Objectives To identify factors predicting maternal sex steroid hormone concentrations in early pregnancy. Methods The Infant Development and the Environment Study recruited healthy pregnant women from academic medical centers in four US cities. Gold standard liquid chromatography–tandem mass spectrometry was used to measure maternal sex steroids concentrations (total testosterone [TT], free testosterone [FT], estrone [E1], estradiol [E2], and estriol [E3] concentrations) in serum samples from 548 women carrying singletons (median = 11.7 weeks gestation). Women completed questionnaires on demographic and lifestyle characteristics. Results In multivariable linear regression analyses, hormone concentrations varied in relation to maternal age, body mass index (BMI), race, and parity. Older mothers had significantly lower levels of most hormones; for every year increase in maternal age, there was a 1–2% decrease in E1, E2, TT, and FT. By contrast, each unit increase in maternal BMI was associated 1–2% lower estrogen (E1, E2, E3) levels, but 1–2% higher androgen (TT, FT) concentrations. Hormone concentrations were 4–18% lower among parous women, and for each year elapsed since last birth, TT and FT were 1–2% higher (no difference in estrogens). Androgen concentrations were 18–30% higher among Black women compared to women of other races. Fetal sex, maternal stress, and lifestyle factors (including alcohol and tobacco use) were not related to maternal steroid concentrations. Conclusions for Practice Maternal demographic factors predict sex steroid hormone concentrations during pregnancy, which is important given increasing evidence that the prenatal endocrine environment shapes future risk of chronic disease for both mother and offspring.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
Tax calculation will be finalised during checkout.
Anderson, W. F., Pfeiffer, R. M., Wohlfahrt, J., et al. (2017). Associations of parity-related reproductive histories with ER+/− and HER2+/− receptor-specific breast cancer aetiology. International Journal of Epidemiology, 46(1), 86–95. https://doi.org/10.1093/ije/dyw286.
Arslan, A. A., 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 Epidemiology and Prevention Biomarkers, 15(11), 2123–2130. https://doi.org/10.1158/1055-9965.epi-06-0470.
Bammann, B. L., Coulam, C. B., & Jiang, N. S. (1980). Total and free testosterone during pregnancy. American Journal of Obstetrics & Gynecology, 137(3), 293–298.
Barbieri, R. L., Makris, A., Randall, R. W., et al. (1986). Insulin stimulates androgen accumulation in incubations of ovarian stroma obtained from women with hyperandrogenism. Journal of Clinical Endocrinology and Metabolism, 62(5), 904–910. https://doi.org/10.1210/jcem-62-5-904.
Barbieri, R. L., Sluss, P. M., Powers, R. D., et al. (2005). Association of body mass index, age, and cigarette smoking with serum testosterone levels in cycling women undergoing in vitro fertilization. Fertility and Sterility, 83(2), 302–308. https://doi.org/10.1016/j.fertnstert.2004.07.956.
Barkai G, Goldman B, Ries L, et al. (1996). Effect of gravidity on maternal serum markers for Down’s syndrome. Prenatal Diagnosis, 16(4), 319–322. https://doi.org/10.1002/(sici)1097-0223(199604)16:4%3C319::aid-pd859%3E3.0.co;2-u
Barrett, E., Parlett, L. E., Sathyanarayana, S., et al. (2015) Prenatal life events stress modifies associations between phthalate exposure and male reproductive development. (In preparation).
Barrett, E. S., Parlett, L. E., Windham, G. C., et al. (2014). Differences in ovarian hormones in relation to parity and time since last birth. Fertility and Sterility, 101(6), 1773–1780 e1. https://doi.org/10.1016/j.fertnstert.2014.02.047.
Barrett, E. S., Sathyanarayana, S., Janssen, S., et al. (2014). Environmental health attitudes and behaviors: Findings from a large pregnancy cohort study. European Journal of Obstetrics, Gynecology, and Reproductive Biology, 176, 119–125. https://doi.org/10.1016/j.ejogrb.2014.02.029.
Bremme, K., Lagerstrom, M., Andersson, O., et al. (1990). Influences of maternal smoking and fetal sex on maternal serum oestriol, prolactin, hCG, and hPI levels. Archives of Gynecology and Obstetrics, 247(2), 95–103.
Caanen, M. R., Kuijper, E. A., Hompes, P. G., et al. (2016). Mass spectrometry methods measured androgen and estrogen concentrations during pregnancy and in newborns of mothers with polycystic ovary syndrome. European Journal of Endocrinology, 174(1), 25–32. https://doi.org/10.1530/eje-15-0699.
