A Randomized Trial of Vitamin E Supplementation and Cognitive Function in Women

AS Kapoor

Obstetrics & Gynecology

Mar 2007

DOI: 10.1097/01.AOG.0000244711.35161.e1

Citations:186

Influential Citations:3

Interventional (Human) Studies

Enhanced Details

Methods

Design: 1-year double-blind, randomized, controlled trial conducted at Group Health, Washington. Participants: 351 perimenopausal or postmenopausal women aged 45–55 years with 2+ vasomotor symptoms per day for 2 weeks; exclusions included contraindications to hormone therapy, recent hormone therapy or oral contraceptives, recent use of herbal remedies or soy allergy, bilateral oophorectomy, history of breast cancer, or nonadherence during run-in. Randomization to 5 arms (herbs, hormone therapy, placebo) with a later shift to 4 arms (no hormone therapy) after WHI findings; stratified by prior hormone therapy and hysterectomy; follow-up at 3, 6, and 12 months; primary outcomes included frequency and intensity of vasomotor symptoms and Wiklund Vasomotor Symptom Subscale; adherence and adverse events monitored.

Intervention

Black cohosh: 160 mg daily; Actaea racemosa or Cimicifuga racemosa; 2.5% triterpene glycosides; 70% ethanol extract; delivered in capsules; duration 12 months. Multibotanical: ProGyne; daily doses via encapsulated capsules: black cohosh 200 mg; alfalfa 400 mg; boron 4 mg; chaste tree 200 mg; dong quai 400 mg; false unicorn 200 mg; licorice 200 mg; oats 400 mg; pomegranate 400 mg; Siberian ginseng 400 mg; duration 12 months. Multibotanical plus soy diet counseling: same multibotanical regimen plus dietary soy counseling to increase intake to 2 servings per day (12–20 g soy protein); 5 telephone calls from a clinical dietitian; 34-page booklet; duration 12 months. Soy diet: dietary plan to achieve 2 soy servings per day (12–20 g soy protein) via soy foods; 5 telephone calls from a clinical dietitian; 34-page booklet; duration 12 months.

Results

Herbal regimens did not reduce vasomotor symptoms vs placebo over 12 months. The average difference in daily vasomotor symptoms between placebo and herbal regimens was <1 symptom/day at 3 months and <0.6/day across follow-up. Hormone therapy substantially reduced vasomotor symptoms vs placebo (≈4.5 fewer symptoms/day at 3 months and ≈4 fewer/day across follow-ups). Wiklund subscale improved with hormone therapy but not with herbal regimens. Adverse events more common with hormone therapy included breast pain and menstrual disorders; rare cancers occurred (endometrial cancer in multibotanical plus soy; breast cancer in multibotanical). Overall adherence ~86% across groups. Conclusion: Black cohosh alone or in multibotanical regimens shows little potential to relieve vasomotor symptoms; hormone therapy remains the more effective option but carries risks; findings mainly apply to white, well-educated women; longer, diverse trials are needed to assess safety and subgroup effects.

Limitations

Population largely white and well-educated; limited generalizability to diverse populations. 12-month duration limits assessment of longer-term efficacy and safety. Herbal product composition and extraction variability may affect outcomes. Randomization adjustments after WHI may influence applicability. Adverse events were rare but underscore need for larger, longer studies.

