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Clinical Chemistry and Laboratory Medicine (CCLM)

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Volume 42, Issue 9 (Sep 2004)


Comparison between creatinine and pregnanediol adjustments in the retrospective analysis of urinary hormone profiles during the human menstrual cycle

Fernando Miro
  • Unipath Limited, Stannard Way, Priory Business Park, Bedford, United Kingdom of Great Britain and Northern Ireland
/ John Coley
  • Unipath Limited, Stannard Way, Priory Business Park, Bedford, United Kingdom of Great Britain and Northern Ireland
/ Mohamed M. Gani
  • Unipath Limited, Stannard Way, Priory Business Park, Bedford, United Kingdom of Great Britain and Northern Ireland
/ Paul W. Perry
  • Unipath Limited, Stannard Way, Priory Business Park, Bedford, United Kingdom of Great Britain and Northern Ireland
/ Duncan Talbot
  • Unilever Research Colworth, Sharnbrook, Bedford, United Kingdom of Great Britain and Northern Ireland
/ Laurence J. Aspinall
  • Unilever Research Colworth, Sharnbrook, Bedford, United Kingdom of Great Britain and Northern Ireland
Published Online: 2005-06-01 | DOI: https://doi.org/10.1515/CCLM.2004.210


Measurement of reproductive hormones in urine is a practical way of obtaining large amounts of information; however, there is still controversy on how to overcome problems derived from volume fluctuations between samples. Creatinine adjustment is a widely accepted solution, however, it introduces an extra cost, and large studies involving multiple sequential determinations would benefit from more economical solutions.

We determined the value of creatinine adjustment, and compared it with a mathematical method that uses the smoothed profile of pregnanediol (PdG) as a reference to adjust other hormonal markers. To do this, we investigated the effects on three major urinary reproductive hormonal markers (luteinizing hormone (LH), estrone 3-glucuronide (E1G) and PdG) in 17 complete menstrual cycles. Detection of the day of LH peak did not differ between raw and adjusted data. Creatinine adjustment reduced variation in pre-ovulatory E1G levels between individuals, though the effect was negligible within individuals. No significant differences were found regarding post-ovulatory PdG rise. Although creatinine adjustment significantly reduces variability, producing smoother profiles, an equivalent degree of smoothness is obtained using the PdG adjustment.

We conclude that under the current technology, for the retrospective study of urinary hormonal profiles in the human menstrual cycle, PdG adjustment is a valid alternative to creatinine.

Keywords: creatinine; luteinizing hormone; menstrual cycle; pregnanediol; steroids


  • 1

    Wilcox AJ, Dunson D, Baird DD. The timing of the “fertile window” in the menstrual cycle: day specific estimates from a prospective study. Br Med J 2000; 321:1259–62.Google Scholar

  • 2

    Santoro N, Crawford SL, Allsworth JE, Gold EB, Greendale GA, Korenman S, et al. Assessing menstrual cycles with urinary hormone assays. Am J Physiol Endocrinol Metab 2003; 284:E521–30.Google Scholar

  • 3

    O’Connor KA, Holman DJ, Wood JW. Menstrual cycle variability and the perimenopause. Am J Human Biol 2001; 13:465–78.CrossrefGoogle Scholar

  • 4

    Boeniger MF, Lowry LK, Rosenberg J. Interpretation of urine results used to assess chemical exposure with emphasis on creatinine adjustments: a review. Am Ind Hyg Assoc J 1993; 54:615–27.CrossrefGoogle Scholar

  • 5

    Nicolas JC, Chikhaoui Y, Bressot N, Bornadet A, Descomps B, Cristol P, et al. Dosage enzymatique de l’estrone et de l’estradiol urinaires: correlations avec l’estradiol plasmatique au cours du cycle menstruel chez la femme. J Gyn Obst Biol Reprod 1982; 11:477–81.Google Scholar

  • 6

    Wilcox AJ, Baird DD, Weinberg CR, Armstrong EG, Musey PI, Wehmann RE, et al. The use of biochemical assays in epidemiological studies of reproduction. Environ Health Perspect 1987; 75:29–35.CrossrefGoogle Scholar

