Clustering of adverse drug events: analysis of risk factors for cerebellar toxicity with high-dose cytarabine.

BACKGROUND: Cerebellar toxicity is a severe, therapy-limiting adverse reaction of cytarabine given in high doses. The Food and Drug Administration received a report of an increased frequency of cerebellar toxicity at the University of Wisconsin Hospital and Clinics after a switch from the product (Cytosar-U) manufactured by The Upjohn Co., Kalamazoo, Mich., to the generic form made by Quad Pharmaceuticals, Inc., Indianapolis, Ind. PURPOSE: To compare the incidence of cerebellar toxicity in Quad-treated patients with Upjohn-treated patients, a record-based cohort study was conducted at the University of Wisconsin Hospital and Clinics between January 1986 and August 1989. METHODS: The incidence of cerebellar toxicity was studied in 63 leukemia patients according to the manufacturer of the product received (34 Upjohn only, 25 Quad only, and four both manufacturers). The relative risk of cerebellar toxicity was adjusted for other known risk factors. RESULTS: Patients in the manufacturer-defined treatment groups did not differ significantly with respect to age, sex, type of leukemia, disease stage, calculated creatinine clearance, presence of abnormal liver function tests, or total dose received. The crude relative risk of cerebellar toxicity comparing the Quad product with the Upjohn product was 5.0 (95% confidence interval = 1.8-13.7). Adjustment for potential confounders did not alter the association. Other risk factors for cerebellar toxicity, independent of manufacturer, were age greater than 50 years, type of leukemia, disease stage, total dose greater than or equal to 20 g/m2, abnormal pretreatment liver function, and reduced creatinine clearance. CONCLUSION: This study found a significantly higher incidence of cerebellar toxicity with high-dose cytarabine manufactured by Quad Pharmaceuticals when compared with the incidence of cerebellar toxicity with the Upjohn product. Further research at independent institutions would be necessary to allow generalization of this finding. In addition, our findings suggest that a dose reduction in high-dose cytarabine therapy may be indicated for patients with reduced glomerular filtration rates.

Breast cancer detection in relation to oral contraception.

Analyses of tumor size and breast cancer stage were used to determine whether biased detection of breast cancer could have materially influenced estimates of risk associated with use of oral contraceptives. In a population-based case-control study conducted from 1980-1982, surveillance for breast cancer by breast exams, but not mammography, was found to be strongly linked to use of oral contraceptives. Tumors were slightly smaller and less likely to be late-stage (TNM stage III or IV) in patients who had used oral contraceptives. The net effect of any diagnostic bias on advancing the date of cancer diagnosis, whether from breast exams or other sources, was estimated to be less than 8 weeks. This corresponds to spuriously increasing the risk of early-occurring breast cancer in oral contraceptive users by at most 2.4% (relative risk = 1.024).

A method of pharmacoepidemiologic analysis that uses computerized Medicaid.

A method of pharmacoepidemiologic data analysis that utilizes computerized Medicaid data is presented. A cohort design in which Medicaid enrollees receiving drugs that are normally used to treat similar underlying conditions is described. A period of time in which Medicaid service transactions are evident is required before an individual is eligible for selection into a cohort. Selection of study subjects and descriptions of cohorts are based on Medicaid service histories occurring during the preliminary, prerequisite period. Time at risk is considered to begin after a prescription for a study drug is dispensed and continues until either a refill is dispensed, a prescription for an alternative drug within the same therapeutic class is dispensed, or a predetermined number of days has passed. Subjects are followed forward in time and relevant health care transactions that are suggestive of suspected adverse drug reactions are noted. Incidence densities associated with sequentially ranked prescriptions within sequential courses of therapy are compared. Methods to increase the accuracy of case ascertainment are briefly discussed. Separate validation studies may be used to evaluate the validity of computerized case ascertainment methods and to compensate for misclassification of outcome. The proposed method is intended to provide timely estimates of risk for selected outcomes. For outcomes that cannot be accurately ascertained from computerized data, this method may be useful in determining the feasibility of more customized studies.

