Decline In Estrogen Levels Research Articles

Subjective and objective measures of hot flashes

Up to 75% of women in the US report having experienced hot flashes during the menopausal transition. The purpose of this review is to describe the physiology of hot flashes, and the ways in which hot flashes have been examined by subjective report and by objective measurement. Hot flashes occur because of an activation of the heat dissipation response, possibly triggered by a hypothalamic mechanism within the context of declining estrogen levels. There is cross-population variation in the frequency of self-reported hot flashes, although cross-study comparisons are problematic because of incompatibilities in study design. Diaries are a good way to collect information on the time and severity of hot flashes, and body diagrams allow researchers to study the pattern of heat and sweating. Hot flashes can be objectively measured by increases in heart rate, finger blood flow, respiratory exchange ratio, skin temperature, and core body temperature. Sternal skin conductance is the method most highly correlated with subjective hot flash report. In a laboratory, concordance between subjective report and sternal skin conductance can approach 100%. Ambulatory monitoring allows for the tracking of hot flashes during a woman's daily routine or sleep; however, concordance is much lower with ambulatory, compared to laboratory, monitoring. The study of hot flashes at menopause provides a model for the study of any experience that can be assessed by both self-report and biometric measurement.

Pleiotropic actions of estrogen: a mitochondrial matter

Estrogen provides many beneficial effects early in life by regulating normal tissue development and several physiological functions. While estrogen replacement therapy (ERT) in women was expected to reduce the health risks associated with the age-related decline in estrogen levels during menopause, ERT also resulted in increased progression to other types of diseases. Hence, distinguishing the signaling pathways that regulate the beneficial and detrimental effects of estrogen is important for developing interventions that selectively harness the hormone's beneficial effects, while minimizing its side effects. Estrogen can minimize mitochondrial dysfunction, which is thought to contribute to aging phenotypes. Decline in estrogen levels during menopause may lead to progressive mitochondrial dysfunction and may permanently alter cellular response, including that of estrogen (i.e., ERT). This review discusses the interplay between estrogen and mitochondrial function during the aging process and suggests a potential role of mitochondria in influencing the pleiotropic action of estrogen.

Pharmacological Estrogen Administration Causes a FSH-Independent Osteo-Anabolic Effect Requiring ER Alpha in Osteoblasts

Postmenopausal osteoporosis is characterized by declining estrogen levels, and estrogen replacement therapy has been proven beneficial for preventing bone loss in affected women. While the physiological functions of estrogen in bone, primarily the inhibition of bone resorption, have been studied extensively, the effects of pharmacological estrogen administration are still poorly characterized. Since elevated levels of follicle-stimulating hormone (FSH) have been suggested to be involved in postmenopausal bone loss, we investigated whether the skeletal response to pharmacological estrogen administration is mediated in a FSH-dependent manner. Therefore, we treated wildtype and FSHβ-deficicent (Fshb−/−) mice with estrogen for 4 weeks and subsequently analyzed their skeletal phenotype. Here we observed that estrogen treatment resulted in a significant increase of trabecular and cortical bone mass in both, wildtype and Fshb−/− mice. Unexpectedly, this FSH-independent pharmacological effect of estrogen was not caused by influencing bone resorption, but primarily by increasing bone formation. To understand the cellular and molecular nature of this osteo-anabolic effect we next administered estrogen to mouse models carrying cell specific mutant alleles of the estrogen receptor alpha (ERα). Here we found that the response to pharmacological estrogen administration was not affected by ERα inactivation in osteoclasts, while it was blunted in mice lacking the ERα in osteoblasts or in mice carrying a mutant ERα incapable of DNA binding. Taken together, our findings reveal a previously unknown osteo-anabolic effect of pharmacological estrogen administration, which is independent of FSH and requires DNA-binding of ERα in osteoblasts.

Is interaction between age-dependent decline in mechanical stimulation and osteocyte–estrogen receptor levels the culprit for postmenopausal-impaired bone formation?

