Effects Of Estrogen In Women Research Articles

Antipsychotic-induced prolactin elevation in premenopausal women with schizophrenia: associations with estrogen, disease severity and cognition

PurposeAntipsychotic-induced prolactin elevation may impede protective effects of estrogens in women with schizophrenia-spectrum disorders (SSD). Our study sought to confirm whether the use of prolactin-raising antipsychotics is associated with lower estrogen levels, and to investigate how estrogen and prolactin levels relate to symptom severity and cognition in premenopausal women with SSD.MethodsThis cross-sectional study included 79 premenopausal women, divided in three groups of women with SSD treated with prolactin-sparing antipsychotics (n = 21) or prolactin-raising antipsychotics (n = 27), and age-matched women without SSD (n = 31). Circulating 17β-estradiol was compared among groups. In patients, we assessed the relationship between prolactin and 17β-estradiol, and the relationships of these hormones to symptom severity and cognition, using correlation analyses and backward regression models.ResultsIn women receiving prolactin-raising antipsychotics, 17β-estradiol levels were lower as compared to both other groups (H(2) = 8.34; p = 0.015), and prolactin was inversely correlated with 17β-estradiol (r=-0.42, p = 0.030). In the prolactin-raising group, 17β-estradiol correlated positively with verbal fluency (r = 0.52, p = 0.009), and 17β-estradiol and prolactin together explained 29% of the variation in processing speed (β17β−estradiol = 0.24, βprolactin = -0.45, F(2,25) = 5.98, p = 0.008). In the prolactin-sparing group, 17β-estradiol correlated negatively with depression/anxiety (r = -0.57, p = 0.014), and together with prolactin explained 26% of the variation in total symptoms (β17β−estradiol = -0.41, βprolactin = 0.32, F(2,18) = 4.44, p = 0.027).ConclusionsIn women with SSD, antipsychotic-induced prolactin elevation was related to lower estrogen levels. Further, estrogens negatively correlated with symptom severity and positively with cognition, whereas prolactin levels correlated negatively with cognition. Our findings stress the clinical importance of maintaining healthy levels of prolactin and estrogens in women with SSD.

The Role of Estrogen and Estrogen Receptors in Head and Neck Tumors.

Head and neck squamous cell carcinoma (HNSCC) is the most common histological form of head and neck tumors (HNTs), which originate from the epithelium of the lips and oral cavity, pharynx, larynx, salivary glands, nasal cavity, and sinuses. The main risk factors include consumption of tobacco in all forms and alcohol, as well as infections with high-risk human papillomaviruses or the Epstein-Barr virus. Regardless of the etiological agent, the risk of developing different types of HNTs is from two to more than six times higher in males than in females. The reason for such disparities probably lies in a combination of both biological and psychosocial factors. Therefore, it is hypothesized that exposure to female sex hormones, primarily estrogen, provides women with protection against the formation and metastasis of HNTs. In this review, we synthesized available knowledge on the role of estrogen and estrogen receptors (ERs) in the development and progression of HNTs, with special emphasis on membrane ERs, which are much less studied. We can summarize that in addition to epidemiologic studies unequivocally pointing to the protective effect of estrogen in women, an increased expression of both nuclear ERs, ERα, and ERβ, and membrane ERs, ERα36, GPER1, and NaV1.2, was present in different types of HNSCC, for which anti-estrogens could be used as an effective therapeutic approach.

Progesterone and endometrial cancer

It is well established that unopposed estrogen, either endogenous or therapeutic, can induce endometrial hyperplasia and potentially endometrial cancer (EC). Anovulatory cycles, obesity, and insulin resistance are major risk factors for EC. Progestogen (progesterone and progestin), including levonorgestrel intrauterine device, are able to prevent or to treat hyperplasia, atypical hyperplasia, and even well-differentiated EC, as presented in this review. During menopausal hormone therapy, progestogens protect the endometrium against the proliferative effects of estrogens in women with a uterus. Whereas, recent epidemiologic data suggest that micronized progesterone (MP) is apparently safer for the breast, it could be less efficient than synthetic progestin on the endometrium. However, several studies from biopsies during treatment with MP do not show any increased risk of hyperplasia. Lack of compliance could explain the results on EC.

