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Purpose: This study aimed to find the associations between vasomotor symptoms (VMS) and metabolic syndrome (MetS) in Chinese middle-aged women in a cross-sectional study., Methods: A total of 675 participants were recruited from an urban Chinese community. MetS was defined by the 2009 criteria of the Joint Interim Statement. VMS including hot flashes and sweats, blood pressure, weight, height, waist circumference (WC), serum glucose, triglycerides, high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), estradiol, and follicle-stimulating hormone (FSH) were collected., Results: The presence of hot flashes was independently associated with the risk of MetS after adjusting for age, menopausal status, FSH log , estradiol log , and physical activity (odds ratio: 1.98, 95% confidence interval: 1.21-3.24, p  = 0.006). Both hot flashes and sweats were also independently associated with WC (for hot flashes, p  = 0.016; and for sweats, p  = 0.007) and triglycerides (for hot flashes, p  = 0.041; and for sweats, p  = 0.014) significantly. However, VMS were not significantly associated with blood pressure, glucose, HDL, and LDL., Conclusion: Women with hot flashes had a higher risk of MetS. Both hot flashes and sweats were related to a higher amount of central fat indicated by WC and higher triglycerides, but were not related to blood pressure, glucose, and HDL in Chinese women.

Objectives: Menopausal women suffer from various menopausal symptoms due to estrogen deficiency caused by the decline of ovarian function. Estrogen plays a key role in regulating body metabolism in women. Its effects on skeletal muscle metabolism, however, need to be elucidated. The aim of our study was to investigate the effects of 17β-estradiol (E2) and/or running exercise on skeletal muscle metabolism in ovariectomized (OVX) mice. Methods: Female C57BL/6J mice were divided into five groups: sham operated, OVX, OVX with running, OVX with E2, and OVX with running and E2. The estrous cycle, body weight, and body composition of the mice were monitored after the operation. The animals were sacrificed after treatment for 7 weeks. The serum and tissue samples were collected. Results: The results showed increased fat mass, reduced lean mass, impaired mitochondrial function, and inhibited mammalian target of rapamycin complex 1 signaling pathway in skeletal muscle of OVX mice. The treatment of OVX mice with E2 and running had better effects on ameliorating these impairments than running exercise or E2 alone. Conclusions: The combined intervention of E2 and running exercise ameliorated energy metabolism of skeletal muscle and body composition in OVX mice, which exceled over E2 treatment or running exercise alone.

Objectives: This study aimed to compare metabolic syndrome and its components in naturally and surgically menopausal women., Methods: This is a longitudinal study, with incident case and control groups, conducted on 446 women participants of the Tehran Lipid and Glucose Study, who experienced surgical or natural menopause over a 10-year period. In both groups, data collection was conducted using questionnaires including information on demographic, reproductive and metabolic characteristics at baseline and again after 3 years. Physical examinations and the biochemical profiles were also assessed., Results: During the follow-up, metabolic syndrome was observed in 28.7% and 32.5% of the naturally menopause and surgically menopausal women, respectively. Mean fasting blood sugar and 2-h plasma glucose were significantly higher in the surgically menopause group, compared to the naturally menopause one, whereas mean systolic blood pressure was significantly higher in naturally menopausal women as compared to surgically menopause ones, after further adjustment for premenopausal status., Conclusions: Although no difference in the prevalence of metabolic syndrome in naturally menopausal women and in surgically menopausal women was found, the components of metabolic syndrome were more prevalent among those with surgical menopause.

Telomere length is a marker of cell aging, since shorter telomeres and a higher rate of telomere shortening with time are associated with poorer health status and survival. Various factors may determine telomere length and the function of the telomere maintenance system, including the hereditary load and several modifiable variables such as diet and lifestyle. Telomere length and telomerase activity were investigated extensively in a variety of diseases, such as malignancies (i.e. breast and colon cancer), cardiovascular disease and its related metabolic risk factors, cognitive, mental and psychiatric conditions, and many others. Some evidence points at an association between longer endogenous estrogen exposure (length of reproductive years of life) and greater telomere length and lower telomerase activity. However, there is probably no correlation in regard to menopause per se or the use of hormone therapy. Changing the nutrition and implementing healthy lifestyles may improve the telomere/telomerase parameters in postmenopausal women, but better understanding of this system is still needed.

