A population based case control study of early menopause is proposed to identify environmental and genetic risk factors for this condition. A 50% sample of women 45 to 54 years wi-11 be selected from west suburban Boston using town resident's lists and called to determine their menopausal status. All women who report a natural menopause prior to age 40 and a sample of women menopausal at age 40 but before age 47 are eligible as cases (expected n=278). Controls are matched individually by age and residence to cases and must have been premenopausal at the age when the matched case became menopausal (n=278). Personal interviews of the cases and selected controls, and whenever possible their mothers, will be obtained to assess primarily dietary factors but also occupational history, reproductive history, family history, and active or passive smoking. Our major dietary hypothesis is that a diet high in galactose (from dairy Products) consumed by the subject or her mother (during the subjects pregnancy) may increase risk for this condition. This hypothesis is supported by an experimental model in which mother rats fed a high galactose diet produced offspring with decreased oocyte numbers. A preliminary analysis which we have done also suggests that a key enzyme in galactose metabolism, galactose transferase, may be a genetic marker for this condition and will be measured in all subjects consenting to a blood test. Menopause prior to age 47 is estimated to occur in 12% of women, and may prematurely end her reproductive life and increase her risk for coronary artery disease or osteoporosis. The possible association between early menopause and galactose consumption is one of considerable public health importance because of a substantial increase in the use of galactose rich foods in this country, especially yogurt, whose use has quadrupled since 1970.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD023661-03
Application #
3323812
Study Section
Epidemiology and Disease Control Subcommittee 2 (EDC)
Project Start
1989-08-01
Project End
1993-04-30
Budget Start
1991-05-01
Budget End
1992-04-30
Support Year
3
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
071723621
City
Boston
State
MA
Country
United States
Zip Code
02115
Kenneson, A; Cramer, D W; Warren, S T (1997) Fragile X premutations are not a major cause of early menopause. Am J Hum Genet 61:1362-9
Cramer, D W; Xu, H (1996) Predicting age at menopause. Maturitas 23:319-26
Cramer, D W; Xu, H; Harlow, B L (1995) Does ""incessant"" ovulation increase risk for early menopause? Am J Obstet Gynecol 172:568-73
Harlow, B L; Cramer, D W; Annis, K M (1995) Association of medically treated depression and age at natural menopause. Am J Epidemiol 141:1170-6
Cramer, D W; Xu, H; Harlow, B L (1995) Family history as a predictor of early menopause. Fertil Steril 64:740-5
Cramer, D W; Harlow, B L; Xu, H et al. (1995) Cross-sectional and case-controlled analyses of the association between smoking and early menopause. Maturitas 22:79-87
Lau, C C; Mok, S C; Kelley, A et al. (1994) Detection of a RsaI polymorphism within the human galactokinase gene (GK2) by PCR-SSCP. Hum Mol Genet 3:1916
Harlow, B L; Crea, E C; East, M A et al. (1993) Telephone answering machines: the influence of leaving messages on telephone interviewing response rates. Epidemiology 4:380-3
Cramer, D W; Korf, B R; Fortier, L J (1991) Galactose metabolism and reproductive history in women with type 1 neurofibromatosis. Am J Med Genet 39:502-8