Declining estrogen levels during menopause are widely considered to be a major cause of age-dependent bone loss, which is primarily manifested by increased bone resorption by osteoclasts. We present accumulating evidence supporting another aspect of metabolic bone loss, suggesting that the combined interaction between age-dependent factors, namely, estrogen deficiency and reduced day-by-day activity/mechanical stimulation, directly leads to a reduction in anabolic processes. Such decreased bone formation results in diminished bone strength and failure to maintain the load-bearing competence of a healthy skeleton and to postmenopausal osteoporosis disorder. Estrogen receptors (ERs), as mediators of estrogenic actions, are essential components of bone osteocyte and osteoblast mechano-adaptive responses. ER expression appears to be upregulated by adequate circulating estrogen levels. ERα signaling pathways participate in the mechanotransduction response through obligatory "non-genomic" actions that occur independently of estrogen binding to ER and by a potentially "genomic", estrogen-dependent mode. The experimental data indicate that cross talk between the ERα-"non-genomic" and Wnt/β-catenin signaling pathways constitutes the major regulatory mechanism. This interaction uses mechanically and ER-induced prostaglandin E2 as a mediator for the downregulation of osteocyte production of sclerostin. Sclerostin suppression, in turn, is a central prerequisite for load-induced formation and mineralization of the bone matrix. It is therefore plausible that future strategies for preventing and treating postmenopausal osteoporosis may use estrogenic compounds (such as selective estrogen receptor modulators or phytoestrogens) with physical activity, to complement antiresorptive therapy, aimed at stopping further bone loss and possibly even reversing it by stimulation of bone gain.

BONE MINERAL DENSITY AND VASCULAR WALL CHARACTERISTICS IN WOMEN AFTER OVARIECTOMY AND PROLONGED HORMONE THERAPY

Osteoporosis and atherosclerosis are the most socially significant chronic non-infectious diseases. This is due to their high prevalence and medical, social and economic consequences from osteoporotic bone fractures and myocardial infarction and stroke as a result of cardiovascular diseases (CVD). The level of estrogen is essential for the formation and maintenance of bone mass in women. The sharp decline in estrogen levels after bilateral ovariectomy plays the role of trigger factor in the development of complex disorders of the bone and the cardiovascular system. Pathogenetically justified approach to the correction of the estrogen-deficient states is the use of hormone replacement therapy (HRT). To study the effect of HRT on the cardiovascular system and bone mineral density (BMD) we examined 50 women with surgical menopause which received HRT for more than a 10-year period. We studied the anthropometric and biochemical parameters (blood cholesterol and its fractions, fasting blood glucose), performed Doppler ultrasonography of head and neck vessels with measurement of pulse velocity, dual-energy x-ray absorptiometry (DEXA) for BMD estimation. Examination was carried out twice - in the early period after the operation (the first year) and after 10 years. Analysis of the cardio-vascular system and the BMD has demonstrated more severe atherosclerotic vascular changes and a greater decrease in BMD in patients who discontinued use of HRT. The severity of atherosclerosis and the level of the BMD were dependent on HRT use.

Biopsychosocial Predictors of Postmenopausal Dyspareunia: The Role of Steroid Hormones, Vulvovaginal Atrophy, Cognitive‐Emotional Factors, and Dyadic Adjustment