  • 7

    Santoro N, Rosenberg Brown J, Adel T, Skurnick JH. Characterization of reproductive hormonal dynamics in the perimenopause. J Clin Endocrinol Metab 1996; 81:1495–501.Google Scholar

  • 8

    Munro CJ, Stabenfeldt GH, Cragun JR, Addiego LA, Overstreet JW, Lasley BL. Relationship of serum estradiol and progesterone concentrations to the excretion profiles of their major urinary metabolites as measured by enzyme immunoassay and radioimmunoassay. Clin Chem 1991; 37:838–44.Google Scholar

  • 9

    Seki K, Seki M, Koichi K. Correlation between urinary oestrogen levels determined by haemagglutination inhibition reaction and serum oestradiol levels determined by radioimmunoassay. Acta Endocrinol 1985; 110:130–4.Google Scholar

  • 10

    Stanczyk FZ, Miyakawa I, Goebelsmann U. Direct radioimmunoassay of urinary estrogen and pregnanediol glucuronides during the menstrual cycle. Am J Obstet Gynecol 1980; 137:443–50.Google Scholar

  • 11

    Collins WP, Collins PO, Kilpatrick MJ, Manning PA, Pike JM, Tyler JPP. The concentrations of urinary estrone-3-glucuronide, LH and pregnanediol-3α-glucuronide as indices of ovarian function. Acta Endocrinol 1979; 90:336–48.Google Scholar

  • 12

    Denari JH, Farinati Z, Figueroa Casas PR, Oliva A. Determination of ovarian function using first morning urine steroid assays. Obstet Gynecol 1980; 58:5–9.Google Scholar

  • 13

    Hakim R, Gray RH, Zacur HA. Is there a need for creatinine adjustment of urinary steroid hormone levels in studies of early fetal loss? Clin Chim Acta 1994; 230:209–14.CrossrefGoogle Scholar

  • 14

    Demir A, Alfthan H, Stenman UH, Voutilainen R. A clinically useful method for detecting gonadotropins in children: assessment of luteinizing hormone and follicle-stimulating hormone from urine as an alternative to serum by ultrasensitive time-resolved immunofluorometric assays. Pediatr Res 1994; 36:221–6.CrossrefGoogle Scholar

  • 15

    Zacur H, Kaufman SC, Smith B, Westhoff C, Helbig D, Lee YJ, et al. Does creatinine adjustment of urinary pregnanediol glucuronide reduce or introduce measurement error? Gynecol Endocrinol 1997; 11:29–33.CrossrefGoogle Scholar

  • 16

    Gault MH, Chafe L, Prabhakaran V. Mid-menstrual cycle decline in creatinine and urea clearances. Nephron 1994; 67:158–66.CrossrefGoogle Scholar

  • 17

    Davison JM, Noble MC. Serial changes in 24 hour creatinine clearance during normal menstrual cycles and the first trimester of pregnancy. Br J Obstet Gynecol 1981; 88:10–7.CrossrefGoogle Scholar

  • 18

    Paaby P, Moller-Petersen J, Larsen CE, Raffn K. Endogenous overnight creatinine clearance, serum beta 2-microglobulin and serum water during the menstrual cycle. Acta Med Scand 1987; 221:191–7.CrossrefGoogle Scholar

  • 19

    Kesner JS, Knecht EA, Krieg Jr EF. Measuring endocrine profiles of women in field studies. Scand J Work Environ Health 1999; 25(Suppl):17–9.Google Scholar

  • 20

    Hedricks CA, Schramm W, Dry JR. Effects of creatinine correction to urinary LH levels on the timing of the LH peak and the distribution of coitus within the human menstrual cycle. Ann NY Acad Sci 1994; 709:204–6.Google Scholar

  • 21

    Hedricks CA, Piccinino L, Udry JR, Chimbira THK. Peak coital rate coincides with onset of luteinizing hormone (LH) surge. Fertil Steril 1985; 48:234–8.CrossrefGoogle Scholar

