Hormonal content and potency of oral contraceptives and breast cancer risk among young women.

Recent use of oral contraceptive pills is associated with a modest risk of breast cancer among very young women. In this US population-based case-control study, we evaluated whether the excess risk associated with recent oral contraceptive use is ubiquitous for all pill types or attributable to specific oral contraceptive preparations. Hormonal content and potency of combination oral contraceptives used for the longest duration within 5 years of interview for breast cancer cases aged 20-44 years (N=1640) were compared with age-matched community controls (N=1492). Women who recently used oral contraceptives containing more than 35 microg of ethinyl oestradiol per pill were at higher risk of breast cancer than users of lower dose preparations when compared to never users (respective relative risks of 1.99 and 1.27, P(trend)<0.01). This relationship was more marked among women <35 years of age, where risks associated with high- and low-dose ethinyl oestradiol use were 3.62 and 1.91 (P(trend)<0.01), respectively. We also found significant trends of increasing breast cancer risk for pills with higher progestin and oestrogen potencies (P(trend)<0.05), which were most pronounced among women aged <35 years of age (P(trend)<0.01). Risk was similar across recently used progestin types. Our findings suggest that newer low-potency/low oestrogen dose oral contraceptives may impart a lower risk of breast cancer than that associated with earlier high-potency/high-dose preparations.

Risk of breast cancer in young women in relation to body size and weight gain in adolescence and early adulthood.

Findings have been inconsistent on effects of adolescent body size and adult weight gain on risk of breast cancer in young women. These relations were examined in a population-based case control study of 1590 women less than 45 years of age newly diagnosed with breast cancer during 1990-1992 in three areas of the US and an age-matched control group of 1390 women. Height and weight were measured at interview and participants asked to recall information about earlier body size. Logistic regression was used to estimate the relative risk of breast cancer adjusted for other risk factors. Women who were either much heavier or lighter than average in adolescence or at age 20 were at reduced risk. Weight gain after age 20 resulted in reduced risk, but the effect was confined to early-stage and, more specifically, lower grade breast cancer. Neither the risk reduction nor the variation by breast cancer stage or grade was explained by the method of cancer detection or by prior mammography history. These findings suggest that relations between breast cancer risk in young women and body weight at different ages is complex and that the risk reduction with adult weight gain is confined to less aggressive cancers.

Intake of food groups and associated micronutrients in relation to risk of early-stage breast cancer.

Epidemiologic studies have evaluated the risk of breast cancer related to dietary fat intake, but only recently have other dietary factors received attention. Frequent intakes of fruit, vegetables and fiber have been associated with low risk of the disease in some studies but results are inconsistent. In a large case-control study of early-onset breast cancer, we evaluated risk related to a variety of food groups, associated micronutrients and non-nutritive constituents. Cases treated with chemotherapy appeared to have altered reporting of food intake and were excluded. Analyses were restricted to 568 cases with in situ and localized disease and 1,451 population-based controls. Reduced risks were observed for high intake of cereals and grains [odds ratio (OR) = 0.84, 95% confidence interval (CI) = 0.6-1.1 for highest compared with lowest quartile], vegetables (OR = 0.86, 95% CI = 0.6-1.1), beans (OR = 0.87, 95% CI = 0.7-1.2) and fiber from beans (OR = 0.88, 95% CI = 0.7-1.2). However, no trends of decreasing risk across quartiles of increasing intake were observed. Risk was not associated with dietary constituents related to these food groups including dietary fiber, carotenoids, vitamins A, C and E and folate. Incorporation of information from vitamin supplements did not alter the results for micronutrients. Our data suggest that intakes of cereals and grains, vegetables and beans are associated with minimal, if any, reduction in risk of early-stage breast cancer among young women.

Pregnancy characteristics and maternal risk of breast cancer.

In a population-based case-control study of parous women less than 45 years of age, we evaluated the relations of various pregnancy characteristics to maternal breast cancer risk. Cases (N = 1,239) diagnosed with in situ or invasive breast cancer from 1990 to 1992 in Atlanta, GA, Seattle/Puget Sound, WA, and five counties in central New Jersey, and population controls (N = 1,166) identified by random-digit dialing, were interviewed regarding the details of their pregnancies. We used logistic regression to estimate relative risks (RR) and 95% confidence intervals (CI) and to adjust for breast cancer risk factors. Women who reported nausea or vomiting in their first pregnancy had a slightly lower risk of breast cancer (RR = 0.87; 95% CI = 0.72-1.0). We found no strong or consistent associations for maternal risk related to gestational length, pregnancy weight gain, gestational diabetes, pregnancy hypertension, or gender of the offspring, although we found some evidence for reductions in risk for toxemia (RR = 0.81; 95% CI = 0.61-1.1) and specific sex (RR for female twins vs singletons = 0.48; 95% CI = 0.20-1.3) and timing characteristics of twinning. Overall, these data provide little support for the hypothesis that pregnancy hormone levels are associated with subsequent maternal risk of breast cancer in young women.

