Polybrominated Biphenyl Exposure and Menstrual Cycle Function

Abstract

Background: Brominated flame retardants, including polybrominated biphenyls (PBB), are persistent compounds reported to affect sex hormones in animals; less is known about potential effects in humans. An industrial accident in 1973-1974 exposed Michigan residents to PBB through contaminated food. We examined whether this exposure to PBB had long-term effects on menstrual cycle function.

Methods: In 2004-2006, we recruited reproductive-aged women in the Michigan PBB Registry who were not pregnant, lactating, or taking hormonal medications. Participants kept daily diaries and provided daily urine samples for up to 6 months. We assayed the urine samples for estrone 3-glucuronide (E13G), pregnanediol 3-glucuronide (Pd3G), and follicle stimulating hormone (FSH). We fit linear mixed models among women aged 35-42 years to describe the relation between serum PBB levels and log-transformed, creatinine-adjusted daily endocrine levels among women who were premenarchal during the exposure incident in 1973-1974 (n = 70).

Results: We observed that high (>3.0 parts per billion [ppb]) and medium (>1.0-3.0 ppb) PBB exposure were associated with lower E13G levels across the menstrual cycle and lower FSH levels during the follicular phase, compared with low PBB exposure (≤1.0 ppb). High PBB exposure was also associated with lower Pd3G levels across the cycle compared with low PBB exposure, whereas Pd3G levels were similar in women with medium and low PBB exposure.

Conclusion: Our results are consistent with a hypothesized effect of exposure to an exogenous estrogen agonist but the modest sample size of the study requires cautious interpretation.

Figure 1.

Predicted daily log creatinine-adjusted urinary hormone metabolite levels and 95% confidence intervals for a 38-year-old woman centered on the day of luteal transition (DLT) by level of polybrominated biphenyl exposure (PBB). The dotted light blue line represents ≤ 1.0 parts per billion (ppb), the dashed dark purple line represents >1.0–3.0 ppb, and the solid red line represents >3.0 ppb. (A) Estrone 3-glucuronide (E₁3G) and (B) Pregnanediol 3-glucuronide (Pd3G). Models are adjusted for continuous age centered on 38 years, the mean age of the study population.

Figure 1.

Predicted daily log creatinine-adjusted urinary hormone metabolite levels and 95% confidence intervals for a 38-year-old woman centered on the day of luteal transition (DLT) by level of polybrominated biphenyl exposure (PBB). The dotted light blue line represents ≤ 1.0 parts per billion (ppb), the dashed dark purple line represents >1.0–3.0 ppb, and the solid red line represents >3.0 ppb. (A) Estrone 3-glucuronide (E₁3G) and (B) Pregnanediol 3-glucuronide (Pd3G). Models are adjusted for continuous age centered on 38 years, the mean age of the study population.

Figure 2.

Predicted daily log creatinine-adjusted hormone metabolite and hormone levels and 95% confidence intervals for a 38-year-old woman centered on the day of menses onset by level of polybrominated biphenyl exposure (PBB). The dotted light blue line represents ≤ 1.0 parts per billion (ppb), the dashed dark purple line represents >1.0–3.0 ppb, and the solid red line represents >3.0 ppb. (A) Estrone 3-glucuronide (E₁3G), (B) Pregnanediol 3-glucuronide (Pd3G), and (C) Follicle stimulating hormone (FSH). Models are adjusted for continuous age centered on 38 years, the mean age of the study population.

Figure 2.

Predicted daily log creatinine-adjusted hormone metabolite and hormone levels and 95% confidence intervals for a 38-year-old woman centered on the day of menses onset by level of polybrominated biphenyl exposure (PBB). The dotted light blue line represents ≤ 1.0 parts per billion (ppb), the dashed dark purple line represents >1.0–3.0 ppb, and the solid red line represents >3.0 ppb. (A) Estrone 3-glucuronide (E₁3G), (B) Pregnanediol 3-glucuronide (Pd3G), and (C) Follicle stimulating hormone (FSH). Models are adjusted for continuous age centered on 38 years, the mean age of the study population.

Figure 2.

Predicted daily log creatinine-adjusted hormone metabolite and hormone levels and 95% confidence intervals for a 38-year-old woman centered on the day of menses onset by level of polybrominated biphenyl exposure (PBB). The dotted light blue line represents ≤ 1.0 parts per billion (ppb), the dashed dark purple line represents >1.0–3.0 ppb, and the solid red line represents >3.0 ppb. (A) Estrone 3-glucuronide (E₁3G), (B) Pregnanediol 3-glucuronide (Pd3G), and (C) Follicle stimulating hormone (FSH). Models are adjusted for continuous age centered on 38 years, the mean age of the study population.