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Maternal hormones during early pregnancy: a cross-sectional study

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Abstract

Background

Little is known about correlates of first-trimester pregnancy hormones as in most studies maternal hormones have been measured later in gestation. We examined the associations of maternal characteristics and child sex with first-trimester maternal concentrations of four hormones implicated in breast cancer: human chorionic gonadotropin (hCG), α-fetoprotein (AFP), insulin-like growth factor (IGF)-I, and IGF-II.

Methods

About 338 serum samples donated to the Northern Sweden Maternity Cohort (NSMC), 1975–2001, during the first trimester of uncomplicated pregnancies, were analyzed for the hormones of interest as a part of a case–control study. The associations of maternal characteristics and child sex with hormone concentrations were investigated by correlation, general linear regression, and multivariate regression models.

Results

In the first trimester, greater maternal age was inversely correlated with IGF-I and IGF-II. In comparison with women carrying their first child, already parous women had higher IGF-I but lower hCG. Greater maternal weight and smoking were inversely correlated with hCG. No differences in hormone levels by child sex were observed.

Conclusions

Our analyses indicated that potentially modifiable maternal characteristics (maternal weight and smoking) influence first-trimester pregnancy maternal hormone concentrations.

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References

  1. Medina D (2005) Mammary developmental fate and breast cancer risk. Endocr Relat Cancer 12:483–495

    Article  CAS  PubMed  Google Scholar 

  2. Russo IH, Russo J (2007) Primary prevention of breast cancer by hormone-induced differentiation. Recent Results Cancer Res 174:111–130

    Article  CAS  PubMed  Google Scholar 

  3. Richardson BE, Peck JD, Wormuth JK (2000) Mean arterial pressure, pregnancy-induced hypertension, and preeclampsia: evaluation as independent risk factors and as surrogates for high maternal serum alpha-fetoprotein in estimating breast cancer risk. Cancer Epidemiol Biomarkers Prev 9:1349–1355

    CAS  PubMed  Google Scholar 

  4. Melbye M, Wohlfahrt J, Lei U et al (2000) Alpha-fetoprotein levels in maternal serum during pregnancy and maternal breast cancer incidence. J Natl Cancer Inst 92:1001–1005

    Article  CAS  PubMed  Google Scholar 

  5. Lukanova A, Andersson R, Wulff M et al (2008) Human chorionic gonadotropin and alpha-fetoprotein concentrations in pregnancy and maternal risk of breast cancer: a nested case–control study. Am J Epidemiol 168:1284–1291

    Article  PubMed  Google Scholar 

  6. Xue F, Michels KB (2007) Intrauterine factors and risk of breast cancer: a systematic review and meta-analysis of current evidence. Lancet Oncol 8:1088–1100

    Article  PubMed  Google Scholar 

  7. Innes KE, Byers TE (1999) Preeclampsia and breast cancer risk. Epidemiology 10:722–732

    Article  CAS  PubMed  Google Scholar 

  8. Troisi R, Hoover RN, Thadhani R et al (2008) Maternal, prenatal and perinatal characteristics and first trimester maternal serum hormone concentrations. Br J Cancer 99:1161–1164

    Article  CAS  PubMed  Google Scholar 

  9. Kleinberg DL, Feldman M, Ruan W (2000) IGF-I: an essential factor in terminal end bud formation and ductal morphogenesis. J Mammary Gland Biol Neoplasia 5:7–17

    Article  CAS  PubMed  Google Scholar 

  10. Russo J, Wilgus G, Russo IH (1979) Susceptibility of the mammary gland to carcinogenesis: I differentiation of the mammary gland as determinant of tumor incidence and type of lesion. Am J Pathol 96:721–736

    CAS  PubMed  Google Scholar 

  11. Mullis PE, Tonella P (2008) Regulation of fetal growth: consequences and impact of being born small. Best Pract Res Clin Endocrinol Metab 22:173–190

    Article  CAS  PubMed  Google Scholar 

  12. Garner M, Turner MC, Ghadirian P et al (2008) Testicular cancer and hormonally active agents. J Toxicol Environ Health B Crit Rev 11:260–275

