Alhaji M. Buhari

Urinary markers of estrogen metabolism 2- and 16α-hydroxylation in premenopausal women

Abstract There is considerable scientific interest in whether measurement of the major estrogen metabolites 2- and 16α-hydroxyestrone will shed light on the role of estrogen in the risk of breast cancer. These have been difficult to measure in large numbers because of the need for radiolabeled tracers, but a new assay is able to utilize spot urine samples. The main objective of this study was to assess the reliability of a newly developed enzyme immunoassay (EIA) for the measurement of 2- and 16α-hydroxyestrone in urine samples collected from a large group of healthy premenopausal women enrolled in a clinical trial. A secondary objective was to assess the impact of several factors such as body weight on the urinary estrogen metabolite ratios. The study cohort included 174 women aged 44–50, who were enrolled in the Cardiovascular Risk Factors and Menopause Trial, also referred to as the Womens Healthy Lifestyle Project (WHLP), an ongoing 5-year clinical trial of 535 premenopausal women randomized either to an intensive dietary life-style intervention group or to an assessment-only control group. Measurements of 2- and 16α-hydroxyestrone showed a high intraclass correlation for blind duplicate urine samples ( R = 0.94 and R = 0.80), cross-sectionally and over time ( R = 0.79 and R = 0.62), in this population of healthy premenopausal women. The intervention diet (of 25% of total calories from fat) did not appear to influence the estrogen metabolite ratio. This new estrogen metabolite EIA demonstrates good reliability and thus may be appropriate for use in large epidemiologic studies of estrogen-related diseases. There was no relation between dietary fat reduction, weight loss, and increased exercise and change in the ratio among premenopausal women in this study.

Prevalence of thyroid antibodies among healthy middle-aged women: Findings from the thyroid study in healthy women

Autoimmune thyroiditis is the most common cause of subclinical hypothyroidism in North America, is more common in women than men, and is a risk factor for the development of coronary heart disease (CHD). We measured thyroid-stimulating hormone (TSH) and two thyroid antibodies, thyroid peroxidase and thyroglobulin, in stored sera of the participants (aged 44 to 54 years) of the Healthy Women Study. We selected 254 samples from the premenopausal baseline examination in 1983 to 1985 and from a follow-up examination that occurred an average of 5.7 years later (range, 3 to 7.7 years). At follow-up, 95 women remained premenopausal, 98 had ceased menstruating for at least 12 months, and 61 were taking postmenopausal hormone therapy. Overall, the prevalence of the thyroid antibodies in this healthy population was high at both time points (21 to 26%). Women with antibodies had higher TSH concentrations than did those with no antibodies (2.68 +/- 1.3 versus 1.51 +/- .73 mU/L, P < 0.001); this relationship was statistically significant even after excluding those with subclinical hypothyroidism (TSH > 6.0 mU/L). TSH and antibody levels did not differ by menopausal status or hormone therapy use at follow-up. Given the high prevalence of thyroid antibodies among healthy middle-aged women, long-term follow-up is warranted to ascertain whether the presence of antibodies is associated with subsequent excess risk of disease, in particular, CHD.

Electroencephalographic sleep studies in depressed patients during long-term recovery

Analytic electroencephalographic (EEG) sleep procedures were used to examine specific changes in rapid eye movement (REM) and slow wave sleep (SWS) as they unfolded during depressive illness and recovery. The subjects were 15 patients with recurrent depression who remained well during 3 years of nonpharmacologic maintenance treatment without a recurrent episode of major depression. The analyses were performed on EEG sleep studies conducted before acute treatment, after 3 months in maintenance treatment, and every 3 months thereafter for 3 full years of maintenance treatment. There was no change between the index sleep and sleep during the first year of maintenance treatment as determined by period analysis or visual inspection of REM sleep parameters, except that average REM counts decreased over time. Thus, it is possible that REM parameters may represent one indicator of long-term recovery from depression. Finally, a significantly higher amount of 12-20 Hz spectral power density was found during the index episode than during the period of remission.

The Women on the Move Through Activity and Nutrition (WOMAN) Study: Final 48-Month Results

The Women on the Move through Activity and Nutrition (WOMAN) study was designed to test whether a nonpharmacological intervention including qualitative and quantitative dietary changes to induce weight loss and increased physical activity levels would reduce blood triglyceride levels and number of low‐density lipoprotein particles (LDL‐P). Such decreases in lipoproteins and other risk factors could reduce or slow progression of subclinical cardiovascular disease (CVD). Study participants were randomized to either the intervention (Lifestyle Change) or assessment (Health Education) group. Most of the intervention ended at the 30‐month visit. The last 48‐month examination was completed in 9/2008. There was very substantial weight loss and increased exercise during the first 30 months of the trial resulting in significant decreases in CV risk factors. Most of the intervention effect was lost through 48 months. Weight loss was 3.4 kg in Lifestyle Intervention and 0.2 kg in the Health Education at 48 months (P = 0.000). There were no significant changes at 48 months in lipid levels, blood pressure (BP), glucose, insulin, or in the subclinical measures of coronary calcium, carotid intima media thickness, or plaque. There was a significant decrease in long‐distance corridor walk time in the Lifestyle vs. Health Education groups. Significant lifestyle changes can be achieved that result in decreases in CV risk factors. Whether such changes reduce CV outcomes is still untested in clinical trials of weight loss or exercise. Long‐term maintenance of successful lifestyle changes, weight loss and reduced risk factors is the hurdle for lifestyle interventions attempting to prevent CV and other chronic diseases.