CDC. (2016). Health, United States, 2016 with chartbook on long-term trends in health: National Center for Health Statistics.
Chen, T., Lundin, E., Grankvist, K., et al. (2010). Maternal hormones during early pregnancy: A cross-sectional study. Cancer Causes and Control, 21(5), 719–727. https://doi.org/10.1007/s10552-009-9500-2.
Chen, T., Surcel, H. M., Lundin, E., et al. (2011). Circulating sex steroids during pregnancy and maternal risk of non-epithelial ovarian cancer. Cancer Epidemiology and Prevention Biomarkers, 20(2), 324–336. https://doi.org/10.1158/1055-9965.epi-10-0857.
Danforth, D. N. (2013). Disparities in breast cancer outcomes between Caucasian and African American women: A model for describing the relationship of biological and nonbiological factors. Breast Cancer Research: BCR, 15(3), 208. https://doi.org/10.1186/bcr3429.
de Graaf, I. M., Cuckle, H. S., Pajkrt, E., et al. (2000). Co-variables in first trimester maternal serum screening. Prenatal Diagnosis, 20(3), 186–189.
Freeman, E. W., Sammel, M. D., Gracia, C. R., et al. (2005). Follicular phase hormone levels and menstrual bleeding status in the approach to menopause. Fertility and Sterility, 83(2), 383–392. https://doi.org/10.1016/j.fertnstert.2004.06.066.
French, D. (2016). Advances in bioanalytical techniques to measure steroid hormones in serum. Bioanalysis, 8(11), 1203–1219. https://doi.org/10.4155/bio-2015-0025.
Haavaldsen, C., Fedorcsak, P., Tanbo, T., et al. (2014). Maternal age and serum concentration of human chorionic gonadotropin in early pregnancy. Acta obstetricia et gynecologica Scandinavica, 93(12), 1290–1294. https://doi.org/10.1111/aogs.12471.
Haddow, J. E., Palomaki, G. E., & Knight, G. J. (1995). Effect of parity on human chorionic gonadotrophin levels and Down’s syndrome screening. Journal of Medical Screening, 2(1), 28–30. https://doi.org/10.1177/096914139500200108.
Henderson, B. E., Bernstein, L., Ross, R. K., et al. (1988). The early in utero oestrogen and testosterone environment of blacks and whites: Potential effects on male offspring. British Journal of Cancer, 57(2), 216–218.
Jarvela, I. Y., Zackova, T., Laitinen, P., et al. (2012). Effect of parity and fetal sex on placental and luteal hormones during early first trimester. Prenatal Diagnosis, 32(2), 160–167. https://doi.org/10.1002/pd.2921.
Kallak, T. K., Hellgren, C., Skalkidou, A., et al. (2017). Maternal and female fetal testosterone levels are associated with maternal age and gestational weight gain. European Journal of Endocrinology, 177(4), 379–388. https://doi.org/10.1530/eje-17-0207.
Keelan, J. A., Mattes, E., Tan, H., et al. (2012). Androgen concentrations in umbilical cord blood and their association with maternal, fetal and obstetric factors. PLoS ONE, 7(8), e42827. https://doi.org/10.1371/journal.pone.0042827.
Kragie, L. (2002). Aromatase in primate pregnancy: A review. Endocrine Research, 28(3), 121–128.
Krasowski, M. D., Drees, D., Morris, C. S., et al. (2014). Cross-reactivity of steroid hormone immunoassays: Clinical significance and two-dimensional molecular similarity prediction. BMC Clinical Pathology, 14, 33. https://doi.org/10.1186/1472-6890-14-33.
Kunovac-Kallak, T., Hellgren, C., Skalkidou, A., et al. (2017). Maternal and female fetal testosterone levels are associated with maternal age and gestational weight gain. European Journal of Endocrinology. https://doi.org/10.1530/eje-17-0207.
Lagerstrom, M., Bremme, K., & Eneroth, P. (1990). Maternal serum levels of estriol, prolactin, human placental lactogen and chorionic gonadotrophin related to fetal sex in normal and abnormal pregnancies. Gynecologic and Obstetric Investigation, 30(4), 198–203.
Lagiou, P., Samoli, E., Hsieh, C. C., et al. (2014). Maternal and cord blood hormones in relation to birth size. European Journal of Epidemiology, 29(5), 343–351. https://doi.org/10.1007/s10654-014-9914-3.
Manson, J. M., Sammel, M. D., Freeman, E. W., et al. (2001). Racial differences in sex hormone levels in women approaching the transition to menopause. Fertility and Sterility, 75(2), 297–304.