T14. HYPOTHALAMIC-PITUITARY-GONADAL AXIS HORMONES IN ANTIPSYCHOTIC NAïVE FIRST-EPISODE OF PSYCHOSIS AND HEALTHY CONTROLS

BackgroundKraepelin (1909) wrote about the association between female sex hormones and psychotic symptoms. He observed that women diagnosed with schizophrenia showed signs of gonadal dysfunction and hypoestrogenism. Antipsychotic drugs had not yet been introduced, so it cannot be interpreted as side effects. At the beginning of the 20th-century rhythmicity of psychotic symptoms through menstrual cycle was observed. The symptoms ameliorated when higher levels of estrogens were found. It was also noted during pregnancy. Reported cases and some studies confirmed these observations.Epidemiology shows a later peak of onset of psychosis in women. This protective role, also observed in clinical and animal studies, remains for the reproductive years and decreases by the time of menopause, when there’s a second important peak of onset in women.In spite of all these observations, few systematic investigations have been published about the effects of estrogens in women with schizophrenia. This study aims to investigate differences in the levels of sexual hormones between antipsychotic-naïve women with and without psychosis.MethodsWe performed a retrospective case-control study to compare the levels of sex hormones in blood of first-episode psychosis (FEP) and healthy control women (HC) of reproductive age, as a part of a NIH-NIDDK project on the study of hormonal factors and metabolism in psychosis. All participants were antipsychotic-naïve, in order to avoid bias from antipsychotic medication use. Four cases and four controls were recruited: cases were women newly diagnosed with primary non-affective psychosis at the emergency department of our hospital, and controls were mental health workers of similar age with no history of psychosis. Blood samples were obtained at the luteal phase of the menstrual cycle. We registered the following variables: age, psychosis status, last menstrual day and hormone blood levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol and progesterone. We used descriptive statistics for age and hormone blood levels (mean and standard deviation -SD-) and we performed the Kruskal-Wallis test to determine any statistical differences of these variables regarding psychosis status.All participants provided informed consent. Ethical approval was obtained from the institutional ethics review board.ResultsThe mean age of FEP was 31.4 years (SD 1.9) and 26.1 years (SD 3.5) for HC, with no statistically significant differences. Both FSH and LH were higher in FEP (FSH: mean 7 U/L, SD 1.7; LH: mean 8.4 U/L, SD 2.6) compared to HC (FSH: mean 3.5 U/L, SD 1.2; LH: mean 5.7 U/L, SD 3.3), reaching statistical significance in the case of FSH (p=0.015). 17-b-estradiol was lower in FEP (mean 75.3 pg/mL, SD 54.6) than in HC (mean 151 ng/mL, SD 102.1), although differences were not statistically significantDiscussionWe observed higher levels of FSH in women with psychosis compared to controls in the luteal phase. These women were antipsychotic-naïve; thus, these results are not a consequence of medication use. Our observations add evidence to the known relationship between altered hormonal levels and schizophrenia in women. The increase in FSH stimulates the production of estrogens, which are known to be low in psychosis compared to healthy controls. This finding supports the hypoestrogenism hypothesis of schizophrenia.Future studies with larger samples evaluating hormonal levels, psychotic symptoms and differences with hormonal treatments could lead to research of new adjunctive therapies or approaches.

Association Between Age at Onset of Schizophrenia and Age at Menarche.

Increasing evidence from clinical practice, as well as from epidemiological and basic research shows that there are gender differences in clinical features of schizophrenia, and this may be related to estrogens. There may be a relationship between earlier puberty and later onset of the disease, because of the protective effects of estrogens in women with schizophrenia. In this study, our aim was to analyze the correlation between age of menarche and age of onset of schizophrenia and to investigate the protective effects of estrogens in schizophrenia. In this study, we included 289 patients who were diagnosed with schizophrenia. Those with mental deficiency or organic brain disorders were excluded from the study. All subjects were given a socio-demographic form to determine their personal information, age at menarche, age at first odd behavior, age at onset of the disease and first hospitalization. Data on factors which may affect the association between age at onset of schizophrenia and age at menarche such as family history, head or birth trauma etc. were recorded on the information form. We found out that age at menarche was negatively associated with age at first odd behavior and age at first psychotic symptoms. Our study verifies the protective effects of estrogens and shows that the earlier puberty may be the cause of later onset of schizophrenia. A gender-sensitive approach in psychiatry improves our understanding of mental illness and our therapeutic strategies.

