Effects Of Estrogen Replacement Therapy Research Articles

Medicina di genere e malattie cardiovascolari: che cosa non si è fatto e che cosa si dovrebbe fare

Although women believe that cancer is their most important health problem, around 50% of women die for a cardiovascular disease. In addition, despite a different perception, cardiovascular disease is more prevalent in women than in men. The reason for this different incidence of cardiovascular disease between women and men is caused by the fact that fertile woman is protected by estrogen against the development of cardiovascular disease. In contrast, after menopause and the consequent decrease of plasma levels of estrogen, cardiovascular risk in women drammatically increases and, as a consequence, it causes the increase of the incidence of diseases such as myocardial infarction or stroke. Unfortunately, at the present time, no sure information is available about the best practice to prevent or cure cardiovascular disease in women. Most of therapeutical strategies derive from study conducted mainly in men. Studies specifically dedicated to women are only those aimed to evaluate the effect of estrogen replacement therapy on cardiovascular events in post menopausal women and all these studies have produced negative results. The hope for the future is that the new awareness of scientific community about the relevance of cardiovascular disease in women lead to develop specific trials which might give definitive answers for a more effective therapuetic approach.

The Biochemical and histopathological effects of estrogen replacement therapy on the heart of ovariectomized female rats subjected to myocardial infarction

Objective The aim of this study was to evaluate the biochemical and histopathological effects of estrogen replacement therapy on the heart of ovariectomized female rats subjected to myocardial infarction. Methods Sixty young (30 days old) and adult (60 days old) female rats weighing 150–200 g were taken for the study and divided into three groups: group I, sham-operated rats; group II, ovariectomized (OVX) and isoproterenol (ISO) induced myocardial infarction (MI) rats; and group III, OVX and ISO induced MI rats treated with 17β-estradiol (E2), with each group comprising 20 rats (n=20). Four weeks after ovariectomy, isoproterenol was injected subcutaneously at a dose of 150 mg/kg/day for 2 successive days into the rats to induce MI. The rats in group III were injected intraperitoneally with 10 µg/kg/day E2 for 10 weeks. Electrocardiograms (ECG) was conducted 12 h after the second dose of isoproterenol. Biochemical estimation of plasma creatine kinase (CPK) and lactate dehydrogenase (LDH) levels was carried out. The hearts of the rats were collected for clinical biochemical analyses, which include measuring the levels of malondialdehyde (MDA) in tissue, enzymatic antioxidants such as superoxide dismutase (SOD) and catalase (CAT), and nonenzymatic antioxidants such as reduced glutathione (GSH), and were studied histopathologically by light and electron microscopy, as well as by immunohistochemical analysis. Results Plasma CPK, LDH and MDA levels were highly significantly increased in the ovariectomy and ISO induced MI group II compared with the control group I, but significantly decreased in ovariectomy and ISO induced MI treated E2 group III. In contrast, levels of SOD, CAT and GSH were highly significantly decreased in the ovariectomy and ISO induced MI group II compared with the control group I, but significantly increased in the ovariectomy and isoproterenol induced MI treated E2 group III. Histopathological analysis of the hearts of ovariectomized and ISO induced MI rats showed pathological changes. However, treatment with E2 attenuated the histopathological changes and corrected the biochemical parameters mentioned above. Conclusion 17β-estradiol E2 has a cardioprotective effect; it has been shown to inhibit structural and functional aspects of MI and attenuate the oxidative stress involved in isoproterenol-induced MI.

