Birth Weight, Sex Hormones and Sexual Maturation in Girls
Open Access
- Author:
- Ruder, Elizabeth Hill
- Graduate Program:
- Nutrition
- Degree:
- Doctor of Philosophy
- Document Type:
- Dissertation
- Date of Defense:
- June 16, 2008
- Committee Members:
- Terryl Johnson Hartman, Committee Chair/Co-Chair
Sibylle Kranz, Committee Chair/Co-Chair
Michael J Rovine, Committee Member
Penny Margaret Kris Etherton, Committee Member
Joanne Dorgan, Committee Member - Keywords:
- sex steroid hormones
menarche
pubertal development
hormones adn cancer
fetal origins
breast cancer - Abstract:
- Breast cancer is the most frequently diagnosed cancer among American women with over 200,000 new cases diagnosed annually. There is growing interest in the relationship between early life exposures as an antecedent for disease later in life. Birth weight, which is associated with maternal hormone levels during pregnancy, is related to timing of puberty and incidence of hormone dependent cancers in adulthood. The Dietary Intervention Study in Children (DISC) and Hormone Ancillary Study (HAS) was a multi-center, randomized controlled clinical trial that evaluated the effect of a reduced fat diet intervention during puberty on serum lipids, growth, maturation, and sex hormone concentrations in 301 girls enrolled at 8-10 years of age and followed for a median of 7 years. The present investigation allows us to use the longitudinal data from the DISC in combination with birth weight and sex hormone concentrations available for a subset of DISC participants to further understand the role of early life exposures on known and suspected breast cancer risk factors. Early age at menarche is a known risk factor for breast cancer. The purpose of the first study was to test the hypothesis that birth weight is associated with age at menarche after controlling for potential confounders such as physical activity, body size, and mother’s age at menarche. Birth weight data was obtained via maternal / guardian report and was available for 203 girls (mean= 3399 g, standard deviation= 508, range 1899 – 5103). Information regarding onset of first menses was ascertained annually until menarche. For the girls with a documented onset of menses during the study period, the mean age at menarche was 12.79 y (range 9.75 y – 15.71 y). Cox regression models were used to determine the independent effect of birth weight on age at menarche. Follow-up or survival time was calculated in days from date of birth until date of menarche. Low birth weight (defined as birth weight < 1 standard deviation below sample mean) was nearly significantly associated with age at menarche (HR= 1.53, 95% CI 0.96, 2.45, p = 0.07) after controlling for BMI-for-age percentile, physical activity, race and treatment group. Among the 130 individuals for whom both birth weight and mother’s age at menarche data were available, the relationship of earlier menarche among girls belonging to the low birth weight group was strengthened (HR= 1.92, 95% CI 1.07, 3.43, p = 0.03). The purpose of the second study was to evaluate the association between birth weight and levels of serum hormones (estrone, estradiol, estrone sulfate, progesterone, testosterone, androstenedione, dehydroepiandrosterone sulfate (DHEAS)) and sex hormone binding globulin (SHBG). Exposure to elevated estrogens throughout life is thought to play an important role in increasing breast cancer risk. Serum hormone concentrations were collected at 5 points during the study, and capture the participants’ hormone levels before, during, and after puberty. Of the 301 girls randomized into one of two study arms of DISC, 286 participated in the HAS at one of more visits. Girls were not eligible to participate in the HAS if they were pregnant or had used oral contraceptives within three months of blood collection, if they were postmenarcheal and had missing data on the date they started menses after blood collection, or if their next menses started more than 33 days after blood collection. A total of 203/286 girls (71%) who participated in the HAS also provided birthweight data. Mean birth weight for the sample was 3399 g (standard deviation = 508, range 1899 – 5103). Birth weight was associated with DHEAS concentration throughout the 7 years of follow-up and androstenedione concentration prior to menarche. Low birth weight girls exhibited higher concentrations of these hormones compared to average birth weight girls. Birth weight was also associated with post-menarche SHBG concentrations. Low birth weight girls presented decreased SHBG concentrations compared to high birth weight girls. In addition, certain luteal phase estrogen concentrations were positively associated with birth weight. For pre-menarche DHEAS and androstenedione concentrations, the association with birth weight may have occurred via birth weight’s effect on age at menarche. Conversely, the relationship between post-menarche DHEAS, post-menarche SHBG, and luteal phase estradiol, non-SHBG estradiol and estrone appeared to be independent of the effect of birth weight on age at menarche. These studies provide evidence for the association of birth weight with age at menarache (a documented risk factor for breast cancer); and pubertal concentrations of sex hormones. In a secondary analyses, we the previsouly documented association of body composition with age at menarche was confirmed. This research provides insight to understanding risk factors for an etiologically complex disease. As the biologic mechanisms underlying these associations become better understood, there is potential for the increased development of breast cancer prevention strategies in early life and adolescence.