High affinity nuclear and nongenomic estradiol binding sites in the human and mouse lens

Estrogen is reported to be protective against cataracts in women and animal models. Immunodetection methods have identified the classic estrogen receptors (ER), ERα and ERβ, in human lens epithelial cells and their RNAs have been detected in the rat and human lens. To verify that estrogen binding occurs in the lens, sensitive [125I]-17β-estradiol binding analyses were performed on subcellular lens fractions from women (ages 39–78 years). The presence of high affinity estradiol binding sites in the nuclear, cytoplasmic, and membrane fractions indicate the lens is able to respond to estrogens, even up to age 78, although fewer binding sites were detected in the postmenopausal women. Additionally, due to the importance of mouse models in estrogen action and lens research, lenses from intact female mice were also analyzed. Both the C57BL/6 and FVB/N mouse strains also possessed high affinity binding sites in all three lens fractions. Furthermore, transcripts for ERα, ERβ, and G protein-coupled estrogen receptor (GPER; previously called GPR30) that bind estradiol with high affinity were expressed in the human and mouse lenses. These data provide the first evidence of GPER expression in the lens. Its role, functions, and subcellular location are currently unknown, but a G-shift assay in the membrane fractions of human and mouse lenses did not show evidence that estradiol induced classic G protein-coupled receptor activation. All three receptor transcripts were also detected in the lens capsule region isolated from female C57BL/6 mice, which is mainly comprised of epithelial cells. In contrast, only ERα and GPER were expressed in the cortex/nuclear region, which is primarily composed of differentiating and organelle-free fiber cells. No significant differences in specific estradiol binding and receptor RNA expression were observed in the lenses between male and female C57BL/6 mice. These findings indicate that the lens is an estrogen target tissue in both sexes. The identification of GPER, in addition to ERα and ERβ, in the lens also adds to the complexity of possible estrogen responses in the lens. Accordingly, the protective effects of estrogen in women and animals may be mediated by all three estrogen receptors in the lens. In addition, the similarities in binding and receptor RNA expression in the lenses of both species suggest that mice can be used to model estrogen action in the human lens.

Estrogens: mechanisms of neuroprotective effects

Within the last few years, there has been a growing interest in the neuroprotective effects of estrogen and the possible beneficial effects of estrogen in neurodegenerative diseases such as stroke, Alzheimer's disease, and Parkinson's disease. The concept of neuroprotective effects of estrogen in women remains controversial because these effects may vary with the timing of treatment. Research increasingly suggests that changes in estrogen levels during aging may increase risk for Alzheimer's disease, the most common type of dementia. This update reviews the newest information about estrogen and cognitive aging, including information regarding the role of bioavailable estrogen in older women and men.

Increased Estradiol and Improved Sleep, But Not Hot Flashes, Predict Enhanced Mood during the Menopausal Transition

The antidepressant effect of estrogen in women undergoing the menopause transition is hypothesized to be mediated by central nervous system effects of increasing estradiol on mood or through a pathway involving suppression of hot flashes and associated sleep disturbance. Estrogen therapy (ET) and the hypnotic agent zolpidem were selected as interventions in a three-arm, double-blind, placebo-controlled trial to distinguish the effects of estradiol, sleep, and hot flashes on depression. Women with depressive disorders, hot flashes, and sleep disturbance were randomly assigned to transdermal 17β-estradiol 0.05 mg/d, zolpidem 10 mg/d, or placebo for 8 wk. Changes in serum estradiol, perceived sleep quality, objectively measured sleep, and hot flashes were examined as predictors of depression improvement [Montgomery-Åsberg Depression Rating Scale (MADRS)] using multivariate linear regression. Seventy-two peri/postmenopausal women with depression disorders were randomized to 17β-estradiol (n = 27), zolpidem (n = 31), or placebo (n = 14). There was no significant difference between groups in depression improvement (overall MADRS decrease 11.8 ± 8.6). Increasing estradiol (P = 0.009) and improved sleep quality (P < 0.001) predicted improved mood in adjusted models but reduced hot flashes (P = 0.99) did not. Post hoc subgroup analyses revealed that the therapeutic effect of increasing estradiol levels on mood was seen in perimenopausal (P = 0.009), but not postmenopausal, women. For women with menopause-associated depression, improvement in depression is predicted by improved sleep, and among perimenopausal women, by increasing estradiol levels. These results suggest that changes in estradiol and sleep quality, rather than hot flashes, mediate depression during the menopause transition. Therapies targeting insomnia may be valuable in treating menopause-associated depression.

