Research Article| Volume 49, ISSUE 2, P97-106, October 15, 2004

Time to menopause in relation to PBBs, PCBs, and smoking


      Objectives: Because halogenated biphenyl exposure is suspected to disrupt endocrine function, we assessed time to menopause in women aged 24 years and older who were exposed orally to polybrominated biphenyls (PBBs) and polychlorinated biphenyls (PCBs) (n=874). We also examined smoking in relation to menopause. Methods: To define menopausal status, women were interviewed in 1997 and asked whether they had had any menstrual periods in the previous year, why their menstrual periods had stopped (e.g. surgery), and age at their last menstrual period. Serum PBB and PCB taken at enrollment (1976–1978) into the Michigan PBB registry was used as the measure of halogenated biphenyl exposure. Women whose menopause occurred before their PBB exposure were excluded. Proportional hazard modeling was used to analyze the “risk” for menopause in relation to exposure. Premenopausal women contributed person-time until their interview date, at which time they were censored. Results: We did not find an association between either PBB or PCB exposure and time to menopause. Women who were current smokers had a shorter time to menopause than never smokers (menopause ratio 2.02, 95% C.I. 1.21–3.37). Time to menopause was shortest among women who reported started smoking when they were <18 years of age, smoked at least 20 cigarettes per day, or had at least 10 pack-years of smoking.


      ppb (parts per billion), PBBs (polybrominated biphenyls), PCBs (polychlorinated biphenyl), S.D. (standard deviation)


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        • Carter L.J.
        Michigan’s PBB incident: chemical mix-up leads to disaster.
        Science. 1976; 192: 240-243
        • Fries G.F.
        The PBB episode in Michigan: an overall appraisal.
        CRC Crit. Rev. Toxicol. 1988; 16: 105-156
        • McCormack K.M.
        • Arneric S.P.
        • Hook J.B.
        Action of exogenously administered steroid hormones following perinatal exposure to polybrominated biphenyls.
        J. Toxicol. Environ. Health. 1979; 5: 1085-1094
        • Dent J.G.
        Characteristics of cytochrome P-450 and mixed function oxidase enzymes following treatment with PBBs.
        Environ. Health Perspect. 1978; 23: 301-307
        • McCormack K.M.
        • Melrose P.
        • Rickert D.E.
        • Dent J.G.
        • Gibson J.E.
        • Hook J.B.
        Concomitant dietary exposure to polychlorinated biphenyls and polybrominated biphenyls: tissue distribution and arylhydrocarbon hydroxylase activity in lactating rats.
        Toxicol Appl. Pharmacol. 1979; 47: 95-104
        • Johnston C.A.
        • Demarest K.T.
        • McCormack K.M.
        • Hook J.B.
        • Moore K.E.
        Endocrinological, neurochemical, and anabolic effects of polybrominated biphenyls in male and female rats.
        Toxicol Appl. Pharmacol. 1980; 56: 240-247
        • Allen J.R.
        • Barsotti D.A.
        • Lambrecht L.K.
        • Van Miller J.P.
        Reproductive effects of halogenated aromatic hydrocarbons on nonhuman primates.
        Ann. NY Acad. Sci. 1979; 320: 419-425
        • Lambrecht L.K.
        • Barsotti D.A.
        • Allen J.R.
        Responses of nonhuman primates to a polybrominated biphenyl mixture.
        Environ. Health Perspect. 1978; 23: 139-145
        • Harlow B.L.
        • Signorello L.B.
        Factors associated with early menopause.
        Maturitas. 2000; 35: 3-9
        • Meek M.D.
        • Finch G.L.
        Diluted mainstream cigarette smoke condensates activate estrogen receptor and aryl hydrocarbon receptor-mediated gene transcription.
        Environ. Res. 1999; 80: 9-17
        • Lambert G.H.
        • Schoeller D.A.
        • Humphrey H.E.
        • et al.
        The caffeine breath test and caffeine urinary metabolite ratios in the Michigan cohort exposed to polybrominated biphenyls: a preliminary study.
        Environ. Health Perspect. 1990; 89: 175-181
        • Merrill J.C.
        • Beck D.J.
        • Kaminski D.A.
        • Li A.P.
        Polybrominated biphenyl induction of cytochrome P450 mixed function oxidase activity in primary rat and human hepatocytes.
        Toxicology. 1995; 99: 147-152
        • Sowers M.R.
        • La Pietra M.T.
        Menopause: its epidemiology and potential association with chronic diseases.
        Am J. Epidemiol. 1995; 17: 287-302
        • Burse V.W.
        • Needham L.L.
        • Liddle J.A.
        • Bayse D.D.
        Interlaboratory comparison for results of analyses for polybrominated biphenyls in human serum.
        J. Anal. Toxicol. 1980; 4: 22-26
        • Needham L.L.
        • Burse V.W.
        • Price H.A.
        Temperature-programmed gas chromatographic determination of polychlorinated and polybrominated biphenyls in serum.
        J. Assoc. Anal. Chem. 1981; 64: 1131-1137
        • Burse V.W.
        • Korver M.O.
        • Needham L.L.
        • et al.
        Gas chromatographic determination of polychlorinated biphenyls (as Arochlor 1254) in serum: collaborative study.
        J. Assoc. Anal. Chem. 1989; 72: 649-659
        • H Hass J.R.
        • McConnel E.E.
        • Harvan D.J.
        Chemical and toxicologic evaluation of FireMaster BP-6.
        J. Agric. Food Chem. 1978; 26: 94
      1. Kleinbaum DG. Survival analysis: a self-learning text. New York (NY): Springer-Verlag; 1999.