Perinatal exposure to diethylstilbestrol alters the functional differentiation of the adult rat uterus

The exposure to endocrine disrupters and female reproductive tract disorders has not been totally clarified. The present study assessed the long-term effect of perinatal (gestation+lactation) exposure to diethylstilbestrol (DES) on the rat uterus and the effect of estrogen replacement therapy. DES (5μg/kg bw/day) was administered in the drinking water from gestational day 9 until weaning and we studied the uterus of young adult (PND90) and adult (PND360) females. To investigate whether perinatal exposure to DES modified the uterine response to a long-lasting estrogen treatment, 12-month-old rats exposed to DES were ovariectomized and treated with 17β-estradiol for 3 months (PND460). In young adult rats (PND90), the DES treatment decreased both the proliferation of glandular epithelial cells and the percentage of glandular perimeter occupied by α-smooth muscle actin-positive cells. The other tissue compartments remained unchanged. Cell apoptosis was not altered in DES-exposed females. In control adult rats (PND360), there were some morphologically abnormal uterine glands. In adult rats exposed to DES, the incidence of glands with cellular anomalies increased. In response to estrogens (PND460), the incidence of cystic glands increased in the DES group. We observed glands with daughter glands and conglomerates of glands only on PND460 and in response to estrogen replacement therapy, independently of DES exposure. The p63 isoforms were expressed without changes on PND460. Estrogen receptors α and β showed no changes, while the progesterone receptor decreased in the subepithelial stroma of DES-exposed animals with estrogen treatment. The long-lasting effects of perinatal exposure to DES included the induction of abnormalities in uterine tissues of aged female rats and an altered response of the adult uterus to estradiol.

Cellular Mechanism by Which Estradiol Protects Female Ovariectomized Mice From High-Fat Diet-Induced Hepatic and Muscle Insulin Resistance

Estrogen replacement therapy reduces the incidence of type 2 diabetes in postmenopausal women; however, the mechanism is unknown. Therefore, the aim of this study was to evaluate the metabolic effects of estrogen replacement therapy in an experimental model of menopause. At 8 weeks of age, female mice were ovariectomized (OVX) or sham (SHAM) operated, and OVX mice were treated with vehicle (OVX) or estradiol (E2) (OVX+E2). After 4 weeks of high-fat diet feeding, OVX mice had increased body weight and fat mass compared with SHAM and OVX+E2 mice. OVX mice displayed reduced whole-body energy expenditure, as well as impaired glucose tolerance and whole-body insulin resistance. Differences in whole-body insulin sensitivity in OVX compared with SHAM mice were accounted for by impaired muscle insulin sensitivity, whereas both hepatic and muscle insulin sensitivity were impaired in OVX compared with OVX+E2 mice. Muscle diacylglycerol (DAG), content in OVX mice was increased relative to SHAM and OVX+E2 mice. In contrast, E2 treatment prevented the increase in hepatic DAG content observed in both SHAM and OVX mice. Increases in tissue DAG content were associated with increased protein kinase Cε activation in liver of SHAM and OVX mice compared with OVX+E2 and protein kinase Cθ activation in skeletal muscle of OVX mice compared with SHAM and OVX+E2. Taken together, these data demonstrate that E2 plays a pivotal role in the regulation of whole-body energy homeostasis, increasing O(2) consumption and energy expenditure in OVX mice, and in turn preventing diet-induced ectopic lipid (DAG) deposition and hepatic and muscle insulin resistance.

CHANGES IN THE URINARY BLADDER MORPHOLOGY, MAST CELL POPULATION AND ESTROGEN RECEPTOR ALPHA EXPRESSION FOLLOWING OVARECTOMY AND CHRONIC ESTROGEN REPLACEMENT THERAPY IN ALBINO RATS

