Shorter Menstrual Cycles Associated with Chlorination By-Products in Drinking Water Gayle Windham, K Waller, M Anderson, L Fenster, P Mendola, S Swan California Department of Health Services Environmental Health Investigations Branch (Work supported in large part by USEPA)

TTHM Levels and Menstrual Cycling Background Found association of SAB and high consumption of water with high TTHM and BDCM levels. Other studies confirm increased risk of adverse pregnancy outcomes with chlorination by-products. Purpose THMs associated with other reproductive endpoints? Identify possible mechanisms for the SAB effects. Examine THM exposure and menstrual cycle function in a study of 400 premenopausal women.

Women’s Reproductive Health Study Methods Prospective Study of Kaiser members in Santa Clara County Women “at risk” of pregnancy, married, ages Urine collected daily (about 6 months) to measure: –Steroid metabolites (E1C, PdG) — menstrual cycle function –hCG — early pregnancy loss Data collected (follow-up 2 years later)

Data Collection Instruments Screening Interview — phone –eligibility criteria Baseline Questionnaire — phone –# glasses unheated tap water at home –# glasses hot tap at home –# glasses bottled water/day (and brand) –# showers at home (and length)/week –Demographics and covariates Daily Diary — self-administered

Individual Hormone Results

Assignment of THM Level Geocode residence address to identify water utility company Obtain utility THM monitoring data (total and individual) Cycle-specific THM levels estimated: –90-day window, starting 60 days before cycle start –average all utility monitoring points –weighted if moved –average two closest to window, if none during Woman-level TTHM from average of cycle-specific levels

Results — Subject Characteristics (N=401) % TTHM Characteristic N% >80 µg/L Age21-29 years years years RaceWhite Hispanic Other EducationNo College Some College College Graduate Pregnancies ≥1, no losses ≥1, ≥1 loss

Menstrual Cycle Length Parameters by Total Trihalomethane Level TTHM Level (µg/L) 0-40>40-60>60 Cycle Length Mean (s.e.)29.7 (0.26)29.3 (0.28)28.7 (0.28) Adj. Difference (CI) Ref-0.50 (-1.1, 0.11) -1.1 (-1.8, -0.40) Follicular Phase Mean (s.e.)16.9 (0.27)16.5 (0.29)16.0 (0.30) Adj. Difference (CI) Ref-0.39 (-0.98, 0.20) (-1.6, -0.24) Luteal Phase Mean (s.e.)12.9 (0.09)12.8 (0.11)13.0 (0.10) Adj. Difference (CI) Ref-0.08 (-0.33, 0.18) 0.07 (-0.20, 0.35)

Menstrual Cycle Outcomes by TTHM Level % Affected

Length Parameters by Total Trihalomethane Daily Consumption Level TTHM Consumption Level (µg/day) 0>0-40>40 Cycle Length N Mean (s.e.)29.8 (0.39)29.43 (0.28)28.5 (0.33) Adj. Difference (CI)Ref-0.23 (-1.2, 0.77) -1.1 (-2.2, -0.06) Follicular Phase N Mean (s.e.)17.1 (0.43)16.6 (0.30)15.8 (0.34) Adj. Difference (CI) Ref-0.32 (-1.4, 0.77) -1.1 (-2.2, 0.03)

Length Parameters by Quartiles of Chloroform and Brominated Trihalomethane Levels Quartile of Exposure Mean in DaysDifferenceDifference (s.e.)(95% CI)(95% CI) Cycle Length Chloroform29.6 (0.30) (-0.99, 0.13)-0.30 (-1.0, 0.40) Sum of Brominated30.0 (0.34) (-1.4, -0.04)-1.2 (-2.0, -0.40) Follicular Phase Chloroform 16.8 (0.31) (-0.96, 0.12) (-0.82, 0.56) Sum of Brominated 17.2 (0.35)-0.66 (-1.3, 0.02)-1.1 (-1.9, -0.29)

TTHM Levels and Menstrual Cycling Strengths Prospective study TTHM exposure from existing records in narrow time frame Information on some water use patterns Endpoint determined from biologic measures (vs. self-report) Adjusted for several potential confounders First study of reproductive function in non-pregnant women Limitations Potential exposure misclassification (utility average) No information on exposure outside the home Study sample may not represent full range of cycle variability

Conclusions and Summary Increasing TTHM level is associated with decreasing cycle length, primarily in the follicular phase This decrease is associated with the brominated THMs, primarily chlorodibromomethane Combining consumption and TTHM level reveals similar, but not greater, associations Accounting for showering also does not reveal stronger associations Confirm effects on ovarian function in other studies