Catherine Allen

The women's health initiative recruitment methods and results

One of the most challenging aspects of the Women’s Health Initiative (WHI) was the recruitment of more than 161,000 women for this long-term prevention trial and observational study. The WHI had many enrollment goals that made recruitment efforts formidable (1). These included the recruitment of postmenopausal women, a group seldom targeted for clinical trials; enrolling minority groups in at least the same proportion as they existed in the general population; and enrolling women willing to participate in a long-term (8–12 year) study. The success of the WHI in meeting these goals can be attributed to several factors: the experience gained from prior studies, such as the National Cancer Institute (NCI)-sponsored Women’s Health Trial (2), the subsequent Women’s Health Trial Feasibility Study in Minority Populations (3), and the Postmenopausal Estrogen/Progestin Interventions Trial (4); detailed planning by the WHI investigators; the dedication of recruiters, staff, and investigators at the clinical centers; and, a social and political climate that enhanced women’s interest in health research. Prior to the WHI, few large-scale prevention or clinical trials focused on postmenopausal women. Indeed, until recently, relatively little emphasis was placed on the recruitment of women of any age into such studies (5). However, during the last decade, a number of forces have come together to change this situation. The stance that women

Prevalence and Treatment of Menopausal Symptoms Among Breast Cancer Survivors

Women diagnosed with breast cancer often experience early menopause secondary to treatment effects, yet physicians may be reluctant to prescribe hormone replacement therapy (HRT) because of the potential increased risk of recurrence. To assess the burden of menopausal symptoms, HRT use, and alternative treatments in recent breast cancer survivors, a population-based, case-control study was conducted among breast cancer survivors and age-matched controls. Wisconsin women 18-69 years old with a new diagnosis of breast cancer 8-11 months prior to interview (n = 110) and control subjects randomly selected from population lists (n = 73) responded to a standardized telephone questionnaire that elicited information on menopausal symptoms, estrogen and alternative therapies (prescription medications, vitamins, herbal preparations, soy products, acupuncture, chiropractic) used to alleviate symptoms. We used multivariate logistic regression to obtain odds ratios and 95% confidence intervals (CI) for symptoms of menopause, use of estrogen, and use of alternative therapies. Breast cancer survivors were 5.3 (95% CI 2.7-10.2) times more likely to experience symptoms, 25 (95% CI 8.3-100) times less likely to use estrogen, and 7.4 (95% CI 2.5-21.9) times more likely to use alternatives than controls. Soy, vitamin E, and herbal remedies were the most common alternative therapies reported by participants; use was greater in cases compared to controls. Most soy users reported increasing soy products specifically to reduce the chances of a diagnosis of recurrent breast cancer. Among cases, tamoxifen users (n = 62) reported a higher prevalence of symptoms and a higher prevalence of alternative treatments. This is the first population-based survey of menopausal symptoms and treatments that compares breast cancer cases with disease-free controls. Cases are both more likely to experience menopausal symptoms and less likely to use HRT than controls. Instead, cases treat menopausal symptoms with vitamin E and soy products, even though the safety and efficacy of these therapies are unproven. The increased use of soy products in this population has not been previously documented.

Risk of Cardiovascular Disease by Hysterectomy Status, With and Without Oophorectomy The Women’s Health Initiative Observational Study

Background—Cardiovascular disease (CVD) is a leading cause of morbidity and mortality in women and may vary by hysterectomy (or oophorectomy) status. This study compared CVD risk factors and rates between postmenopausal women who had and had not undergone hysterectomy, with or without oophorectomy. Methods and Results—This analysis was conducted on 89 914 women in the Women’s Health Initiative (WHI) Observational Study. Participants reported demographic characteristics, medical history, dietary habits, physical activity, medications, and previous hysterectomy (with or without oophorectomy). Baseline weight, height, waist circumference, and blood pressure were measured. CVD events were ascertained during 5.1 years of mean follow-up and adjudicated with standard criteria. Black, Hispanic, and American Indian women had higher rates of hysterectomy than white women (52.9%, 44.6%, and 49.2% versus 40.0%, respectively), and Asian/Pacific Islander women had lower rates (33.8%). Women with a hysterectomy (regardless of oophorectomy status) had an adverse risk profile at baseline compared with women with no hysterectomy, including a higher proportion of hypertension, diabetes, high cholesterol, obesity, and lower education, income, and physical activity (all P<0.01). Total mortality and fatal and nonfatal CVD were higher among women with a hysterectomy. Hysterectomy (regardless of oophorectomy status) was a significant predictor of CVD (HR: 1.26, P<0.001). After adjustment for demographic variables and CVD risk factors, the effect was reduced and nonsignificant. Conclusions—Women with a hysterectomy had a worse risk profile and higher prevalence and incidence of CVD in this cohort. Multivariate models suggest that hysterectomy is not the major determinant of this outcome; rather, CVD risk may be due to the more adverse initial risk profile of women who had undergone hysterectomy.

