Relationship between hormone replacement therapy use with body fat distribution and insulin sensitivity in obese postmenopausal women.

The aim of this study was to compare the effect of hormone replacement therapy (HRT) on insulin resistance and central adiposity in obese postmenopausal women. Forty-five obese postmenopausal women (16 HRT users and 29 nonusers), with a mean age of 56.6 +/- 5.3 years and duration of current, continuous HRT use of 4.7 +/- 2.9 years, were included in the study. Subjects were studied using oral glucose tolerance tests, euglycemic clamping, dual photon x-ray absorptiometry, computed tomography, doubly labeled water, and treadmill testing. Insulin sensitivity, total fat, visceral fat, subcutaneous abdominal fat, thigh muscle attenuation, daily physical activity energy expenditure, peak oxygen consumption (Vo(2)) were measured. HRT users had lower body weight (88.0 +/- 11.0 v 98.2 +/- 15.0 kg, P =.05), lower body mass index (33.1 +/- 3.5 v 36.8 +/- 5.2 kg/m(2), P =.05), lower fat mass (38.3 +/- 7.3 v 44.1 +/- 10 kg, P =.05), less visceral adipose tissue (157 +/- 47 v 211 +/- 81 cm(2); P =.05), and higher peak Vo(2) (21.1 +/- 4.6 v 17.6 +/- 2.2 mL/kg/min, P =.001) than nonusers. After adjustment for total fat, we noted a trend for decreased visceral adipose tissue in HRT users (P =.09). After adjustment for peak Vo(2), the decreased visceral adipose tissue persisted in HRT users (P <.01). Insulin sensitivity per kilogram of lean body mass did not differ between HRT users (0.51 +/- 0.22 mmol/kg/min) and nonusers (0.49 +/- 0.22 mmol/kg/min). It was concluded that obese postmenopausal women using HRT have a more favorable body composition and fat distribution pattern than nonusers. Although visceral adipose tissue is decreased in HRT users, insulin sensitivity does not differ between HRT users and nonusers.

Previous exposure to hormone replacement therapy and confounders in metabolic studies.

OBJECTIVE: The quantity of intra-abdominal fat is highly associated with the development of diabetes mellitus. We sought to determine whether recent hormone replacement therapy (HRT) use modifies central fat and insulin sensitivity in postmenopausal women compared with women who had never used HRT. DESIGN: We measured intra-abdominal fat, subcutaneous abdominal fat, and sagittal diameter at the L4-L5 vertebral disc space using computed tomography imaging. Total body fat and fat-free mass were measured using dual energy x-ray absorptiometry. Insulin sensitivity was assessed using the euglycemic hyperinsulinemic clamp technique in 42 nonobese postmenopausal women, age 51 +/- 4 years (12 recent HRT users plus 30 never-users). All women who were taking HRT discontinued it for 2 months before the study. RESULTS: After statistical adjustment for age, previous use of HRT was associated with decreased intra-abdominal fat (72 +/- 34 cm2) compared with no HRT use (96 +/- 33 cm2; p = 0.05). This difference remained significant after adjustment for time since menopause. When previous HRT users were compared with nonusers, there were no differences in subcutaneous abdominal fat, sagittal diameter, fat-free mass, total fat, insulin sensitivity, or body weight. CONCLUSIONS: Recent HRT use is associated with lower intra-abdominal fat in nonobese, early postmenopausal women. This finding suggests a carry-over effect of HRT on intra-abdominal fat. Recent HRT use does not seem to be associated with differences in glucose disposal.

Determinants of insulin-stimulated glucose disposal in middle-aged, premenopausal women.