Extent of surgery for pelvic inflammatory disease in relation to duration of intrauterine device use.

The risk of a first episode of pelvic inflammatory disease resulting in extensive surgery was examined in relation to duration of intrauterine device (IUD) use in a case-control study. Extensive surgery for pelvic inflammatory disease was defined as hysterectomy or bilateral adenexal surgery, with pelvic inflammatory disease as the only gynecologic discharge diagnosis. Of 690 hospitalized pelvic inflammatory disease patients with no prior history of the disease, 55 had extensive (requiring surgery) disease. These were compared to 2569 controls who were hospitalized with nongynecologic conditions. Current IUD users (within 30 days of admission) were considered to be long-term or short-term users, depending upon whether the same IUD had been used for five or more years or less than five years. Past IUD users and never-users were considered to be nonusers. For long-term users as compared to nonusers, the relative risk of extensive pelvic inflammatory disease was about 5.4; for short-term users as compared to nonusers, the relative risk was only about 1.4. Continuous use of the same IUD for five or more years appears to increase the risk of pelvic inflammatory disease, requiring extensive surgery to a greater extent than use for less than five years.

Oral contraceptive use in women with a family history of breast cancer.

To evaluate the effect of oral contraceptive use on the risk of breast cancer from 20-54 years of age in women with a family history of the disease, we analyzed data from the Cancer and Steroid Hormone Study of the Centers for Disease Control and the National Institute of Child Health and Human Development. For 2 years, beginning December 1980, the study enrolled from eight geographical areas in the United States 4730 women with breast cancer and 4646 controls who were breast cancer-free. For women with a first-degree family history of breast cancer, 554 cases and 280 controls, there was no evidence that use of oral contraceptives, even long-term, contributed to their risk of the disease. Neither total duration of use nor duration of use before first term pregnancy bore any relationship with breast cancer risk. Analyses designed to reveal a potential latent effect also showed no evidence of an adverse effect. For women with a second-degree family history of breast cancer, 777 cases and 595 controls, some isolated elevations in risk were observed for selected subgroups of oral contraceptive users. Detailed analyses of oral contraceptive formulation, the characteristics of the women involved, and the patterns of risk observed by latent period and duration of use suggest that these results, most within the limits of chance variation, are not likely to be a consequence of oral contraception.

Variation of ethinylestradiol blood levels among healthy women using oral contraceptives.

Data concerning ethinylestradiol (EE) blood levels among 93 healthy women using oral contraceptives are presented. Seventy-two per cent of the observed variation in EE blood levels was unexplainable on the basis of time since ingestion of the last oral contraceptive, day of menstrual cycle, race, age, weight, height, blood pressure, cigarette consumption, alcohol consumption, diurnal variation, or lifetime use of oral contraceptives.

PIP: This 2-fold investigation studied 1) the extent to which women vary in blood levels of ethinylestradiol (EE) after ingesting oral contraceptives (OCs) containing similar amounts of EE or mestranol (ME), which is metabolized to EE; and 2) whatever variations might be accountable on the basis of physical, behavioral, or other characteristics. 93 healthy OC users were given either OCs with 50 mcg of ME (84 subjects) of 50 mcg of EE (9 subjects). Linear regression was used to determine relevance of variation in EE blood levels based on hours since pill ingestion, day of menstrual cycle, or any other variables. Hours since OC showed the strongest relationship to log EE, accounting for 25% of the variation. Another 3% could be accounted for by day of menstrual cycle. The remaining 72% of observed variation in EE levels could not be explained in terms of time since ingestion of last OC, day of menstrual cycle, race, age, weight, height, or use-duration of OCs.

Tubal infertility in relation to prior induced abortion.