Abstract

The following abstracts of articles from leading journals have been selected on the basis of their importance to the practice of obstetrics and gynecology. Factors Influencing Adverse Perinatal Outcomes in Pregnancies Achieved Through Use of In Vitro Fertilization Objective: To determine the associations of specific components of in vitro fertilization (IVF) treatment with abnormal perinatal outcomes. Design: Case-control study. Setting: University-based and community-based infertility centers. Patient(s): All viable pregnancies achieved through IVF procedures performed between January 1999 and March 2004. Intervention(s): None. Main Outcome Measure(s): Infertility etiology, gonadotropin exposure, embryo manipulation, and quality. Result(s): Of 455 viable pregnancies identified during the study period, 435 met inclusion criteria. While adjusting for maternal age, race, parity, body mass index, infertility center, and year of IVF procedure, multiple gestations were associated with a 12-fold increased risk of poor perinatal outcome compared to singletons. Ovarian hyperstimulation syndrome significantly increased the risk more than 3-fold (odds ratio 3.14, 95% confidence interval [CI] 1.08–9.14), while endometrial thickness was found to have a significant protective effect (odds ratio 0.89, 95% CI 0.80–0.99). We found no effect of etiology of infertility, dose or type of medication used for stimulation, use of embryo-manipulation techniques, or quality on perinatal outcome. Conclusion: These data confirm and quantify the risk of perinatal morbidity associated with multiple births. After adjusting for multiple births, ovarian hyperstimulation syndrome and suboptimal endometrial development are associated with adverse outcomes in pregnancies achieved through IVF. Our findings suggest that it may be the endometrium rather than the embryo that influences fetal growth and perinatal outcomes after IVF. Chung K, Coutifaris C, Chalian R, Lin K, Ratcliffe SJ, Castelbaum AJ, Freedman MF, Barnhart KT. Fertil Steril 2006;86:1634– 41. Epub 2006 Oct 30. (http://www.fertstert.org) A Randomized Trial of Vitamin E Supplementation and Cognitive Function in Women Background: Oxidative stress may play a key role in the development of cognitive impairment. Long-term supplementation with vitamin E, a strong antioxidant, may provide cognitive benefits. Methods: The Women’s Health Study is a randomized, double-blind, placebocontrolled trial of vitamin E supplementation (600 International Units [ -tocopherol acetate], on alternate days) begun between 1992 and 1995 among 39,876 healthy U.S. women. From 1998, 6,377 women 65 years or older participated in a cognitive substudy. Three cognitive assessments of general cognition, verbal memory, and category fluency were administered by telephone at 2-year intervals. The primary outcome was a global composite score averaging performance on all tests. Repeated measures analyses were conducted to examine mean performance and mean differences in cognitive change, and logistic regression was used to estimate relative risks of substantial decline. Results: There were no differences in global score between the vitamin E and placebo groups at the first assessment (5.6 years after randomization: mean difference 0.01, 95% confidence interval [CI] –0.04 to 0.03) or at the last assessment (9.6 years of treatment: mean difference 0.00, 95% CI –0.04 to 0.04). Mean cognitive change over time was also similar in the vitamin E group compared with the placebo group for the global score (mean difference in change 0.02, 95% CI –0.01 to 0.05; P .16). The relative risk of substantial decline in the global score in the vitamin E group compared with the placebo group was 0.92 (95% CI 0.77 to 1.10). Conclusion: Long-term use of vitamin E supplements did not provide cognitive benefits among generally healthy older women. Kang JH, Cook N, Manson J, Buring JE, Grodstein F. Arch Intern Med 2006;166: 2462–8. (http://archinte.ama-assn.org) Effects of Continuing or Stopping Alendronate After 5 Years of Treatment: The Fracture Intervention Trial Long-Term Extension (FLEX): A Randomized Trial Context: The optimal duration of treatment of women with postmenopausal osteoporosis is uncertain. Objective: To compare the effects of discontinuing alendronate treatment after 5 years with continuing for 10 years. Design and Setting: Randomized, double-blind trial conducted at 10 U.S. clinical centers that participated in the Fracture Intervention Trial (FIT). Participants: One thousand ninetynine postmenopausal women who had been randomized to alendronate in FIT, with a mean of 5 years of prior alendronate treatment. Intervention: Randomization to alendronate, 5 mg/d (n 329) or 10 mg/d (n 333), or placebo (n 437) for 5 years (1998–2003). Main Outcome Measures: The primary outcome measure was total hip bone mineral density; secondary measures were bone mineral density at other sites and biochemical markers of bone remodeling. An exploratory outcome measure was fracture incidence. © 2007 by The American College of Obstetricians and Gynecologists. Published by Lippincott Williams show less