Scott A. Washburn

Effect of soy protein supplementation on serum lipoproteins, blood pressure, and menopausal symptoms in perimenopausal women.

OBJECTIVE To investigate the effect of soy protein supplementation with known levels of phytoestrogens on cardiovascular disease risk factors and menopausal symptoms in perimenopausal women. METHODS A randomized, double-blind crossover trial was conducted in 51 women consuming isocaloric supplements containing 20 g of complex carbohydrates (comparison diet), 20 g of soy protein containing 34 mg of phytoestrogens given in a single dose, and 20 g of soy protein containing 34 mg of phytoestrogens split into two doses. Women were randomly assigned to one of the three diets for 6-week periods and subsequently were randomized to the remaining two interventions to determine whether differences existed between the treatment diets for cardiovascular disease risk factors, menopausal symptoms, adherence, and potential adverse effects. RESULTS Significant declines in total cholesterol (6% lower) and low density lipoprotein cholesterol (7% lower) were observed in both soy diets compared with the carbohydrate placebo diet. A significant decline in diastolic blood pressure (5 mm Hg lower) was noted in the twice-daily soy diet, compared with the placebo diet. Although nonsignificant effects were noted for a number of measures of quality of life, a significant improvement was observed for the severity of vasomotor symptoms and for hypoestrogenic symptoms in the twice-daily group compared with the placebo group. No significant effects were noted for triglycerides, high density lipoprotein cholesterol or frequency of menopausal symptoms. Adherence was excellent in all groups. CONCLUSIONS Soy supplementation in the diet of nonhypercholesterolemic, nonhypertensive, perimenopausal women resulted in significant improvements in lipid and lipoprotein levels, blood pressure, and perceived severity of vasomotor symptoms. These data corroborate the potential importance of soy supplementation in reducing chronic disease risk in Western populations.

Effects of hormone replacement therapy on reactivity of atherosclerotic coronary arteries in cynomolgus monkeys

OBJECTIVES We attempted to determine whether continuous and cyclic medroxyprogesterone acetate modulates the effects of estrogen on dilation of atherosclerotic coronary arteries in surgically postmenopausal female monkeys. BACKGROUND Estrogen replacement in postmenopausal women preserves normal dilator responses of atherosclerotic coronary arteries. The effects of progestins on coronary artery reactivity have not been determined. METHODS Repeated quantitative coronary angiography was used to study the effects after 1 month of 1) no hormone replacement (control) or oral administration of 2) continuous conjugated equine estrogens, 3) cyclic high dose medroxyprogesterone acetate (MPA) given on days 16 to 26 of the month, 4) conjugated equine estrogens plus continuous low dose MPA, or 5) conjugated equine estrogens plus cyclic high dose MPA on endothelium-mediated dilation of atherosclerotic coronary arteries in 12 cynomolgus monkeys. Change in diameter of the left circumflex coronary artery was measured in response to intracoronary infusions of acetylcholine (10(-6) mol/liter per min) and nitroglycerin (15 micrograms/min). RESULTS Coronary arteries constricted during no hormone treatment (-8 +/- 3% [mean +/- SEM]), dilated during conjugated equine estrogen treatment (+3 +/- 1%, p < 0.05 vs. control) and constricted during cyclic MPA treatment (-3 +/- 2%). Addition of cyclic or continuous MPA to the conjugated equine estrogen regimen inhibited acetylcholine responses by 50% (p < 0.05 vs. conjugated equine estrogens). There was no effect of treatment on vascular response to nitroglycerin (p > 0.05). CONCLUSIONS Treatment with conjugated equine estrogens, but not MPA, augmented endothelium-mediated dilation of atherosclerotic coronary arteries. Addition of cyclic or continuous MPA to the conjugated equine estrogen regimen diminished endothelium-mediated dilation.

Health potential of soy isoflavones for menopausal women

OBJECTIVE To review the current literature on the effects of soy isoflavones, one class of phyto-oestrogens, on cardiovascular diseases, osteoporosis, cancer and climacteric symptoms. DESIGN Many study designs were employed in the reports reviewed here, including prospective human trials, observational human studies, animal experiments and in vitro cell studies that explored the protective or preventive effects of soy isoflavones (genistein, daidzein and glycitein alone or mixed). SETTING Diverse settings were employed, depending on study design. SUBJECTS Human subjects, mostly menopausal or postmenopausal, were included, as were animal models and specific cell types. RESULTS The findings were: (i) isoflavones plus soy protein together were needed to obtain the highly significant beneficial results on blood lipids and arterial dimensions; (ii) isoflavone treatments alone at high doses (relative to above) consistently improved bone parameters in rodent ovariectomized models, but not in humans or primates; (iii) isoflavones were not consistent in exerting positive effects regarding the prevention or treatment of cancers of the mammary glands, uterus and colon; and (iv) the effects of isoflavones on climacteric symptoms were not clear-cut. CONCLUSIONS The promise of soy isoflavones reducing chronic disease risk seems to be non-uniform, with the most conclusive benefits occurring in the prevention of cardiovascular diseases, but other organ systems, such as skeletal and reproductive tissues, may also benefit from the consumption of soy and soy-derived products.