One hundred twenty-seven women who had been given diagnoses of tubal infertility between 1979 and 1981 in King County, Washington, yet previously had been pregnant, were interviewed to determine their prior history of legally induced abortion. Their responses were compared with those of 395 women who conceived a child at the same time the infertile women began their unsuccessful attempt to become pregnant. In making the comparison, we adjusted for the effects of variables that in this population were related both to having an induced abortion and to the occurrence of infertility, i.e., age, number of prior pregnancies, number of sexual partners, cigarette smoking habits, Dalkon Shield (A. H. Robins Company, Richmond, VA) use, and whether the woman worked outside the home. The risk of tubal infertility in women who had had an induced abortion was not increased above that of other women (relative risk, 1.15; 95% confidence interval, 0.70 to 1.89). For women with two or more abortions, the relative risk was 1.29 (95% confidence interval, 0.39 to 4.20). When only the most recent pregnancy was considered, the relative risk was 1.19 (95% confidence interval, 0.72 to 1.97). Our results suggest that legal abortion, as performed during the past decade in the United States, does not carry an excess risk for future tubal infertility.

PIP: 127 women who had been given diagnoses of tubal infertility between 1979-81 in King County, Washington, yet previously had been pregnant, were interviewed to determine their prior history of legally induced abortion. Their responses were compared with those of 395 women who had conceived a child at the same time the infertile women began their unsuccessful attempt to become pregnant. In making the comparison, the authors adjusted for the effects of variables that in this population were related to both having an induced abortion and to the occurrence of infertility; i.e., age, number of prior pregnancies, number of sexual partners, cigarette smoking habits, Dalkon Shield (A.H. Robins Co., Richmond, Virginia) use, and whether the woman worked outside the home. The risk of tubal infertility in women who had had an induced abortion was not increased above that of other women (relative risk, 1.15; 95% confidence interval, 0.70-1.89). For women with 2 or more abortions, the relative risk was 1.29 (95% confidence interval, 0.39-4.20). When only the most recent pregnancy was considered, the relative risk was 1.19 (95% confidence interval, 0.72-1.97). Results suggest that that abortion, as performed during the past decade in the U.S., does not carry an excess risk for risk tubal infertility.

Oral contraceptives and premenopausal breast cancer in nulliparous women.

Characteristics of women with potential for modifying the relationship between use of oral contraceptives (OCs) and the risk of premenopausal breast cancer were investigated using data from the Cancer and Steroid Hormone study, a population-based, case-control study conducted in eight geographic areas of the United States. Cases consisted of 2945 women who were premenopausal and 20-54 years of age when breast cancer was diagnosed between December 1, 1980, and December 31, 1982; controls consisted of 2646 women with no history of breast cancer who were also premenopausal and 20-54 years of age when selected during the same period. Results are presented with the cases and controls divided into eight groups on the basis of age at diagnosis on selection (20-44, 45-54), parity (0, greater than or equal to 1), and age at menarche (less than 13, greater than or equal to 13). Among nulliparous women who experienced menarche before age 13, the relative risk of developing breast cancer in the age interval 20-44 years is estimated to be 1.0 for never-users of OCs (reference), 1.3 for greater than 0-3 years of use (95% confidence intervals 0.7-2.4), 1.3 for 4-7 years (95% CI 0.7-2.6), 2.7 for 8-11 years (95% CI 1.2-6.3), and 11.8 for 12 years or longer (95% CI 1.4-95.7). OC use is not significantly related to the risk of breast cancer among women in any of the other seven groups. These findings suggest that prolonged OC use may accelerate the onset of breast cancer for a small group of susceptible women while having no appreciable impact on overall risk. The findings should be regarded as tentative, however, since they are based upon numerous comparisons and because age of menarche was stratified at 13 years to highlight the concentration of breast cancer risk apparent in our data.

Breast cancer risk in relation to type of estrogen contained in oral contraceptives.