Controversy exists regarding the relative importance of adiposity, physical fitness, and physical activity in the regulation of insulin-stimulated glucose disposal. To address this issue, we measured insulin-stimulated glucose disposal [mg. kg fat-free mass (FFM)(-1). min(-1); oxidative and nonoxidative components] in 45 nondiabetic, nonobese, premenopausal women (mean +/- SD; 47 +/- 3 yr) by use of hyperinsulinemic euglycemic clamp (40 mU. m(-2). min(-1)) and [6,6-2H2]glucose dilution techniques. We also measured body composition, abdominal fat distribution, thigh muscle fat content, maximal oxygen consumption (VO2 max), and physical activity energy expenditure ((2)H(2)(18)O kinetics) as possible correlates of glucose disposal. VO2 max was the strongest correlate of glucose disposal (r = 0.63, P < 0.01), whereas whole body and abdominal adiposity showed modest associations (range of r values from -0.32 to -0.46, P < 0.05 to P < 0.01). A similar pattern of correlations was observed for nonoxidative glucose disposal. None of the variables measured correlated with oxidative glucose disposal. The relationship of VO2 max to glucose disposal persisted after statistical control for FFM, percent body fat, and intra-abdominal fat (r = 0.40, P < 0.01). In contrast, correlations of total and regional adiposity measures to insulin sensitivity were no longer significant after statistical adjustment for VO2 max. VO2 max was the only variable to enter stepwise regression models as a significant predictor of total and nonoxidative glucose disposal. Our results highlight the importance of VO2 max as a determinant of glucose disposal and suggest that it may be a stronger determinant of variation in glucose disposal than total and regional adiposity in nonobese, nondiabetic, premenopausal women.

Contribution of abdominal adiposity to age-related differences in insulin sensitivity and plasma lipids in healthy nonobese women.

OBJECTIVE: We examined the hypothesis that an age-related increase in the compartments of visceral fat would account, in part, for the deleterious changes in insulin sensitivity and blood lipid profile in nonobese women. RESEARCH DESIGN AND METHODS: We directly assessed visceral and subcutaneous abdominal adipose tissue areas (computed tomography), glucose disposal (hyperinsulinemic-euglycemic clamp), body composition (dual energy X-ray absorptiometry), blood-lipid profile, and aerobic fitness (VO2max) in 178 nonobese women categorized into four age groups: group 1, 28 +/- 4 years, n = 88; group 2, 46 +/- 2 years, n = 38; group 3, 53 +/- 2 years, n = 31; and group 4. 67 +/- 6 years, n = 21. RESULTS: Visceral abdominal adipose tissue area increased with age (2.36 cm2 per year, P < 0.0001). We noted an age-related increase in total cholesterol (P < 0.0003), triglycerides (P < 0.0009), LDL cholesterol (P < 0.027), and the ratio of total cholesterol to HDL cholesterol (P < 0.042). However, age-related changes in insulin sensitivity exhibited a different age-related pattern. That is, insulin sensitivity, expressed on an absolute basis or indexed per kilogram of fat-free mass, was lowest in group 4 but was not significantly different among groups 1, 2, and 3. After statistical control for visceral fat, lower insulin sensitivity persisted in group 4, although differences were diminished relative to other groups. However, the effect of visceral fat on age-related changes in the blood-lipid profile was stronger. That is, differences in visceral and deep subcutaneous adipose tissue area abolished age-related differences in total cholesterol, triglycerides, and LDL cholesterol. No independent effects of VO2max or leisure-time physical activity on age-related changes in insulin sensitivity or on the blood-lipid profile were noted. CONCLUSIONS: We conclude that 1) visceral fat shows an increase with advancing age, whereas a decrease in insulin sensitivity was noted only in older women; 2) age-related differences in visceral fat explain only a modest part of the decline in insulin sensitivity in nonobese women; and 3) unfavorable changes in plasma lipids were strongly associated with the age-related increase in visceral abdominal adipose tissue.

What are the physical characteristics associated with a normal metabolic profile despite a high level of obesity in postmenopausal women?