Nursing Home Deaths Which Fall Under the Jurisdiction of the Coroner: An 11-Year Retrospective Study

Twenty percent of deaths in the United States occur in nursing homes, yet less than 1% come to autopsy. The current study analyzed causes and manners of death in all nursing homes between 1993 and 2003, investigated by the coroner of Allegheny County, PA, which has the second highest elderly population in the United States. Two hundred eight decedents were identified, aged 19 to 91 years, 58% women and 42% men, 88% Caucasian and 22% African-American. Fifty-eight percent were accidental and 38.5% were natural manners of death, with 2 homicides, 2 suicides, and 3 undetermined cases. The manner of death was significantly different between Caucasians and African-Americans, with 92.6% of accidental deaths occurring in Caucasians and 6.6% in African-Americans (P < 0.1). Most common natural deaths were arteriosclerotic cardiovascular disease, nonarteriosclerotic cardiovascular disease, pneumonia, pulmonary thromboembolism, chronic obstructive pulmonary disease (COPD), seizure disorder, and atraumatic intracranial hemorrhage. Blunt force trauma was the single most commonly identified traumatic accidental death. Accidental deaths were more common in Caucasians than African-Americans. Homicides and suicides were rare events (<2%). Blunt force trauma is a major autopsy finding in accidental nursing home deaths, and a root-cause analysis may be helpful in developing policies and procedures to decrease the incidence of blunt force trauma.

Relationship between circulating serum osteoprotegerin and total receptor activator of nuclear κ-B ligand levels, triglycerides, and coronary calcification in postmenopausal women.

ObjectiveThis study evaluates the relationship of blood osteoprotegerin (OPG) and receptor activator of nuclear &kgr;-B ligand (RANKL) levels with coronary artery calcium (CAC) and cardiovascular risk factors in two studies of postmenopausal women. OPG, a marker of bone turnover, and its ligand, RANKL, may contribute to cardiovascular disease risk. MethodsWe tested the hypothesis that serum OPG and RANKL levels were associated with CAC and cardiovascular disease risk factors among postmenopausal women in the Women On the Move through Activity and Nutrition Study (WOMAN Study; n = 86; mean [SD], age 58 [2.9] y) and replicated our findings in the Healthy Women Study (HWS; n = 205; mean [SD] age, 61 [2.3] y). Serum OPG, total RANKL, and CAC were measured at baseline and 48 months in the WOMAN Study and on the eighth postmenopausal visit in the HWS. ResultsIn the WOMAN Study, higher OPG was associated with higher CAC, and higher total RANKL was associated with lower CAC and triglycerides. In the HWS, higher total RANKL was also associated with lower CAC and triglycerides. In logistic regression models adjusted for body mass index and triglycerides, the odds ratios (95% CIs) for CAC per unit increase in OPG were 1.78 (1.17-2.73) for the WOMAN Study and 1.02 (0.84-1.24) for the HWS, and the odds ratios (95% CIs) for CAC per unit increase in log total RANKL were 0.86 (0.64-1.17) for the WOMAN Study and 0.83 (0.72-0.96) for the HWS. ConclusionsThe inverse association of total RANKL with CAC and triglycerides is a new finding and may have important implications given the increasing use of drugs that modify total RANKL and its receptor, receptor activator of nuclear &kgr;-B.

Reproductive history in relation to plasma hormone levels in healthy post-menopausal women

OBJECTIVES We sought to examine the relationship between reproductive history and measures of selected gonadotrophins and steroid hormones among post-menopausal women. Previous studies have suggested that there is a negative correlation between parity and post-menopausal serum estrogens, which may be a mechanism by which pregnancies protect women from the development of breast cancer. METHODS We analyzed women who experienced a natural menopause within the Healthy Women Study cohort both 1 and 8 years after menopause. Lifetime reproductive history was obtained and blood was assayed for estrone, estradiol, androstenedione, testosterone, follicle stimulating hormone (FSH), and luteinizing hormone (LH) at 1 year post-menopause and for many of these steroid hormones at 8 years post-menopause. Also at 8 years post-menopause, a hip bone mineral density measure was obtained. RESULTS Age at menopause related to a modest increase in estrone at 1 year but a decrease in estrone and estradiol at eight years. Adjustment for body mass index (BMI), oral contraceptive use, alcohol use, cigarette smoking, and education had little impact on these findings. There were no other internally consistent relationships between reproductive variables and steroid hormones or hip-bone mineral density. CONCLUSIONS These observations do not support the hypothesis that parity acts to diminish endogenous levels of post-menopausal estrogens.

Clinical Experience With Continuous Intrathecal Baclofen Trials Prior to Pump Implantation

To report our clinical experience using continuous intrathecal baclofen (ITB) trials prior to permanent pump implantation.