Effect of estrogen plus progestin on global cognitive function in postmenopausal women: the Women's Health Initiative Memory Study: a randomized controlled trial

Context  Observational studies have suggested that postmenopausal hormone treatment may improve cognitive function, but data from randomized clinical trials have been sparse and inconclusive. The Women's Health Initiative Memory Study (WHIMS) is an ancillary study of the Women's Health Initiative (WHI) hormone therapy trials. On July 8, 2002, the estrogen plus progestin therapy in the WHI trial was discontinued because of certain increased health risks for women. Objective  To determine whether estrogen plus progestin therapy protects global cognitive function in older postmenopausal women. Design, Setting, and Participants  A randomized, double-blind, placebo-controlled clinical trial, WHIMS is an ancillary study of geographically diverse, community-dwelling women aged 65 years or older from 39 of 40 clinical centers within the WHI estrogen plus progestin trial that started in June 1995. Of 4894 eligible postmenopausal women aged 65 years or older and free of probable dementia at baseline, 4532 (92.6%) were enrolled in the estrogen plus progestin component of WHIMS. A total of 4381 participants (96.7%) provided at least 1 valid cognitive function score between June 1995 and July 8, 2002. Interventions  Participants received either 1 daily tablet containing 0.625 mg of conjugated equine estrogen with 2.5 mg of medroxyprogesterone acetate (n = 2145) or matching placebo (n = 2236). Main Outcome Measure  Global cognitive function measured annually with the Modified Mini-Mental State Examination. Results  The Modified Mini-Mental State Examination mean total scores in both groups increased slightly over time (mean follow-up of 4.2 years). Women in the estrogen plus progestin group had smaller average increases in total scores compared with women receiving placebo (P = .03), but these differences were not clinically important. Removing women by censoring them after adjudicated dementia, mild cognitive impairment, or stroke, and nonadherence to study protocol, did not alter the findings. Prior hormone therapy use and duration of prior use did not affect the interpretation of the results, nor did timing of prior hormone therapy initiation with respect to the final menstrual period. More women in the estrogen plus progestin group had a substantial and clinically important decline (2 SDs) in Modified Mini-Mental State Examination total score (6.7%) compared with the placebo group (4.8%) (P = .008). Conclusions  Among postmenopausal women aged 65 years or older, estrogen plus progestin did not improve cognitive function when compared with placebo. While most women receiving estrogen plus progestin did not experience clinically relevant adverse effects on cognition compared with placebo, a small increased risk of clinically meaningful cognitive decline occurred in the estrogen plus progestin group.      

Relation between changes in intakes of dietary fiber and grain products and changes in weight and development of obesity among middle-aged women

BACKGROUND: Although increased consumption of dietary fiber and grain products is widely recommended to maintain healthy body weight, little is known about the relation of whole grains to body weight and long-term weight changes. OBJECTIVE: We examined the associations between the intakes of dietary fiber and whole- or refined-grain products and weight gain over time. DESIGN: In a prospective cohort study, 74,091 US female nurses, aged 38-63 y in 1984 and free of known cardiovascular disease, cancer, and diabetes at baseline, were followed from 1984 to 1996; their dietary habits were assessed in 1984, 1986, 1990, and 1994 with validated food-frequency questionnaires. Using multiple models to adjust for covariates, we calculated average weight, body mass index (BMI; in kg/m(2)), long-term weight changes, and the odds ratio of developing obesity (BMI > or = 30) according to change in dietary intake. RESULTS: Women who consumed more whole grains consistently weighed less than did women who consumed less whole grains (P for trend < 0.0001). Over 12 y, those with the greatest increase in intake of dietary fiber gained an average of 1.52 kg less than did those with the smallest increase in intake of dietary fiber (P for trend < 0.0001) independent of body weight at baseline, age, and changes in covariate status. Women in the highest quintile of dietary fiber intake had a 49% lower risk of major weight gain than did women in the highest quintile (OR = 0.51; 95% CI: 0.39, 0.67; P < 0.0001 for trend). CONCLUSION: Weight gain was inversely associated with the intake of high-fiber, whole-grain foods but positively related to the intake of refined-grain foods, which indicated the importance of distinguishing whole-grain products from refined-grain products to aid in weight control.     

Dietary carotenoids and risk of coronary artery disease in women

BACKGROUND: Numerous studies have shown that higher intakes or higher blood concentrations of carotenes are associated with a lower risk of coronary artery disease (CAD). Given the null results in trials of beta-carotene supplementation, considerable attention has focused on the potential role of other dietary carotenoids in the prevention of CAD. OBJECTIVE: Our objective was to prospectively examine the relation between dietary intakes of specific carotenoids and risk of CAD in women. DESIGN: In 1984, 73 286 female nurses completed a semiquantitative food-frequency questionnaire that assessed their consumption of carotenoids and various other nutrients. The women were followed for 12 y for the development of incident CAD (nonfatal myocardial infarction and fatal CAD), and dietary information was updated in 1986, 1990, and 1994. RESULTS: During 12 y of follow-up (803 590 person-years), we identified 998 incident cases of CAD. After adjustment for age, smoking, and other CAD risk factors, we observed modest but significant inverse associations between the highest quintiles of intake of beta-carotene and alpha-carotene and risk of CAD but no significant relation with intakes of lutein/zeaxanthin, lycopene, or beta-cryptoxanthin. For women in the highest compared with the respective lowest quintile of intake, the relative risks for beta-carotene and alpha-carotene were 0.74 (95% CI: 0.59, 0.93) and 0.80 (95% CI: 0.65, 0.99), respectively. The association between the specific carotenoids and CAD risk did not vary significantly by current smoking status. CONCLUSION: Higher intakes of foods rich in alpha-carotene or beta-carotene are associated with a reduction in risk of CAD.     