Soy protein and isoflavone effects on vasomotor symptoms in peri- and postmenopausal women: the Soy Estrogen Alternative Study

Objective To investigate the efficacy of dietary soy proteins containing differing amounts of isoflavones on the number and severity of vasomotor symptoms (hot flashes and night sweats) in peri- and postmenopausal women. Design A double-masked, randomized, controlled, clinical trial was conducted. A total of 241 community-dwelling women reporting vasomotor symptoms at baseline were randomized into one of three groups. In all groups, participants consumed a daily supplement containing 25 g of soy protein and were randomly assigned to one of three groups: (a) isoflavone extracted soy protein (control), (b) soy protein with a medium dose of isoflavones (42 mg/day), or (c) soy protein with a higher dose of isoflavones (58 mg/day). The primary outcome measure in this trial was change in reported vasomotor symptoms. Results A reduction in the number and severity of vasomotor symptoms was observed in all three treatment groups. No significant differences in the number and severity of vasomotor symptoms were observed among the high isoflavone, middle isoflavone, or control groups. The lack of a between-treatment group effect was observed even after stratified by number of baseline symptoms and use of traditional hormone replacement therapy. Conclusions These data suggest that soy protein containing 42 or 58 mg of isoflavones is no more effective than isoflavone-extracted soy protein for improving the number and severity of vasomotor symptoms in peri- and postmenopausal women.

A conjugated equine estrogen with differential effects on uterine weight and plasma cholesterol in the rat

OBJECTIVE Our purpose was to determine the effect of Premarin (conjugated estrogens) and three of its component estrogens on uterine weight and plasma cholesterol concentrations in surgically menopausal female rats. STUDY DESIGN A randomized trial of Premarin and three component estrogens--estrone sulfate, 17 alpha-estradiol sulfate, and 17 alpha-dihydroequilenin sulfate--in female rats after oophorectomy. RESULTS High-dose Premarin and high- and middle-dose estrone sulfate significantly increased uterine weight relative to untreated controls (high-dose Premarin, 243.34 +/- 0.15 mg; high-dose estrone sulfate, 376.1 +/- 9.36 mg; middle-dose estrone sulfate, 249.0 +/- 6.34 mg; untreated controls, 124.63 +/- 3.17 mg; for all, p < 0.05). 17 alpha-Dihydroequilenin sulfate had no effect on uterine weight relative to controls. All 17 alpha-dihydroequilenin sulfate doses markedly reduced total plasma cholesterol concentrations versus controls (34.02 +/- 3.44 mg/dl, 32.49 +/- 1.08 mg/dl, and 71.55 +/- 5.16 mg/dl vs 90.44 +/- 1.06 mg/dl; for all, p < 0.02). 17 alpha-Dihydroequilenin sulfate had a more pronounced effect on low- or very-low-density lipoprotein cholesterol than total plasma cholesterol or high-density lipoprotein cholesterol concentrations. CONCLUSIONS 17 alpha-Dihydroequilenin sulfate reduced total plasma cholesterol concentrations without inducing uterine growth in rats after oophorectomy.

Effects of estrogen and progestin replacement on the urogenital tract of the ovariectomized cynomolgus monkey

Menopause is presumed to have a causative role in the development of female urinary incontinence. While some clinical trials have shown that estrogen can affect urinary tract function, our knowledge of the pathophysiologic changes resulting from menopause and hormone replacement therapy is poor.

Outpatient hysterectomy: Determinants of discharge and rehositalization in 133 patients

OBJECTIVE This study examines our continuing experience in performing vaginal hysterectomies and laparoscopy-assisted vaginal hysterectomies with an outpatient protocol. The purpose was to review factors associated with discharge and hospitalization. STUDY DESIGN Surgical records from all women entering our previously reported outpatient hysterectomy protocol were reviewed. Demographics, surgical indications, intraoperative data, and postoperative data were studied, and their associations with patient discharge and hospitalization were determined. Specific attention was directed to complications. RESULTS The study group consisted of 133 women. Twelve women (9.0%) were not discharged from the hospital and 5 (3.8%) required readmission. Surgical indications, the type of hysterectomy, and the requirement for pain medication revealed no association with hospitalization. The occurrence of an intraoperative complication (p < 0.000), the need for transfusion (p = 0.043), and postoperative antiemetics (p = 0.013) were statistically associated with hospitalization. In addition, low hematocrit values and elevated temperatures on the first and second postoperative days were associated with hospitalization. CONCLUSION Long-term experience with outpatient hysterectomy reveals a hospitalization rate of 12.8%. Complications, blood loss, elevated temperatures, and postoperative nausea are the major determinants of patient discharge and hospitalization. Readmission rates continue to remain low.

17α-Dihydroequilenin increases hippocampal dendritic spine density of ovariectomized rats

The effects of estradiol and 17alpha-dihydroequilenin on the apical dendrite spine density of pyramidal cells of the CA1 region of rat hippocampus were compared. 17alpha-Dihydroequilenin was as effective as estradiol in increasing spine densities relative to controls. 17alpha-Dihydroequilenin is not uterotrophic like estradiol but does have beneficial effects on the cardiovascular system, suggesting that it may be an effective single-agent hormone replacement therapy to treat menopausal symptoms and reduce chronic disease risk in menopausal women.