  • 22

    Kesner JS, Knecht EA, Krieg Jr EF, Wilcox AJ, O’Connor JF. Detecting pre-ovulatory luteinizing hormone surges in urine. Hum Reprod 1998; 13:15–21.CrossrefGoogle Scholar

  • 23

    Littell RC, Milliken GA, Stroup WW, Wolfinger RD. SAS System for Mixed Models. Cary NC, USA: SAS Institute Inc, 1996.Google Scholar

  • 24

    Lasley BL, Mobed K, Gold EB. The use of urinary hormonal assessments in human studies. Ann NY Acad Sci 1994; 709:299–311.Google Scholar

  • 25

    Baird DD, Weinberg CR, Wilcox AJ, McConnaughey DR. Using the ratio of urinary oestrogen and progesterone metabolites to estimate day of ovulation. Stat Med 1991; 10:255–66.CrossrefGoogle Scholar

  • 26

    O’Connor KA, Brindle E, Holman DJ, Klein NA, Soules MR, Campbell KL, et al. Urinary estrone conjugate and pregnanediol 3-glucuronide enzyme immunoassays for population research. Clin Chem 2003; 49:1139–48.Google Scholar

  • 27

    Gray RH, Campbell OM, Zacur HA, Labbok MH, MacRae SL. Postpartum return of ovarian activity in nonbreast-feeding women monitored by urinary assays. J Clin Endocrinol Metab 1987; 64:645–50.CrossrefGoogle Scholar

  • 28

    Dennerstein L, Brown JB, Gotts G, Morse CA, Farley TM, Pinol A. Menstrual cycle hormonal profiles of women with and without premenstrual syndrome. J Psychosom Obstet Gynaecol 1994; 14:259–68.CrossrefGoogle Scholar

  • 29

    Jacobsen FK, Christensen CK, Mogensen CE, Heilskov NSC. Evaluation of kidney function after meals. Lancet 1980; i:319.CrossrefGoogle Scholar

  • 30

    van Beek E, Houben AJHM, van Es PN, Willekes C, Korten ECCM, de Leeuw PW, et al. Peripheral haemodynamics and renal function in relation to the menstrual cycle. Clin Sci 1996; 91:163–8.CrossrefGoogle Scholar

  • 31

    Phipps WR, Duncan AM, Merz BE, Kurzer MS. Effect of the menstrual cycle on creatinine clearance in normally cycling women. Obstet Gynecol 1998; 92:585–8.Google Scholar

  • 32

    Kovalevskaya G, Birken S, O’Connor J, Schlatterer J, Maydelman Y, Canfield R. hLH beta core fragment immunoreactivity in the urine of ovulating women: a sensitive and specific immunometric assay for its detection. Endocrine 1995; 3:881–7.CrossrefGoogle Scholar

  • 33

    O’Connor JF, Kovalevskaya G, Birken S, Schlatterer JP, Schechter D, McMahon DJ, et al. The expression of the urinary forms of human luteinizing hormone beta fragment in various populations as assessed by a specific immunoradiometric assay. Hum Reprod 1998; 13:826–35.CrossrefGoogle Scholar

  • 34

    Miller RC, Brindle E, Holman DJ, Shofer J, Klein NA, Soules MR, et al. Comparison of specific gravity and creatinine for normalizing urinary reproductive hormone concentrations. Clin Chem 2004; 50:924–32.CrossrefGoogle Scholar

About the article

Corresponding author: F. Miro, Unipath Limited, Stannard Way, Priory Business Park, Bedford, MK44 3UP, UK. Phone: +44(0) 1234 835454, Fax: +44(0) 1234 835002, E-mail:

Received: 2004-02-27

Accepted: 2004-07-23

Published Online: 2005-06-01

Published in Print: 2004-09-01

Citation Information: Clinical Chemistry and Laboratory Medicine (CCLM), ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/CCLM.2004.210.

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