    CAS  PubMed  Google Scholar 

  13. Lukanova A, Toniolo P, Zeleniuch-Jacquotte A et al (2006) Insulin-like growth factor I in pregnancy and maternal risk of breast cancer. Cancer Epidemiol Biomarkers Prev 15:2489–2493

    Article  CAS  PubMed  Google Scholar 

  14. Speroff L, Fritz M (2005) The endocrinology of pregnancy. In: Speroff L, Fritz M (eds) Clinical gynecologic endocrinology and infertility, 7th edn. Lippincott Williams & Wilkins, Philadelphia, PA, pp 259–318

    Google Scholar 

  15. Lund PK (1999) Insulin-like growth factors: gene structure and regulation. In: Kostyo JL, Goodman HM (eds) Hormonal control of growth. Oxford University Press, New York, pp 537–571

    Google Scholar 

  16. Chen T, Lukanova A, Kjell G et al. (2009) IGF-I during primiparous pregnancy and maternal risk of breast cancer. Breast Cancer Res Treat. doi:10.1007/s10549-009-0519-6 (in press)

  17. Cnattingius S, Ericson A, Gunnarskog J, Kallen B (1990) A quality study of a medical birth registry. Scand J Soc Med 18:143–148

    CAS  PubMed  Google Scholar 

  18. Cleveland WS, Loader C (1996) Smoothing by local regression: principles and methods. In: Schimek MG (ed) Statistical theory and computational aspects of smoothing. Springer, New York, pp 113–120

    Google Scholar 

  19. Monaghan JM, Godber IM, Lawson N et al (2004) Longitudinal changes of insulin-like growth factors and their binding proteins throughout normal pregnancy. Ann Clin Biochem 41:220–226

    Article  CAS  PubMed  Google Scholar 

  20. Olajide F, Kitau MJ, Chard T (1989) Maternal serum AFP levels in the first trimester of pregnancy. Eur J Obstet Gynecol Reprod Biol 30:123–128

    Article  CAS  PubMed  Google Scholar 

  21. Stenman UH, Tiitinen A, Alfthan H, Valmu L (2006) The classification, functions and clinical use of different isoforms of HCG. Hum Reprod Update 12:769–784

    Article  CAS  PubMed  Google Scholar 

  22. Yu H, Mistry J, Nicar MJ et al (1999) Insulin-like growth factors (IGF-I, free IGF-I and IGF-II) and insulin-like growth factor binding proteins (IGFBP-2, IGFBP-3, IGFBP-6, and ALS) in blood circulation. J Clin Lab Anal 13:166–172

    Article  CAS  PubMed  Google Scholar 

  23. Wald NJ, Watt HC (1996) Serum markers for Down’s syndrome in relation to number of previous births and maternal age. Prenat Diagn 16:699–703

    Article  CAS  PubMed  Google Scholar 

  24. Wald NJ, Kennard A, Hackshaw A, McGuire A (1998) Antenatal screening for Down’s syndrome. Health Technol Assess 2(i–iv):1–112

    Google Scholar 

  25. Arslan AA, Zeleniuch-Jacquotte A, Lukanova A et al (2006) Effects of parity on pregnancy hormonal profiles across ethnic groups with a diverse incidence of breast cancer. Cancer Epidemiol Biomarkers Prev 15:2123–2130

    Article  CAS  PubMed  Google Scholar 

  26. Lukanova A, Toniolo P, Akhmedkhanov A et al (2001) A cross-sectional study of IGF-I determinants in women. Eur J Cancer Prev 10:443–452

    Article  CAS  PubMed  Google Scholar 

  27. Morimoto LM, Newcomb PA, White E, Bigler J, Potter JD (2005) Variation in plasma insulin-like growth factor-1 and insulin-like growth factor binding protein-3: personal and lifestyle factors (United States). Cancer Causes Control 16:917–927