Predictors, prodromes and incidence of postpartum depression

The purpose of this study was to determine the incidence of clinically significant depression occurring between 7 and 4 months postpartum and to investigate whether somatic complaints, subsyndromal depressive symptoms, or birth-related concerns among non-depressed women at 1 month were predictive of postpartum depression. This is a prospective cohort study of 465 women from the Wisconsin Maternity Leave and Health Project (WMLHP). Women who were not depressed at 1 month postpartum were reassessed 3 months later for depression occurring at any time in the interval between 1 and 4 months postpartum. Depression was defined as either meeting the criteria for major depression on the National Institute of Mental Health (NIMH) Diagnostic Interview Schedule (DIS) or scoring above 15 on the Center for Epidemiologic Studies Depression Scale (CES-D). Physical symptoms were assessed by an adapted Health Responses Scale. Other measures were developed specifically for the WMLHP. Of 465 women, 27 (5.8%) became clinically depressed between 1 and 4 months postpartum. In a logistic regression analysis, four variables (maternal age, depression during pregnancy, thoughts of death and dying at 1 month postpartum, and difficulty falling asleep at 1 month postpartum) were predictive of depression at 4 months postpartum. Breast-feeding, mode of delivery, family income, parity and mother‘s education did not predict depression. The existence of subsyndromal depressive symptoms, particularly thoughts of death and dying, may represent a prodromal phase of depression and should alert clinicians to the possibility of future postpartum depression. Women with a history of depression during pregnancy should be monitored for signs of postpartum depression for a minimum of 4 months. Obstetricians are in a unique position during the postpartum check-up to screen women for these predictors of future postpartum depression and possibly to avert the development of a clinically significant depressive episode.

Risk of Diabetes in Siblings and Other Relatives of IDDM Subjects

The risk of insulin-dependent diabetes mellitus (IDDM) was examined in siblings of an unselected population (n = 194) of newly diagnosed diabetic individuals <30 yr old. From 1 July 1984 to 30 June 1987, diabetic subjects (proband) identified within a geographically defined area of southern Wisconsin were studied. IDDM occurred among siblings of probands in 13.5% of families and was associated with proband age at diagnosis. The highest risk was found for diabetic subjects <10 yr old at diagnosis (P = 0.04). We did not find an association between sibling IDDM and proband sex, HLA-DR3/4, duration of symptoms, or ketosis at diagnosis. In addition, the odds ratio (OR) for the association of IDDM in the proband with IDDM in parents and second- and third-degree family members was examined by case-control methodology. Diabetic subjects were matched to two types of control subjects (friends and general population) by age stratum and sex. The OR for IDDM was not increased significantly if parental IDDM or non-insulin-dependent diabetes mellitus (NIDDM) was reported. However, there were very few parents with diabetes among diabetic or control subjects. In 6.4% of diabetic subjects, one parent had IDDM, 54% of whom were fathers. In 4.3% of diabetic subjects, one parent had NIDDM, and 57.1% of these were fathers. The OR for IDDM was significantly increased if second- and/or third-degree relatives had IDDM (OR diabetic subjects vs. general population 2.33 [P < 0.05]) or NIDDM (OR diabetic subjects vs. friends 2.05 [P < 0.01]). We conclude that the increased risk of sibling IDDM for younger probands suggests variation in etiological factors by family.

Incidence and differences in urban-rural seasonal variation of Type 1 (insulin-dependent) diabetes in Wisconsin

SummaryIn a hospital-based records study of Type 1 (insulin-dependent) diabetes mellitus among persons aged 0 to 29 years in two Wisconsin, USA counties (1970–79), the age-adjusted yearly incidence rate for white males (16.4/100,000) was significantly higher than for white females (11.6/100,000) (p = 0.006). Overall age-adjusted rates are similar to rates previously reported for the United States and the northern European countries of Denmark and Norway. Seasonal variation in diagnosis was found for total cases and males aged 10 to 19 years. A striking difference also was found in seasonal diagnosis between urban and rural cases. A diagnosis peak in the third and fourth quarter among rural cases contrasted with even quarterly distribution among urban cases. In addition, 52% of rural male cases aged 10 to 19 years were diagnosed during the fourth quarter while no seasonal pattern occurred among urban males the same ages. These findings identify subgroups for focus of future etiologic investigations.

Long-Term Hyperglycemia Is Related to Peripheral Nerve Changes at a Diabetes Duration of 4 years

OBJECTIVE To examine longitudinal hyperglycemia and peripheral nerve responses in a population-based incident cohort. RESEARCH DESIGN AND METHODS A sample from an incident cohort of young people was comprehensively followed from diagnosis of IDDM. Participants were invited to submit blood samples three times per year for central testing of GHb. During their 4th year of diabetes, nerve conduction studies were performed on the median sensory and motor, peroneal motor, and sural sensory nerves. Relationships between mean GHb and nerve latencies, velocities, and amplitudes were explored. RESULTS GHb was positively related to all nerve latencies and negatively related to all nerve velocities. The relationships between mean GHb and nerve conduction latencies and velocities differed by sex for the peroneal nerve latency (β = 0.17 male subjects, β = −0.01 female subjects; P < 0.001). Pubertal participants had lower velocities and longer latencies than prepubertal participants (β = 0.37; P = 0.05 peroneal latency), after adjustment for GHb, height, and extremity temperature. Sensory and motor nerve amplitudes were related to GHb, and these relationships did not differ by sex. CONCLUSIONS Our study indicates that sustained hyperglycemia is related to functional changes, at the minimum, in peripheral sensory and motor nerve conduction at a diabetes duration of 4 years. Our findings are consistent with a dying-back neuropathy, and there is some suggestion that chronic hyperglycemia may be more detrimental to nerves in male subjects than in female subjects.