Dietary glycemic load assessed by food-frequency questionnaire in relation to plasma high-density-lipoprotein cholesterol and fasting plasma triacylglycerols in postmenopausal women

BACKGROUND: In metabolic studies, both greater carbohydrate intakes and higher glycemic indexes (GIs) raise fasting triacylglycerol concentrations. In epidemiologic studies, dietary glycemic load (GL) is positively associated with risk of coronary artery disease and type 2 diabetes. OBJECTIVE: We examined both the physiologic relevance of GI and GL and the ability of dietary questionnaires to measure these variables. DESIGN: In the Nurses' Health Study, we measured plasma triacylglycerol concentrations in fasting blood samples from 185 healthy postmenopausal women and HDL-cholesterol concentrations in an additional 95 nonfasting samples. Dietary carbohydrate, GI, and GL were assessed by use of semiquantitative food-frequency questionnaires. The cross-sectional associations between these 3 variables and plasma triacylglycerol and HDL were assessed, with adjustment for potential confounding factors. RESULTS: For the lowest and highest quintiles of GL, the multivariate-adjusted geometric mean triacylglycerol concentrations were 0.98 and 1.75 mmol/L (87 and 155 mg/dL; P for trend < 0.001). Both overall GI (P for trend = 0.03) and carbohydrate (P for trend < 0.01) contributed independently to the strong positive association between GL and fasting triacylglycerol concentrations. GL was also inversely associated with HDL-cholesterol concentrations. For the lowest and highest quintiles of GL, the mean HDL-cholesterol concentrations were 1.50 and 1.34 micromol/L (58 and 52 mg/dL; P for trend = 0.03). The relation between GL and fasting triacylglycerol concentrations differed significantly by body mass index (BMI; in kg/m(2)) categories (P < 0.001 for interaction). For the lowest to the highest quintiles of GL, the mean triacylglycerol concentrations were 0.92 and 2.24 mmol/L (81 and 198 mg/dL) in women with BMIs > 25 (P for trend < 0.001) and 1.02 and 1.42 mmol/L (90 and 126 mg/dL) in women with BMIs < or = 25 (P for trend < 0.001). CONCLUSION: These data support the physiologic relevance of the GL as a potential risk factor for coronary artery disease in free-living women, particularly those prone to insulin resistance. These findings also document the ability of a semiquantitative food-frequency questionnaire to assess dietary GIs and GLs.     

Dietary fat intake and risk of type 2 diabetes in women

BACKGROUND: The long-term relations between specific types of dietary fat and risk of type 2 diabetes remain unclear. OBJECTIVE: Our objective was to examine the relations between dietary fat intakes and the risk of type 2 diabetes. DESIGN: We prospectively followed 84204 women aged 34-59 y with no diabetes, cardiovascular disease, or cancer in 1980. Detailed dietary information was assessed at baseline and updated in 1984, 1986, and 1990 by using validated questionnaires. Relative risks of type 2 diabetes were obtained from pooled logistic models adjusted for nondietary and dietary covariates. RESULTS: During 14 y of follow-up, 2507 incident cases of type 2 diabetes were documented. Total fat intake, compared with equivalent energy intake from carbohydrates, was not associated with risk of type 2 diabetes; for a 5% increase in total energy from fat, the relative risk (RR) was 0.98 (95% CI: 0.94, 1.02). Intakes of saturated or monounsaturated fatty acids were also not significantly associated with the risk of diabetes. However, for a 5% increase in energy from polyunsaturated fat, the RR was 0.63 (0.53, 0.76; P < 0.0001) and for a 2% increase in energy from trans fatty acids the RR was 1.39 (1.15, 1.67; P = 0.0006). We estimated that replacing 2% of energy from trans fatty acids isoenergetically with polyunsaturated fat would lead to a 40% lower risk (RR: 0.60; 95% CI: 0.48, 0.75). CONCLUSIONS: These data suggest that total fat and saturated and monounsaturated fatty acid intakes are not associated with risk of type 2 diabetes in women, but that trans fatty acids increase and polyunsaturated fatty acids reduce risk. Substituting nonhydrogenated polyunsaturated fatty acids for trans fatty acids would likely reduce the risk of type 2 diabetes substantially.     

Utility of the lateral arm flap in head and neck reconstruction

Soft-tissue defects of the head and neck are often reconstructed with fasciocutaneous free flaps. The radial forearm flap is used most commonly, however the lateral arm flap may be the flap of choice in certain situations. Advantages include flap elevation with simultaneous tumor ablation, avoidance of intraoperative patient position changes, and primary closure of the donor site. After extirpative procedures of the head and neck region, 4 patients were reconstructed with the lateral arm flap. Flap survival was 100%, a vein graft to supplement the short pedicle length was necessary in 1 patient, all donor sites were closed primarily, and secondary procedures to reduce flap bulk were necessary in 2 patients. The lateral arm flap is an excellent alternative to the radial forearm flap and should be included in the armamentarium of the reconstructive head and neck surgeon.