Breast cancer risk among women under 55 years of age by joint effects of usage of oral contraceptives and hormone replacement therapy.

OBJECTIVE: To assess effects on breast cancer risk of exposure to both oral contraceptives and menopausal hormones, an increasingly common exposure. DESIGN: A case-control study of breast cancer among women under the age of 55 years in Atlanta, GA involving 1,031 cases and 919 population controls was conducted. RESULTS: Ever use of oral contraceptives was associated with a relative risk of 1.1 (95% 0.9-1.4), whereas the relative risk for hormone replacement therapy was 0.9 (95% CI 0.7-1.2). Seventeen percent of the cases versus 19% of the population controls reported exposure to both agents, resulting in a relative risk of 1.0 (95% CI 0.7-1.4) relative to those unexposed to either preparation. Although there was little variation in risk associated with joint effects by either age or race, there were statistically nonsignificant elevations in risk for this exposure among women who had experienced a natural menopause (relative risk = 2.0, 95% CI 0.7-5.6), were relatively thin (relative risk = 1.5, 0.8-3.0), or who had a first degree relative with breast cancer (relative risk = 2.0, 0.6-7.0). When joint effects of longer term use of both agents were considered, subjects who reported use of oral contraceptives for 10 or more years and hormone replacement for 3 or more years had a relative risk of 3.2 (95% CI 1.4-7.4) compared with nonusers of either preparation. CONCLUSIONS: Although our results must be cautiously interpreted given small numbers within subgroups, they raise concern and emphasize the need for further evaluation on breast cancer risk of the increasingly common exposure to both oral contraceptives and hormone replacement therapy.

Ethnicity and variation in breast cancer incidence.

A breast cancer case-control study in Atlanta and 5 counties of central New Jersey involving interviews with 960 white and 281 black cases younger than 54 years of age enabled assessment of reasons for the varying incidence rates among these 2 ethnic groups. Of interest was why rates of breast cancer are higher among older white women, a trend that is reversed among very young women (<40 years). Calculation of the prevalence of exposure to classic and speculative risk factors and associated relative risks enabled derivation of population attributable risks (PARs) for the various combinations of age and ethnic groups. A higher PAR was derived for older (40-54 years) white (62%) than black (54%) women, which appeared to account for the observed difference in incidence between the 2 ethnic groups. Most of the difference in PARs between older whites and blacks was accounted for by whites having fewer births, later ages at first birth and slightly higher risks associated with reproductive and menstrual factors. Consideration of only well-established breast cancer risk factors showed a PAR among older whites of 57%, an estimate comparable to those previously published. Slightly higher overall PARs were derived when analyses considered several speculative but modifiable risk factors, including years of use of oral contraceptives, body size and alcohol consumption. Many of the analyses among younger women (20-39 years) were limited by available numbers, but it appeared that very little disease occurrence in young black women was associated with the factors studied.

Dietary relationships with early onset (under age 45) breast cancer in a case-control study in the United States: influence of chemotherapy treatment.

Methodologic investigations have addressed selection and recall bias in case-control studies of diet and breast cancer, whereas the effect of disease progression and medical treatment on estimates of dietary intake has been largely overlooked. In a multicenter, population-based case-control study of breast cancer in the United States, 1,588 newly diagnosed cases and 1,451 controls completed a self-administered food-frequency questionnaire. Initial evaluation suggested increased risk related to high intakes of calories, carbohydrates, fat, and protein. All nutrient associations were diminished after adjustment for calories. Evaluation by stage of disease revealed no relation of calories to risk among women with in situ disease, but elevated risks among women with localized (odds ratio [OR] = 1.33, 95 percent confidence interval [CI] = 1.0-1.7 highest cflowest quartile) or regional and distant disease (OR = 1.79, CI = 1.3-2.4). Further evaluation showed that the increased risk associated with calories was restricted to cases who reported having been treated with chemotherapy (OR = 1.66, CI = 1.3-2.1). A gradient of increasing risk with time interval from diagnosis to interview suggested the chemotherapy regimen itself and not necessarily characteristics of tumors requiring this treatment was responsible for the observed increased risk. These results indicate that epidemiologic studies of diet and breast cancer, particularly among young women, should evaluate possible bias related to post-diagnosis influences.

Neonatal tetanus mortality in Veracruz, Mexico, 1989.

