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93147713 Estrogen replacement therapy and cognitive function in older women
JOURNAL OF THE CLIMACTERIC B POSTMENOPAUSE
ELSEVIER
Maturitas
20 (1994) 53-59
Abstract section 93144016 Biological and eodocriwlogical insights into the possible breast caocer risk from menopausal estrogen replacement therapy Zumoff B. Division of Endocrinology/Metabolism. Department of Medicine, Beth Israel Medical Center, First Avenue at 16th Street, New York, NY 10003 STEROIDS 1993 58/5 (196-204) The question of whether estrogen therapy increases the risk of breast cancer is reviewed. Despite more than 60 epidemiological studies and several meta-analyses over a five-decade period, there is no consensus about the answer. At present, the majority of investigators agree that short-term or medium-term therapy (less than 10 years) poses no measurable risk; some, but not all, investigators feel that there is a modest risk with longterm therapy (more than 15 years). Even this semi-consensus is clouded by the startling and clear-cut finding of the largest ever epidemiological study, the Nurses Surveillance Study, that a small increase in risk with estrogen therapy occurred only in women who also ingested alcohol, itself a known risk factor for breast cancer; women who did not ingest alcohol were at no increased risk. Because virtually none of the other epidemiological studies has controlled for alcohol ingestion, the conclusions of all of them are placed in doubt. To try to shed light on this problem, the 60-year-old studies of Lacassagne et al. on the induction of breast cancer in mice by estrogens were reviewed. They found that the magnitude and timing of the inducing effect of estrogen depended on the spontaneous breast cancer incidence in the mouse strain studied: in no-incidence strains, no cancer was induced; in high-incidence strains, induction was rapid and universal; in low-incidence strains, only a low percentage of animals had cancer induced, and it required prolonged estrogen administration. Because (in animal terms) humans are a low-incidence group, it is to be expected that any increase in breast cancer incidence with estrogen therapy would be modest and would require prolonged administration. This is approximately what is actually observed, but several factors may confound the picture: [1] the role of alcohol ingestion may be important; [2] genetic variability in the capacity to l6-hydroxylate may be important, because increased 16-hydroxylation has been found to be a risk factor for breast cancer; [3] the specific estrogen administered may be important, because different estrogens vary in their ability to be lbhydroxylated; 141 the presence of atypical duct-cell hyperplasia may increase the risk; [5] a personal history of breast cancer or of premenopausal breast cancer in a mother or sister may increase the risk. In
SSDI
03785122(94)00873-6
view of the overwhelming benefits of menopausal estrogen replacement therapy (diminished coronary disease, diminished osteoporosis, and prolongation of life-span, as well as relief of menopausal symptoms), it is concluded that all postmenopausal women should receive it unless they themselves have had breast cancer or a mother or sister has had premenopausal breast cancer.
93147713 Estrogen replacement therapy and cognitive function in older women Barrett-Connor E., Kritz-Silverstein D. Community/Famil,v Medicine Department, University of Cabfornia, 9500 Gilman Dr. San Diego, CA 92093-0607 J. AM. MED. ASSOC. 1993 269120 (2637-2641) Objective - To determine whether replacement estrogen delays or prevents loss of cognitive function in elderly women. Design - A l5-year prospective and cross-sectional study. Setting - Ranch0 Bernardo, a geographically defined community in Southern California. Participants - Eight hundred women (80% of local surviving women from the original Ranch0 Bernardo cohort) aged 65 to 95 years. Estrogen use was evaluated at baseline between 1972 and 1974 and at follow-up between 1988 and 1991. Main Outcome Measures - Twelve tests of cognitive function from eight standard instruments administered at follow-up between 1988 and 1991. Results -~ Almost half of this older, educated cohort had used estrogen at some time after menopause, and one third were current users. The age-related decrement in cognitive function was similar for women who were current. past, or never users of estrogen. Ageand education-adjusted comparisons also failed to show any consistent association between performance on tests of cognitive function and baseline, past, current, or never estrogen use: estrogen dose: or duration of use. Among 132 statistical comparisons, only five statistically significant differences were observed, less than the number expected by chance alone. Furthermore, these significant differences occurred with different tests of cognitive function, and in only one instance was the better test score associated with current estrogen use. No biases were identified that could explain these negative results. Conclusions - No compelling or internally consistent evidence for an effect of estrogen on cognitive function was found in these older women. These data do not support the hypothesis that estrogen use after the menopause preserves cognitive function in old age.