Although dyspareunia experienced after menopause is widely attributed to declining estrogen levels and vulvovaginal atrophy, critical reviews of the literature have suggested that these factors are incomplete as explanatory mechanisms. Little is known about psychosocial factors that may also be implicated in postmenopausal dyspareunic pain. To determine the extent to which levels of estrogens and progesterone, vulvovaginal atrophy, cognitive-emotional factors, and dyadic adjustment are predictive of postmenopausal dyspareunic pain intensity. A total of 182 postmenopausal dyspareunia sufferers underwent a structured interview concerning sociodemographic status as well as medical and pain histories, gynecological examination, cytological evaluation, a blood draw, and answered a series of self-report questionnaires. Given the large number of genital and pelvic pain variables measured, a principal components analysis was undertaken to identify a smaller number of components representing meaningful dimensions of genital and pelvic pain. Pain severity ratings during intercourse were obtained using the McGill Pain Questionnaire. Pain ratings were also obtained during gynecological assessment. Serum estrone, estradiol, and progesterone levels were measured via immunoassay. The Vaginal Atrophy Index and maturation value were used to determine vulvovaginal atrophy severity. Participants completed the Pain Catastrophizing Scale, State-Trait Anxiety Inventory, The Beck Depression Inventory-II, and Dyadic Adjustment Scale. Hormone levels were not found to be consistent predictors of pain severity. Maturation value and cognitive-emotional variables (e.g., catastrophization, depression, anxiety) were significant predictors of vestibular pain, which affected over 90% of our sample. Relationship adjustment variables were inversely associated with pain severity within several genital locations. Results suggest that the traditional hypoestrogen and vulvovaginal atrophy conceptualization of postmenopausal dyspareunia is an insufficient explanatory model, and that pain is also influenced by cognitive, affective, and dyadic factors.

Effects of vitamin E on bone turnover markers among US postmenopausal women

Increased oxidative stress and inflammation resulting from aging and declining estrogen levels can lead to increased bone loss in postmenopausal women. Alpha-tocopherol and gamma-tocopherol, the two predominant isomers of vitamin E, have antioxidant and anti-inflammatory properties, but their effects on bone metabolism have not been well studied in humans. We examined the associations between dietary and total (diet and supplements) alpha-tocopherol intake, serum alpha-tocopherol and gamma-tocopherol levels and their ratio, and bone turnover markers (BTMs) among postmenopausal women aged ≥45 years. We used cross-sectional data from the National Health and Nutrition Examination Survey 1999–2002. Multiple regression models with adjustments for relevant confounders were used to examine the associations between intake and serum levels of tocopherols, and serum bone-specific alkaline phosphatase (BAP), a biomarker of bone formation, and urinary N-telopeptides/creatinine (uNTx/Cr), a biomarker of bone resorption. The study sample included 497 postmenopausal women who were not taking estrogen, steroids, or osteoporosis medications, were free from kidney and liver disease, cancer, and rheumatoid arthritis, and were fasting >9 hours prior to examination. Participants had a mean age of 65.5 ± 0.6 years and over 45% used vitamin E (alpha-tocopherol) supplements in the past month. Vitamin E supplement users had significantly lower serum gamma-tocopherol, higher serum alpha-tocopherol levels, and higher ratio of serum alpha-tocopherol to gamma-tocopherol than nonusers. High serum gamma-tocopherol levels and low ratio of serum alpha-tocopherol to gamma-tocopherol were associated with increased BAP levels (p < 0.01 for both). There were no associations between any of the vitamin E variables and uNTx/Cr. In conclusion, we hypothesize that gamma-tocopherol may uncouple bone turnover, resulting in more bone formation than resorption. Vitamin E supplements in the form of alpha-tocopherol suppress serum gamma-tocopherol levels and may have negative effects on bone formation. Further research is needed to investigate the potential anabolic effect of gamma-tocopherol from food sources on bone.