McCartney, C. R., Blank, S. K., Prendergast, K. A., et al. (2007). Obesity and sex steroid changes across puberty: Evidence for marked hyperandrogenemia in pre- and early pubertal obese girls. Journal of Clinical Endocrinology and Metabolism, 92(2), 430–436. https://doi.org/10.1210/jc.2006-2002.
McGinley, K. F., Tay, K. J., & Moul, J. W. (2016). Prostate cancer in men of African origin. Nature reviews. Urology, 13(2), 99–107. https://doi.org/10.1038/nrurol.2015.298.
McGlynn, K. A., Devesa, S. S., Graubard, B. I., et al. (2005). Increasing incidence of testicular germ cell tumors among black men in the United States. Journal of Clinical Oncology, 23(24), 5757–5761. https://doi.org/10.1200/jco.2005.08.227.
Mendes, P. H., Martelli, D. R., de Melo Costa, S., et al. (2016). Comparison of digit ratio (2D:4D) between Brazilian men with and without prostate cancer. Prostate Cancer and Prostatic Diseases, 19(1), 107–110. https://doi.org/10.1038/pcan.2015.62.
Mendiola, J., Sanchez-Ferrer, M. L., Jimenez-Velazquez, R., et al. (2016). Endometriomas and deep infiltrating endometriosis in adulthood are strongly associated with anogenital distance, a biomarker for prenatal hormonal environment. Human Reproduction. https://doi.org/10.1093/humrep/dew163.
Mendiola, J., Stahlhut, R. W., Jorgensen, N., et al. (2011). Shorter anogenital distance predicts poorer semen quality in young men in Rochester, New York. Environmental Health Perspectives, 119(7), 958–963. https://doi.org/10.1289/ehp.1103421.
Middle, J. G. (2007). Dehydroepiandrostenedione sulphate interferes in many direct immunoassays for testosterone. Annals of Clinical Biochemistry, 44(Pt 2), 173–177. https://doi.org/10.1258/000456307780118082.
Mooney, R. A., Arvan, D. A., Saller, D. N. Jr., et al. (1995). Decreased maternal serum hCG levels with increasing gravidity and parity. Obstetrics & Gynecology, 86(6), 900–905.
Musey, V. C., Collins, D. C., Brogan, D. R., et al. (1987). Long term effects of a first pregnancy on the hormonal environment: Estrogens and androgens. Journal of Clinical Endocrinology and Metabolism, 64(1), 111–118.
O’Leary, P., Boyne, P., Flett, P., et al. (1991). Longitudinal assessment of changes in reproductive hormones during normal pregnancy. Clinical Chemistry, 37(5), 667–672.
Poretsky, L., Cataldo, N. A., Rosenwaks, Z., et al. (1999). The insulin-related ovarian regulatory system in health and disease. Endocrine Reviews, 20(4), 535–582. https://doi.org/10.1210/edrv.20.4.0374.
Qoubaitary, A., Meriggiola, C., Ng, C. M., et al. (2006). Pharmacokinetics of testosterone undecanoate injected alone or in combination with norethisterone enanthate in healthy men. Journal of Andrology, 27(6), 853–867. https://doi.org/10.2164/jandrol.106.000281.
Rasmussen, E. L., Hannibal, C. G., Dehlendorff, C., et al. (2017). Parity, infertility, oral contraceptives, and hormone replacement therapy and the risk of ovarian serous borderline tumors: A nationwide case–control study. Gynecologic Oncology, 144(3), 571–576. https://doi.org/10.1016/j.ygyno.2017.01.002.
Rosner, W., Auchus, R. J., Azziz, R., et al. (2007). Position statement: utility, limitations, and pitfalls in measuring testosterone: An Endocrine Society position statement. Journal of Clinical Endocrinology and Metabolism, 92(2), 405–413. https://doi.org/10.1210/jc.2006-1864.
Salazar-Martinez, E., Lazcano-Ponce, E. C., Gonzalez Lira-Lira, G., et al. (1999). Reproductive factors of ovarian and endometrial cancer risk in a high fertility population in Mexico. Cancer Research, 59(15), 3658–3662.
Sathyanarayana, S., Barrett, E., Butts, S., et al. (2014). Phthalate exposure and reproductive hormone concentrations in pregnancy. Reproduction, 147(4), 401–409. https://doi.org/10.1530/rep-13-0415.
Sathyanarayana, S., Butts, S., Wang, C., et al. (2017). Early prenatal phthalate exposure, sex steroid hormones, and birth outcomes. Journal of Clinical Endocrinology and Metabolism, 102(6), 1870–1878. https://doi.org/10.1210/jc.2016-3837.