11 Acta Endocrinologica (Buc), vol. IX, no. 1, p. 11-22, 2013 *Correspondence to: Dr. Flaviu Alexandru Tabaran, University of Agricultural Sciences and Veterinary Medicine Cluj-Napoca, Department of Pathology, Manastur Street, Nr.3-5, Cluj-Napoca, Cluj, 400372, Romania, E-mail: flaviu_tabaran@yahoo.com Abstract Context. The inflammatory disorders of the urinary bladder represent one of the most frequent disorders associated with hormonal unbalances caused by menopause. The involvement of estrogens and mast cells in this complex mechanism mediated by neuro-hormonal pathway is well known, but the pathogenesis through which the hormonal deprivation is affecting the Estrogen Receptor expression and is predisposing to urinary bladder inflammatory changes is still argued. Objective. To determine the structural changes associated with surgically induced menopause, and the effect of estrogen replacement therapy (ERT) in the urinary bladder morphology, mast cell population and Estrogen Receptor (ERα) expression. Subjects and methods. The effect of ovariectomy and ERT was monitored by quantifying the number of mast cells and the structural changes that the urinary bladder suffers. By immunohistochemistry we assessed the changes of the Estrogen Receptor Alpha (ERα) expression in the urothelium and detrusor muscle. The study was carried out on ovariectomised female rats over a period of 42 days. Results. The main alterations associated with the hormonal deprivation were represented by the growth in number of the bladder mast cells, atrophy of the urothelium and amplification of the expression of ERα from the urothelium, but not from the detrusor muscle. ERT significantly decreased the tissue expression for ERα, reduced the severity of bladder atrophy and the number of mast cells. Conclusions. The estrogenic hormonal substitution can diminish the severity of the atrophic, inflammatory and ERα changes in bladder disorders associated with ovarectomy in rat.

Effects of estrogen replacement therapy on apoptosis and vascular endothelial growth factor expression in ocular surface epithelial cells: An experimental study.

To investigate the effects of estrogen replacement therapy (ERT) on apoptosis and vascular endothelial growth factor (VEGF) expression in ocular surface in an experimental rat model. Forty female, Wistar rats were randomized in 4 groups in the study. Subcutaneous ERT (17β-estradiol, 10µg/kg/day) was administered to the first group without ovariectomy and to the second group with ovariectomy for three months. Third group had only ovariectomy and fourth group had sham operation. All rats were sacrificed in estrous cycles determined by vaginal smear test and their right eyes were enucleated at the end of the third month. Enucleated eyes were analyzed by immunohistochemical method for expressions of caspase-3, bcl-2, VEGF and TUNEL assay. Caspase-3 expression of conjunctival epithelium was significantly higher in group 3 than group 1 (P=0.005), and group 2 (P=0.007). TUNEL score of conjunctival epithelium was significantly higher in group 3 than group1 (P=0.006). TUNEL score of corneal epithelium was significantly higher in group 3 than group 2 (P=0.012), and group 4 (P=0.002). There was no significant difference between groups in that bcl-2 and VEGF expressions. We determined increased apoptosis in ocular surface epithelial cells in ovariectomized rats. ERT and endogen estrogen decreased the apoptosis, and did not result in difference in VEGF expression between the groups. Estrogen may be beneficial for the treatment of apoptosis-mediated ocular surface disorders such as dry eye. Further studies are needed on this subject for a better understanding of the role of estrogen and to provide a new insight for treatment and prevention of apoptosis-mediated ocular surface disorders.

Abstract 203: Chronic and Acute Estrogen Replacement Therapy Has Different Effects in Aged Animals After Experimental Stroke