Although obesity is often associated with insulin resistance and a cluster of metabolic disturbances, the existence of a subgroup of healthy but obese individuals has been postulated. It is unclear why some obese individuals fail to show traditional risk factors associated with the insulin resistance syndrome despite having a very high accumulation of body fat. To address this issue, we identified and studied a subgroup of metabolically normal but obese (MNO) postmenopausal women to gain insight into potential physiological factors that may protect them against the development of obesity-related comorbidities. We carefully examined the metabolic characteristics of 43 obese, sedentary postmenopausal women (mean +/- SD, 58.0 +/- 6.0 yr). Subjects were classified as MNO or as metabolically abnormal obese (MAO) based on an accepted cut-point for insulin sensitivity (measured by the hyperinsulinemic/euglycemic clamp technique). Thereafter, we determined 1) body composition (fat mass and lean body mass), 2) body fat distribution (abdominal visceral and sc adipose tissue areas, midthigh sc adipose tissue and muscle attenuation), 3) plasma lipid-lipoprotein levels, 4) plasma glucose and insulin concentrations, 5) resting blood pressure, 6) peak oxygen consumption, 7) physical activity energy expenditure, and 8) age-related onset of obesity with a questionnaire as potential modulators of differences in the risk profile. We identified 17 MNO subjects who displayed high insulin sensitivity (11.2 +/- 2.6 mg/min.kg lean body mass) and 26 MAO subjects with lower insulin sensitivity (5.7 +/- 1.1 mg/min.kg lean body mass). Despite comparable total body fatness between groups (45.2 +/- 5.3% vs. 44.8 +/- 6.6%; P: = NS), MNO individuals had 49% less visceral adipose tissue than MAO subjects (141 +/- 53 vs. 211 +/- 85 cm(2); P: < 0.01). No difference was noted between groups for abdominal sc adipose tissue (453 +/- 126 vs. 442 +/- 144 cm(2); P: = NS), total fat mass (38.1 +/- 10.6 vs. 40.0 +/- 11.8 kg), muscle attenuation (42.2 +/- 2.6 vs. 43.6 +/- 4.8 Houndsfield units), and physical activity energy expenditure (1060 +/- 323 vs. 1045 +/- 331 Cal/day). MNO subjects had lower fasting plasma glucose and insulin concentrations and lower insulin levels during the oral glucose tolerance test (P: values ranging between 0.01-0.001). No difference was observed between groups for 2-h glucose levels and glucose area during the oral glucose tolerance test. MNO subjects showed lower plasma triglycerides and higher high density lipoprotein cholesterol concentrations than MAO individuals (P: < 0.01 in both cases). Results from the questionnaire indicated that 48% of the MNO women presented an early onset of obesity (<20 yr old) compared with 29% of the MAO subjects (P: = 0.09). Stepwise regression analysis showed that visceral adipose tissue and the age-related onset of obesity explained 22% and 13%, respectively, of the variance observed in insulin sensitivity (total r(2) = 0.35; P: < 0.05 in both cases). Our results support the existence of a subgroup of obese but metabolically normal postmenopausal women who display high levels of insulin sensitivity despite having a high accumulation of body fat. This metabolically normal profile is associated with a lower accumulation of visceral adipose tissue and an earlier age-related onset of obesity.

Menopause-related changes in body fat distribution.

Menopause-related changes in body fat distribution may partially explain the greater risk of cardiovascular and metabolic disease during the postmenopausal years. To date, however, the effect of the menopause transition on body fat distribution remains unclear. Cross-sectional and longitudinal studies using waist circumference or the waist-to-hip ratio show no effect of menopause on body fat distribution. By contrast, studies using dual-energy X-ray absorptiometry showed increased trunk fat in postmenopausal women. Moreover, studies using computed tomography (CT) and magnetic resonance imaging (MRI) show that postmenopausal women have greater amounts of intra-abdominal fat compared to premenopausal women. Collectively, these studies suggest that the menopause transition is associated with an accumulation of central fat and, in particular, intra-abdominal fat. Whether menopause-related differences in trunk or intra-abdominal fat are independent of age and/or adiposity, however, is unclear. Thus, we recently examined the effect of menopausal status on body composition and abdominal fat distribution in 53 middle-aged, premenopausal women (47 +/- 3 years) and 28 early postmenopausal women (51 +/- 4 years). Postmenopausal women had 36% more trunk fat (p < 0.01), 49% greater intra-abdominal fat area (p < 0.01), and 22% greater subcutaneous abdominal fat area (p < 0.05) than premenopausal women. The menopause-related difference in intra-abdominal fat persisted (p < 0.05) after statistical adjustment for age and fat mass, whereas no differences were noted in trunk or abdominal subcutaneous fat. A similar pattern of differences in trunk, subcutaneous, and intra-abdominal fat was observed in subsamples of pre- and postmenopausal women matched for age or fat mass. Our data and that of others suggest that early postmenopausal status is associated with a preferential increase in intra-abdominal fat that is independent of age and total adiposity. Thus, CT and MRI should be used when examining menopause-related changes in body fat distribution.