This article describes a survey conducted in the State of Veracruz, Mexico, to estimate neonatal tetanus (NNT) mortality. The survey, which entailed visits to 72,720 households, collected data on 8,401 live births and 209 infant deaths occurring between April 1988 and May 1989. Twenty-six of the 209 fatalities conformed to a WHO standard case definition of death from neonatal tetanus. The estimated neonatal tetanus mortality was thus 3.1 deaths per 1,000 live births (95% confidence limits = 1.7, 4.5). Comparison of this rate to reported figures suggests that for every NNT death recorded in Veracruz during the study period, as many as 50 others went unreported. A case-control study nested within the survey was conducted to assess preventable NNT risk factors. Limited information on 13 NNT deaths and 217 controls showed an increased risk for neonates who were delivered at home and whose parents' ethnic background was Mexican Indian. Five of the 13 fatalities had their umbilical cords cut with a domestic or traditional cutting tool such as a reed cane, as compared to none of the 217 controls. The observed vaccine efficacy of 2+ doses of tetanus toxoid was 70% (95% confidence limits = 52, 100). Both the mothers of neonates who died of NNT and their controls missed an average of five opportunities to receive tetanus toxoid. These findings underscore the need to launch a perinatal health program serving Mexico's high-risk populations.

Long term effects of a first pregnancy on the hormonal environment: estrogens and androgens.

An early (but not a late) first pregnancy is known to be protective for breast cancer. This effect might be mediated through a long term change in the hormonal environment caused by the early first pregnancy. To investigate the possibility of such a change we carried out a prospective longitudinal study of serum and urinary estrogens and serum androgens in four groups of women, namely early (age, 18-23 yr) first pregnancy (n = 15), early control (n = 20), late (age, 29-40 yr) first pregnancy (n = 9), and late control (n = 20). The pregnancy groups were studied before (initial visit) and 7-19 months after a first pregnancy (return visit). The control groups were similarly studied, but without an intervening pregnancy. The following were measured: serum estrone (E1), 17 beta-estradiol (E2), estriol (E3), and E1 sulfate; urinary total E1, E2, E3, and glucosiduronates of these three estrogens; and serum testosterone, dehydroepiandrosterone sulfate (DHAS), and dehydroepiandrosterone (DHA). There was no significant change between the initial and return visits in serum E1, E2, E1 sulfate, or any of the urinary estrogens in either pregnancy group or in the corresponding control groups. There was, however, a significant increase in serum E3 between initial and return visits for both pregnancy groups compared with the control values. There was no significant change in serum testosterone. There was a marked significant decrease in both serum DHAS and DHA between initial and return visits in both pregnancy groups compared with the corresponding control group values. There was also a significant increase in the serum E3 to DHA ratio in both pregnancy groups. A cross-sectional study (measuring serum DHAS and DHA only) was then carried out in a series of parous and nulliparous women. The serum DHAS and DHA levels were markedly and significantly lower in parous than in nulliparous women, as expected. There was no significant relationship between serum DHAS or DHA levels and months elapsed (up to 150) since last delivery, indicating that the changes last at least for this period of time. There was no significant relationship between serum DHAS or DHA levels and parity (one to three previous pregnancies), indicating that the changes occur only after a first pregnancy.(ABSTRACT TRUNCATED AT 400 WORDS)

Hypertension detection, treatment, and control in the United States: not as bad as it seems?

A 1982 report from the National Center for Health Statistics presents rates of awareness, treatment, and control among US adult hypertensives. These rates are age-adjusted by the direct method to permit comparisons among three surveys of US adults conducted over 20 years. The choice of a standard population for the age adjustment, however, results in a systematic decrease in the adjusted rates for awareness, treatment, and control. This decrease leads the casual reader of this often quoted report to conclude that awareness, treatment, and control of hypertension are worse than they actually are. An alternative choice for the standard population is suggested when the inference population is hypertensives rather than the general population.

Prolactin and blood pressure responses to perphenazine in human subjects: comparison of the oral and intramuscular routes.

Although several phenothiazines are known to stimulate prolactin (PRL) secretion, only chlorpromazine is in general use for this purpose in humans. However, chlorpromazine has severe sedative and hypotensive effects. Therefore, the effects of perphenazine on human PRL release and on blood pressure were evaluated. Perphenazine was administered orally (8mg) and intramuscularly (5mg and 2mg) to determine the optimal route and dose for evaluating PRL release. The postural hypotensive effect of perphenazine was evaluated with the 2mg intramuscular (IM) dose. The mean time of peak PRL response (hr +/- SD) was significantly shorter (p less than 0.05) for the 5mg IM (1.7 +/- 0.4) than the oral (4.5 +/- 0.6) route. Also, the mean ratio of peak/baseline PRL was significantly greater for the 5mg IM (8.87 +/- 5.69) than the oral (5.12 +/- 2.90) route. The major side-effect produced by perphenazine was drowsiness, which was moderate to severe with the 5mg IM dose. A lower IM dose (2 mg) retained PRL releasing activity, reduced drowsiness, and did not produce hypotension. For clinical testing, intramuscular perphenazine is preferred over oral perphenazine because of the shorter latency period and the higher PRL levels. Intramuscular perphenazine (2 mg) is preferred to chlorpromazine since it did not produce a clinically significant hypotensive effect. This is the first report on the dynamic responses of PRL and blood pressure to intramuscular perphenazine in humans.