    Article  PubMed  Google Scholar 

  28. DeLellis K, Rinaldi S, Kaaks RJ et al (2004) Dietary and lifestyle correlates of plasma insulin-like growth factor-I (IGF-I) and IGF binding protein-3 (IGFBP-3): the multiethnic cohort. Cancer Epidemiol Biomarkers Prev 13:1444–1451

    CAS  PubMed  Google Scholar 

  29. Tislaric D, Brajenovic-Milic B, Ristic S et al (2002) The influence of smoking and parity on serum markers for Down’s syndrome screening. Fetal Diagn Ther 17:17–21

    Article  PubMed  Google Scholar 

  30. de Graaf IM, Cuckle HS, Pajkrt E et al (2000) Co-variables in first trimester maternal serum screening. Prenat Diagn 20:186–189

    Article  PubMed  Google Scholar 

  31. Canick JA, Lambert-Messerlian GM, Palomaki GE et al (2006) Comparison of serum markers in first-trimester down syndrome screening. Obstet Gynecol 108:1192–1199

    CAS  PubMed  Google Scholar 

  32. Voskuil DW, Buenode Mesquita HB, Kaaks R et al (2001) Determinants of circulating insulin-like growth factor (IGF)-I and IGF binding proteins 1–3 in premenopausal women: physical activity and anthropometry (Netherlands). Cancer Causes Control 12:951–958

    Article  CAS  PubMed  Google Scholar 

  33. Juul A (2003) Serum levels of insulin-like growth factor I and its binding proteins in health and disease. Growth Horm IGF Res 13:113–170

    Article  CAS  PubMed  Google Scholar 

  34. Hunt KJ, Toniolo P, Akhmedkhanov A et al (2002) Insulin-like growth factor II and colorectal cancer risk in women. Cancer Epidemiol Biomarkers Prev 11:901–905

    CAS  PubMed  Google Scholar 

  35. Walker K, Fletcher O, Johnson N et al (2009) Premenopausal mammographic density in relation to cyclic variations in endogenous sex hormone levels, prolactin, and insulin-like growth factors. Cancer Res 69:6490–6499

    Article  CAS  PubMed  Google Scholar 

  36. Chellakooty M, Vangsgaard K, Larsen T et al (2004) A longitudinal study of intrauterine growth and the placental growth hormone (GH)-insulin-like growth factor I axis in maternal circulation: association between placental GH and fetal growth. J Clin Endocrinol Metab 89:384–391

    Article  CAS  PubMed  Google Scholar 

  37. Lambert-Messerlian G, Palomaki GE, Canick JA (2009) Adjustment of serum markers in first trimester screening. J Med Screen 16:102–103

    Article  PubMed  Google Scholar 

  38. Bestwick JP, Huttly WJ, Wald NJ (2008) First trimester Down’s syndrome screening marker values and cigarette smoking: new data and a meta-analysis on free beta human chorionic gonadotrophin, pregnancy-associated plasma protein-A and nuchal translucency. J Med Screen 15:204–206

    Article  PubMed  Google Scholar 

  39. Crossley JA, Aitken DA, Waugh SM, Kelly T, Connor JM (2002) Maternal smoking: age distribution, levels of alpha-fetoprotein and human chorionic gonadotrophin, and effect on detection of Down syndrome pregnancies in second-trimester screening. Prenat Diagn 22:247–255

    Article  CAS  PubMed  Google Scholar 

  40. Rudnicka AR, Wald NJ, Huttly W, Hackshaw AK (2002) Influence of maternal smoking on the birth prevalence of Down syndrome and on second trimester screening performance. Prenat Diagn 22:893–897

    Article  PubMed  Google Scholar 

  41. Ermis B, Altinkaynak K, Yildirim A, Ozkan B (2004) Influence of smoking on serum and milk of mothers, and their infants’ serum insulin-like growth factor-I and insulin-like growth factor binding protein-3 levels. Horm Res 62:288–292

