Abstract: The past decade has seen marked fluctuations in opinions concerning the merits and risks of postmenopausal hormone therapy. In July 2002, menopause management faced a major turning point when the f...

Abstract: Background Metabolic syndrome (METS) is a strong predictor of cardiovascular risk. Since the prevalence of METS increases after menopause, gynecological routine consultation offers an excellent screening opportunity.Objectives To assess the prevalence of METS in Latin American postmenopausal women and factors modifying its risk; as well as to assess the role of simple routine care measurements in the diagnosis of the METS.Methods A total of 3965 postmenopausal women, aged 45–64 years, seeking health care at 12 gynecological centers in major Latin American cities were included in this cross-sectional study. The US National Cholesterol Education Programme Adult Treatment Panel III (NCEP ATP III) guidelines were applied to assess METS. This was present if three or more of the following conditions were present: waist circumference ≥ 88 cm; blood pressure ≥ 130/85 mmHg; fasting plasma triglycerides ≥ 150 mg/dl; high density lipoprotein (HDL) cholesterol < 50 mg/dl; glucose ≥ 110 mg/dl or subjects were receivin...

Abstract: Objective To evaluate the efficacy of two ultra-low-dose 17b-estradiol plus norethisterone acetate (NETA) treatment regimens for relieving menopausal symptoms. Design A total of 577 postmenopausal women were enrolled, in three treatment groups in a double-blind, randomized, placebo-controlled study of 0.5 mg 17b-estradiol þ 0.1 mg NETA or 0.5 mg 17b-estradiol þ 0.25 mg NETA or placebo. Participants returned at weeks 4, 8, 12 and 24 for climacteric complaint evaluation based on a daily diary vasomotor symptom record. Patients were assessed by the Greene Climacteric Scale and urogenital symptoms were also evaluated. Results Treatment with ultra-low-dose 0.5 mg 17b-estradiol þ 0.1 mg NETA (0.1 Group) or 0.5 mg 17b-estradiol þ 0.25 mg NETA (0.25 Group) effectively reduced the severity and number of hot flushes within the initial weeks of therapy. Compared to placebo, a rapid, statistically significant decrease in the frequency and severity of hot flushes was achieved by week 3, followed by further improvement which continued throughout the study. There were no statistically significant differences between the active treatment arms. Conclusions The data show that both ultra-low-dose regimens are effective in reducing the severity and number of hot flushes compared to placebo, with good safety profiles.

Abstract: Estrogens have a profound influence on skin The relative hypoestrogenism that accompanies menopause exacerbates the deleterious effects of both intrinsic and environmental aging Estrogens prevent skin aging They increase skin thickness and improve skin moisture Beneficial effects of hormone replacement therapy (HRT) on skin aging have been well documented, but HRT cannot obviously be recommended solely to treat skin aging in menopausal women Topical estrogen application is highly effective and safe if used by a dermatologist with expertise in endocrinology The question of whether estrogen alternatives such as phytoestrogens and selective estrogen receptor modulators are effective estrogens for the prevention of skin aging in postmenopausal women remains unanswered However, preliminary data indicate that such treatment may be of benefit for skin aging treatment

Abstract: Cardiovascular risk is poorly managed in women, especially during the menopausal transition when susceptibility to cardiovascular events increases. Clear gender differences exist in the epidemiology, symptoms, diagnosis, progression, prognosis and management of cardiovascular risk. Key risk factors that need to be controlled in the perimenopausal woman are hypertension, dyslipidemia, obesity and other components of the metabolic syndrome, with the avoidance and careful control of diabetes. Hypertension is a particularly powerful risk factor and lowering of blood pressure is pivotal. Hormone replacement therapy is acknowledged as the gold standard for the alleviation of the distressing vasomotor symptoms of the menopause, but the findings of the Women's Health Initiative (WHI) study generated concern for the detrimental effect on cardiovascular events. Thus, hormone replacement therapy cannot be recommended for the prevention of cardiovascular disease. Whether the findings of WHI in older postmenopausal women can be applied to younger perimenopausal women is unknown. It is increasingly recognized that hormone therapy is inappropriate for older postmenopausal women no longer displaying menopausal symptoms. Both gynecologists and cardiovascular physicians have an important role to play in identifying perimenopausal women at risk of cardiovascular morbidity and mortality, and should work as a team to identify and manage risk factors, such as hypertension.