We report analyses designed to address the recent hypothesis that women who use combination-type OCs containing ethinylestradiol (EE) are at increased risk of breast cancer before age 45, if use of such OCs occurs prior to first term pregnancy (FTP). Our findings, based on data from 1679 cases and 1689 controls, 20-44 years of age, from the population-based Cancer and Steroid Hormone Study, are against the hypothesis. The relative risk of breast cancer by duration of exclusive use prior to FTP of OCs containing EE is estimated to be 1.0 (1-12 months EE use), 1.2 (13-48 months EE use), and 0.9 (49+ months EE use). There was no evidence of a latent effect. Among parous women with 49+ months exclusive use prior to FTP of EE-containing OCs, the relative risk of breast cancer was estimated as 0.9 (0-4 years after FTP) and 0.6 (5-9 years after FTP). Among nulliparous women with 49+ months exclusive use of EE-containing OCs, the relative risk of breast cancer was estimated as 1.0 (0-4 years since first use), 0.7 (5-9 years since first use), and 1.1 (10-14 years since first use). With regard to exclusive use of OCs containing mestranol, parous women who used such preparations long-term before their FTP showed no alteration of breast cancer risk, even 15 years or more after pregnancy. Nulliparous women with exclusive use of ME-containing OCs did show elevations in breast cancer risk, but the magnitude of risk in relation to duration of use and latent interval shows no pattern that suggests a cause-effect relationship.

PIP: This report present analyses addressing the recent hypothesis that women who use combination-type oral contraceptives (OC) containing ethinylestradiol (EE) are at increased risk of breast cancer before age 45, if they use OCs before the 1st term of pregnancy (FTP). Our findings, based on data from 1679 controls, 20-44 years of age, from the population-based Cancer and Steroid Hormone Study, are against the hypothesis. The relative risk of breast cancer by duration of exclusive use prior to FTP of OCs containing EE is estimated to be 1.0 (1-12 months EE use), 1.2 (13-48 months EE use), and 0.9 (49+ months EE use). There was no evidence of a latent effect. Among parous women with the 49+ months exclusive use prior to FTP of EE-containing OCs, the relative risk of breast cancer was estimated as 0.9 (0-4 years after FTP) and 0.6 (5-9 years after FTP). Among nulliparous women with 49+ months exclusive use of EE-containing OCs, the relative risk of breast cancer was estimated as 1.0 (0-4) years since 1st use), 0.7 (5-9 years since 1st use), and 1.1 (0-4 years since 1st use). With regard to exclusive use of OCs containing mestranol (ME); parous women who used such preparations long-term before their FTP showed no alteration of breast cancer risk, even 15 years or more after pregnancy. Nulliparous women with exclusive use of ME containing OCs did show elevations in breast cancer risk, but the magnitude of risk in relation to duration of use and latent interval show no pattern that suggests a cause-effect relationship.

Progestins and oral contraceptive-induced lipoprotein changes: a prospective study.

In order to determine the effects on plasma lipoproteins of oral contraceptives containing progestins with varying androgenic potency, 136 healthy women were randomized into 3 groups and followed prospectively for one year while receiving either 50 mcg ethinyl estradiol and 1.0 mg ethynodiol diacetate (EED), 50 mcg ethinyl estradiol and 1.0 mg norethindrone acetate (ENA), or 50 mcg ethinyl estradiol and 0.5 mg d-1 norgestrel (ENG). Comparison was made to a self-selected group of 50 women using alternative means of contraception. Plasma cholesterol increased by 7-9% and triglycerides by 32-57% in all 3 groups (p less than 0.05). ENG use resulted in other significant lipoprotein changes including an 18% increase in low density lipoprotein cholesterol (LDL-C), a 13% fall in high density lipoprotein cholesterol (HDL-C) and a 27% decline in HDL2 cholesterol (HDL2-C) (p less than 0.05). Apoprotein A-I (Apo A-I) increased by 9% with ENA and by 11% with EED (p less than 0.05), but did not change significantly with ENG. This prospective study demonstrates that in oral contraceptive agents with identical estrogen, progestins with different androgenic potency produce major and different changes in plasma lipoproteins.