Introduction: The effect of estrogen replacement therapy (ERT) on stroke incidence and severity has been extensively debated. Clinical trials of ERT demonstrated an increased risk of stroke in treated women, but study participants were well past menopause when therapy was initiated. It has been suggested that detrimental effects of ERT may be unmasked after prolonged periods of hypoestrogenicity. To date, very few studies have examined the effect of ERT in aged animals although the timing of replacement may be critical to the neuroprotective effects of ERT. Hypothesis: We hypothesized that chronic estrogen replacement (CER) initiated in late middle age, would decrease infarct size after an induced stroke whereas acute estrogen replacement (AER) would have no beneficial effects in the aged female brain. Methods: CER was administered to aged C57BL6 mice from 17 to 20 months of age, and AER was initiated at 20 months of age. Both CER and AER treated mice were subjected to 90-minute middle cerebral artery occlusion (MCAO) at 20.5 months of age. Stroke outcomes at 24 hours of MCAO were measured. Protein levels of nuclear factor κB (NFκB), estrogen receptor α (ERα) and serum levels of pro-inflammatory cytokines were also examined. Results: Female mice that received CER showed improved stroke outcomes after MCAO (total infarct: CER vs. vehicle 34.7±2.4% vs. 58.2±2.6%; n=9/gp, p <0.05); whereas females that had AER did not. CER females exhibited diminished levels of NFκB translocation compared to AER females after stroke. AER females demonstrated both an increase in nuclear NFκB and enhanced expression of pro-inflammatory cytokines. The differential NFκB translocation was related to corresponding changes in ERα expression. Aged males benefited from ERT regardless of the timing of initiation of ERT, and had significantly reduced expression of pro-inflammatory markers after stroke compared to age-matched females. Conclusions: AER worsened stroke outcomes whereas CER was protective in aged females. A pro-inflammatory milieu emerges with age in females which was attenuated by CER treatment. Interestingly both AER and CER reduced stroke injury in aged males, suggesting sexually dimorphic effects on inflammation.

Effects of Chronic and Acute Oestrogen Replacement Therapy in Aged Animals after Experimental Stroke

The effect of oestrogen replacement therapy (ERT) on stroke incidence and severity has been extensively debated. Clinical trials of ERT have demonstrated an increased risk of stroke in treated women, although the study participants were well past menopause when therapy was initiated. It has been suggested that detrimental effects of ERT may be unmasked after prolonged periods of hypoestrogenicity. To date, very few studies have examined the effect of ERT in aged animals, although the timing of replacement may be critical to the neuroprotective effects of ERT. We hypothesised that chronic ERT initiated in late middle age would decrease infarct size in the brain after an induced stroke, whereas acute ERT would have no beneficial effects in aged females. To test this hypothesis, two paradigms of ERT were administered to aged mice of both sexes aiming to determine the effects on stroke outcome and to explore the possible mechanisms by which ERT interacts with age. Female mice that received chronic ERT from 17-20 months of age showed improved stroke outcomes after experimental stroke, whereas females that had acute ERT initiated at 20 months of age did not. Chronic ERT females exhibited diminished levels of nuclear factor kappa B (NF-κB) translocation compared to acute ERT females after stroke. Acute ERT females demonstrated both an increase in nuclear NF-κB and enhanced expression of pro-inflammatory cytokines. In addition, a sexual dimorphic effect of ERT was seen because males benefited from ERT, regardless of the timing of initiation. Aged males had significantly reduced expression of pro-inflammatory markers after stroke compared to age-matched females, suggesting a pro-inflammatory milieu emerges with age in females. These results are consistent with the emerging clinical literature suggesting that ERT should be initiated at the time of menopause to achieve beneficial effects. The present study demonstrates the importance of using appropriate animal models in preclinical studies.

Effects of estrogen replacement therapy on symptoms and clinical parameters in post menopausal women

Effects of estrogen replacement therapy on symptoms and clinical parameters in post menopausal women

Melatonin supplementation therapy as a potent alternative to ERT in ovariectomized rats

ABSTRACTAim To evaluate the efficacy of melatonin supplementation therapy as an alternative to estrogen replacement therapy in an ovariectomized rat model and to assess diabetogenic metabolic dysregulation caused by estrogen deficiency in postmenopausal individuals.Methods Ovariectomized adult Wistar rats were treated with either estrogen/progesterone, melatonin or a combination of estrogen and melatonin. Body weight gain, feed efficiency, serum glucose, insulin, glucose tolerance and insulin response, serum and tissue lipids, tissue glycogen contents and activities of glycogen phosphorylase and glucose-6-phosphatase were analyzed in all the experimental groups.Results Ovariectomized animals showed increased body weight gain, feed efficiency, fasting insulin resistance, greater area under curve for the glucose tolerance test, higher serum and tissue lipids and reduced glycogen content and insulin sensitivity. A low dose of melatonin was more efficient than estrogen in reversing all the ovariectomy-induced changes. The combination of estrogen + melatonin was found to be best in correcting glycemic dysregulation while high doses of melatonin could effectively regulate dyslipidemia.Conclusion The present study provides strong evidence for melatonin supplementation therapy to be more potent and effective in comparison to estrogen replacement therapy due to its single-handed ability to revert all the ovariectomy-induced changes. No reported side-effect or long-term effect of melatonin, against the known effects of estrogen replacement therapy, make it more attractive as a candidate to treat postmenopausal symptoms.