Effect of menopausal status on insulin-stimulated glucose disposal: comparison of middle-aged premenopausal and early postmenopausal women.

OBJECTIVE: Studies in animal models suggest that ovarian hormone deficiency is associated with the development of insulin resistance. In women, ovarian hormone levels are dramatically reduced after the menopause transition. However, the effect of the menopause transition on insulin sensitivity is unclear. Thus, we examined the effect of menopausal status on insulin sensitivity. RESEARCH DESIGN AND METHODS: Insulin-stimulated glucose disposal was measured in 43 middle-aged premenopausal women (47 +/- 3 years of age) during the luteal phase of the menstrual cycle and 40 early postmenopausal women (51 +/- 4 years; time since menopause, 21 +/- 13 months) using the hyperinsulinemic-euglycemic clamp technique. Body composition was measured by dual-energy X-ray absorptiometry and abdominal fat distribution by computed tomography RESULTS: No difference in fat-free mass (FFM) was found between groups. Total body (P < 0.01), subcutaneous abdominal (P < 0.05), and intra-abdominal (P < 0.01) adiposity were greater in postmenopausal women compared with premenopausal women. No differences in insulin-stimulated glucose disposal were found between premenopausal and postmenopausal women on an absolute basis (pre, 436 +/- 130 vs. post, 446 +/- 120 mg/min), when expressed relative to FFM (pre, 10.7 +/- 3.0 vs. post, 11.5 +/- 3.6 mg x kg(-1) FFM x min(-1)) or when statistically adjusted for FFM (pre, 436 +/- 125 vs. post, 445 +/- 126 mg/min). CONCLUSIONS: These results suggest that menopausal status does not affect insulin sensitivity, as measured by the hyperinsulinemic-euglycemic clamp technique.

Prediction of endometrial ablation success according to perioperative findings.

OBJECTIVE: The aim of this study was to determine which factors in the perioperative period influence the success of endometrial ablation in alleviating menorrhagia. STUDY DESIGN: We performed a retrospective chart review of 120 women aged 27 to 49 years who underwent endometrial ablation after 2 months of preoperative treatment with danazol (Danocrine, 800 mg/d orally) or leuprolide (Lupron, 3.75 mg in one intramuscular injection each month). Patients who required medical management or additional operations to control the vaginal bleeding during follow-up (median follow-up, 37 weeks) were considered to have ablation failures. RESULTS: Sixty-three percent of patients (76/120) had a successful procedure. The chance of success was greater if a cavity of normal appearance was found (odds ratio, 2.3; P =.04). The finding of an intramural fibroid before the procedure resulted in a reduced trend toward success (odds ratio, 0.4; P =.06). The use of danazol pretreatment improved the rate of success overall (odds ratio, 2.2; P =.05) and especially among women <40 years old (P =.01) CONCLUSION: Perioperative findings may provide useful information in counseling patients regarding endometrial ablation. Success is greater among patients with a normal intrauterine cavity and after preoperative treatment with danazol.

Effect of menopausal status on body composition and abdominal fat distribution.

OBJECTIVE: Preliminary studies suggest that the menopause transition is associated with deleterious changes in body composition and abdominal fat distribution. Limitations of the methodology used in these studies, however, render their conclusions controversial. Thus, the present study used radiologic imaging techniques to examine the effect of menopausal status on body composition and abdominal fat distribution. DESIGN: Cross-sectional. SUBJECTS: Fifty-three healthy, middle-aged, premenopausal women (mean+/-SD; 47+/-3 y) and 28 early-postmenopausal women (51+/-4 y). MEASUREMENTS: Total and regional body composition by dual energy X-ray absorptiometry and abdominal fat distribution by computed tomography. RESULTS: No differences in total body fat-free mass or appendicular skeletal muscle mass were noted between groups. In contrast, total body fat mass was 28% higher (23+/-7 vs 18+/-7 kg) and percentage fat 17% higher (35+/-6 vs 30+/-9%; both P<0.01) in postmenopausal women compared with premenopausal women. Postmenopausal women had a 49% greater intra-abdominal (88+/-32 vs 59+/-32 cm2; P<0.01) and a 22% greater abdominal subcutaneous fat area (277+/-93 vs 227+/-108 cm2; P<0.05) compared to premenopausal women. The menopause-related difference in intra-abdominal fat persisted (P<0.05) after statistical adjustment for age and total body fat mass, whereas no difference in abdominal subcutaneous fat was noted. A similar pattern of differences in total and abdominal adiposity was noted in sub-samples of pre- and postmenopausal women matched for age or fat mass. CONCLUSION: Our data suggest that early-postmenopausal status is associated with a preferential increase in intra-abdominal fat that is independent of age and total body fat mass. International Journal of Obesity (2000) 24, 226-231