    Article  CAS  PubMed  Google Scholar 

  42. Allen NE, Appleby PN, Kaaks R et al (2003) Lifestyle determinants of serum insulin-like growth-factor-I (IGF-I), C-peptide and hormone binding protein levels in British women. Cancer Causes Control 14:65–74

    Article  PubMed  Google Scholar 

  43. Yaron Y, Lehavi O, Orr-Urtreger A et al (2002) Maternal serum HCG is higher in the presence of a female fetus as early as week 3 post-fertilization. Hum Reprod 17:485–489

    Article  CAS  PubMed  Google Scholar 

  44. Yaron Y, Wolman I, Kupferminc MJ et al (2001) Effect of fetal gender on first trimester markers and on Down syndrome screening. Prenat Diagn 21:1027–1030

    Article  CAS  PubMed  Google Scholar 

  45. Larsen SO, Wojdemann KR, Shalmi AC et al (2002) Gender impact on first trimester markers in Down syndrome screening. Prenat Diagn 22:1207–1208

    Article  PubMed  Google Scholar 

  46. Mueller VM, Huang T, Summers AM, Winsor SH (2005) The effect of fetal gender on the false-positive rate of Down syndrome by maternal serum screening. Prenat Diagn 25:1258–1261

    Article  CAS  PubMed  Google Scholar 

  47. Spencer K (2000) The influence of fetal sex in screening for Down syndrome in the second trimester using AFP and free beta-hCG. Prenat Diagn 20:648–651

    Article  CAS  PubMed  Google Scholar 

  48. Caufriez A, Frankenne F, Hennen G, Copinschi G (1993) Regulation of maternal IGF-I by placental GH in normal and abnormal human pregnancies. Am J Physiol 265:E572–E577

    CAS  PubMed  Google Scholar 

  49. Vatten LJ, Nilsen ST, Odegard RA, Romundstad PR, Austgulen R (2002) Insulin-like growth factor I and leptin in umbilical cord plasma and infant birth size at term. Pediatrics 109:1131–1135

    Article  PubMed  Google Scholar 

  50. Ibanez L, Sebastiani G, Lopez-Bermejo A et al (2008) Gender specificity of body adiposity and circulating adiponectin, visfatin, insulin, and insulin growth factor-I at term birth: relation to prenatal growth. J Clin Endocrinol Metab 93:2774–2778

    Article  CAS  PubMed  Google Scholar 

  51. Engstrom E, Niklasson A, Wikland KA, Ewald U, Hellstrom A (2005) The role of maternal factors, postnatal nutrition, weight gain, and gender in regulation of serum IGF-I among preterm infants. Pediatr Res 57:605–610

    Article  PubMed  CAS  Google Scholar 

  52. Lagiou P, Hsieh CC, Lipworth L et al (2009) Insulin-like growth factor levels in cord blood, birth weight and breast cancer risk. Br J Cancer 100:1794–1798

    Article  CAS  PubMed  Google Scholar 

  53. Sivaraman L, Medina D (2002) Hormone-induced protection against breast cancer. J Mammary Gland Biol Neoplasia 7:77–92

    Article  PubMed  Google Scholar 

  54. Zhang Y, Graubard BI, Klebanoff MA et al (2005) Maternal hormone levels among populations at high and low risk of testicular germ cell cancer. Br J Cancer 92:1787–1793

    Article  CAS  PubMed  Google Scholar 

  55. Bernstein L, Lipworth L, Ross RK, Trichopoulos D (1995) Correlation of estrogen levels between successive pregnancies. Am J Epidemiol 142:625–628

    CAS  PubMed  Google Scholar 

  56. Wald NJ, Huttly WJ, Rudnicka AR (2004) Prenatal screening for Down syndrome: the problem of recurrent false-positives. Prenat Diagn 24:389–392

    Article  PubMed  Google Scholar 

  57. de Medeiros SF, Norman RJ (2009) Human choriogonadotrophin protein core and sugar branches heterogeneity: basic and clinical insights. Hum Reprod Update 15:69–95

    Article  PubMed  CAS  Google Scholar 

  58. Russo J, Russo IH (1995) Hormonally induced differentiation: a novel approach to breast cancer prevention. J Cell Biochem Suppl 22:58–64