Abstract: Objective: To assess if transdermal or oral estrogens, acupuncture and applied relaxation decrease the number of menopausal hot flushes/24 h and improve climacteric symptoms, as assessed by the Kup ...

Abstract: The incidence of stroke increases substantially after menopause, and in the United States it is the third leading cause of death. Data exist suggesting that women have worse outcomes for stroke than do men. Trials of aspirin use further suggest that there is a gender difference regarding stroke. While men may have a coronary benefit from aspirin, postmenopausal women do not; yet ischemic stroke may be decreased in women but not in men. Among the traditional risk factors for stroke (such as smoking, hypertension, diabetes, obesity), hormonal therapy (HT) has been suggested to be a risk as well, although the data are not consistent. The previous Position Statement of the IMS published in 2004 was relatively silent on the issue of stroke. The annual rate of stroke in women increases rapidly with aging in postmenopausal women. While the rate is approximately 0.6-0.8/1000/year at age 50-59, it is over 2/1000 after age 60. In white women in the USA, it is 4.2/1000 at 65-74 years of age, and 11.3/1000 between ages 75 and 84 years. Thus, in trials such as the Women's Health Initiative (WHI), most of the strokes occurred in older women. Both the conjugated equine estrogen/medroxyprogesterone acetate (CEE/MPA) and CEE-alone trials in the WHI reported an increased risk of stroke in the entire population using nominal statistics: 1.41 (95% confidence interval (CI) 1.07-1.85) and 1.39 (95% CI 1.10-1.77), respectively. The increased risk was related to ischemic stroke and not hemorrhagic stroke. The absolute risk for the entire population was 0.8/1000 and 1.2/1000 woman-years (<1/1000 signifies a 'rare' event using the CIOMS classification). However, the risk was not increased in the 50-59-year-old age group, although the numbers are small. Here, the background prevalence of stroke is much lower as noted above. The results of the observational trial of the WHI were not consistent with the randomized clinical trial data and were more in keeping with older observational data showing no increased risk of stroke. The authors reconcile these differences by suggesting differences in the timing of initiation of hormones, which was at an earlier age in the observational cohort. Several recent observational studies, which will be presented, show no increased risk of ischemic stroke in younger cohorts, but possibly an increase in the risk of transient ischemic attack. These recent studies suggested the risk to be less with lower doses of estradiol < or =1 mg and to be consistent with older studies showing no risk with doses < 0.625 mg CEE. In addition, the risk was possibly lower with non-oral therapy, and was reduced if started prior to menopause. The existence of hypertension was shown to substantially increase the risk. However, data on progestogen use versus unopposed estrogen have not been consistent. At the same time, a recent body of evidence from basic science studies has reaffirmed the neuronal and stroke protective effects of estrogen. Thus, the discrepancy between these data and clinical data showing no benefit or increased risk of stroke remains to be explained. Recent trials in older women with osteoporosis have suggested an increased risk of stroke with tibolone and of stroke mortality with raloxifene. In conclusion, the current data suggest no increased risk of stroke with hormone therapy in younger (50-59 years) normotensive postmenopausal women, particularly when lower doses are prescribed soon after menopause.

Abstract: Background There is mounting evidence that menopause affects some functions of the skin. Hormone replacement therapy (HRT) appears to limit some of the climacteric aspects of cutaneous aging.Objective In the light of a growing interest in the endocrinological influence of skin, we performed a study evaluating the effects of HRT on skin aging in postmenopausal women.Methods Forty non-hysterectomized, postmenopausal women were included in this prospective, randomized, double-blind, placebo-controlled study on the influence of oral sequential treatment with a combination of 2 mg 17β-estradiol/10 mg dydrogesterone (Femoston®) for seven 28-day cycles. Skin elasticity, skin surface lipids, skin hydration and skin thickness were measured by non-invasive methods, and both adverse-event profile and clinical-dermatological status were evaluated.Results After 7 months of HRT, skin elasticity increased significantly at the right ramus of the mandible, while skin hydration tended to improve significantly at the right ...