ELSEVIER
Maturitas
20 (1994) 53-59
Abstract section 93144016 Biological and eodocriwlogical insights into the possible breast caocer risk from menopausal estrogen replacement therapy Zumoff B. Division of Endocrinology/Metabolism. Department of Medicine, Beth Israel Medical Center, First Avenue at 16th Street, New York, NY 10003 STEROIDS 1993 58/5 (196-204) The question of whether estrogen therapy increases the risk of breast cancer is reviewed. Despite more than 60 epidemiological studies and several meta-analyses over a five-decade period, there is no consensus about the answer. At present, the majority of investigators agree that short-term or medium-term therapy (less than 10 years) poses no measurable risk; some, but not all, investigators feel that there is a modest risk with longterm therapy (more than 15 years). Even this semi-consensus is clouded by the startling and clear-cut finding of the largest ever epidemiological study, the Nurses Surveillance Study, that a small increase in risk with estrogen therapy occurred only in women who also ingested alcohol, itself a known risk factor for breast cancer; women who did not ingest alcohol were at no increased risk. Because virtually none of the other epidemiological studies has controlled for alcohol ingestion, the conclusions of all of them are placed in doubt. To try to shed light on this problem, the 60-year-old studies of Lacassagne et al. on the induction of breast cancer in mice by estrogens were reviewed. They found that the magnitude and timing of the inducing effect of estrogen depended on the spontaneous breast cancer incidence in the mouse strain studied: in no-incidence strains, no cancer was induced; in high-incidence strains, induction was rapid and universal; in low-incidence strains, only a low percentage of animals had cancer induced, and it required prolonged estrogen administration. Because (in animal terms) humans are a low-incidence group, it is to be expected that any increase in breast cancer incidence with estrogen therapy would be modest and would require prolonged administration. This is approximately what is actually observed, but several factors may confound the picture: [1] the role of alcohol ingestion may be important; [2] genetic variability in the capacity to l6-hydroxylate may be important, because increased 16-hydroxylation has been found to be a risk factor for breast cancer; [3] the specific estrogen administered may be important, because different estrogens vary in their ability to be lbhydroxylated; 141 the presence of atypical duct-cell hyperplasia may increase the risk; [5] a personal history of breast cancer or of premenopausal breast cancer in a mother or sister may increase the risk. In
SSDI
03785122(94)00873-6
view of the overwhelming benefits of menopausal estrogen replacement therapy (diminished coronary disease, diminished osteoporosis, and prolongation of life-span, as well as relief of menopausal symptoms), it is concluded that all postmenopausal women should receive it unless they themselves have had breast cancer or a mother or sister has had premenopausal breast cancer.
93147713 Estrogen replacement therapy and cognitive function in older women Barrett-Connor E., Kritz-Silverstein D. Community/Famil,v Medicine Department, University of Cabfornia, 9500 Gilman Dr. San Diego, CA 92093-0607 J. AM. MED. ASSOC. 1993 269120 (2637-2641) Objective - To determine whether replacement estrogen delays or prevents loss of cognitive function in elderly women. Design - A l5-year prospective and cross-sectional study. Setting - Ranch0 Bernardo, a geographically defined community in Southern California. Participants - Eight hundred women (80% of local surviving women from the original Ranch0 Bernardo cohort) aged 65 to 95 years. Estrogen use was evaluated at baseline between 1972 and 1974 and at follow-up between 1988 and 1991. Main Outcome Measures - Twelve tests of cognitive function from eight standard instruments administered at follow-up between 1988 and 1991. Results -~ Almost half of this older, educated cohort had used estrogen at some time after menopause, and one third were current users. The age-related decrement in cognitive function was similar for women who were current. past, or never users of estrogen. Ageand education-adjusted comparisons also failed to show any consistent association between performance on tests of cognitive function and baseline, past, current, or never estrogen use: estrogen dose: or duration of use. Among 132 statistical comparisons, only five statistically significant differences were observed, less than the number expected by chance alone. Furthermore, these significant differences occurred with different tests of cognitive function, and in only one instance was the better test score associated with current estrogen use. No biases were identified that could explain these negative results. Conclusions - No compelling or internally consistent evidence for an effect of estrogen on cognitive function was found in these older women. These data do not support the hypothesis that estrogen use after the menopause preserves cognitive function in old age.