The relationship between iron status and the restless legs syndrome (RLS) was examined in 18 elderly patients with RLS and in 18 matched control subjects. A rating scale with a maximum score of 10 was used to assess the severity of RLS symptoms. Serum ferritin levels were reduced in the RLS patients compared with control subjects (median 33 micrograms/l vs. 59 micrograms/l, p < 0.01, Wilcoxon signed rank test); serum iron, vitamin B12 and folate levels and haemoglobin levels did not differ between the two groups. Serum ferritin levels were inversely correlated with the severity of RLS symptoms (Spearman's rho -0.53, p < 0.05). Fifteen patients with RLS were treated with ferrous sulphate for 2 months. RLS severity score improved by a median value of 4 points in six patients with an initial ferritin < or = 18 micrograms/l, by 3 points in four patients with ferritin > 18 micrograms/l, < or = 45 micrograms/l and by 1 point in five patients with ferritin > 45 micrograms/l, < 100 micrograms/l. Iron deficiency, with or without anaemia, is an important contributor to the development of RLS in elderly patients, and iron supplements can produce a significant reduction in symptoms.

Abstract-The compliance of large elastic arteries in the cardiothoracic region decreases with advancing age/menopause and plays an important role in the increased prevalence of cardiovascular diseases in postmenopausal women. We determined whether oxidative stress contributes to the reduced large elastic artery compliance of postmenopausal women. Carotid artery compliance was measured during acute intravenous infusions of saline (baseline control) and supraphysiological doses of the potent antioxidant ascorbic acid in premenopausal (nϭ10; 23Ϯ1; meanϮSE) and estrogen-deficient postmenopausal (nϭ21; 55Ϯ1 years) healthy sedentary women. Carotid artery compliance was 56% lower in postmenopausal compared with premenopausal women during baseline control (PϽ0.0001 ). Carotid artery diameter, blood pressure, and heart rate were unaffected by ascorbic acid. In the pooled population, the change in arterial compliance with ascorbic acid correlated with baseline waist-to-hip ratio (rϭ0.56; Pϭ0.001), plasma norepinephrine (rϭ0.58; Pϭ0.001), and LDL cholesterol (rϭ0.54; Pϭ0.001). These results suggest that oxidative stress may be an important mechanism contributing to the reduced large elastic artery compliance of sedentary, estrogen-deficient postmenopausal women. Increased abdominal fat storage, sympathetic nervous system activity, and LDL cholesterol may be mechanistically involved in oxidative stress-associated suppression of arterial compliance in postmenopausal women. Key Words: aging Ⅲ cholesterol Ⅲ oxidative stress C ardiovascular disease (CVD) is the leading cause of death in women in the United States. 1 "Vascular aging" has been emphasized recently as the major risk factor for development of CVD. 2 One clinically important change that occurs with vascular aging is a reduction in the compliance of large elastic arteries within the cardiothoracic region. In turn, this contributes to a number of adverse age-associated changes, including increased aortic impedance, left ventricular hypertrophy, and reduced cardiovagal baroreflex sensitivity. [2][3][4] As such, identifying the mechanisms that contribute to reduced large elastic artery compliance with age is an important goal. 2 Cardiovascular aging in women is unique in that it appears to be delayed or occurs at a slower rate than in men during the premenopausal years, thereafter "catching up" with men during the postmenopausal period, particularly in estrogendeficient women. [5][6][7] The mechanisms underlying the accelerated cardiovascular aging of estrogen-deficient postmenopausal women are unclear but could be related in part to the development of oxidative stress. Markers of oxidative stress are higher and endogenous antioxidant defenses lower in some estrogen-deficient postmenopausal women compared with premenopausal controls. 8,9 Because oxidative stress modulates vascular smooth muscle cell (VSMC) tone, a key determinant of large artery compliance, 10,11 we hypothesized that oxidative stress may contribute to the reduced large artery compliance of estrogen-defic...

These results provide the first evidence that expression of ER alpha in vascular endothelial cells is modulated by estrogen status and may be a key determinant of vascular endothelial function in healthy pre- and postmenopausal women. ER alpha expression may influence vascular endothelial function in women by affecting protein levels and activation of eNOS.

White adipocytes in adults are typically derived from tissue resident mesenchymal progenitors. The recent identification of de novo production of adipocytes from bone marrow progenitor-derived cells in mice challenges this paradigm and indicates an alternative lineage specification that adipocytes exist. We hypothesized that alternative lineage specification of white adipocytes is also present in human adipose tissue. Bone marrow from transgenic mice in which luciferase expression is governed by the adipocyte-restricted adiponectin gene promoter was adoptively transferred to wild-type recipient mice. Light emission was quantitated in recipients by in vivo imaging and direct enzyme assay. Adipocytes were also obtained from human recipients of hematopoietic stem cell transplantation. DNA was isolated, and microsatellite polymorphisms were exploited to quantify donor/recipient chimerism. Luciferase emission was detected from major fat depots of transplanted mice. No light emission was observed from intestines, liver, or lungs. Up to 35% of adipocytes in humans were generated from donor marrow cells in the absence of cell fusion. Nontransplanted mice and stromal-vascular fraction samples were used as negative and positive controls for the mouse and human experiments, respectively. This study provides evidence for a nontissue resident origin of an adipocyte subpopulation in both mice and