Glycemic Control and Peripheral Nerve Conduction in Children and Young Adults After 5–6 Mo of IDDM

Objective A cohort of people (n = 86) was examined in the first few months after insulin-dependent diabetes mellitus (IDDM) diagnosis to evaluate the effect of hyperglycemia on nerve conduction velocities and latencies. Research Design and Methods Unselected cases with IDDM, who were 6–29 yr of age, were identified at diagnosis from a large, geographically defined area of southern Wisconsin. Peripheral nerve conduction was measured on a sample from this cohort. Results Peroneal nerve conduction velocity was significantly inversely related to glycosylated hemoglobin (P <0.05, age and height adjusted). All other nerve conduction velocities and latencies (median motor, median sensory, and sural) showed the same tendency, but the associations were not statistically significant. Twenty-four-hour urine C-peptide and duration of diabetes (3–11 mo) were not consistently related to nerve conduction parameters after controlling for age and height. Conclusions These findings suggest that as early as 5–6 mo after diabetes diagnosis, and at a time frequently characterized by partial remission of IDDM, hyperglycemia has a role in the acute slowing of nerve conduction velocity. Other factors such as residual endogenous insulin production do not appear to influence these early changes.

Glycemic Control in Early IDDM

OBJECTIVE A cohort (n = 277) was followed from diabetes diagnosis to evaluate longitudinal glycemic control, urinary C-peptide levels, and certain features of diabetes self-management. RESEARCH DESIGN AND METHODS Unselected cases with IDDM, who were < 30 yr of age, were identified at diagnosis from a 28-county area in Wisconsin. Subjects were asked to submit blood every 4 mo for GHb testing, to report aspects of diabetes self-management every 6 mo, and to collect a 24-h urine specimen 4 mo after diagnosis. RESULTS In the 1st yr of diabetes, the rate of increase (0.23%/mo) in GHb was significant for the cohort (P < 0.001) and for almost all age and sex subgroups. In the 2nd yr, there was no significant rate of increase for the cohort as a whole (P > 0.10). Adolescent males (10–19 yr of age) had a mean GHb level for year 2 higher than males of other age-groups and higher than female adolescents (P < 0.001). Adolescent males had a significant rate of increase in GHb for year 2 (P = 0.02), unlike all other age and sex subgroups. Adolescents had higher initial 24-h urine C-peptide levels than children < 10 yr of age (P < 0.01). During the 2nd yr of diabetes, the percentage of adolescent males reporting three or more insulin injections/day was lower than any other subgroup. CONCLUSIONS These data-suggest that glycemic control stabilizes during the 2nd yr of IDDM, except in adolescent males, and that this may be due partly to aspects of self-management.

Chronic disease: #22 Does increase in blood pressure predict increase in urinary albumin excretion rate in the first 9 years of type 1 diabetes?

PURPOSE: The prevalence of hypertension and microalbuminuria (MA) has been described for individuals with type 1 diabetes of many years duration, but less is known about the early years of this condition. This study sought to determine the frequency of MA (⩾20 mcgs/min), a marker for early diabetic kidney disease, and hypertension in the first 9 years of diabetes, and to determine if changes in blood pressure precede kidney disease. METHODS: This population-based cohort includes 517 predominantly white individuals <29 years of age followed prospectively from diagnosis of type 1 diabetes. An average of four blood pressure and UAE measurements were collected over a 9-year period. Early (the first 5 years of diabetes) and late (6–9 years) frequencies, within-individual means and slopes were determined for blood pressure and urinary albumin variables. Multivariable linear regression was used to compare within individual means and slopes. RESULTS: Early and late mean urinary albumin excretion (UAE) rates were 8.36 and 9.36 mcgs/min, respectively. In years 6–9, 6.9% of individuals had MA, 3.1% had systolic and 6.8% had diastolic blood pressures considered hypertensive according to age and height standardized data. The rate of hypertension in this cohort is similar to the general population as described by the Working Group Report from the National High Blood Pressure Education Program. Early increased diastolic blood pressure (slope) marginally significantly predicted late increased UAE (slope) in males, but not females, after adjustment for age. CONCLUSION: Microalbuminuria and hypertension are infrequent in the first 9 years of diabetes. Microalbuminuria is less frequent than expected. The marginal relationship between blood pressure and UAE in males may provide insight into the greater lifetime risk of overt diabetic renal disease observed in males.