors affecting fertilization: endometrial placental protein 14 reduces the capacity of human spermatozoa to bind to the human zona pellucida.
        Fertil Steril. 1995; 63: 377-383
        • Bolton A.E.
        • Pockley A.G.
        • Clough K.J.
        • et al.
        Identification of placental protein 14 as an immunosuppressive factor in human reproduction.
        Lancet. 1987; 1: 593-595
        • Okamoto N.
        • Uchida A.
        • Takakura K.
        • et al.
        Suppression by human placental protein 14 of natural killer cell activity.
        Am J Reprod Immunol. 1991; 26: 137-142
        • Clark G.F.
        • Oehninger S.
        • Patankar M.S.
        • et al.
        A role for glycoconjugates in human development: the human feto-embryonic defence system hypothesis.
        Hum Reprod. 1996; 11: 467-473
        • Larrea F.
        • Sandoval J.L.
        • Salinas E.
        • Franco-Rodr��guez A.
        • M��ndez I.
        • Ulloa-Aguirre A.
        Evidence for an altered luteinizing hormone sensitivity to naloxone in pathological hyperprolactinemia.
        Clin Endocrinol. 1995; 43: 591-600
        • Koistinen H.
        • Koistinen R.
        • Dell A.
        • et al.
        Glycodelin from seminal plasma is a differentially glycosylated form of contraceptive glycodelin-A.
        Mol Hum Reprod. 1996; 2: 759-765
        • Rittinen L.
        • Julkunen M.
        • Seppala M.
        • Koistinen R.
        • Huhtala M.-L.
        Purification and characterization of endometrial protein PP14 from mid-trimester amniotic fluid.
        Clin Chim Acta. 1989; 184: 19-29
        • Riittinen L.
        • Stenman U.-H.
        • Afthan H.
        • Suikkari A.-M.
        • Bohn H.
        • Seppala M.
        Time resolved immunofluorometric assay for placental protein PP14.
        Clin Chim Acta. 1989; 183: 115-123
        • Kamarainen M.
        • Leivo I.
        • Koistinen R.
        • et al.
        Normal human ovary and ovarian tumors express glycodelin, a glycoprotein with immunosuppressive and contraceptive properties.
        Am J Pathol. 1996; 148: 1435-1443
        • Koistinen H.
        • Koistinen R.
        • Kamarainen M.
        • Salo J.
        • Seppala M.
        Multiple forms of messenger ribonucleic acid encoding glycodelin in male genital tract.
        Lab Invest. 1997; 76: 683-690
        • Noyes R.W.
        • Hertig A.T.
        • Rock J.
        Dating the endometrial biopsy.
        Fertil Steril. 1950; 1: 3-25
        • Hendrickson M.R.
        • Kempson R.L.
        Normal histology of the uterus and fallopian tubes.
        in: Sternberg S.S. Histology for Pathologists. Lippincott-Raven, Philadelphia (NY)1997: 879-927
        • Lessey B.A.
        • Castelbaum A.J.
        • Wolf L.
        • et al.
        Use of integrins to date the endometrium.
        Fertil Steril. 2000; 73: 779-787
        • Croxatto H.B.
        • Fuentealba B.
        • Brache V.
        • et al.
        Effects of the Yuzpe regimen, given during the follicular phase, on ovarian function.
        Contraception. 2002; 65: 121-128
        • Ugocasi G.
        • R��zsa M.
        • Ugocasi P.
        Scanning electron microscopic (SEM) changes of the endometrium in women taking high doses of levonorgestrel as emergency postcoital contraception.
        Contraception. 2002; 66: 433-437
        • Landgren B.M.
        • Johannisson E.
        • Aedo A.R.
        • Kumar A.
        • Yong-en S.
        The effects of levonorgestrel administered in large doses at different stages of the cycle on ovarian function and endometrial morphology.
        Contraception. 1989; 39: 275-289
        • Mandelin E.
        • Koistinen H.
        • Koistinen R.
        • Affandi B.
        • Seppala M.
        Levonorgestrel-releasing intrauterine device-wearing women express contraceptive glycodelin A in endometrium during the midcycle: another contraceptive mechanism?.
        Hum Reprod. 1997; 12: 2671-2675
        • Mandelin E.
        • Koistinen H.
        • Koistinen R.
        • Arola J.
        • Affandi B.
        • Seppala M.
        Endometrial expression of glycodelin in women with levonorgestrel-releasing subdermal implants.
        Fertil Steril. 2001; 76: 474-478
        • Morris H.R.
        • Dell A.
        • Easton R.L.
        • et al.
        Gender-specific glycosylation of human glycodelin affects its contraceptive activity.
        J Biol Chem. 1996; 271: 32159-32167
        • Li T.C.
        • Ling E.
        • Dalton C.
        • Bolton A.E.
        • Cooke I.D.
        Concentration of endometrial protein PP14 in uterine flushings throughout the menstrual cycle in normal fertile women.
        Br J Obstet Gynaecol. 1993; 100: 460-464
        • Raymond E.G.
        • Lovely L.P.
        • Chen-Mok M.
        • Sepp��l�� M.
        • Kurman R.J.
        • Lessey B.A.
        Effect of the Yuzpe regimen of emergency contraception on markers of endometrial receptivity.
        Hum Reprod. 2000; 15: 2351-2355
        • Seppala M.
        • Alfthan H.
        • Vartiainen E.
        • Stenman U.H.
        The post-menopausal uterus: the effect of hormone replacement therapy on the serum levels of secretory endometrial protein pp14/beta-lactoglobulin homologue.
        Hum Reprod. 1987; 2: 741-743
        • Julkunen M.
        • Apter D.
        • Seppala M.
        • Stenman U.H.
        • Bohn H.
        Serum levels of placental protein 14 reflect ovulation in nonconceptional menstrual cycles.
        Fertil Steril. 1986; 45: 47-50
        • Li T.C.
        • Pockley G.
        • Bolton A.E.
        • Cooke I.D.
        The variation of endometrial protein PP14 in different parts of the human endometrium.
        Int J Gynaecol Obstet. 1991; 34: 257-260
        • Tse J.Y.M.
        • Chiu P.C.N.
        • Lee K.J.
        • et al.
        The synthesis and fate of glycodelin in human ovary during folliculogenesis.
        Mol Hum Reprod. 2002; 8: 142-148