Vascular Effects of Estrogenic Menopausal Hormone Therapy

Cardiovascular disease (CVD) is more common in men and postmenopausal women (Post-MW) than premenopausal women (Pre-MW). Despite recent advances in preventive measures, the incidence of CVD in women has shown a rise that matched the increase in the Post-MW population. The increased incidence of CVD in Post-MW has been related to the decline in estrogen levels, and hence suggested vascular benefits of endogenous estrogen. Experimental studies have identified estrogen receptor ERα, ERβ and a novel estrogen binding membrane protein GPR30 (GPER) in blood vessels of humans and experimental animals. The interaction of estrogen with vascular ERs mediates both genomic and non-genomic effects. Estrogen promotes endothelium-dependent relaxation by increasing nitric oxide, prostacyclin, and hyperpolarizing factor. Estrogen also inhibits the mechanisms of vascular smooth muscle (VSM) contraction including [Ca2+]i, protein kinase C and Rho-kinase. Additional effects of estrogen on the vascular cytoskeleton, extracellular matrix, lipid profile and the vascular inflammatory response have been reported. In addition to the experimental evidence in animal models and vascular cells, initial observational studies in women using menopausal hormonal therapy (MHT) have suggested that estrogen may protect against CVD. However, randomized clinical trials (RCTs) such as the Heart and Estrogen/ progestin Replacement Study (HERS) and the Women's Health Initiative (WHI), which examined the effects of conjugated equine estrogens (CEE) in older women with established CVD (HERS) or without overt CVD (WHI), failed to demonstrate protective vascular effects of estrogen treatment. Despite the initial set-back from the results of MHT RCTs, growing evidence now supports the 'timing hypothesis', which suggests that MHT could increase the risk of CVD if started late after menopause, but may produce beneficial cardiovascular effects in younger women during the perimenopausal period. The choice of an appropriate MHT dose, route of administration, and estrogen/progestin combination could maximize the vascular benefits of MHT and minimize other adverse effects, especially if given within a reasonably short time after menopause to women that seek MHT for the relief of menopausal symptoms.

Role of T cells in ovariectomy induced bone loss—revisited

Role of T cells in ovariectomy induced bone loss—revisited

Mental health around and after the menopause

The menopause is a time in a woman's life when it is recognized that biological and social changes can impact upon mental wellbeing. Several studies have investigated the relationship between menopause and psychological symptoms, especially depression, with mixed results. In part, this is due to a considerable overlap between depressive symptoms and those due to declining estrogen levels, causing challenges in assessment. However it appears that vulnerable women are at a higher risk of succumbing to depression during menopausal transition. Antidepressants remain the mainstay of treating depressive symptoms, with little conclusive evidence for hormone replacement therapy. Memory problems during menopause are a common complaint, but there is no demonstrated link to subsequent dementia. This paper also reviews considerations of diagnosis and treatment of postmenopausal depression.

Modulatory effect of cod liver oil on bone mineralization in overiectomized female Sprague Dawley rats

Osteoporosis represents a major public health problem through its association with fragility fractures, primarily of the hip, spine and distal forearm. The risk of osteoporosis increased in postmenopausal women due to decline in estrogen levels. Replicable hormone therapy is associated with undesirable side effects. Cod liver oil (CLO) is a rich source of docosahexaenoic acid eicosapentaenoic acid linolenic acid and vitamins A, E and D. In this study, the effect of CLO will be tested in the prevention of bone loss in the ovariectomized (OVX) female rats. One group of OVX rats (n = 12) received an estrogen implantation at the time of operation and the second group was supplemented orally with CLO (200 μl/kg body weight) daily for 8 weeks. At the end of the experiment, blood was analysed for serum calcium, phosphorous, bone-specific alkaline phosphatase, osteocalcin and estrogen and femur for calcium determination. Estrogen implantation as well as CLO supplementation in OVX rats increased the calcium level in femur as compared with sham rats (p < 0.05). It is concluded that supplementation of CLO have a positive effect on bone mineralization in rat, and this could offer a new strategy to avoid the side effects of replaceable hormonal therapy.