Relation of regional fat distribution to insulin sensitivity in postmenopausal women.

OBJECTIVE: To examine the relation between insulin sensitivity and total and regional body fat in nonobese postmenopausal women. DESIGN: Cross-sectional study. SETTING: A clinical research center. PATIENT(S): Twenty-seven women in the early postmenopausal period, with a mean (+/-SD) age of 50.8 +/- 4.1 years, who had had their last menstrual period 6 months to 3 years before the study. None were taking hormone replacement therapy, and all had an FSH level of >35 mIU/mL, a body mass index of <30 kg/m2, and a waist circumference of <94 cm. INTERVENTION(S): Computed tomography scans at the L4-5 vertebral disk space, dual-photon x-ray absorptiometry scans, and euglycemic hyperinsulinemic clamps were performed. MAIN OUTCOME MEASURE(S): Intraabdominal fat, subcutaneous abdominal fat, sagittal diameter, total body fat, percent body fat, and insulin sensitivity. RESULT(S): The natural log of insulin sensitivity correlated significantly with intraabdominal fat (r = -.39), subcutaneous fat (r = -.43), and sagittal diameter (r = -.48). After adjusting for total fat, sagittal diameter remained significantly related to insulin sensitivity. CONCLUSION(S): Central abdominal fat is inversely and independently related to insulin sensitivity after adjusting for total fat in women in the early postmenopausal period. Efforts to reduce either subcutaneous abdominal fat or intraabdominal fat should be helpful in reducing the risk of noninsulin-dependent diabetes mellitus in postmenopausal women.

Effect of prolactin on follicle-stimulating hormone receptor binding and progesterone production in cultured porcine granulosa cells.

OBJECTIVE: To determine the effect of prolactin (PRL) on follicle-stimulating hormone receptor (FSH-R) binding and progesterone (P) production in cultured porcine granulosa cells. DESIGN: Controlled experiment. SETTING: Academic research laboratory. INTERVENTION(S): Immature granulosa cells were cultured in a serum-free medium. All cell populations were supplemented with porcine (p) FSH and cultured in the absence or presence of ovine (o) PRL. MAIN OUTCOME MEASURE(S): Specific pFSH-R binding and P in medium. RESULT(S): In the control cells, FSH-R binding increased 31-fold and P production increased 700-fold by day 4. Physiologic levels of oPRL potentiated the action of pFSH and resulted in a further 50% increase in pFSH-R binding and P production by day 4 over that in controls. In contrast, higher concentrations of oPRL blocked the rise in both pFSH-R binding and P production. The alteration in pFSH-R binding was associated with a change in FSH-R number. CONCLUSION(S): Physiologic levels of PRL amplify the stimulatory effects of FSH on the acquisition of the FSH-R and P production in cultured granulosa cells. Higher concentrations of PRL cause a decrease in FSH-R binding and P production. Prolactin may act as a "co-gonadotropin" and fine-tune the process of folliculogenesis by altering the acquisition of granulosa FSH receptors.

Effect of short-term medroxyprogesterone acetate on left ventricular mass: role of insulin-like growth factor-1.

