Hormonal and Reproduction

The Hormonal and Reproduction Special Interest Group focus on the early life factors affecting male and female reproductive function. Data collection has included hormonal measures in pregnancy from mothers of boys and girls within the Raine Study, measurement of sex steroid hormones in the umbilical cord blood, hormonal measures, questionnaires and pelvic ultrasound in adolescent girls and questionnaires about pelvic pain and menstrual disorders in young women, and a male reproductive assessment was performed on the boys at 20 years. Data on the timing of the first menstrual period (menarche) and menstrual bleeding patterns have also been collected and a subset of adolescents age 14-16 were tested for Polycystic Ovary Syndrome. Use of hormonal contraception, pregnancies and fertility are still being measured.

Fertility measures from young women and men from the Raine Study have provided new information about normal fertility relevant internationally and new evidence to inform how the early life environment affects fertility in men and women. This Special Interest Group works closely with allied Groups in mental health, cardiometabolic health, sexual risk-taking and breast health to better understand the relationships between hormones, behaviour and long-term health outcomes in the Raine Study. The group have generated world-first data informing how the prenatal environment may influence ovarian reserve. The Raine Study hormonal and reproductive data is currently being used to understand how the early life environment may influence the male reproductive function and female menstrual cycle, with respect to pelvic pain and menstrual bleeding patterns and ovulation.

 

SIG Leaders:

Prof Roger Hart, The University of Western Australia

Prof Martha Hickey, The University of Melbourne

Dr Melanie Walls, The University of Western Australia

 

Key findings over the last 30 years:

Using information collected from the Raine Study participants, researchers found:

  • Menarche (timing of the first menstrual period) represents the start of female reproductive life and age at menarche is a strong predictor of long-term physical and emotional health.
  • How early life exposures affect age at menarcheand how body mass index (a measure of body fat) and age at menarche affect risk of heart, vessels, and metabolic disease in young adults.
  • Female fertility (the “ovarian reserve”) is fixed during fetal life (pre-birth) and ovarian follicles cannot be replaced after birth.
  • Polycystic Ovary Syndrome (PCOS) affects around 6% of reproductive age women. The reasons why PCOS develops are not fully understood. Data from the Raine Study was the first to demonstrate the prenatal exposures to androgens may not predict PCOS in adolescents.
  • How early life events influence male reproduction including new evidence for how early life exposures and the early life environment affect male reproductive function.

 

Higher estrogen exposures before birth are associated with earlier age of first menstrual period in girls.

Hickey M, Lawson LP, Marino JL, Keelan JA, Hart R. Relationship between umbilical cord sex hormone binding globulin, sex steroids, and age at menarche: a prospective cohort study. Fertility and Sterility. 2018;110(5):965-73. doi: 10.1016/j.fertnstert.2018.06.008.

 

Maternal smoking reduces uterine volume in adolescent daughters.  

Hart R, Sloboda DMDoherty DA, Norman RJ, Atkinson HC, Newnham JP, Dickinson JE, Hickey M. Prenatal determinants of uterine volume and ovarian reserve in adolescence.  The Journal of Clinical Endocrinology and Metabolism. 2009;94(12):4931-7. doi: 10.1210/jc.2009-1342.

 

Maternal smoking leads to reduced sperm counts in young men.

Hart RJ, Doherty DA, Keelan JA, McLachlan R, Skakkebaek NE, Norman RJ, Dickinson JE, Pennell CE, Newnham JP, Hickey M, Handelsman DJ. Early Life Events Predict Adult Testicular Function; Data Derived From the Western Australian (Raine) Birth Cohort. The Journal of Clinical Endocrinology and Metabolism. 2016;101(9):3333-44. doi: 10.1210/jc.2016-1646.

 

Exposure to endocrine disrupting chemicals during prenatal life affects reproductive function of adolescent girls and young men.  

Hart RJ, Frederiksen H, Doherty DA, Keelan JA, Skakkebaek NE, Minaee NS, McLachlan R, Newnham JP, Dickinson JE, Pennell CE, Norman RJ, Main KM. The Possible Impact of Antenatal Exposure to Ubiquitous Phthalates Upon Male Reproductive Function at 20 Years of Age. Frontiers in Endocrinology. 2018;9:288.  doi: 10.3389/fendo.2018.00288.

 

Hart RJ, Doherty DA, Keelan JA, Minaee NS, Thorstensen EB, Dickinson JE, Pennell CE, Newnham JP, McLachlan R, Norman RJ, Handelsman DJ. The impact of antenatal Bisphenol A exposure on male reproductive function at 20-22 years of age. Reproductive Biomedicine Online. 2018;36(3):340-47. doi: 10.1016/j.rbmo.2017.11.009.

 

Hart R, Doherty DA, Frederiksen H, Keelan JA, Hickey M, Sloboda D, Pennell CE, Newnham JP, Skakkebaek NE, Main KM. The influence of antenatal exposure to phthalates on subsequent female reproductive development in adolescence: a pilot study. Reproduction. 2014;147(4):379-90. doi: 10.1530/REP-13-0331.

 

Testicular function in a birth cohort of young men.  

Hart RJDoherty DA, McLachlan RI, Walls ML, Keelan JA, Dickinson JE, Skakkebaek NE, Norman RJ, Handelsman DJ. Testicular function in a birth cohort of young men.  Human Reproduction. 2015;30(12):2713-24. doi: 10.1093/humrep/dev244.

 

Adult diagnostic criteria for PCOS cannot be applied to adolescent girls  

Hickey M, Doherty DA, Atkinson H, Sloboda DM, Franks S, Norman RJHart R. Clinical, ultrasound and biochemical features of polycystic ovary syndrome in adolescents: implications for diagnosis. Human Reproduction. 2011;26(6):1469-77. doi: 10.1093/humrep/der102.

 

Adolescent girls with features of PCOS may be at risk for metabolic disorders in later life.

Hart R, Doherty DA, Mori T, Huang RC, Norman RJ, Franks S, Sloboda D, Beilin L, Hickey M. Extent of metabolic risk in adolescent girls with features of polycystic ovary syndrome. Fertility and Sterility. 2011;95(7):2347-53. doi: 10.1016/j.fertnstert.2011.03.001.

“Data from the Raine Study has advanced the understanding of how the early life environment may have a substantial influence over adult male and female reproductive many years later.”

Martha Hickey, Professor of Obstetrics and Gynaecology, University of Melbourne

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