Estrogen and Skin

Aging of the skin is associated with skin thinning, atrophy, dryness, wrinkling, and delayed wound healing. These undesirable aging effects are exacerbated by declining estrogen levels in postmenopausal women. With the rise in interest in long-term postmenopausal skin management, studies on the restorative benefits that estrogen may have on aged skin have expanded. Systemic estrogen replacement therapy (ERT) has been shown to improve some aspects of skin. Estrogen restores skin thickness by increasing collagen synthesis while limiting excessive collagen degradation. Wrinkling is improved following estrogen treatment since estrogen enhances the morphology and synthesis of elastic fibers, collagen type III, and hyaluronic acids. Dryness is also alleviated through increased water-holding capacity, increased sebum production, and improved barrier function of the skin. Furthermore, estrogen modulates local inflammation, granulation, re-epithelialization, and possibly wound contraction, which collectively accelerates wound healing at the expense of forming lower quality scars. Despite its promises, long-term ERT has been associated with harmful systemic effects. In the search for safe and effective alternatives with more focused effects on the skin, topical estrogens, phytoestrogens, and tissue-specific drugs called selective estrogen receptor modulators (SERMs) have been explored. We discuss the promises and challenges of utilizing topical estrogens, SERMs, and phytoestrogens in postmenopausal skin management.

Estrogen receptor-alpha in the Alzheimer's disease brain

The decline in estrogen levels around the menopause was suggested to be an important factor in the pathogenesis of Alzheimer's disease (AD). Therefore, we investigated whether estrogen receptors (ER) may change in the brain of AD patients. ER alpha and its splice variants were studied at the mRNA level using polymerase chain reaction and DNA sequencing in the frozen human brain samples and at the protein level in the paraffin embedded sections using immunocytochemistry. Nuclear ER alpha expression was increased in the cholinergic basal forebrain (the nucleus basalis of Meynert (NBM) and the vertical limb of the diagonal band of Broca (VDB)) and in the hypothalamic nuclei but was diminished in the hippocampus of AD cases. These alterations in nuclear ER alpha staining could not be related to the occurrence of neurofibrillary tangles or to the changes in the local estrogen biosynthesis. We further identified 62 ER alpha mRNA splice variants in the brain of AD patients andelderly control donors and classified them according to the type of deletion and the presence ofinserts. Forty-eight of these ER alpha splice forms were found for the first time. The average number of the ER alpha mRNA splice variants per brain area was significantly lower in the AD cases compared with control donors. The incidence of large deletions with alternative usage of 5' and 3' splice sites inside exons was more prevalent in AD female cases. Immunoreactivity of the hippocampal ER alpha splice variant TADDI was decreased in the hippocampus, the NBM and the tuberomamillary nucleus of the hypothalamus of AD women. Our data show that alternative splicing of the ER alpha mRNA is reduced in the AD brain and more significantly in AD female cases. High incidence of the dominant negative del.7 isoform in the brain of the elderly suggests diminished estrogen signaling through both canonical ER alpha and beta. It is plausible that the brain area-specific alterations in nuclear ER alpha may be related to the differential degree of the tau pathology in the hypothalamus, basal forebrain and hippocampus that may affect the intracellular trafficking of the receptor.

Current treatment options for vulvovaginal atrophy

Vulvovaginal atrophy (VVA), a condition associated with declining estrogen levels, is commonly seen in postmenopausal women. VVA is marked by vaginal dryness, itching, dyspareunia and incontinence, which can contribute to diminishing quality of life for millions of postmenopausal women worldwide. Most available treatments contain estrogen, whether administered locally or systemically. Other treatment options include lubricants and moisturizers. These therapeutic approaches can provide temporary relief of some VVA symptoms while on therapy, but do not address the underlying condition, and they are not without potential side effects. However, promising new VVA therapies are in development that target the underlying condition with acceptable side-effect profiles. In this article, the benefits and drawbacks of current therapies and new treatments under development for VVA are discussed.