Previous studies using 17beta-estradiol and medroxyprogesterone acetate (MPA) have shown that hormone replacement therapy (HRT) increases left ventricular mass (LVM). To determine if insulin-like growth factor-1 (IGF-1) is associated with the increase in LVM, we measured IGF-1 and IGF-binding protein-3 (IGFBP-3) levels in 19 postmenopausal women before and after 8 weeks of oral treatment with MPA 5 mg/d. LVM was measured by two-dimensional echocardiography. Changes in IGF-1, IGFBP-3, and LVM from baseline were analyzed by paired ttest. Regression analysis was used to determine if changes in the IGF-1 axis with MPA treatment affect the increase in LVM. LVM increased 4.4% during the study (P = .006 vbaseline). IGF-1 increased 17% with MPA (P = .008), whereas IGFBP-3 did not change. The IGF-1/IGFBP-3 ratio increased 16.8% (P = .0003). Regression analysis of LVM with IGF-1, IGFBP-3, and the IGF-1/IGFBP-3 ratio suggested that IGF-1 during MPA therapy explains 2.4% and the IGF-1/IGFBP-3 ratio explains 3.2% of the variation in LVM. There was no effect of IGFBP-3 on LVM. Most of the variation in LVM with MPA (90.5%) was explained by baseline LVM. The IGF-1/IGFBP-3 ratio on MPA treatment was inversely related to the change in LVM: women with a lower LVM at baseline had the greatest increase in LVM with MPA. These findings suggest that MPA increases IGF-1 and LVM. Because the increase in IGF-1 with MPA treatment explains a fraction of the increase in LVM, other mechanisms must also be operative.

Hormonal and physiological correlates of energy expenditure and substrate oxidation in middle-aged, premenopausal women.

An understanding of the hormonal and physiological correlates of energy expenditure and substrate oxidation in middle-aged women will increase our knowledge of factors that promote changes in energy balance and adiposity. We measured resting and postprandial energy expenditure and substrate oxidation in 59 middle-aged, premenopausal women (mean+/-sD age, 47+/-2 yr) to examine the hormonal and physiological correlates of energy and substrate metabolism. Energy expenditure and substrate oxidation were measured at rest using indirect calorimetry and urinary nitrogen excretion and for 180 min after the ingestion of a liquid meal (10 kcal/kg fat-free mass; 410+/-44 Cal). Fasting hormone levels were measured by RIA, glucose tolerance was determined by a 75-g oral glucose tolerance test, body composition was measured by dual energy x-ray absorptiometry, and peak aerobic capacity was determined by a treadmill test. Using stepwise regression analysis, we found that resting energy expenditure was predicted by fat-free mass and serum leptin concentration (r2 = 66%; P < 0.01), fat oxidation was predicted by resting energy expenditure (r2 = 17%; P < 0.01), and carbohydrate oxidation was predicted by serum leptin and appendicular skeletal muscle mass (r2 = 21%;P < 0.01). Novariables were related to postprandial energy expenditure or substrate oxidation. We conclude that in middle-aged, premenopausal women, variation in resting energy expenditure and substrate oxidation is primarily explained by fat-free mass and serum leptin levels. Thus, changes in metabolically active tissue mass or leptin concentration may partially contribute to changes in resting energy expenditure or substrate oxidation in middle-aged women.

Effect of short-term hormone replacement therapy on left ventricular mass and contractile function.

OBJECTIVE: To determine the effect of hormone replacement therapy (HRT) on cardiac structure and function and whether these changes are related to changes in blood volume. DESIGN: Open-label pilot study. SETTING: Academic medical center. PATIENT(S): Eighteen healthy postmenopausal women. INTERVENTION(S): We administered medroxyprogesterone acetate orally, 5 mg/d for 2 months followed by 2 months of oral sequential 17beta-estradiol, 1 mg/d plus medroxyprogesterone acetate, 10 mg/d for the last 12 days of each month. MAIN OUTCOME MEASURE(S): Cardiac output, stroke volume, heart rate, end diastolic volume, end systolic volume, ejection fraction, and left ventricular mass were measured by echocardiography; blood and plasma volumes were measured using 125I-albumin dilution. RESULT(S): Cardiac output, stroke volume, left ventricular mass, end diastolic volume, and ejection fraction increased by 12.8%, 11.7%, 9.4%, 7.2%, and 10.9%, respectively, by 16 weeks. End systolic volume decreased, whereas heart rate was unaffected. There was a significant increase in blood volume (5.2%) and plasma volume (4.8%) from baseline during treatment, which could explain the increased cardiac output but not the increased ejection fraction. CONCLUSION(S): Hormone replacement therapy causes modest but significant increases in cardiac output, ejection fraction, and left ventricular mass. These pilot data suggest a direct myocardial effect of HRT that is preload independent.