Background: Metalloproteinases (MMPs) are synthesized in the subendothelium and are involved in the atherosclerosis and cardiovascular disease process because of their major significance in vascular remodeling and plaque rupture. MMPs are also synthesized in adipose tissue during angiogenesis; however, the role of these enzymes in obesity and insulin-resistant states is still controversial., Objective: To evaluate MMP-2 activity in the circulation of overweight and obese women and in normal-weight controls, and to associate the levels of these factors with metabolic, adipose tissue and inflammation biomarkers., Methods: Plasma MMP-2 activity, adiponectin and C-reactive protein concentration, lipoprotein profile and HOMA were determined in 39 healthy women (13 normal weight and 26 overweight/obese)., Results: Overweight/obese women were older (p < 0.001) than normal-weight women; 20/26 of overweight/obese women were postmenopausal compared with 4/13 of normal-weight women. Overweight/obese women had significantly higher plasma activity of MMP-2 than controls (mean relative area: 0.81 (range 0.4-1.92) vs. 1.33 (range 0.4-3.1); p < 0.005); this difference was lost after adjusting for menopausal status. MMP-2 activity positively correlated with waist circumference (p < 0.002), HOMA (p < 0.003), and high-sensitivity C-reactive protein (p < 0.05), apolipoprotein B (p = 0.006) and triglyceride/high density lipoprotein (HDL) cholesterol index (p < 0.001), and negatively with HDL cholesterol (p < 0.001), HDL2 cholesterol (p < 0.008), HDL3 cholesterol (p < 0.05) and adiponectin (p < 0.05). The association with HOMA and adiponectin persisted even after adjusting for menopausal status., Conclusion: Our finding of increased plasma activity of MMP-2 in overweight/obese women, associated with menopausal status, is important given that it fits in with an early stage of cardiovascular disease; the association of MMP-2 activity with obesity markers may be a link between adipose tissue and risk for cardiovascular disease.

The prevalence of major depression disorder in women is double that seen in men, with the menopause transition being associated with increased vulnerability to depression. Selective serotonin reuptake inhibitors (SSRIs), which constitute 70-80% of antidepressant prescriptions, are associated with secondary sexual dysfunction in 35-70% of users. Different strategies for approaching sexual dysfunction secondary to SSRI medication have been investigated. Most interventions fail to show significant benefit on sexual function compared to placebo; moreover, adjuvant therapies commonly result in side-effects and tolerability problems. While antidepressant-associated sexual dysfunction in women has been a concern for many years, there remains a need for more research into the optimal management of antidepressant-associated sexual dysfunction in women, including multidisciplinary approaches. Further randomized, controlled trials assessing multidisciplinary approaches are required before clinicians or patients can be confident of the benefits of any intervention. Despite the efficacy of testosterone in improving sexual function in non-depressed women, there is no information regarding the efficacy of testosterone in treating antidepressant-associated sexual dysfunction in women.

Objective: Vasoactive intestinal peptide (VIP) is a neuropeptide with elevated expression in regions that control urogenital functions. Estrogen appears to modulate VIP expression in various organs, but this effect has not been demonstrated in the vaginal wall. The aim of this study was to evaluate the influence of estrogen status on VIP expression in vessels of the vaginal wall., Methods: Surgical specimens were removed from the vaginal walls of 18 premenopausal women and 12 postmenopausal women who were given surgery for genital prolapse grade I or II. Vaginal specimens were stained with estrogen receptor-alpha (ER-α) and VIP antibodies. Levels of follicle stimulating hormone (FSH), estradiol, prolactin, fasting glucose and serum thyroxine stimulating hormone were also measured. Estrogen status was assessed on the basis of FSH and ER-α scores., Results: The vaginal walls of premenopausal women had significantly higher ER-α scores than those of menopausal women (premenopausal group, 3.6 ± 2.2; menopausal group, 1.4 ± 1.8; p = 0.01). Premenopausal women also had significantly higher levels of VIP in the vaginal wall than menopausal women (p = 0.02). Increasing age was associated with lower level of VIP staining (odds ratio 0.88; 95% confidence interval 0.78-0.99)., Conclusion: Levels of ER-α and VIP expression in the posterior vaginal wall were higher in premenopausal than in menopausal women, but VIP expression was not associated with estrogen status. Age was an independent predictor of VIP staining in vaginal wall biopsies.

The aromatase inhibitor anastrazole proved effective in the treatment of endometrial hyperplasia and postmenopausal bleeding in an obese 65-year-old woman with high operative risk. During anastrazole administration for 12 months, the endometrial thickness decreased from 9.8 mm to 2.4 mm and the control endometrial histology showed an atrophic endometrium. Uterine bleeding did not occur in the post-treatment, 3-year follow-up period. The endometrial thicknesses measured yearly by ultrasonography were 2.9, 3.5 and 3.3 mm. The plasma estradiol levels increased from < 73 pmol/l post-treatment to 112, 98 and 103 pmol/l. This case demonstrates that long-term aromatase inhibitor treatment can result in a refractory status of the endometrium and the estradiol produced in the adipose tissue does not exert a proliferative effect.