Down‐regulation of serum gonadotropins is as effective as estrogen replacement at improving menopause‐associated cognitive deficits

Declining levels of estrogen in women result in increases in gonadotropins such as luteinizing hormone (LH) through loss of feedback inhibition. LH, like estrogen, is modulated by hormone replacement therapy. However, the role of post-menopausal gonadotropin increases on cognition has not been evaluated. Here, we demonstrate that the down-regulation of ovariectomy-driven LH elevations using the gonadotropin releasing hormone super-analogue, leuprolide acetate, improves cognitive function in the Morris water maze and Y-maze tests in the absence of E2. Furthermore, our data suggest that these effects are independent of the modulation of estrogen receptors alpha and beta, or activation of CYP19 and StAR, associated with the production of endogenous E2. Importantly, pathways associated with improved cognition such as CaMKII and GluR1-Ser831 are up-regulated by leuprolide treatment but not by chronic long-term E2 replacement suggesting independent cognition-modulating properties. Our findings suggest that down-regulation of gonadotropins is as effective as E2 in modulating cognition but likely acts through different molecular mechanisms. These findings provide a potential novel protective strategy to treat menopause/age-related cognitive decline and/or prevent the development of AD.

Effect of microdose transdermal 17β-estradiol compared with raloxifene in the prevention of bone loss in healthy postmenopausal women

Declining estrogen levels after menopause result in bone loss and increased fracture risk. This study investigated whether transdermal microdose 17beta-estradiol (E2) has efficacy and safety comparable to those of raloxifene, a selective estrogen-receptor modulator approved for the prevention and treatment of postmenopausal osteoporosis. This study involved a multicenter, randomized, double-blind, active-controlled, noninferiority trial in 500 osteopenic postmenopausal women comparing transdermal microdose E2 (0.014 mg/d) versus oral raloxifene (60 mg/d), administered for 2 years. Percent change from baseline in bone mineral density at the lumbar spine was measured after 2 years of treatment. Secondary endpoints included proportion of women with no loss of bone mineral density in lumbar spine, change in bone mineral density at hip, biochemical markers of bone turnover, and safety parameters. In the per protocol set, lumbar spine bone mineral density increased by 2.4% (95% CI, 1.9-2.9) with microdose E2 versus 3.0% (95% CI, 2.5-3.5) with raloxifene after 2 years; 77.3% of E2 recipients and 80.5% of those taking raloxifene had no bone loss in the lumbar spine. Both treatments were well tolerated. Most women (99% in the E2 group and 100% in the raloxifene group) showed no histological evidence of endometrial stimulation after 2 years. Mean dense area in breast mammograms was 19.8% in the E2 group versus 19.0% in the raloxifene group after 2 years. Transdermal microdose E2 was similarly effective as raloxifene in preventing bone loss at the lumbar spine. Both treatments were well tolerated, with no clinically significant effect on endometrium or breast density.

Regular consumption of apples may promote cardiovascular health

Decline in estrogen levels in postmenopausal women is associated with unfavorable changes in lipid profiles and markers of inflammation placing them at a higher risk for cardiovascular disease (CVD). The present short‐term study examined the effects of daily consumption of 75 g dried apples on lipid profiles, independent atherogenic risk factors including lipoprotein (a) [Lp(a)] and high‐sensitive C‐reactive protein (hs‐CRP), in postmenopausal women. Fifty‐five postmenopausal women not on hormone replacement therapy consumed 75 g of dried apple daily for three months. Overnight fasting blood was collected at baseline and at the end of three months. The findings suggest that CVD protective effect of apple consumption is beyond improving lipid profiles (TC, LDL‐C, and TG) as evident by significant reductions in serum levels of Lp (a) (21±3.2 vs. 19±3.1 ) and hs‐CRP (1.8±0.16 vs. 1.3±0.17). Future studies are warranted to investigate the long‐term favorable effects of apple or its bioactive components consumption in improving endothelial function which is compromised as a result of aging.Grant Funding SourceAbstract submitted to the competition shall just have a title and the abstract body and nothing else

Women’s health in menopause with a focus on hypertension

In menopause transition many women have vasomotor symptoms which may affect their normal daily activities. With the decline in oestrogen levels, risk factors for coronary heart disease (CHD) become more apparent, especially hypertension. The onset of hypertension can cause a variety of complaints that are often attributed to the menopause. Risk factor identification is poorly managed in middle-aged women and should be the first step in the evaluation and treatment of women with perimenopausal symptoms. In women at low risk for CHD, there is still a window of opportunity for safe hormone prescription in the first years proximal to menopause. (Neth Heart J 2009;17:68-72.).