PIP: In order to determine the effects on plasma lipoproteins of oral contraceptives containing progestins with varying androgenic potency, 136 healthy women were randomized into 3 groups and followed prospectively for 1 year while receiving either 50 mcg ethinyl estradiol and 1.0 mg ethynodiol diacetate (EED), 50 mcg ethinyl estradiol and 1.0 mg norethindrone acetate (ENA), or 50 mcg ethinyl estradiol and 0.5 mg d-1 norgestrel (ENG). Comparison was made to a self-selected group of 50 women using alternative means of contraception. Plasma cholesterol increased by 7-9% and triglycerides by 32-57% in all 3 groups. ENG use resulted in other significant lipoprotein changes including an 18% increase in low density lipoprotein cholesterol, a 13% fall in high density lipoprotein cholesterol and a 27% decline in high density lipoprotein-2 cholesterol. Apoprotein A-1 increased by 9% with ENA and by 11% with EED, but did not change significantly with ENG. Khis prospective study demonstrates that in oral contraceptive agents with identical estrogen, progestins with different androgenic potency produce major and different changes in plasms lipoproteins.

Dietary iodine and risk of breast, endometrial, and ovarian cancer.

Geographic differences in the rates of breast, endometrial, and ovarian cancer appear to be inversely correlated with dietary iodine intake. Endocrinological considerations suggest that a low dietary iodine intake may produce a state of increased effective gonadotrophin stimulation, which in turn may produce a hyperoestrogenic state characterised by relatively high production of oestrone and oestradiol and a relatively low oestriol to oestrone plus oestradiol ratio. This altered endocrine state may increase the risk of breast, endometrial, and ovarian cancer. Increasing dietary iodine intake may reduce the risk of these cancers.

Estrogen therapy and endometrial carcinoma.

PIP: Dr. Boyd C. Quint recently presented important data regarding the relationship of estrogen therapy to the risk of endometrial carcinoma, but the data seem to have been inappropriately analyzed. Dr. Quint studied 291 postmenopausal women who received primary treatment for endometrial carcinoma at the Swedish Hospital Medical Center in Seattle, Washington between 1960 and 1973. The 1st step in Quint's analysis was a determination of the ratio of new endometrial carcinoma cases to the total "major gynecologic operations" for the intervals 1960-1966 and 1966-1973. This ratio was observed to increase from about 2% for 1960-1966 to about 4% for 1966-1973, but this change -- while statistically significant - cannot be used to support the hypothesis that the absolute incidence of endometrial carcinoma increased from the 1st to the 2nd interval. The 2nd step in the analysis was a determination of the incidence of nulliparity, obesity and hypertension, and/or diabetes and prior estrogen therapy among the endometrial carcinoma patients 1st treated in each of the 2 intervals. The prevalence of the constitutional stigma commonly associated with endometrial carcinoma, obesity and hypertension and/or diabetes can be seen to be significantly lower among the 203 patients 1st treated between 1966 and 1973 than among the 88 patients 1st treated between 1960 and 1966. Conversely, the prevalence of prior estrogen therapy is seen to be much higher. Data indicating that approximately 50% of Seattle area women had used or were using estrogen therapy by 1973 to 1974 - median use of about 10 years - are in press. Quint's data do support the hypothesis that estrogen therapy may be an etiologic factor among the more recent cases of endometrial carcinoma.^ieng

Prepubertal gynecomastia during growth hormone therapy.

We report 22 cases of prepubertal gynecomastia diagnosed during growth hormone (GH) treatment. The age and dose range were 2 to 12 years and 0.18 [corrected] to 0.3 mg/kg per week, respectively. In most of the patients, gynecomastia appeared between 0.5 and 7 months after GH was started. Three boys were using drugs other than GH. This condition appears to be self-limited and benign.

Exposure opportunity in epidemiologic studies.

We have shown that consideration of exposure opportunity is crucial to planning epidemiologic investigations because it focuses studies on questions of relevance, it helps to identify links to variables that can distort the assessment of an exposure's effect, and the cost of investigation can be reduced by the use of appropriate eligibility criteria. The reasons given by Poole for ignoring exposure opportunity are based on misleading claims of increased precision, disregard for probable confounding by factors related to exposure opportunity, and failure to consider realistically the cost of obtaining data on persons whose experience is irrelevant to the issues under investigation.