Abstract: The aim of this meeting was to suggest state-of-the-art guidelines for research and practice on these themes. This paper was prepared following the presentations and the discussion during the Works...

Abstract: Menopausal status and estrogen-containing hormone therapy may influence several neurological disorders, including Alzheimer's disease, epilepsy, migraine headache, multiple sclerosis, Parkinson's disease, sleep disorders, and stroke. For most of these illnesses, evidence on hormone therapy is insufficient to guide practice decisions. For stroke, clinical trial evidence indicates that hormone therapy increases risk of cerebral infarction. For women with Alzheimer's disease, estrogen treatment trials have tended to be small and of short duration. Most suggest that estrogen started after the onset of dementia symptoms does not meaningfully improve cognition or slow disease progression. Hormone therapy initiated after age 64 increased all-cause dementia in the Women's Health Initiative Memory Study. Many observational studies, however, report protective associations between hormone use and Alzheimer risk. Apparent risk reduction may represent a bias toward hormone therapy, since hormones are more often prescr...

Abstract: Many women complain of memory and other cognitive/emotional difficulties at times that are associated with changes in estrogen levels. However, the biological mechanisms through which estrogen may exert these effects remain poorly understood. The effect of estrogen treatment on cognition and brain function in healthy women, and those with Alzheimer's disease, is controversial. Here we review the evidence that, in healthy women, estrogen affects the dopaminergic, serotonergic, and cholinergic systems, and brain regions crucial to higher cognitive function and mood. We will also present results from recent in vivo randomized-controlled neuroimaging experiments in our laboratory demonstrating that, in young females, and those in mid-life: (1) brain function is modulated by normal variation in ovarian function; (2) acute loss of ovarian hormones increases neuronal membrane breakdown; and (3) acute suppression of ovarian function is associated with reduced activation of brain regions critical to memory.

Abstract: Aim To evaluate, in a population of normal women, the effects of aging and menopause on the height of intervertebral discs by measuring the intervertebral disk space, between the 12th thoracic and 4th lumbar vertebrae, by dual-energy X-ray absorptiometry (DXA).Materials and methods The study was conducted on 2455 consecutive women attending our Department, from whom 464 normal women were selected. The measurement was validated utilizing a spine phantom.Results The phantom mean intervertebral disk space was 0.44 cm, with a coefficient of variation of 1.4%. The coefficients of variation in premenopausal, early postmenopausal and elderly women were 2.2, 2.0 and 6.0%, respectively. Values of intervertebral disk space were stable from age 20 to 50 years, thereafter showing a significant (p < 0.05) decrease, negatively correlated with both age and years since menopause (p < 0.0001). In postmenopausal women younger than 60 years, a correlation (p = 0.042) was evident between intervertebral disk space and years s...

Abstract: Objectives To investigate the influence of sociodemographic characteristics and menopause perception on self-reported menopause-related symptoms among Turkish women and analyze their knowledge and attitudes towards menopause and hormone therapy.Methods This was a population-based, cross-sectional, descriptive study. A total of 1007 women were recruited while attending primary-care health clinics. Women who agreed to participate in the study gave written informed consent. Each woman completed a questionnaire and had an interview to investigate her current health problems.Results Various different problems were reported by 86% of the women, mainly hot flushes. The women who perceived menopause as a pathological period had more complaints. The level of education influenced a more positive perception of the menopause. Only 12% of women were taking a hormonal treatment.Conclusion Different perceptions of menopause among Turkish women are influenced by many factors, including cultural differences, level of educ...

Abstract: Objective To assess the intervertebral disc height in postmenopausal women with osteoporotic vertebral fractures.Methods A total of 203 women were recruited from a bone densitometer directory. The ...

Abstract: Aim The aim of the present study was to evaluate the uterotropic effects of the administration of dietary equol, a metabolite of soy-derived daidzein or formononetin present in red clover, in an ovariectomized rat model of menopause.Method Two doses of racemic equol were used (50 mg/kg of chow and 400 mg/kg of chow) and the results were compared with two doses of estradiol-3 benzoate (E2B) (4.3 mg/kg of chow and 17.3 mg/kg of chow). After 3 months, animals were sacrificed and the uteri were removed, weighed and paraffin-embedded for morphometrical and immunohistochemical evaluation. The expression of selected uterine estrogen-responsive genes was also measured using real-time reverse transcription-polymerase chain reaction.Results Compared to controls, uterine weights in animals treated with high-dose equol were significantly higher, presented histologic features of mild estrogenic stimulation and had greater epithelial height and thickness of the uterine stroma and myometrium. Staining for the presence o...

