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Long-term Behavioral and Reproductive Consequences of Embryonic Exposure to Low-dose Toxicants
Published on: March 6, 2018
In-utero exposure to polybrominated biphenyl (PBB) and menstrual cycle function in adulthood
Suman Barat1, Robert B Hood2, Metrecia L Terrell2
1Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA.
Insights
Prenatal exposure to polybrominated biphenyls (PBBs) was linked to higher progesterone levels during the luteal phase in women. Most other menstrual cycle characteristics remained unaffected by PBB exposure.
Area of Science:
- Environmental Health
- Reproductive Epidemiology
- Toxicology
Background:
- Polybrominated biphenyls (PBBs) are environmental contaminants with known associations with adverse reproductive outcomes, including altered pubertal timing.
- Limited data exist on the impact of in-utero PBB exposure on adult menstrual cycle function and reproductive hormone levels.
Purpose of the Study:
- To investigate the association between in-utero polybrominated biphenyl (PBB) exposure and menstrual cycle characteristics in reproductive-aged women.
- To assess the relationship between PBB exposure levels and specific reproductive hormone metabolites (estrone 3-glucuronide, pregnanediol 3-glucuronide) and follicle-stimulating hormone (FSH).
Main Methods:
- Analysis of data from 41 women in the Michigan PBB Registry with documented in-utero PBB exposure.
- Estimation of in-utero PBB exposure via maternal serum PBB levels and a PBB elimination model.
- Daily urine sample analysis for estrone 3-glucuronide (E13G), pregnanediol 3-glucuronide (Pd3G), and FSH over up to 6 months.
Main Results:
- Women with higher in-utero PBB exposure exhibited significantly elevated maximum 3-day mean luteal phase pregnanediol 3-glucuronide (Pd3G) levels compared to those with low exposure.
- Specifically, luteal phase Pd3G levels increased with increasing categories of in-utero PBB exposure (1.0-3.0 ppb and >3.0 ppb).
- No significant associations were found between in-utero PBB exposure and average cycle length, follicular or luteal phase length, bleed length, E13G, or FSH levels.
Conclusions:
- Higher in-utero PBB exposure is associated with increased progesterone metabolite levels during the luteal phase of the menstrual cycle.
- Most other menstrual cycle parameters were not significantly associated with in-utero PBB exposure in this cohort.
- Results should be interpreted cautiously due to the modest sample size of the study.
Background:
There is evidence that in-utero exposure to PBBs, and similar chemicals, are associated with several adverse reproductive health outcomes including altered pubertal timing. However, less is known about the effects of in-utero exposure to PBBs on menstrual cycle function and reproductive hormone levels in adulthood.
Methods:
For this menstrual cycle study, we recruited reproductive-aged women in the Michigan PBB Registry who were not pregnant, lactating, or taking hormonal medications (2004-2014). A total of 41 women who were born after the PBB contamination incident (1973-1974) and were prenatally exposed to PBBs, were included in this analysis. We estimated in-utero PBB exposure using maternal serum PBB measurements taken after exposure and extrapolated to time of pregnancy using a PBB elimination model. Women were followed for up to 6 months during which they provided daily urine samples and completed daily diaries. The urine samples were assayed for estrone 3-glucuronide (E13G), pregnanediol 3-glucuronide (Pd3G), and follicle stimulating hormone (FSH).
Results:
Women in our study were, on average, 27.5 (SD:5.3) years old and contributed 4.9 (SD:1.9) menstrual cycles of follow-up. Compared to women with low in-utero PBB exposure (≤1 ppb), women with medium (>1.0-3.0 ppb) and high (>3.0 ppb) exposure had higher maximum 3-day mean Pd3G levels during the luteal phase. Specifically, the age- and creatinine-adjusted maximum 3-day mean luteal phase Pd3G levels (95% CI) in increasing categories of in-utero PBB exposure were 9.2 (4.6,13.9), 14.8 (11.6,18.0), and 16.1 (12.9,19.3) μg/mg creatinine. There were no meaningful differences in average cycle length, follicular or luteal phase cycle length, bleed length, or creatinine-adjusted E13G or FSH levels by category of in-utero PBB exposure.
Conclusion:
Higher exposure to PBB in-utero was associated with increased progesterone levels across the luteal phase, however, most other menstrual cycle characteristics were largely unassociated with in-utero PBB exposure. Given our modest sample size, our results require cautious interpretation.
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