PIP: Poole's examples in his article on the relationship of exposure opportunity to validity and efficiency of case-control studies clearly demonstrate that the validity of a case-control study is not affected by inclusion or exclusion of persons who had no opportunity for exposure, provided that opportunity for exposure is not associated with other factors that alter the risk of the study disease. With regard to validity, in other words, exposure opportunity is important only insofar as it indicates confounding by some other factor. On the basis of Poole's reasoning, one might be led to think that opportunity for exposure is irrelevant to planning case-control studies. It will be shown, to the contrary, that consideration of exposure opportunity is important not only for the design of case-control studies but also for epidemiologic studies generally. The rationale for restricting a study to persons with an opportunity for exposure is principally a matter of focus, i.e., designing studies to answer questions of relevance and importance. Thus, despite Poole's suggestion to the contrary, one does not study the effects of oral contraceptive (OC) use in men when the real issue is the risk of disease in women who choose this contraceptive method. Poole's assertion that "exposure opportunity does not seem to concern researchers when they conduct follow-up studies" is clearly wrong. The prototypic followup study is a study that employs randomization to ensure that opportunity for exposure is identical for all participants. Observational followup studies, when appropriately designed, apply enrollment criteria based upon exposure opportunity to approximate the effects of randomization. Examples are cited to show that the target population for epidemiologic studies consists of persons at risk of both the study exposure(s) and disease(s). As a consequence, opportunity for exposure should be a criterion for enrollment of subjects. In case-control studies, opportunity for exposure, like other eligibility criteria, must be applied equally to cases and controls in order that they be sampled from the same target population. In practice, confounding by factors related to exposure opportunity is common. Any exposure that involves an element of choice should be considered a candidate for confounding. Poole's arguments for studying sterile women, based on considerations of "precision" are misleading. Even if a study's precision were "improved" by including subjects with no opportunity for exposure, investigation still should be restricted to persons with exposure opportunity, first, by reason of properly focusing the study, and second, to avoid the possibility that the assumption of no confounding by exposure opportunity might be wrong. Poole exaggerates the practical difficulties of determining exposure opportunity and underestimates its value in avoiding wasted effort. Consideration of exposure opportunity is crucial to planning epidemiologic investigations because it focuses studies on questions of relevants, helps to identify links to variable that can distort the assessment of an exposure's effect, and it reduces the cost of investigation.

Oral contraceptive use and the risk of breast cancer in women with a "prior" history of benign breast disease.

PIP: This article suggests that an improper definition of prior history of benign breast disease may be responsible for research results that show an increased risk of breast cancer among oral contraceptive (OC) users with such a history. It is maintained that women who developed fibrocystic breast disease in the 1960s-late 1970s despite longterm use of OCs were intrinsically at greater risk of breast cancer than nonusers who developed fibrocystic disease. Thus, it is improper in epidemiologic studies of OC use and the risk of breast cancer to define a prior history of fibrocystic disease as prior to the development of breast cancer or to corresponding reference ages of women without breast cancer. Rather, prior history should be defined as prior to the use of OCs. The article further analyzes the 3 major case-control studies of breast cancer that developed before 1978 that have suggested OC use increases the risk of breast cancer in women with a prior history of benign breast disease. In the 1st study, by Paffenbarger et al, the operational definition of prior history of benign breast disease appears to be prior to hospitalization for breast cancer. In the 2nd study, by Lees et al, a prior history was defined as prior to presentation at the clinic. In the 3rd study, by Brinton et al, a prior history of benign breast disease was defined as prior to the 1st screening. When stratification or adjustment for prior history of benign breast disease is restricted to disease that develops prior to any OC use, the epidemiologic studies fail to show that women with existing benign breast disease who initiate OC use alter their risk of developing breast cancer.^ieng

Ectopic pregnancy and tubal ligation.