Suppressing sex hormones in women for 1 wk reduces resting energy expenditure (REE). The effects of more chronic suppression on REE and other components of total energy expenditure (TEE), and whether the reduction in REE is specifically due to loss of estradiol (E2), are not known. We compared the effects of 5 mo of sex hormone suppression (gonadotropin releasing hormone agonist therapy, GnRHAG) with placebo (PL) or E2 add-back therapy on REE and the components of TEE. Premenopausal women received GnRHAG (leuprolide acetate 3.75 mg/mo) and were randomized to receive transdermal therapy that was either E2 (0.075 mg/d; n = 24; means ± SD, aged = 37 ± 8 yr, BMI = 27.3 ± 6.2 kg/m(2)) or placebo (n = 21; aged = 34 ± 9 yr, BMI = 26.8 ± 6.2 kg/m(2)). REE was measured by using a metabolic cart, and TEE, sleep EE (SEE), exercise EE (ExEE, 2 × 30 min bench stepping), non-Ex EE (NExEE), and the thermic effect of feeding (TEF) were measured by using whole room indirect calorimetry. REE decreased in GnRHAG+PL [mean (95% CI), -54 (-98, -15) kcal/d], but not GnRHAG+E2 [+6 (-33, +45) kcal/d] (difference in between-group changes, P < 0.05). TEE decreased in GnRHAG+PL [-128 (-214, -41) kcal/d] and GnRHAG+E2 [-96 (-159, -32) kcal/d], with no significant difference in between-group changes (P = 0.55). SEE decreased similarly in both GnRHAG+PL [-0.07 (-0.12, -0.03) kcal/min] and GnRHAG+E2 [-0.07 (-0.12, -0.02) kcal/min]. ExEE decreased in GnRHAG+PL [-0.46 (-0.79, -0.13) kcal/min], but not GnRHAG+E2 [-0.30 (-0.65, +0.06) kcal/min]. There were no changes in TEF or NExEE in either group. In summary, chronic pharmacologic suppression of sex hormones reduced REE and this was prevented by E2 therapy.

Suppression of ovarian hormones in premenopausal women with gonadotropin releasing hormone agonist therapy (GnRHAG) can cause fat mass (FM) gain and fat-free mass (FFM) loss. It is unknown if this is specifically due to the decline in serum estradiol (E2). Objective To evaluate the effects of GnRHAG with add-back of placebo (PL) or E2 on FM, FFM, and bone mineral density (BMD). An exploratory aim evaluated the effects of resistance exercise on body composition during the drug intervention. Methods Seventy healthy, premenopausal women underwent 5 months of GnRHAG and were randomized to add-back of transdermal E2 (GnRHAG+E2, n=35) or placebo (GnRHAG+PL, n=35). As part of an exploratory aim to evaluate whether exercise can minimize effects of hormone suppression, some women within each drug arm were randomized to a resistance exercise program (GnRHAG+E2+Ex, n=12; GnRHAG+PL+Ex, n=12). Results The groups did not differ in age (mean±SD) (36±8yr, 35±9yr) or BMI (both 28±6kg/m2). FFM declined in response to GnRHAG+PL (mean; 95% CI) (−0.6kg; −1.0, −0.3) but not GnRHAG+E2 (0.3kg; −0.2, 0.8) or GnRHAG+PL+Ex (0.1kg;−0.6, 0.7). Although FM did not change in either group, visceral fat area increased in response to GnRHAG+PL but not GnRHAG+E2. GnRHAG+PL caused decreased BMD at the lumbar spine and proximal femur that were prevented by E2. Preliminary data suggest that exercise may have favorable effects on FM, FFM, and hip BMD. Conclusions Suppression of ovarian E2 resulted in loss of bone and FFM and expansion of abdominal adipose depots. Failure of hormone suppression to increase total FM conflicted with previous studies of the effects of GnRHAG. Further research is necessary to understand the role of estrogen in the regulation of energy balance and fat distribution.

SYNOPSIS Evidence from basic, preclinical, and clinical research points to an important role of estradiol (E2) in the regulation of body composition and bioenergetics. There is consistent evidence from basic and preclinical research that the disruption of E2 signaling, through either genetic manipulation (e.g., estrogen receptor deletion) or surgical intervention (e.g., ovariectomy), accelerates fat accumulation, with a disproportionate increase in abdominal fat. Clinical evidence for the regulation of body composition and bioenergetics by E2 is less consistent. Evidence exists both for and against menopause as the mediator of changes in body composition. This is likely related to the prolonged nature of the menopause transition in women and the associated complexities of distinguishing effects of the loss of gonadal function from other phenomena of aging. However, a need remains to better understand the metabolic actions of estrogens in women because of the potential impact on health after the menopause.

Every year, 2 million women reach menopause in the United States, and they may spend 40% or more of their life in a postmenopausal state. In the years immediately preceding menopause—known as the menopause transition (or perimenopause)—changes in hormones and body composition increase a woman’s overall cardiometabolic risk. In this narrative review, we summarize the changes in weight, body composition, and body fat distribution, as well as the changes in energy intake, energy expenditure, and other cardiometabolic risk factors (lipid profile, glucose metabolism, sleep health, and vascular function), that occur during the menopause transition. We also discuss the benefits of lifestyle interventions in women in the earlier stages of menopause before these detrimental changes occur. Finally, we discuss how to include perimenopausal women in research studies so that women across the life‐span are adequately represented.