Schock, H., Zeleniuch-Jacquotte, A., Lundin, E., et al. (2016). Hormone concentrations throughout uncomplicated pregnancies: A longitudinal study. BMC Pregnancy and Childbirth., 16(1), 146. https://doi.org/10.1186/s12884-016-0937-5.
Schooling, C. M., Houghton, L. C., & Terry, M. B. (2016). Potential intervention targets in utero and early life for prevention of hormone related cancers. Pediatrics, 138(Suppl 1), S22–Ss33. https://doi.org/10.1542/peds.2015-4268E.
Steier, J. A., Ulstein, M., & Myking, O. L. (2002). Human chorionic gonadotropin and testosterone in normal and preeclamptic pregnancies in relation to fetal sex. Obstetrics and Gynecology, 100(3), 552–556.
Tejada, F., Cremades, A., Monserrat, F., et al. (1998). Interference of the antihormone RU486 in the determination of testosterone and estradiol by enzyme-immunoassay. Clinica Chimica Acta, 275(1), 63–69.
Toriola, A. T., Vaarasmaki, M., Lehtinen, M., et al. (2011). Determinants of maternal sex steroids during the first half of pregnancy. Obstetrics and Gynecology, 118(5), 1029–1036. https://doi.org/10.1097/AOG.0b013e3182342b7f.
Troisi, R., Hoover, R. N., Thadhani, R., et al. (2008). Maternal, prenatal and perinatal characteristics and first trimester maternal serum hormone concentrations. British Journal of Cancer., 99(7), 1161–1164. https://doi.org/10.1038/sj.bjc.6604639.
Troisi, R., Potischman, N., Roberts, J., et al. (2003). Associations of maternal and umbilical cord hormone concentrations with maternal, gestational and neonatal factors (United States). Cancer Causes and Control, 14(4), 347–355.
van de Beek, C., Thijssen, J. H., Cohen-Kettenis, P. T., et al. (2004). Relationships between sex hormones assessed in amniotic fluid, and maternal and umbilical cord serum: What is the best source of information to investigate the effects of fetal hormonal exposure? Hormones and Behavior, 46(5), 663–669. https://doi.org/10.1016/j.yhbeh.2004.06.010.
Wald NJ, Watt HC. (1996). Serum markers for Down’s syndrome in relation to number of previous births and maternal age. Prenatal Diagnosis, 16(8), 699–703. https://doi.org/10.1002/(sici)1097-0223(199608)16:8%3C699::aid-pd919%3E3.0.co;2-p
Wu, Y., Zhong, G., Chen, S., et al. (2017). Polycystic ovary syndrome is associated with anogenital distance, a marker of prenatal androgen exposure. Human Reproduction, 32(4), 937–943. https://doi.org/10.1093/humrep/dex042.
Zhang, Y., Graubard, B. I., Klebanoff, M. A., et al. (2005). Maternal hormone levels among populations at high and low risk of testicular germ cell cancer. British Journal of Cancer, 92(9), 1787–1793. https://doi.org/10.1038/sj.bjc.6602545.
We wish to acknowledge the contributions of the TIDES Study Team: Coordinating Center: Fan Liu, Erica Scher; UCSF: Marina Stasenko, Erin Ayash, Melissa Schirmer, Jason Farrell, Mari-Paule Thiet, Laurence Baskin; UMN: Heather L. Gray, Chelsea Georgesen, Brooke J. Rody, Carrie A. Terrell, Kapilmeet Kaur; URMC: Erin Brantley, Heather Fiore, Lynda Kochman, Lauren Parlett, Jessica Marino, William Hulbert, Robert Mevorach, Eva Pressman; UW/SCH: Kristy Ivicek, Bobbie Salveson, Garry Alcedo and the families who participated in the study. We thank the TIDES families for their participation and the residents at URMC and UCSF who assisted with birth exams. This analysis was supported by the following NIH Grants: R21ES023883, R01ES016863, R01ES06863-02S4. Additional support for the current analyses was provided by: T32ES007271, P30ES001247, P30ES005002, and UL1TR000124.
TIDES was approved by institutional review boards at all participating institutions, and all subjects signed informed consent prior to starting any study activities.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Electronic supplementary material
Below is the link to the electronic supplementary material.
About this article
Cite this article
Barrett, E.S., Mbowe, O., Thurston, S.W. et al. Predictors of Steroid Hormone Concentrations in Early Pregnancy: Results from a Multi-Center Cohort. Matern Child Health J 23, 397–407 (2019). https://doi.org/10.1007/s10995-018-02705-0
- Fetal origins
- Steroid hormones