The Long-Term Effects of Oophorectomy on Cognitive and Motor Aging Are Age Dependent

Background: The evidence for a neuroprotective effect of estrogen in women remains controversial. Objective: We studied the long-term risk of parkinsonism and of cognitive impairment or dementia in women who underwent oophorectomy before menopause. Methods: We conducted a historical cohort study among all women residing in Olmsted County, Minn., USA, who underwent unilateral or bilateral oophorectomy before the onset of menopause for a noncancer indication from 1950 through 1987. Each member of the oophorectomy cohort was matched by age to a referent woman from the same population who had not undergone oophorectomy. In total, we studied 1,252 women with unilateral oophorectomy, 1,075 women with bilateral oophorectomy, and 2,368 referent women. Women were followed for a median of 25–30 years. Parkinsonism was assessed using screening and examination, through a medical records- linkage system, and through death certificates. Cognitive status was assessed using a structured questionnaire via a direct or proxy telephone interview. Results: The risk of parkinsonism and of cognitive impairment or dementia increased following oophorectomy. In particular, we observed significant linear trends of increasing risk for either outcome with younger age at oophorectomy. Conclusion: Our findings, combined with previous laboratory and epidemiologic findings, suggest that estrogen may have an age-dependent neuroprotective effect.

The effect of short-term estradiol therapy on clotting and inflammatory markers in older men receiving hormonal suppression therapy for prostate cancer

The cardio protective effect of estrogen in women has come under scrutiny as recent evidence from long-term trials has demonstrated negative findings. In contrast, the effect of endogenous sex hormones, specifically estrogen, on cardiovascular disease, inflammation and clotting parameters in men has not been well-studied. Men receiving androgen deprivation therapy for prostate cancer provide a unique model to study the effect of estrogen alone on inflammation and clotting factors. In a short-term randomized controlled trial of 17-β estradiol (E2) versus placebo, we measured sex hormones, markers of inflammation including homocysteine (HC), C-reactive protein (CRP), interleukin-6 (IL-6) and coagulation factors including fibrinogen, plasminogen activator-inhibitor-1 (PAI-1) and anti-thrombin-III (AT-III) in 27 older men without bone metastases receiving androgen deprivation therapy or neoadjuvant treatment for prostate cancer. After 9 weeks of E2 treatment, there was no difference in inflammation or clotting parameters between groups, but after 9 weeks of treatment AT-III increased in the E2 treated group and decreased in the placebo group. CRP, homocysteine and IL-6 did not show any significant differences. We also evaluated the above parameters in 12 men 3 weeks after acute steroid withdrawal with androgen deprivation therapy and found no significant changes.We found an increase in AT-III in men receiving E2 which may be related to gonadal steroid withdrawal, but no significant differences in other inflammatory or clotting factor parameters. While the current report is very preliminary in a small group of subjects, further studies are needed to determine the long-term effects of E2 in this population of hypogonadal men.

Effects of 17β-estradiol on growth and apoptosis in human vascular endothelial cells: Influence of mechanical strain and tumor necrosis factor-α

Vascular endothelial cell (EC) integrity is key to arterial health; endothelial dysfunction is linked to atherogenesis. Atherosclerosis shows a male preponderance, possibly related to the protective effect of estrogens in women. This study examined the effect of estrogens on growth, apoptosis and adhesion molecule expression in cultured human EC. The effects of 17β-estradiol (E2) were studied in human umbilical vein endothelial cells (HUVEC) under normal culture conditions, and following exposure to cyclic mechanical strain or tumor necrosis factor α (TNFα). E2 enhanced HUVEC growth in serum-enriched media, in a concentration-dependent manner. This up-regulation of EC growth by E2 was associated with an increase in telomerase activity, assessed by PCR-based TRAP analysis. Cyclic strain enhanced [ 3H]-thymidine incorporation into DNA, and increased activation of mitogen-activated protein (MAP) kinase ERK1/2 and expression of early growth genes (Egr-1 and Sp-1); E2 attenuated the strain-induced ERK1/2 activation but not the early growth gene expression or DNA synthesis. TNFα (20 ng/mL) induced apoptosis in HUVEC, causing a decrease in DNA synthesis, increase in floating and Annexin-V-stained cell numbers, and morphological changes. TNFα also upregulated ERK1/2 activity and expression of adhesion molecules (ICAM-1, VCAM-1 and E-selectin). E2 significantly attenuated the effects of TNFα on ERK1/2 activity, apoptosis, and E-selectin expression in the cells. Thus, estradiol enhances growth and reduces TNFα-induced apoptosis in EC; enhanced EC growth may be mediated via upregulation of telomerase activity. These effects are possible cellular mechanisms underlying female gender-associated cardiovascular protection.