Dopaminergic neuroprotection of hormonal replacement therapy in young and aged menopausal rats: role of the brain angiotensin system

There is a lack of consensus about the effects of the type of menopause (surgical or natural) and of oestrogen replacement therapy on Parkinson's disease. The effects of the timing of replacement therapy and the female's age may explain the observed differences in such effects. However, the mechanisms involved are poorly understood. The renin-angiotensin system mediates the beneficial effects of oestrogen in several tissues, and we have previously shown that dopaminergic cell loss is enhanced by angiotensin via type 1 receptors, which is activated by ageing. In rats, we compared the effects of oestrogen replacement therapy on 6-hydroxydopamine-induced dopaminergic degeneration, nigral renin-angiotensin system activity, activation of the nicotinamide adenine dinucleotide phosphate oxidase complex and levels of the proinflammatory cytokine interleukin-1β in young (surgical) menopausal rats and aged menopausal rats. In young surgically menopausal rats, the renin-angiotensin system activity was higher (i.e. higher angiotensin converting enzyme activity, higher angiotensin type-1 receptor expression and lower angiotensin type-2 receptor expression) than in surgically menopausal rats treated with oestrogen; the nicotinamide adenine dinucleotide phosphate oxidase activity and interleukin-1β expression were also higher in the first group than in the second group. In aged menopausal rats, the levels of nigral renin-angiotensin and nicotinamide adenine dinucleotide phosphate oxidase activity were similar to those observed in surgically menopausal rats. However, oestrogen replacement therapy significantly reduced 6-hydroxydopamine-induced dopaminergic cell loss in young menopausal rats but not in aged rats. Treatment with oestrogen also led to a more marked reduction in nigral renin-angiotensin and nicotinamide adenine dinucleotide phosphate oxidase activity in young surgically menopausal rats (treated either immediately or after a period of hypo-oestrogenicity) than in aged menopausal rats. Interestingly, treatment with the angiotensin type-1 receptor antagonist candesartan led to remarkable reduction in renin-angiotensin system activity and dopaminergic neuron loss in both groups of menopausal rats. This suggests that manipulation of the brain renin-angiotensin system may be an efficient approach for the prevention or treatment of Parkinson's disease in oestrogen-deficient females, together with or instead of oestrogen replacement therapy.

Nicotine and vascular endothelial dysfunction in female ovariectomized rats: role of estrogen replacement therapy

The protective effects of estrogen replacement therapy (ERT) against oxidative injury and endothelial dysfunction in the aortic tissues induced with nicotine in ovariectomized (OVX) rats were investigated. Female rats were divided into a sham-operated group (n = 8) and four groups in which OVX rats received either vehicle (0.1 ml sesame oil, i.m., n = 8), or nicotine (0.1 mg/kg, s.c., n = 8), or estradiol benzoate (0.1 mg/kg, i.m., n = 8), or both nicotine and estradiol benzoate (n = 8) starting at week 5 after the surgery and continuing for the following 6 weeks. ERT was effective in preventing the rise in plasma lipid profile, atherogenic index and the level of induced endothelin-1 (ET-1) in nicotine-treated OVX rats. It also reduced aortic malondialdehyde, hydroxyproline levels, calcium content and caspase-3 expression induced in nicotine-treated OVX rats. ERT increased serum estradiol, high-density lipoprotein cholesterol and nitric oxide levels in nicotine-treated OVX rats. Furthermore, ERT was effective in restoring reduced glutathione and cyclic guanosine monophosphate contents and endothelial nitric oxide synthase expression in aortic tissues of nicotine-treated OVX rats. Short-term ERT could be a promising therapeutic strategy to minimize nicotine-induced oxidative stress and vascular endothelial dysfunction in menopausal women subjected to environmental smoke.