Abstract: Non-estrogenic alternatives for the treatment of climacteric symptoms have their origin lost in history. Recent clinical trial data have shown that lifestyle and diet adjustment have some effect in improving both hot flushes and mood. Over-the-counter phytotherapeutic extracts are very popular and women often try a variety of products before resorting to traditional medicine. Preparations containing isoflavones in variable doses, such as soy extract and red clover, or extracts from evening primrose, Cimifuga racemosa, ginseng and black cohosh are often used for treating the climacteric syndrome. The scientific support for their efficacy certainly does not equal their popularity. The most tested pharmacological alternatives to estrogens are serotonin reuptake inhibitors (SSRIs). All available SSRIs have undergone trials for the relief of hot flushes. In spite of the difference between the compounds in both half-life and engagement of serotonin receptors, they appear to have very similar effectiveness in reducing hot flushes. At their best, SSRIs reduce hot flushes by 50-60%, compared with 80% for estrogen, and their effect appears only in the short term. SSRIs have mood-improving effects that appear to be independent of the effect on hot flushes. When used for the treatment of the climacteric syndrome, SSRIs do not adversely affect libido. Dependence is a major concern in women when offered this type of treatment, but does not appear to be a problem with this class of drugs. Withdrawal symptoms have never been reported in trials for hot flushes but are known to occur when SSRIs are used in the long term. In order to avoid these symptoms, the dose should be tapered slowly. Gabapentin, a drug used for the treatment of neuropathic pain and epilepsy, has shown that, in high doses, it has an efficacy similar to that of estrogen; however, this needs further confirmation.

Abstract: Hormone therapy (HT) is the most efficacious intervention for the relief of climacteric symptoms. Controversies surrounding HT have left many women puzzled and afraid. Gynecologists are faced with long-standing beneficial assumptions challenged by an abundance of robust detrimental new data, with little guidance on how to interpret these findings. Prescriptions for HT (and incidence of breast cancers in some areas) have fallen over the last 3 years due to anxiety provoked about breast cancer risk and recurrence. The current ‘clinical climate’ is against HT. Due to a lack of effective alternatives, women suffering from estrogen-deficiency symptoms are still requesting objective information about HT, particularly those at higher risk of breast cancer or those with a past history of breast cancer. In this situation, discussion of the current clinical uncertainty surrounding the use of HT must be undertaken to ensure that women are adequately informed. The objective of this presentation is to provide a framew...

Abstract: Background The 2003 Workshop of the International Menopause Society considered the epidemiological evidence collected up to that time on the effects of female hormone therapy (HT). New evidence relevant to the clinical management of the menopause has since been published.Objectives To summarize the new evidence, to offer critiques of important recently published studies, and to consider the implications for clinical practice.Cardiovascular disease Recent evidence from two studies, the Women's Health Initiative (WHI) clinical trial, and an observational component of the WHI, suggests that combined hormone therapy (estrogen plus progestin) (CHT) initially increases the risk of coronary heart disease (CHD), stroke, and venous thromboembolism (VTE), followed by a decline. For CHD, the hazard ratio exceeds 1.0 during the first year of follow-up, followed by a progressive decline to 5 years. Other studies show the same trend.Breast cancer In the WHI data, recent evidence suggests that estrogen thera...

Abstract: Objective To compare the effects of two different ultra-low doses of continuous combined hormone therapy and placebo on mammographic breast density in postmenopausal women.Methods A subpopulation of 255 postmenopausal women from the CHOICE trial were randomly assigned to 0.5 mg 17β-estradiol (E2) + 0.25 mg norethisterone acetate (NETA), 0.5 mg E2 + 0.1 mg NETA, or placebo. Women using hormone replacement therapy (HRT) up to 2 months prior to the study were excluded; 154 women fulfilled the inclusion criteria. Mammograms were performed at baseline and after 6 months. Breast density was evaluated by visual classification scales and a computer-assisted digitized technique.Results No significant differences were detected between the active treatment groups and the placebo group in the digitized quantification. The mean baseline values for density around 20% were unchanged after 6 months. Also, visual classifications showed no increase in breast density in any study group.Conclusion In contrast to currently av...