Sex Steroids and the Periosteum—Reconsidering the Roles of Androgens and Estrogens in Periosteal Expansion

Traditionally, differences in periosteal bone formation between men and women have been assumed to reflect two diverging endocrine effects: stimulatory effects of androgens in men and inhibitory effects of estrogens in women. In line with this concept, it is tempting to speculate that men experience more periosteal bone expansion than women because they are exposed to more endogenous androgens and less estradiol. However, recent data challenge this traditional concept. A PubMed search was conducted for relevant most recent findings in both humans and animals in the context of an intriguing observation of ongoing periosteal expansion after estrogen treatment in an aromatase-deficient boy. Human experiments of nature have provided evidence that androgens and estrogens are both required for the process of pubertal periosteal bone expansion typically associated with the male bone phenotype. Androgens alone appear insufficient to drive male periosteal bone formation. In both sexes, androgens may stimulate periosteal bone formation, but low levels of estrogen may increase the mechanical sensitivity of the periosteum. Higher concentrations of endogenous estrogen, however, inhibit periosteal bone apposition and/or its interaction with mechanical loading. This biphasic action of estrogen on the periosteum may result from a direct effect on its receptor, either alpha or beta, but may also depend on changes in serum IGF-I. Simple concepts of the roles of sex steroids in periosteal apposition have to be reconsidered in the context of these recent findings.

Selective estrogen receptor modulators (SERMs): Mechanisms of anticarcinogenesis and drug resistance

Despite the beneficial effects of estrogens in women's health, there is a plethora of evidence that suggest an important role for these hormones, particularly 17β-estradiol (E 2), in the development and progression of breast cancer. Most estrogenic responses are mediated by estrogen receptors (ERs), either ERα or ERβ, which are members of the nuclear receptor superfamily of ligand-dependent transcription factors. Selective estrogen receptor modulators (SERMs) are ER ligands that in some tissues (i.e. bone and cardiovascular system) act like estrogens but block estrogen action in others. Tamoxifen is the first SERM that has been successfully tested for the prevention of breast cancer in high-risk women and is currently approved for the endocrine treatment of all stages of ER-positive breast cancer. Raloxifene, a newer SERM originally developed for osteoporosis, also appears to have preventive effect on breast cancer incidence. Numerous studies have examined the molecular mechanisms for the tissue selective action of SERMs, and collectively they indicate that different ER ligands induce distinct conformational changes in the receptor that influence its ability to interact with coregulatory proteins (i.e. coactivators and corepressors) critical for the regulation of target gene transcription. The relative expression of coactivators and corepressors, and the nature of the ER and its target gene promoter also affect SERM biocharacter. This review summarizes the therapeutic application of SERMs in medicine; particularly breast cancer, and highlights the emerging understanding of the mechanism of action of SERMs in select target tissues, and the inevitable development of resistance.

Estrogen Receptors Act in Atherosclerosis

Men experience a more rapid progression of atherosclerosis, but the basis for this gender difference has not been clear. The prostacyclin PGI 2 prevents many processes associated with the formation of atherosclerotic lesions, and the atheroprotective effect of estrogen in women may be via stimulation of PGI 2 production. Egan et al . (see the news story by Couzin) now show in a mouse model of atherosclerosis that estrogen acts through the estrogen receptor subtype α to generate PGI 2 through cyclooxygenase 2 (COX-2). Female mice lacking a receptor for PGI 2 developed atherosclerosis as rapidly as male mice and had poor response to estrogen therapy. This mechanism may be important in assessing the effects of hormone replacement therapy and selective COX-2 inhibitors. K. M. Egan, J. A. Lawson, S. Fries, B. Koller, D. J. Rader, E. M. Smyth, G. A. FitzGerald, COX-2-derived prostacyclin confers atheroprotection on female mice. Science 306 , 1954-1957 (2004). [Abstract] [Full Text] J. Couzin, Estrogen's ties to COX-2 may explain heart disease gender gap. Science 306 , 1277 (2004). [Summary] [Full Text]

Women have later onset than men in schizophrenia—but only in its paranoid form. Results of the DSP project