Menopause, central body fatness, and insulin resistance: effects of hormone-replacement therapy.

In addition to being associated with termination of reproductive life in women, the menopause coincides with an increase in several comorbidities including cardiovascular disease. This increase in the prevalence of cardiovascular disease in the postmenopausal years has been partially attributed to adverse effects of estrogen deficiency on plasma lipid-lipoprotein levels and on the cardiovascular system, although other factors are contributing. Central body fatness and insulin resistance are components of a cluster of metabolic abnormalities which also increases the risk of cardiovascular disease. This review summarizes studies that have examined the effects of the menopause transition and of estrogen-replacement therapy on central body fatness and insulin resistance. Review of cross-sectional studies suggests that the menopause transition is associated with an increase in abdominal and visceral adipose tissue accumulation, as measured either with dual X-ray absorptiometry or computed tomography. These results appear to be independent of the aging process and total body fatness. In general, cross-sectional studies using circumference measurements did not find any significant effect of the menopause. Longitudinal studies also support that accumulation of central body fatness accelerates with menopause. The effects of the menopause on insulin resistance appear to be moderate, if any, although available studies are clearly insufficient to draw firm conclusions. The majority of interventional studies support the notion that hormone-replacement therapy attenuates the accumulation of central fat in postmenopausal women, compared with control or placebo-treated women. Retrospective comparisons of hormone users and nonusers also support a protective effect of hormone replacement on fat distribution. Moderate effects of estrogen therapy were found on insulin resistance in postmenopausal women, although long-term, controlled trials using accurate measurements of insulin sensitivity are lacking. Treatment with progestins exerts moderate deleterious effects on insulin sensitivity, which may be attributable to the partial androgenicity of progestins used. It is concluded that part of the increased incidence of cardiovascular disease in postmenopausal women may be attributable to increased central body fatness. Therapies aiming at preventing these changes in fat distribution such as hormone-replacement therapy, diet or exercise are likely to provide long-term cardiovascular and metabolic benefits for women's health.

Transvaginal ultrasonographic diagnosis of uterine septa.

OBJECTIVE: To ascertain the sensitivity of transvaginal ultrasound as a screening tool in diagnosing patients with uterine septa. STUDY DESIGN: In this descriptive, retrospective study, the medical records of all patients who had hysteroscopic resection of uterine septa between 1990 and 1996 were reviewed. Specific preoperative imaging techniques were noted, and the sensitivity of transvaginal ultrasonography in correctly identifying the septum was calculated. RESULTS: During the seven-year period, 27 of 39 total patients undergoing hysteroscopic metroplasty had preoperative transvaginal ultrasonography. Twenty-two of the 27 ultrasonograms correctly identified the uterine septum, for a sensitivity of 81%. CONCLUSION: This was the largest study to date that specifically assessed the sensitivity of transvaginal ultrasonography as a reliable method of diagnosing uterine septa. It appears justifiable to use it as the initial screening tool for an accurate evaluation of uterine septa.

Hormone replacement therapy: cardiovascular benefits for aging women.

Observational studies suggest that hormone replacement therapy (HRT) reduces the risk of coronary artery disease by approximately 50%. This review focuses on possible mechanisms for this reduction in disease risk. HRT reverses many of the lipid and lipoprotein change associated with menopause, and the route of hormone delivery influences these changes. Oral HRT improves serum markers of clotting, although it may increase the risk of deep vein thrombosis. Endothelial function, particularly endothelium-dependent vasodilation, improves with estrogen. Central body fat appears to be reduced with oral HRT, possibly reducing the risk of coronary artery disease. Insulin sensitivity, which worsens after menopause, may be improved with HRT. Global systolic function, as measured by ejection fraction, may improve with oral HRT. Understanding how HRT regimens influence cardiovascular risk may allow physicians to make intelligent choices about HRT for particular patients.

Transvaginal ultrasonographic assessment of Hyskon or lactated Ringer's solution instillation after laparoscopy: randomized, controlled study.

