The normal variabilities of the menstrual cycle


      To address conflicts in the normal variabilities of the menstrual cycle using the newest generation test methods and to establish normal ranges for use in clinical practice.


      Daily urine samples were collected from 167 women eager to achieve pregnancy. Samples were tested prospectively for LH and total hCG. A total of 458 nongestational and 111 gestational menstrual cycles were evaluated.


      Division of Women's Health Research, University of New Mexico.


      One hundred sixty-seven women desiring pregnancy.



      Main Outcome Measure(s)

      Levels of hCG and LH.


      Menstrual cycles were 27.7 ± 2.4 days in length. The LH peak indicated the onset of the presumed ovulatory window, which occurs at 14.7 ± 2.4 days. Implantation (first day of sensitive detection of hCG) occurred in gestational menstrual cycles at 24.6 ± 3.1 days, or 4.3 ± 2.2 days before missing the expected onset of menses.


      Our data confirm epidemiological studies on menstrual cycle length and variability and hormonal studies on timing of the ovulatory window and its variability. They dispute, however, the published data on the timing and variance of implantation. As shown, implantation is limited to a 10-day interval culminating in the day of the expected onset of menses. Reference range data provide guidelines for differentiating normal and problem menstrual cycles.

      Key Words

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


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


        • Corner G.W.
        Our knowledge of the menstrual cycle, 1910–1950.
        Lancet. 1951; 1: 919-923
        • Pratt J.P.
        The normal menstrual cycle.
        Southern Med J. 1951; 44: 812-817
        • Persky H.
        Excetion of luteinizing hormone (LH) by normal human subjects.
        J Albert Einstein Med Ctr. 1964; 12: 29-33
        • Midgley Jr., A.R.
        • Jaffe R.B.
        Human luteinizing hormone in serum during the menstrual cycle: determination by radioimmunoassay.
        J Clin Endocrinol Metab. 1966; 26: 1375-1381
        • Ross G.T.
        • Odell W.D.
        • Rayford P.L.
        Luteinizing hormone activity in plasma during the menstrual cycle.
        Science. 1967; 155: 1679-1680
        • Neill J.D.
        • Johansson E.D.
        • Datta J.K.
        • Knobil E.
        Relationship between the plasma levels of luteinizing hormone and progesterone during the normal menstrual cycle.
        J Clin Endocrinol Metab. 1967; 27: 1167-1173
        • Treloar A.E.
        • Boynton R.E.
        • Behn B.G.
        • Brown B.W.
        Variation of the human menstrual cycle through reproductive life.
        lntl J Fert. 1967; 12: 77-126
        • Harlow S.D.
        • Lin X.
        • Ho M.J.
        Analysis of menstrual diary data across the reproductive life span applicability of the bipartite model approach and the importance of within-women variance.
        J Clin Epidemiol. 2000; 53: 722-733
        • Harlow S.D.
        • Ephross S.A.
        Epidemiology of menstruation and its relevance to women's health.
        Epidemiol Rev. 1995; 17: 265-286
        • Lenton E.A.
        • Landgren B.M.
        • Sexton L.
        Normal variation in the length of the luteal phase of the menstrual cycle.
        Br J Obstet Gynecol. 1984; 91: 685-689
        • Lenton E.A.
        • Landgren B.M.
        • Sexton L.
        • Harper R.
        Normal variation in the length of the follicular phase of the menstrual cycle.
        Br J Obstet Gynecol. 1984; 91: 681-684
        • Lenton E.A.
        • Lawrence G.F.
        • Coleman R.A.
        • Cooke I.D.
        Individual variation in gonadotrophin and steroid concentrations and in the lengths of the follicular and luteal phases in women with regular menstrual cycles.
        Clin Reprod Fertil. 1983; 2: 143-150
        • Wilcox A.J.