According to the literature, schizophrenia begins in men earlier than in women. It has been argued that the gender-bound age difference is due to the protective antidopaminergic effect of estrogens in women. However, the effect of gender on the age of onset may vary between different types of schizophrenias, and can also be modulated by marital status and by age at onset of illness. Comprehensive data were collected on 3306 DSM IIR schizophrenia patients, aged 15–64 years, who had been discharged from psychiatric hospitals in Finland in 1982, 1986 and 1990. The age of onset of illness (AOI) was defined by the age at the first admission (AFA). Male patients were admitted earlier than female patients, and a small second peak in women appeared at the age of 40–44. However, there were no gender differences in AFA within diagnostic subgroups, except in paranoid schizophrenia in which AFA was lower in men than in women even when marital status was taken into account. Within paranoid schizophrenia, this effect of gender was significant only in those of the patients whose AFA was higher than 30 years. It is suggested that there is no gender difference in AOI in early onset schizophrenia. In later onset, paranoid schizophrenia, the illness seems to manifest in women later than in men.

Effect of 17beta-estradiol on mRNA expression of large- conductance, voltage-dependent, and calcium-activated potassium channel alpha and beta subunits in guinea pig.

Large-conductance, voltage- and calcium-activated potassium (MaxiK) channels play a key role in cell excitability. MaxiK channels are composed of a pore-forming alpha-subunit and a regulatory beta-subunit, of which four (beta1-4) genes have been identified. Previous findings suggested that MaxiK channel activity is regulated by estradiol. However, the underlying mechanisms have remained incompletely documented. Therefore, we used reverse transcriptase polymerase chain reaction to clone four cDNA fragments that were specific to the guinea pig alpha, beta1, beta2, and beta4 genes. Using a sensitive ribonuclease protection assay, we found that the alpha and beta4 mRNAs were the most abundant mRNAs in the brain and pituitary, whereas in the aorta, the alpha-subunit was coexpressed with the beta1-subunit. Moreover, there was a significant upregulation of the alpha- but not the beta1-subunit mRNA and the alpha-subunit protein in the aorta of the estrogenvs oil-treated ovariectomized animals. In specific brain areas including preoptic area, ventral hypothalamus, hippocampus, and amygdala, and in the pituitary, neither the alpha- nor beta4-subunit mRNAs were affected by estrogen. These findings suggest that estrogen may not affect the mRNA expression of MaxiK channels in the brain and pituitary. However, estrogen causes increased expression of MaxiK alpha in the aorta, which may explain some of the cardioprotective effects of estrogen in women.

VIII. Special Considerations for Different Population Groups

Therapeutic recommendations in this report are based heavily on evidence from controlled clinical trials. Nonetheless, randomized clinical trials have not been carried out to address all therapeutic questions pertaining to all age groups, both sexes, and different racial/ethnic groups. Consequently, ATP III recommendations for various groups often must be made by combining what has been learned from clinical trials with other lines of evidence such as epidemiological findings. Fortunately, a large number of clinical trials have produced a very large set of consistent results that allow for considerable confidence in projections of benefits and drawbacks of cholesterol-lowering therapy in groups that have not been subject to clinical trials. In the discussion to follow, the ATP III panel has crafted its recommendations for different population groups from general evidence statements and general recommendations developed in previous sections. No attempt will be made to grade the category and strength of evidence for all recommendations made in this section. Men of middle-age (35-65 years) are at increasing risk for CHD as they progressively age. Up to one-third of all new CHD events and about one-fourth of all CHD deaths occur in middle-aged men.1017 Most of the excess risk for CHD morbidity and mortality in middle-aged men can be explained by the major risk factors—cholesterol disorders, hypertension, and cigarette smoking.10,11 Men are predisposed to abdominal obesity, which makes them particularly susceptible to the metabolic syndrome. Consequently, metabolic risk factors (elevated cholesterol and triglycerides, low HDL cholesterol, and elevated blood pressure) appear earlier in men than women. Table VIII.1-1 summarizes factors to consider when applying ATP III guidelines to middle-aged men. View this table: Table VIII.1-1. Special Considerations for Cholesterol Management in Middle-Aged Men CHD is a major cause of death in women as well as men and it ultimately kills as many women as men.1017 However, …

Schizophrenia: do men and women suffer from the same disease?