Effect of estrogen replacement therapy on symptoms of depression and anxiety in non-depressive menopausal women

The efficacy of estrogen replacement therapy (ERT) for mood disturbances associated with menopause has yet to be firmly established. The objective of this study was to investigate the efficacy of ERT for improving mood and anxiety of non-depressive postmenopausal women. This double-blind, randomized, placebo-controlled study involved two treatment groups: one receiving conjugated equine estrogens (CEEs; 0.625 mg/day) and the other placebo, for six cycles of 28 days each. Subjects were hysterectomized, healthy, non-depressive (according to Schedule for Affective Disorders and Schizophrenia, Life Time Version [SADS-L]) women. Depressive and anxiety symptoms were assessed with the Beck Depression Inventory (BDI), and the Hamilton Anxiety Scale (HAMA), respectively. The Profile of Mood States (POMS) and other scales were used to characterize symptoms. In both groups, BDI scores were significantly lower at cycles 1, 2, 3, and 6, compared with baseline assessments (p<0.01). Anxiety scores for both groups significantly improved from cycle 3 to study endpoint. The only significant difference favoring the active group occurred at cycle 1. POMS scores were significantly improved at the end of cycles 1, 2, 3 and 6 among treated subjects and at the end of cycles 2, 3, and 6 among placebo subjects. ERT is not associated with improvements in mood or anxiety symptoms in non-depressive, hysterectomized, postmenopausal women.

Estrogen and Insulin Replacement Therapy Modulates the Expression of Insulin‐Like Growth Factor‐I Receptors in the Salivary Glands of Diabetic Mice

Diabetes mellitus results in various complications, also compromising the salivary glands. Hormone levels and interactions with cellular receptors are altered, intensifying the damage caused by this disease. Hormone replacement therapy alone or combined with other treatments may reverse this damage, but doubts still exist regarding the efficacy of this procedure. The objective of this study was to evaluate the effect of estrogen replacement therapy combined with insulin treatment on salivary secretory cells and on the expression of insulin-like growth factor (IGF)-I receptors in salivary glands of spontaneously diabetic (NOD) mice. Twenty-five mice were divided into five groups of five animals each: group I (NOD diabetic), group II (NOD diabetic treated with insulin), group III (NOD diabetic treated with estrogen), group IV (NOD diabetic treated with insulin and estrogen), and group V (control Balb/c mice). Group II received insulin, group III received estrogen, and group IV received insulin plus estrogen administered daily for 20 days. Groups I and V received saline for the same period of time to simulate treatment. Glucose and estrogen levels were monitored during treatment, and salivary gland samples were collected at the end of treatment for stereological analysis and immunofluorescence detection of IGF-I receptors. Tissue restructuring and regulation of IGF-I receptors expression were observed in animals submitted to estrogen replacement therapy plus insulin. Estrogen effectively promoted the recovery of salivary secretory cells, demonstrating that this hormone alone, and especially when combined with insulin, might be important for the reversal of hyperglycemia-induced tissue injury.