We sought to evaluate two common fluids placed in the pelvis after pelvic surgery for their ability to remain in the pelvis for a time thought adequate for prevention of adhesions. Thirteen patients undergoing operative laparoscopy were randomized to receive 250 ml 32% dextran 70 (Hyskon), 250 ml lactated Ringer's solution, or no fluid (control) at the end of surgery. Serial transvaginal ultrasonograms were obtained at 1 hr, 3 hr, 6 hr, 24 hr, 96 hr (4 days), and 168 hr (7 days) after surgery. Patients were asked about side effects of fluid instillation. The volume of lactated Ringer's solution declined rapidly after instillation, with no significant difference from control at 24 hr (12 ml versus 7 ml). The volume of Hyskon did not decline rapidly by 24 hr and remained higher than the volume in controls or those receiving lactated Ringer's solution (188 ml, P = 0.003). Although the volume of Hyskon remained higher than that of lactated Ringer's solution or fluid volume in control patients by days 4 and 7, this difference did not reach statistical significance (45 ml versus 7 ml and 14 ml respectively, P = 0.39, on day 4). Patients in all groups noted abdominal pain. One patient who received Hyskon developed severe vulvar edema and another developed dyspnea. We conclude that the volume of Hyskon in the peritoneal cavity after laparoscopy does not decline as rapidly as does that of lactated Ringer's solution; however, significant side effects may limit its usefulness. Transvaginal ultrasonography is useful in monitoring fluids placed in the pelvis for prevention of adhesions.

Development of a sensitive porcine granulosa cell bioassay for follicle-stimulating hormone (FSH).

PURPOSE: Our objective was to develop a sensitive in vitro bioassay for follicle-stimulating hormone (FSH) that does not require the housing of animals in a research facility. MATERIALS AND METHODS: Porcine granulosa cells from 1- to 3-mm follicles were cultured on laminin for 48 hr in serum-free medium in the absence or presence of FSH or with other purified pituitary hormones, supplemented with 19-OH androstenedione. Estradiol accumulation in medium per microgram of DNA of cells was determined as a reflection of FSH-induced aromatase activity. RESULTS: FSH (0.01-10 ng/ml) caused a dose-dependent increase in estradiol production per microgram of DNA, with 1, 10, and 100 ng/ml significantly higher than control. Porcine FSH was approximately two fold more biopotent than rat FSH in this system. Higher doses of FSH (100 ng/ml) caused less estradiol accumulation, presumably reflecting FSH receptor down regulation. No other pituitary hormone produced significant estradiol accumulation. Unextracted serum from a patient with premature ovarian failure (10-50 microliters) was tested in parallel to purified rat FSH (0-50 ng/ml) in this system, resulting in similar estradiol accumulation per microgram of DNA. CONCLUSIONS: We have developed a porcine granulosa cell bioassay for FSH which is sensitive, is specific for FSH, and does not require the housing of animals on site. It can be completed by a technician within 4 working days and can detect FSH in a sample of human serum.

Adhesion proteins increase cellular attachment, follicle-stimulating hormone receptors, and progesterone production in cultured porcine granulosa cells.

We sought to determine the influence of different constituents of the extracellular matrix on porcine granulosa cell function by assessing cellular attachment, cellular morphology, follicle-stimulating hormone (FSH) receptors, and progesterone production. Cells from immature porcine ovarian follicles were cultured for up to 6 days in serum-free medium containing porcine FSH (pFSH, 10 ng/ml) in culture dishes either uncoated or coated with one of the following adhesion proteins: gelatin (1 mg/cm2), fibronectin (1 microgram/cm2), laminin (1 microgram/cm2), type I collagen (10 micrograms/cm2), or type IV collagen (7.8 micrograms/cm2). Fibronectin, laminin, type I collagen, and type IV collagen increased cellular attachment significantly (P < 0.05). All adhesion proteins except gelatin influenced cellular morphology. Cells cultured on laminin or type IV collagen formed dense clusters of rounded cells. Cells cultured in dishes coated with each adhesion protein except gelatin had higher 125I-pFSH binding per cell than cells cultured in uncoated dishes, with increases of 7- to 12-fold over control (P < 0.05). All adhesion proteins increased progesterone production, ranging from 10- to 50-fold over control (P < 0.05). In summary, not only did adhesion proteins increase attachment to the dishes but they also increased FSH receptors and differentiated function (progesterone production) of granulosa cells from immature porcine ovarian follicles.