        • Baird D.D.
        • Dunson D.
        • McChesney R.
        • Weinberg C.R.
        Natural limits of pregnancy testing in relation to the expected menstrual period.
        J Am Med Assoc. 2001; 286: 1759-1761
        • Wilcox A.J.
        • Baird D.D.
        • Weinberg C.R.
        Time of implantation of the conceptus and loss of pregnancy.
        New Engl J Med. 1999; 340: 1796-1799
        • Wilcox A.J.
        • Weinberg C.R.
        • Baird D.D.
        Timing of sexual intercourse in relation to ovulation. Effects of the probability of conception, survival of the pregnancy, and sex of the baby.
        New Engl J Med. 1995; 333: 1517-1521
        • Elliott M.M.
        • Kardana A.
        • Lustbader J.W.
        • Cole L.A.
        Carbohydrate and peptide structure of the α- and β-subunits of human chorionic gonadotropin from normal and aberrant pregnancy and choriocarcinoma.
        Endocrine. 1997; 7: 15-32
        • Cole L.A.
        • Dai D.
        • Leslie K.K.
        • Butler S.A.
        • Kohorn E.I.
        Gestational trophoblastic diseases. 1. Pathophysiology of hyperglycosylated hCG-regulated neoplasia.
        Gynecol Oncol. 2006; 102: 144-149
        • Sasaki Y.
        • Ladner D.
        • Cole L.A.
        Hyperglycosylated hCG and the source of pregnancy failures.
        Fertil Steril. 6 August 2007; ([E-pub ahead of print])
        • Kovalevskaya G.
        • Birken S.
        • Kakuma T.
        • Ozaki N.
        • Sauer M.
        • Lindheim S.
        • et al.
        Differential expression of human chorionic gonadotropin (hCG) glycosylation isoforms in failing and continuing pregnancies: preliminary characterization of the hyperglycosylated hCG epitope.
        J Endocrinol. 2002; 172: 497-506
        • Cole L.A.
        • Shahabi S.
        • Oz U.A.
        • Bahado-Singh R.O.
        • Mahoney M.J.
        Hyperglycosylated hCG (invasive trophoblast antigen) immunoassay: a new basis for gestational down syndrome screening.
        Clin Chem. 1999; 45: 2109-2119
        • Cho S.I.
        • Goldman M.B.
        • Ryan L.M.
        • Chen C.
        • Damokosh A.I.
        • Christiani D.C.
        • et al.
        Reliability of serial urine hCG as a biomarker to detect early pregnancy loss.
        Hum Reprod. 2002; 17: 1060-1066
        • O'Connor J.F.
        • Birken S.
        • Lustbader T.W.
        • Krichevsky A.
        • Chen Y.
        • Canfield R.E.
        Recent advances in the chemistry and immunochemistry of human chorionic gonadotropin: impact on clinical measurements.
        Endocrine Rev. 1994; 15: 650-682
        • Kovalevskaya G.
        • Kakuma T.
        • Schlatterer J.
        • O'Connor J.F.
        Hyperglycosylated hCG expression in pregnancy: cellular origin and clinical application.
        Mol Cell Endocrinol. 2007; 260: 237-243
        • Baird D.D.
        • Weinberg C.R.
        • Wilcox A.J.
        • McConnaughey D.R.
        • Musey P.I.
        Using the ratio of urinary oestrogen and progesterone metabolites to estimate day of ovulation.
        Stat Med. 1991; 10: 255-266
        • O'Connor K.A.
        • Brindle E.
        • Miller R.C.
        • Shofer J.B.
        • Ferrel T.J.
        • Klein N.A.
        • et al.
        Ovulation detection methods for urinary hormones: precision, daily and intermittent sampling and a combined hierachial method.
        Hum Reprod. 2006; 21: 1442-1452
        • Cole L.A.
        • Khanlian S.A.
        • Sutton J.M.
        • Davies S.
        • Stephens N.
        Hyperglycosylated hCG (invasive trophoblast antigen, ITA) a key antigen for early pregnancy detection.
        Clin Biochem. 2003; 36: 647-655
        • Sutton-Riley J.M.
        • Khanlian S.A.
        • Byrn F.W.
        • Cole L.A.
        A single serum test for measuring early pregnancy outcome with high predictive value.
        Clin Biochem. 2006; 39: 682-687