Vulvovaginal Candidiasis in Postmenopausal Women

: This study aimed to explore the role of hormone replacement therapy (HRT) in susceptibility to vulvovaginal candidiasis (VVC) in a private vulval disease referral practice. : Between January 2009 and December 2010, 149 healthy, nondiabetic patients with vulvar conditions were compared for significant differences in vaginal swab result, age, and diagnosis between those using and not using HRT. Detailed clinical data were collected from those with VVC. : The mean ages of the HRT (n = 70) and non-HRT (n = 79) groups were 62.5 and 62.5 years, respectively. Positive cultures for Candida were found in 34 (48.5%) of 70 patients on HRT and in 2 (3%) of 79 subjects not on HRT (p < .001). Culture-positive, clinical VVC was identified in 34 (49%) of 70 patients on HRT and in 1 (1%) of 79 patients not on HRT (p < .001). Candida species (32 Candida albicans and 2 Candida glabrata) were isolated from the 34 VVC patients, and of these, 23 (67%) had a history of recurrent or chronic candidiasis before menopause. All 34 had been previously treated with antifungal therapy without ceasing HRT and had been unresponsive to treatment or had relapse after treatment. In 27 (79%) of 34 patients, HRT was suspended during treatment. Of those who remained on HRT during treatment or resumed it after treatment, prophylactic antifungal treatment was initiated in 15 (44%) to prevent recurrence. All patients responded to the antifungal treatment provided HRT was suspended or prophylactic treatment was used. : Postmenopausal women taking HRT are significantly more prone to develop VVC than women who are not and those with VVC are likely to have been susceptible to it before menopause.

The neuroprotective effects of phytoestrogen α-zearalanol on β-amyloid-induced toxicity in differentiated PC-12 cells

Although favorable effects of estrogen replacement therapy on Alzheimer's disease on postmenopausal women have been recognized, an associated increased incidence of uterine and breast tumors has jeopardized the clinical use of estrogen. Phytoestrogen α-zearalanol (α-ZAL) is a reductive product of the Gibberella zeae metabolite and abundant in plants and vegetables, which has been shown to protect cell injury with low side-effects on uterine and breast. This study was designed to evaluate the neuroprotective effects of α-ZAL, on the cultured differentiated PC-12 cells, while 17β-estradiol (17β-E2) has been used as an estrogen positive control. Following a 24 h exposure of the cells to amyloid β-peptide fragment 25-35 (Aβ₂₅₋₃₅), a significant reduction in cell survival and activities of total superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), as well as increased of malondialdehyde (MDA) were observed. However, preincubation of the cells with α-ZAL or 17β-E2 prior to Aβ₂₅₋₃₅ exposure elevated the cell survival and SOD and GSH-Px activities, and decreased the level of MDA. In addition, Aβ₂₅₋₃₅ caused a significant cell apoptosis and increased apoptotic rate, accompanied by decreasing of bcl-2 expression and increasing bax, caspase-3 expression, pretreatment of the cells with α-ZAL or 17β-E2 ameliorated these changes induced by Aβ₂₅₋₃₅. Taken together, these data indicated that the phytoestrogen α-ZAL may effectively antagonize Aβ₂₅₋₃₅-induced cell toxicity by attenuating oxidative stress and apoptotic cell death, in a manner similar to 17β-E2. Our results suggested that α-ZAL can be used as a potential substitute of 17β-E2 in postmenopausal women for Alzheimer's disease prevention.

Long-term ovariectomy modulates the antidepressant-like action of estrogens, but not of antidepressants

Controversial results related to effectiveness of estrogen replacement therapy (ERT) to alleviate depression are frequently reported. The discrepancies could be related to (a) time when ERT is initiated after the beginning of menopause and/or (b) type of estrogen used. Furthermore, estrogens modulate the antidepressant effect of different compounds; therefore, the effectiveness of antidepressant drugs could also depend on the menopausal status. The aim of the present study was to analyze whether the time after estrogen decline can influence antidepressant-like effects of two estrogens and/or two antidepressants. Thus, the antidepressant-like actions of 17β-estradiol (E(2)), 17α-ethynyl-estradiol (EE(2)), fluoxetine (FLX) and desipramine (DMI) were studied at different periods (1, 3 and 12 weeks) after ovariectomy (OVX), using the forced swimming test (FST). Results showed that OVX increased depressive-like behavior only 1 week after OVX. The antidepressant-like actions of E(2), but not those of EE(2), were cancelled 12 weeks after OVX. Conversely, antidepressant-like actions of FLX and DMI were observed at 1, 3 and 12 weeks after OVX. In conclusion, while the antidepressant-like effects of estrogens depended on the time at which treatment is initiated after OVX as well as on the estrogenic compound used, antidepressant-like effects of FLX and DMI were not blocked by OVX.