Disability labeling vs. rehabilitation rhetoric for the chronically ill: a case study in policy contradictions.

Among persons with chronic renal disease, limited encouragement to use self-care treatment options and easy access to disability income benefits tend to reinforce the concept of disability rather than foster rehabilitation goals. More than 80% of all chronic renal disease patients on dialysis therapy receive treatment in facilities at which they become highly dependent on medical staff, and estimates of unemployment among persons aged 21-59 years suffering from this disease range from 60% to 75%. The authors' data indicate that patients who receive dialysis treatment within facilities experience negative effects on their perceived health status and health locus of control as compared to patients who practice self-care dialysis at home. Although many factors contribute to unemployment among dialysis patients, the availability of disability income benefits seems to act as the most important deterrent to employment. Increasing the emphasis on the rehabilitation of this chronically ill population will require a movement away from disability labeling by providers of care and the patients themselves, as well as adjustment in the dialysis reimbursement system and in the eligibility requirements for disability compensation.

Proficiency testing and standardization of prothrombin time: effect of thromboplastin, instrumentation, and plasma.

Prothrombin times accumulated from ten different proficiency testing surveys were analyzed in terms of a linear additive model described by Evatt et al (Clin Lab Haemat 1981; 3:331-342). Different types of lyophilized plasma samples were used, i.e., plasmas artificially depleted of coagulation factors by adsorption to aluminum hydroxide, and pooled plasmas of patients receiving coumarin drugs. For each plasma sample, both instruments and thromboplastins had a highly significant effect on the prothrombin time. For most instruments and thromboplastins, a good correlation was found between instrument effect or thromboplastin effect and the mean prothrombin time if various artificially depleted plasma samples from a single manufacturer were used. Artificially depleted plasmas from a second manufacturer gave different relationships between estimated effects and mean prothrombin time. Relationships based on lyophilized pooled patient plasmas were different from those of artificially depleted plasmas from either manufacturer. The potential use of the additive linear model for standardization of the prothrombin time in monitoring oral anticoagulant therapy is discussed. Additional studies are required to establish the suitability of this model to define a universal scale for prothrombin times of fresh plasma samples of anticoagulated patients. If suitable, the model can be linked to the International Normalized Ratio proposed by the World Health Organization.

Professional socialization to a research role: interest in research among graduate students in nursing.

This study was conducted to determine whether graduate coursework in research methods and statistics resulted in socializing graduate students in nursing into a research role. Two cohorts, each of about 60 female graduate students in nursing, completed self-administration questionnaires at three different times during their 6 month coursework in research methods and statistics. Subjects indicated significantly more interest in research methods than in statistics (p less than .01), although they rated statistics as valuable to nursing. At the beginning of graduate work, subjects with more work experience in nursing were significantly more interested (p less than .05) in conducting research. Graduate coursework in research methods and statistics produced no significant change in students' interest in doing research in their future nursing careers.

Rehabilitation service needs: physicians' perceptions and referrals.

A descriptive sample survey of physicians showed that 75% of physicians in an urban area had seen at least 1 patient in the past 6 months who was perceived as needing some type of rehabilitation service, whereas only 8% to 17% of physicians saw more than 25 such patients. Of those physicians who saw such patients, about 15% offered some type of rehabilitation service with their own staff. The great majority of physicians referred of rehabilitation service with their own staff. The great majority of physicians referred such patients elsewhere. Some physicians neither offered rehabilitation services nor referred their patients. A descriptive survey of all hospitals and all health/mental health/rehabilitation/vocational rehabilitation clinics showed that 70% of hospitals and 55% of the clinics offered some outpatient rehabilitation services. Home rehabilitation services were offered by very few organizations. It is concluded that physicians probably do not recognize the extent to which their patients need rehabilitation services and, in addition, may not adequately refer their patients for such services.

Physical environment correlates of psychosocial health among urban residents.

This study examines the hypothesis that the psychosocial health of urban dwellers is related to characteristics of the physical environment in which they reside. For each of 100 Atlanta city blocks, 21 indices of deviant psychosocial behavior were obtained, as were 104 physical environment indices (such as landscaping and nearby land use), and 106 sociocultural environment indices (such as population density and income). Factor analysis was used to define relatively independent variables measuring both the physical and sociocultural environment, and regression analysis was used to establish associations of these variables with the indices of psychosocial health. Results indicate that characteristics of the physical environment are about as important as characteristics of the sociocultural environment in explaining variation in psychosocial health.