Cynthia K. Sites

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.

Menopause‐Related Changes in Body Fat Distribution

Abstract: 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.

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 womens health. Coronary Artery Dis 9:503–511

Menopause-related differences in inflammation markers and their relationship to body fat distribution and insulin-stimulated glucose disposal☆

OBJECTIVE To determine whether postmenopausal status is associated with elevated plasma inflammation markers compared to premenopausal status, and how this explains differences in fat distribution and insulin-stimulated glucose disposal. DESIGN Cross-sectional. SETTING Clinical research center. PATIENT(S) Forty-five premenopausal women and 44 postmenopausal women. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) were measured by ELISA. Intraabdominal, subcutaneous abdominal, and total fat were measured by computed tomographic scan and dual-photon x-ray absorptiometry. Insulin-stimulated glucose disposal was measured by euglycemic clamp. RESULT(S) The TNF-alpha was higher in postmenopausal compared to premenopausal women (4.81 +/- 1.99 vs. 3.54 +/- 0.85 pg/mL). Interleukin-6 and CRP did not differ by menopausal status. In both premenopausal and postmenopausal women, CRP was related positively to total fat. The CRP was related to intraabdominal fat only in postmenopausal women and was negatively related to insulin-stimulated glucose disposal in both premenopausal and postmenopausal women. CONCLUSION(S) Postmenopausal status is characterized by higher TNF-alpha. The CRP may be associated with increased cardiovascular risk in postmenopausal women by its association with higher intraabdominal fat. Higher CRP is associated with lower insulin-stimulated glucose disposal in both premenopausal and postmenopausal women.

Estradiol Interacts with the Cholinergic System to Affect Verbal Memory in Postmenopausal Women: Evidence for the Critical Period Hypothesis

Estradiol has been shown to interact with the cholinergic system to affect cognition in postmenopausal women. This study further investigated the interaction of estradiol and cholinergic system functioning on verbal memory and attention in two groups of healthy younger (ages 50-62) and older (ages 70-81) postmenopausal women. Twenty-two postmenopausal women were randomly and blindly placed on 1 mg of 17-beta estradiol orally for 1 month then 2 mg for 2 months or matching placebo pills after which they participated in three anticholinergic challenge sessions when verbal memory and attention were assessed. Subjects were administered either the antimuscarinic drug scopolamine (SCOP), the antinicotinic drug mecamylamine (MECA), or placebo. After the first challenge phase, they were crossed over to the other hormone treatment for another 3 months and repeated the challenges. Results showed that estradiol pretreatment significantly attenuated the anticholinergic drug-induced impairments on a test of episodic memory (the Buschke Selective Reminding Task) for the younger group only, while estradiol treatment impaired performance of the older group. The results suggest that younger subjects may experience more cholinergic benefit from estradiol treatment than older subjects, supporting the concept of a critical period for postmenopausal estrogen use.

Estrogen treatment effects on anticholinergic-induced cognitive dysfunction in normal postmenopausal women.

Estrogen has been shown to interact with the cholinergic system and influence cognition in animal models. This study investigated the interaction of estrogen and cholinergic system functioning and the effects of this interaction on cognitive task performance in healthy older women. Fifteen post-menopausal women were randomly and blindly placed on 1 mg of 17-β estradiol or placebo for 3 months after which they participated in five anticholinergic challenge sessions, where they were administered one of two doses of the antimuscarinic drug scopolamine (SCOP) or the antinicotinic drug mecamylamine (MECA) or placebo. After the first challenge phase, they were crossed over to the other hormone treatment for another 3 months and repeated the challenges. Performance in multiple domains of cognition was assessed during anticholinergic drug challenge, including attention and verbal and nonverbal learning and memory. Results showed that estrogen pretreatment attenuated the anticholinergic drug-induced impairments on tests of attention and tasks with speed components. This study is the first to demonstrate the interaction of estrogen and the cholinergic system and the effects on cognitive performance in humans. The results suggest that estrogen status may affect cholinergic system tone and may be important for cholinergic system integrity.

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 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.

Metabolic effects of soy supplementation in postmenopausal Caucasian and African American women: a randomized, placebo-controlled trial.

OBJECTIVE We sought to determine the effect of daily soy supplementation on abdominal fat, glucose metabolism, and circulating inflammatory markers and adipokines in obese, postmenopausal Caucasian and African American women. STUDY DESIGN In a double-blinded controlled trial, 39 postmenopausal women were randomized to soy supplementation or to a casein placebo without isoflavones. In all, 33 completed the study and were analyzed. At baseline and at 3 months, glucose disposal and insulin secretion were measured using hyperglycemic clamps, body composition and body fat distribution were measured by computed tomographic scan and dual energy x-ray absorptiometry, and serum levels of C-reactive protein, interleukin-6, tumor necrosis factor-alpha, leptin, and adiponectin were measured by immunoassay. RESULTS Soy supplementation reduced total and subcutaneous abdominal fat and interleukin-6. No difference between groups was noted for glucose metabolism, C-reactive protein, tumor necrosis factor-alpha, leptin, or adiponectin. CONCLUSION Soy supplementation reduced abdominal fat in obese postmenopausal women. Caucasians primarily lost subcutaneous and total abdominal fat, and African Americans primarily lost total body fat.

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 Ringers 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 Ringers 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 Ringers solution (188 ml, P = 0.003). Although the volume of Hyskon remained higher than that of lactated Ringers 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 Ringers solution; however, significant side effects may limit its usefulness. Transvaginal ultrasonography is useful in monitoring fluids placed in the pelvis for prevention of adhesions.