Estrogen replacement therapy and cognitive functions in healthy postmenopausal women: a randomized trial

This study aimed to evaluate the effect of estrogen replacement therapy on verbal cognitive performance of middle-aged postmenopausal women. Middle-aged (40 to 59years) hysterectomized, oligosymptomatic women receiving 0.625mg/day of conjugated equine estrogens (N = 27) or placebo (N = 32) in a double-blind parallel group design were compared according to their performance on a verbal memory battery before and after six 28-day cycles of treatment. Both groups had similar age and educational level. The estrogen group performed better on digit span-forward and on the recall of the easy stimuli on the verbal-paired associates test regardless of age, education, physical symptoms, number of years of menopause, or blood estradiol levels. However, the small magnitude of difference in the effect on attentional span suggests that the estrogen-related improvement is unlikely to be of clinical relevance. Estrogen replacement therapy did not improve verbal memory in middle-aged, hysterectomized, postmenopausal, asymptomatic women.

Recovery of INS-R and ER-alpha expression in the salivary glands of diabetic mice submitted to hormone replacement therapy

The interaction between proteins and cell receptors is related to tissue homeostasis such as in salivary glands. In this respect, alterations in hormone levels caused by hyperglycaemic conditions may interfere with this interaction, intensifying the damage caused by diabetes mellitus. Hormone replacement therapy is an option to reverse this damage, but doubts still exist regarding the efficacy of this procedure. The objective of this study was to evaluate the effect of oestrogen replacement therapy combined with insulin treatment on the expression of oestrogen (ER-alpha) and insulin receptors (INS-R) in the salivary glands of spontaneously diabetic mice. Twenty-five mice were divided into five group of 5 animals each: group I (NOD diabetic), group II (NOD diabetic treated with insulin), group III (NOD diabetic treated with oestrogen), group IV (NOD diabetic treated with insulin and oestrogen), and group V (control BALB/c mice). Group II received insulin, group III received oestrogen, and group IV received insulin plus oestrogen administered daily for 20 days. Groups I and V received saline for the same period of time to simulate treatment. Glucose and oestrogen levels were monitored during the experimental period and salivary gland samples were collected at the end of the experiment for fluorescence microscopy analysis of ER-alpha and INS-R. Animals receiving oestrogen replacement therapy plus insulin showed regulation of the expression of oestrogen and insulin receptors. Oestrogen treatment alone contributed to the recovery of these cell receptors. These results indicate that oestrogen replacement therapy alone, and especially when combined with insulin, is important for the recovery of the interaction between functional proteins and their receptors, thus contributing to the reestablishment of tissues damaged by the hyperglycaemic condition.

Estrogen induces cardioprotection in male C57BL/6J mice after acute myocardial infarction via decreased activity of matrix metalloproteinase-9 and increased Akt-Bcl-2 anti-apoptotic signaling

In general, young men have a greater risk than age-matched women for many types of cardiovascular diseases, including ischemic heart diseases, such as acute or chronic myocardial infarction (MI)-induced heart failure. The effects of estrogen-replacement therapy in men have not been extensively studied. We evaluated the cardioprotective effects of supplemental estrogen against left anterior descending coronary ligation-induced MI in male C57BL/6J mice. A significantly lower prevalence of cardiac rupture was observed in estrogen-treated mice regardless of castration status. A reduced prevalence of cardiac rupture was associated with decreased activities of matrix metalloproteinase 9 (MMP-9) and increased expression of the anti-apoptotic gene Bcl-2. In vitro studies using H9C2 cells under simulated ischemia re-oxygenation treatment further support the role of estrogen receptor β in estrogen-mediated cardioprotection through the Akt-Bcl-2 signaling pathway.