Abstract: In 2002, immediately after the first publication of the Women's Health Initiative (WHI) results[[1]], attitudes to hormone therapy (HT) changed dramatically. Many millions of women in the USA[[2]] ...

Abstract: The efficacy of estrogen with or without a progestogen as hormone replacement therapy (HRT) for menopausal symptoms is well-established. Recent large-scale randomized studies with combined estrogen/progestogen therapy (EPT) have raised a number of safety issues, specifically the potential risk for coronary heart disease. Subsequent analyses and other studies have indicated that HRT may be cardioprotective in younger postmenopausal women. A new continuous EPT combines natural 17beta-estradiol (E2) 1 mg with the novel progestin, drospirenone (DRSP) either 0.5 or 2 mg. DRSP has a physiological profile closer to that of natural progesterone than any other synthetic progestin. This paper reviews recent clinical trial data demonstrating the efficacy and safety of combined DRSP/E2 therapy as EPT in postmenopausal women. DRSP/E2 provides symptomatic relief of vasomotor symptoms and improvement in genitourinary atrophy. DRSP/E2 protects against endometrial hyperplasia and reduces the risk of osteoporosis. Combined DRSP/E2 therapy has a favorable impact on cholesterol and triglyceride levels, and decreases blood pressure in women with elevated blood pressure. The favorable efficacy and safety profile of DRSP/E2, and potential for long-term health benefits, represents a new option for the effective management of menopause and its clinical sequelae.

Abstract: Aim This qualitative review analyzes systematically the safety of drugs used to alleviate menopausal symptoms, other than hormone replacement therapy, in breast cancer patients.Methods We searched systematically studies using tibolone, serotonin reuptake inhibitors, clonidine, veralipride, gabapentin, black cohosh and phytoestrogens in breast cancer patients. We selected five studies for which we evaluated the methodology, characteristics of the studied populations, outcomes in terms of mortality and recurrence rates.Results Four trials were conducted using tibolone in breast cancer patients: one double-blind, randomized trial, one prospective controlled study, and two uncontrolled studies. They considerably lack power to detect any difference in breast cancer recurrence or mortality between the treated and control patients. Similar conclusions have to be drawn from the only controlled retrospective study analyzing the safety of antidepressants and antihistamines. We were unable to find studies reporting ...

Abstract: Drospirenone is a unique progestogen derived from 17alpha-spirolactone, with a pharmacologic profile very similar to that of endogenous progesterone. In contrast with other available progestins, drospirenone is a progestogen with aldosterone receptor antagonism (PARA) through its affinity for the mineralocorticoid receptor. It is thus able to act on the renin-angiotensin-aldosterone system (RAAS), which prevents excessive sodium loss and regulates blood pressure. Estrogen acts on the RAAS to stimulate the synthesis of angiotensinogen, which increases aldosterone levels and promotes sodium and water retention. When these effects are unopposed, for example during estrogen replacement therapy, they can lead to increases in weight and blood pressure. The antialdosterone properties exhibited by drospirenone promote sodium excretion and prevent water retention, conferring potential blood pressure benefits. In addition to its effects on the kidney, aldosterone has effects on the vasculature, myocardium and central nervous system, which may elicit a variety of pathophysiologic processes associated with cardiovascular disease. The antialdosterone properties of drospirenone may therefore confer additional cardiovascular benefits beyond the RAAS system. The combined actions of drospirenone on sodium and water retention and cardiovascular parameters make it a more attractive therapeutic option as a component of hormone replacement therapy than other synthetic progestins.