This article reviews the literature on normal brain development and behavioural development in men and women as well as on aetiological risk factors for schizophrenia, such as pre-, peri- and postnatal complications. The male-female comparisons of age and type of onset, symptomatology, course and outcome were based on a population-based sample of 232 first illness episodes - the ABC Schizophrenia Study sample. The probands were assessed using the IRAOS interview and other instruments retrospectively at first admission and prospectively at six cross sections over five years after first contact. A representative subsample of 130 first admissions or 115 first illness episodes were compared with 130 controls, matched by age, sex and area of residence. Women, 3 to 4 years older than men at illness onset, showed a second peak of onsets in age group 45 to 50 years. After animal experiments and a controlled clinical study this finding was explained by a protective effect of oestrogen persisting until menopause. The underlying neurobiological mechanism consisted in a sensitivity reducing effect of oestrogen on D2 receptors in the brain. The effect of oestrogen, meanwhile confirmed in randomised control trials, also includes genomic effects as well as interactions with free-radical detoxifying systems, thus demonstrating the neuroprotective capabilities of oestrogen. Postmenopausal schizophrenia was more frequent and more severe in women. Men fell ill more frequently and more severely at young age and less frequently and more mildly later in life. Illness course, too, was more unfavourable in postmenopausal women than in their male peers. The protective effect of oestrogen in women depended on the degree of their predisposition to the illness: the higher the familial load for schizophrenia, the weaker the protection by oestrogen. The more favourable illness course in premenopausal women resulted from their higher level of social development at illness onset - determined by their higher age at onset - and from their socially more adaptive behaviour. The illness behaviour of young men showed a significant excess of socially negative behaviours with an unfavourable impact on their early illness course. In contrast, older men were socially better adjusted. With genetic and morphological findings considered the subtypes of schizophrenia did not differ between men and women. Gender differences in symptomatology and course of schizophrenia obviously are not explained by differences in the disease process. They seem to be determined by a complex pattern of interaction between disease variables, hormonal and behavioural differences and their consequences for age at onset and illness course.

Estrogen replacement therapy for the potential treatment or prevention of Alzheimer's disease.

Alzheimer's disease (AD) is an irreversible, progressive brain disorder that occurs gradually and results in memory loss, behavior and personality changes, and a decline in cognitive abilities. Although basic biological data suggest that estrogen may have neuroprotective and neuroenhancing functions, a number of studies have produced conflicting findings on the use of estrogen for maintaining cognitive function in older people. This review summarizes clinical studies that have examined the effects of estrogen in women with AD.

Con: Postmenopausal hormone replacement therapy does not improve outcome in women undergoing coronary artery bypass graft surgery

CARDIOVASCULAR DISEASE is the leading cause of death in the United States in men and women. Deaths from cardiovascular disease outnumber deaths from all cancers combined and include approximately 500,000 women each year.1 The prognosis for women with coronary heart disease is worse than that for men, with higher mortality for women hospitalized for acute myocardial infarction, angioplasty, and coronary artery bypass graft surgery2-4 (CABG). Although the long-term survival for men and women discharged alive after CABG surgery is similar, the incidence of graft patency and survival free of angina is lower in women than in men.5 Despite the alarming prevalence of coronary heart disease in women, the incidence of coronary artery disease is still higher in men, with women developing atherosclerotic heart disease an average of 10 years later than men.6 This apparent female advantage is thought to be due to the protective effects of estrogen in women before menopause. In the Framingham study,7 researchers showed that the incidence of cardiovascular disease was 40 times higher in women aged 75 to 84 years compared with women aged 35 to 44 years. This ratio was not seen in men and likely reflects the relatively lower incidence of coronary artery disease in premenopausal women. Many observational studies have shown a lower risk of coronary heart disease in women who are taking postmenopausal hormone replacement therapy (HRT) when compared with women who are not, providing evidence to support the influential benefit of estrogen on risk for coronary heart disease. Estrogen raises high-density lipoprotein levels and lowers levels of low-density lipoproteins.8 These changes in lipoprotein profiles account for only 25% to 50% of the reduction in cardiovascular risk, however. Studies have shown evidence for estrogen-related endothelial-dependent vasodilation,9 antioxidant effects,10 and potential influences on coagulation.11 Given this information, it may be postulated that HRT would decrease the risk for recurrent cardiac events in women who have a history of coronary artery disease, resulting in improved clinical outcome. The authors conclusively show evidence against HRT in women with coronary artery disease, however, and illustrate that there is a paucity of data to confirm that this HRT improves outcome after CABG surgery.