    Article  CAS  PubMed  Google Scholar 

  59. Kappel B, Hansen K, Moller J, Faaborg-Andersen J (1985) Human placental lactogen and dU-estrogen levels in normal twin pregnancies. Acta Genet Med Gemellol (Roma) 34:59–65

    CAS  Google Scholar 

  60. Bernstein L, Hanisch R, Sullivan-Halley J, Ross RK (1995) Treatment with human chorionic gonadotropin and risk of breast cancer. Cancer Epidemiol Biomarkers Prev 4:437–440

    CAS  PubMed  Google Scholar 

  61. Kinnunen TI, Luoto R, Gissler M, Hemminki E, Hilakivi-Clarke L (2004) Pregnancy weight gain and breast cancer risk. BMC Womens Health 4:7

    Article  PubMed  Google Scholar 

  62. Key TJ, Verkasalo PK, Banks E (2001) Epidemiology of breast cancer. Lancet Oncol 2:133–140

    Article  CAS  PubMed  Google Scholar 

  63. Fink AK, Lash TL (2003) A null association between smoking during pregnancy and breast cancer using Massachusetts registry data (United States). Cancer Causes Control 14:497–503

    Article  PubMed  Google Scholar 

  64. Terry PD, Rohan TE (2002) Cigarette smoking and the risk of breast cancer in women: a review of the literature. Cancer Epidemiol Biomarkers Prev 11:953–971

    PubMed  Google Scholar 

  65. Gram IT, Braaten T, Terry PD et al (2005) Breast cancer risk among women who start smoking as teenagers. Cancer Epidemiol Biomarkers Prev 14:61–66

    PubMed  Google Scholar 

  66. Ishibe N, Hankinson SE, Colditz GA et al (1998) Cigarette smoking, cytochrome P450 1A1 polymorphisms, and breast cancer risk in the Nurses’ health study. Cancer Res 58:667–671

    CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by the US National Cancer Institute [CA114329 and CA120061]. The authors are indebted to Hubert Sjodin, Soren Holmgren and Lena Selbrand for their excellent technical assistance in the conduct of the study.

Conflict of interest statement

None declared.

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Authors and Affiliations

  1. Division of Cancer Epidemiology, German Cancer Research Center, In Neuenheimer Feld 280, Heidelberg, 69120, Germany

    Tianhui Chen, Helena Schock & Annekatrin Lukanova

  2. Department of Medical Biosciences, University of Umeå, Umeå, Sweden

    Eva Lundin & Kjell Grankvist

  3. Department of Environmental Medicine, New York University School of Medicine, New York, USA

    Anne Zeleniuch-Jacquotte, Yelena Afanasyeva & Paolo Toniolo

  4. NYU Cancer Institute, New York, USA

    Anne Zeleniuch-Jacquotte, Yelena Afanasyeva & Paolo Toniolo

  5. Department of Clinical Sciences, University of Umeå, Umeå, Sweden

    Marianne Wulff

  6. Department of Radiation Sciences, University of Umeå, Umeå, Sweden

    Robert Johansson & Per Lenner

  7. Department of Public Health and Clinical Medicine, University of Umeå, Umeå, Sweden

    Goran Hallmans

  8. Department of Clinical Microbiology, University of Umeå, Umeå, Sweden

    Goran Wadell

  9. Department of Obstetrics and Gynecology, New York University School of Medicine, New York, USA

    Paolo Toniolo & Annekatrin Lukanova

  10. Institute of Social and Preventive Medicine, University of Lausanne, Lausanne, Switzerland

    Paolo Toniolo

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  1. Tianhui Chen
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  2. Eva Lundin
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Correspondence to Annekatrin Lukanova.

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Chen, T., Lundin, E., Grankvist, K. et al. Maternal hormones during early pregnancy: a cross-sectional study. Cancer Causes Control 21, 719–727 (2010). https://doi.org/10.1007/s10552-009-9500-2

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