      2. Allison P. Survival analysis using the SAS system: a practical guide. Cary (NC): SAS Institute Inc.; 1995.

        • Cramer D.W.
        • Xu H.
        Predicting age at menopause.
        Maturitas. 1996; 23: 319-326
        • Gold E.B.
        • Bromberger J.
        • Crawford S.
        • Samuels S.
        • Greendale G.A.
        • Harlow S.D.
        • Skurnick J.
        Factors associated with age at natural menopause in a multiethnic sample of midlife women.
        Am. J. Epidemiol. 2001; 153: 865-874
      3. SAS Stat User’s Guide, Version 6. Cary (NC): SAS Institute Inc.; 1990.

        • McKinney J.D.
        • Waller C.L.
        Polychlorinated biphenyls as hormonally active structural analogues Environ.
        Health Perspect. 1994; 102: 290-297
        • Cramer D.W.
        • Harlow B.L.
        • Xu H.
        • Fraer C.
        • Barbieri R.
        Cross-sectional and case-controlled analyses of the association between smoking and early menopause.
        Maturitas. 1995; 22: 79-87
        • Bromberger J.T.
        • Matthews K.A.
        • Kuller L.H.
        • Wing R.R.
        • Meilahn W.N.
        • Plantings P.
        Prospective study of the determinants of the age at menopause.
        Am. J. Epidemiol. 1997; 145: 124-133
        • Cooper G.S.
        • Sandler D.P.
        • Bohlig M.
        Active and passive smoking and the occurrence of natural menopause.
        Epidemiology. 1999; 10: 771-773
        • Willet W.
        • Stampfer M.H.
        • Bain C.
        • et al.
        Cigarette smoking, relative weight, and menopause.
        Am. J. Epidemiol. 1983; 117: 651-658
        • Midgett A.S.
        • Baron J.A.
        Cigarette smoking and the risk of natural menopause.
        Epidemiology. 1990; 1: 464-480
        • Cooper G.S.
        • Baird D.D.
        • Darden F.R.
        Measures of menopausal status in relation to demographic, reproductive and behavioral characteristics in a population-based study of women aged 35–49 years.
        Am. J. Epidemiol. 2001; 153: 1159-1165
        • Stanford J.L.
        • Hartge P.
        • Brinton L.A.
        • Hoover R.N.
        • Brookmeyer R.
        Factors influencing the age at natural menopause.
        J. Chronic. Dis. 1987; 40: 995-1002
        • Whelan E.A.
        • Sandler D.P.
        • McConnaughey D.R.
        • Weinberg C.R.
        Menstrual and reproductive characteristics and age at natural menopause.
        Am. J. Epidemiol. 1990; 131: 625-632
        • Meschia M.
        • Pansini F.
        • Modena A.B.
        • et al.
        Determinants of age at menopause in Italy: results from a large cross-sectional study ICARUS Study Group. Italian Climacteric Research Group Study.
        Maturitas. 2000; 34: 119-125
        • Bean J.A.
        • Leeper J.D.
        • Wallace R.B.
        • Sherman B.M.
        • Jagger H.
        Variations in the reporting of menstrual histories.
        Am. J. Epidemiol. 1979; 109: 181-185
        • den Tonkelaar I.
        Validity and reproducibility of self-reported age at menopause in women participating in the DOM-project.
        Maturitas. 1997; 27: 117-123
        • Clavel-Chapelon F.
        • Dormoy-Mortier N.
        A validation study on status and age of natural menopause reported in the E3N cohort.
        Maturitas. 1998; 3: 99-103
        • Paganini-Hill A.
        • Ross R.K.
        Reliability of recall of drug usage and other health-related information. 1982; 116: 114-122
        • Horwitz R.I.
        • Yu E.C.
        Problems and proposals for interview data in epidemiologic research.
        Int. J. Epidemiol. 1985; 14: 463-467
        • Colditz G.A.
        • Stampfer M.A.
        • Willett W.C.
        • et al.
        Reproducibility and validity of self-reported menopausal status in a prospective cohort study.
        Am. J. Epidemiol. 1987; 126: 319-325
        • Hahn R.A.
        • Eaker E.
        • Rolka H.
        Reliability of reported age at menopause.
        Am. J. Epidemiol. 1997; 146: 771-775
      4. Mattison DR, Thorgeirsson SS. Smoking and industrial pollution and their effects on menopause and ovarian cancer. Lancet 1978;187–8.

        • Mattison D.R.
        • Shiromizu K.
        • Nightingale M.S.
        Oocyte destruction by polycylic aromatic hydrocarbons.
        Am. J. Ind. Med. 1983; 4: 191-202
        • Matikainen T.
        • Perez G.I.
        • Jurisicova A.
        • et al.
        Aromatic hydrocarbon receptor-driven Bax gene expression is required for premature ovarian failure caused by biohazardous environmental chemicals.
        Nat. Genet. 2001; 28: 300-301
        • Pieleszek A.
        • Stanosz S.
        Effect of carbon disulfide on menopause in women.
        Med. Pr. 1994; 45: 383-391
        • Yu M.L.
        • Guo Y.L.
        • Hsu C.C.
        • Rogan W.J.
        Menstruation and reproduction in women with polychlorinated biphenyl (PCB) poisoning: long-term follow-up interviews of the women from the Taiwan Yucheng cohort.
        Int. J. Epidemiol. 2000; 29: 672-677
        • Eskenazi B.
        • Mocarelli P.
        • Warner M.
        Seveso Women’s Health Study: does zone of residence predict individual TCDD exposure?.
        Chemosphere. 2001; 43: 937-942