Estrogen exerts pleiotropic functions on the cardiovascular system through binding to estrogen receptors (ERs). Traditionally, ERs have been recognized as transcription factors regulating the expression of target genes. In the past decades, however, numerous studies have revealed rapid actions of estrogen in different systems, especially in non-reproductive tissues such as the cardiovascular system. At this level, estrogen triggers rapid vasodilatation, exerts anti-inflammatory effects, regulates vascular cell growth and migration, and confers protection to cardiomyocytes. These so-called 'extranuclear actions' do not require gene expression or protein synthesis and are independent of the nuclear localization of ERs. Indeed, some of these actions are elicited by ERs residing at or near the plasma membrane. Through complex interactions with membrane-associated signaling molecules such as ion channels, G proteins and the tyrosine kinase c-Src, liganded extranuclear ERs lead to the activation of downstream cascades such as mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-OH kinase (PI3K). These cascades are responsible for important cardiovascular actions of estrogen, for instance, the activation of nitric oxide synthesis or the remodeling of the endothelial actin cytoskeleton. Moreover, these cascades play crucial roles in regulating the expression of target proteins implicated in cell proliferation, apoptosis, differentiation, movement and homeostasis. Recent advancements in the characterization of the molecular basis of the extranuclear signaling of estrogen help us to understand the biological functions of estrogen and would be beneficial in elucidating current controversies on estrogen's clinical efficacy in the cardiovascular system.

Objective: To establish the relationship between androgens and cardiovascular disease (CVD) risk factors in the menopausal transition., Methods: A total of 124 women were divided into four groups: 29 premenopausal (PreM), 35 women in the menopausal transition still menstruating (MTM), 29 women in the menopausal transition with 3-6 months amenorrhea (MTA), and 31 postmenopausal women (PostM). Levels of triglycerides, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, glucose and insulin were assayed in all samples and waist circumference was measured. In a subgroup of 83 women (19 PreM, 21 MTM, 28 MTA and 15 PostM), levels of total testosterone, androstenedione, dehydroepiandrosterone sulfate (DHEAS) and estradiol were determined. The free androgen index, Homeostasis Model Assessment (HOMA) index, Quantitative Insulin Sensitivity Check Index (QUICKI) and McAuley index, estradiol/total testosterone and triglyceride/HDL cholesterol ratios were calculated., Results: Androstenedione was higher in MTA vs. PostM women (p < 0.05); DHEAS was higher in PreM women vs. the other three groups (p < 0.05). Sex hormone binding globulin (SHBG) in MTM women was higher than in MTA women (p < 0.05); the free androgen index was lower in MTM women than in MTA and PostM women. SHBG and the free androgen index showed negative and positive correlations, respectively with waist circumference, insulin resistance and lipids. In a multiple regression analysis, considering waist circumference, neither free androgen index nor SHBG showed significant differences between groups. The waist circumference correlated only with SHBG (p = 0.022) and correlations between SHBG and insulin resistance markers continued to be significant, but relationships between SHBG and lipoproteins and all correlations found with free androgen index were lost., Conclusions: An increment in the androgenic milieu that correlates with abdominal fat, insulin resistance and atherogenic lipoproteins becomes evident after the menopausal transition and suggests that evaluation of cardiovascular disease risk in these women should include androgens, considering that abdominal obesity is one of the main determinants of the relationship between androgenic parameters and cardiovascular risk factors.

A fairly consistent finding in work on the menopause and hormone replacement therapy is the positive effect of estrogen on connective tissue and its turnover. The menopause has been shown repeatedly to have a negative effect on the connective tissue in the dermis of the skin. Such an effect is prevented and in some cases reversed with estrogen therapy. This is similar to what happens in bone matrix. Similarly, the media in the carotid has been shown to undergo the same change with the menopause and with estrogen therapy as the dermis. The carotid artery media is increased in menopausal women on estrogen therapy and is thinner in untreated women. Recently, new information has revealed that the menopause, i.e. estrogen deprivation, has similar effects on the connective tissue of intervertebral discs. In aged intervertebral discs, the predominant collagen is type III, not type I, which is the predominant collagen in skin and bone, although skin has additional type III. These negative changes are once again prevented or reversed with estrogen therapy. This effect probably also extends to the extracellular non-collagenous matrix in all these systems, i.e. skin, carotid and intervertebral discs. The common thread is that estrogen has profound effects on connective tissue turnover, no matter the site. This has far-reaching implications not only in maintaining the structure and aesthetic appearance of tissue, but also the strength and stiffness of various tissues and the functioning of neighboring and surrounding organs.