Does hormone therapy improve age-related skin changes in postmenopausal women?: A randomized, double-blind, double-dummy, placebo-controlled multicenter study assessing the effects of norethindrone acetate and ethinyl estradiol in the improvement of mild to moderate age-related skin changes in postmenopausal women

In postmenopausal women, declining estrogen levels are associated with a variety of skin changes, many of which are reportedly improved by estrogen supplementation. A study was conducted to assess the effects of continuous combined norethindrone acetate (NA) and ethinyl estradiol (EE) in the control of mild to moderate age-related skin changes in postmenopausal women. Four hundred eighty-five subjects were enrolled in this 48-week randomized, double-blind study. Subjects were randomized to one of three study arms: placebo group (165 subjects), 1 mg NA/5 microg EE group (162 subjects), or a 1 mg NA/10 microg EE group (158 subjects). The primary efficacy parameters of the study were investigator global assessment of coarse and fine facial wrinkling at week 48 and subjective self-assessment of changes in wrinkling from baseline at week 48. Secondary parameters included investigator global assessment of skin laxity/sagging at week 48, investigator global assessment of skin texture/dryness at week 48, patient self-assessment of laxity/sagging, texture/dryness, and wrinkle depth determined by image analysis of skin replicas of the periorbital (crow's feet) and jowl areas, and skin elasticity determined by timed deformation and recoil. There were similar scores in investigator global assessment in wrinkling and sagging modules at baseline across all three treatment groups. There were slight decreases in all parameters for all treatment groups for the primary subject end points, but there were no statistically significant differences between the NA/EE groups and placebo. For subject self-assessment of overall severity of skin wrinkling, there were no significant changes at weeks 24 and 48 compared to baseline. These data were unaffected by smoking status or alcohol consumption. This study assessed the effects of 48 weeks of low-dose estrogen upon facial skin in women who were, on average, 5 years postmenopausal. The effects of higher estrogen doses, longer treatment duration, or effects upon perimenopausal women cannot be extrapolated from this study. Low-dose hormone therapy for 48 weeks in postmenopausal women did not significantly alter mild to moderate age-related facial skin changes.

Associations of endogenous sex hormones with the vasculature in menopausal women

As associations between endogenous sex hormones and the vasculature are not well characterized, the objective was to examine the cross-sectional associations of menopausal status and endogenous sex hormones with vascular characteristics. Common carotid artery adventitial diameter and intima-media thickness were determined using B-mode ultrasonography among 483 middle-aged women enrolled in the Pittsburgh and Chicago sites of the Study of Women's Health Across the Nation. Sixty-two percent of women were pre- or early perimenopausal (<3 mo amenorrhea), 12% were late perimenopausal (3-12 mo amenorrhea), and 27% were postmenopausal (>or=12 mo amenorrhea). After adjustment for age, compared with pre-/early perimenopause, late perimenopause was associated with a 0.28-mm larger adventitial diameter (P=0.001), whereas postmenopause was associated with a 0.15-mm larger adventitial diameter (P=0.040). Adjustment for traditional cardiovascular risk factors slightly attenuated these associations, but the association with late perimenopause remained statistically significant (P=0.001). Each SD lower log estradiol value was associated with a 0.07-mm larger adventitial diameter after adjustment for traditional cardiovascular risk factors (P=0.023), whereas other endogenous hormones showed no associations. Intima-media thickness values were not significantly associated with menopausal status or endogenous sex hormones after adjustment for age. The menopausal transition and declining estrogen levels are associated with alterations of the peripheral vasculature, which may help to explain the increased risk of cardiovascular disease with postmenopause.