PIP: We have read the article "High rate of ectopic pregnancy following laparoscopic tubal coagulation failures," by McCausland (American Journal of Obstetrics and Gynecology 136: 95, 1980), with considerable interest. While we do not underestimate the grave clinical problems presented by unrecognized ectopic pregnancy among women with earlier tubal ligation, we question Dr. McCausland's interpretation of data collected from the literature. The data which were presented in Tables 1 and 2 of the article do not indicate a higher incidence of ectopic pregnancy for laparoscopic tubal coagulation versus nonlaparoscopic tubal ligation. Actually, these data strongly suggest that the occurrence of ectopic pregnancies is the same for the 2 procedures: 13 ectopic pregnancies reported for 13,909 nonlaparoscopic tubal ligations (9.3/1000); 23 ectopic pregnancies observed for 23,238 laparoscopic tubal coagulations (9.9/10,000). What is different is the occurrence of intrauterine pregnancy: 93/13,090 or 66.9/10,000 for the nonlaparoscopic procedures and 22/23,238 or 9.5/10,000 for the laparoscopic procedure. (seen in tabular form) In summary, the risk of ectopic pregnancy appears very similar for nonlaparoscopic tubal ligaroscopic tubal coagulation, while the risk for intrauterine pregnancy appears lower for the laparoscopic procedure. However, since it is not established that the 2 groups of women were observed for equal periods of time, this conclusion is somewhat tentative. What is described by Dr. McCausland as the incidence of ectopic pregnancy (12.3% for nonlaparoscopic tubal ligation and 51% for laparoscopic tubal coagulation) is actually the proportion of failures which were ectopic. As has been demonstrated above, this statistic is quite misleading as an indicator of true risk. Since both laparoscopic tubal coagulation and other laparoscopic techniques are increasingly utilized in female sterilization, another key issue is whether certain of these laparoscopic procedures carry lower risks of later pregnancy than others. Additional data will be required to settle this issue.^ieng

Characteristics of menopausal women: a survey of King and Pierce counties in Washington, 1973-2974.

Age-specific menopause rates, frequency and duration of menopausal estrogen use, and characteristics of users and non-users of menopausal estrogen therapy are presented for the population of King and Pierce counties in the state of Washington from 1973-1974 survey data. Age-specific menopause rates do not differ substantially from rates derived from data from the 1960-1962 US Health Examination Survey, although women over 50 years of age were more likely to report operative menopause in the present study than in the Health Examination Survey. The estimated frequency of menopausal estrogen use of over 3 months' duration in the population was 51%; this is in contrast to an estimated 26% rate of severe menopausal symptoms. Median use of menopausal estrogen therapy was over 10 years. Estrogen users were younger than non-users and reported more formal education. More users had had difficulty with severe menopausal symptoms and more had had a hysterectomy.

PIP: In response to the growing role of estrogen therapy in the lives of menopausal women and the unanswered questions concerning it, a survey of menopausal women residing in King and Pierce counties in Washington - with respect to menopausal characteristics and estrogen treatment - was conducted in 1973-1974. 487 women met the criteria - menstrual periods had stopped or had begun to stop. Of these, 173 (36%) reported having used estrogens and 280 (57%) reported no estrogen use. The 7% who gave an answer other than yes or no were excluded. From each of the 2 remaining groups, 100 women were randomly selected. All women interviewed in person or by telephone were asked for permission to examine their ambulatory medical care records. Age-specific menopause rates do not differ substantially from rates derived from data from the 1960-1962 U.S. Health Examination Survey, although women over age 50 were more likely to report operative menopause in the present study than in the Health Examination Survey. this is in contrast to an estimated 26% rate of severe menopausal sysmptoms. Median use of menopausal estrogen therapy was over 10 years. Estrogen users were younger than non-users and reported more formal education. More users had had difficulty with severe menopausal symtoms and more had had a hysterectomy.