Abstract: Since the publication of the Women's Health Initiative (WHI) study followed by the results of the Million Women Study (MWS), the role of hormonal therapy in postmenopausal women has been further challenged. The risks attributed to hormone therapy have been overestimated and the data has been wrongly extrapolated to the whole class of therapies.The trends in postmenopausal hormonal therapy seem now to favor the non-oral delivery routes for both the estrogen and the progestin for women with an intact uteru,s based on the assumption that a lesser stimulation of the liver proteins and a neutral metabolic profile would be more favorable in terms of cardiovascular and venous risk.The combination of non-oral administration of estradiol and local delivery of progesterone or a progestin such as levonorgestrel by means of gels, sprays, vaginal rings or intrauterine systems would represent new methods of replacement therapy for the menopausal woman, improving compliance and minimizing the risks of hormone replacemen...

Abstract: Context Previous studies in postmenopausal women have demonstrated that, after oral administration of norethisterone, a small proportion of the compound is rapidly converted into ethinylestradiol. The shape of the concentration – time curve suggested that this occurred in the liver. The results were confirmed by in vitro investigations with adult human liver tissue. In 2002, it was shown that, after oral treatment of women with tibolone, aromatization of the compound occurred, resulting in the formation of a potent estrogen, 7α-methyl-ethinylestradiol. The result has been called into question, because the adult human liver does not express cytochrome P450 aromatase, which is encoded by the CYP 19 gene. Moreover, it has been claimed that the serum level of 7α-methyl-ethinylestradiol measured by gas chromatography/mass spectrometry was an artifact.Reply Aromatization of steroids is a complex process of consecutive oxidation reactions which are catalyzed by cytochrome P450 enzymes. The conversion of the natu...

Abstract: Introduction Short-term hormone replacement therapy (HRT) relieves menopausal symptoms and increases bone mineral density (BMD), but bone loss reoccurs upon discontinuation. This study assesses whether short-term HRT provides long-term BMD benefits.Method This was a prospective study of women aged 50–54 years followed up for 9 years. Women were categorized into three groups according to the treatment they received: No-HRT (n = 340), Short-term HRT (2–4 years, n = 60), and Long-term HRT (9 years, n = 187).Results BMD increased significantly at the hip (2.4%, p < 0.001) and spine (8.0%, p < 0.001) over 9 years in the Long-term HRT group. Women without treatment lost BMD at the hip (−4.2%, p < 0.001) and spine (−3.5%, p < 0.001). Women in the Short-term HRT group had no significant loss of BMD at the hip (−1.6%, p = 0.08) or spine (−1.4%, p = 0.18) over 9 years. BMD in the Short-term HRT group was significantly higher at 9 years than in the No-HRT group at both spine (difference 0.023 g/cm2, p = 0.048) and h...

Abstract: Cognitive effects of estrogen have been considered in a number of large, randomized, double-blind, placebo-controlled trials. Most have involved older, postmenopausal women, and results of these provide little support for the view that estrogen-containing hormone therapy initiated after age 60 substantially affects mean cognitive performance over periods of time ranging up to 5 years. This conclusion appears particularly true for episodic memory, a cognitive domain in which impairments are associated with increased risk of Alzheimer's disease. Other domains have been less thoroughly assessed. For women undergoing surgical menopause, limited clinical trial evidence suggests that prompt initiation of estrogen therapy may benefit verbal episodic memory, at least over a period of several months. Among middle-aged women, observational studies indicate no important deleterious effect of the natural menopause transition on cognitive performance. Similarly, limited clinical trial evidence from middle-aged postmen...

Abstract: Objectives Depressive symptoms are frequent through the different stages of a woman's reproductive cycle. The aim of this study was to evaluate a possible correlation of depressive mood before menstruation, during pregnancy, after delivery and around the menopause.Methods The sample consisted of 110 women (mean age 52 years, standard deviation 4 years) who rated their mood at present and retrospectively at different stages of the reproductive cycle. Mood was rated using a visual analogue scale.Results A significant statistical association was found between the present mood and mood at the premenstrual period, but not with mood at pregnancy or after delivery. These findings were independent of age, menopausal status or use of hormone replacement therapy.Conclusions The statistical association between depressed mood around menopause and before menstruation supports the assumption that there is a common etiology, which could be attributed to hormonal or psychological factors, or both.

Abstract: Objectives Equol, a gut bacterial metabolite of the isoflavone daidzein, has been associated with beneficial health effects. Recent studies indicate that women with intestinal capacity to convert d...