Protective effects of beta glucan in brain tissues of post-menopausal rats: a histochemical and ultra-structural study

Decline of estrogen during menopause has been associated with numerous significant changes that have been linked to many pathophysiological complications. In addition, ovarian hormone deficiency increases the production of reactive oxygen radicals which could result in oxidative stress and cell damage. While estrogen therapy is often considered to overcome the behavioral and physiological shortcomings, antioxidants are gaining popularity for their beneficial property. For this purpose, in the present study, utilizing the antioxidant properties of beta glucan has been examined in treatment of menopause induced oxidative stress in cerebral neurons. Four groups of female Wistar rats were used: control, ovariectomy, ovariectomy?+?estrogen treated and ovariectomy?+?beta glucan treated. We observed a significant increase in neural degeneration in ovariectomized rats as compared to controls. Moreover, increased oxidative stress in the brains of the ovariectomized rats has been detected by performing immunohistochemical analysis. A large number of immuno-positive cerebral neurons have been observed in ovariectomy group rat brains. Interestingly, providing beta glucan treatment to ovariectomized rats reduced the number of degenerated neurons. Our study is the first to examine light and electron microscopic examination and immunohistochemical and stereological analysis of estrogen depletion in rats and to test protective role of beta glucan in the experimental study.     

Progesterone stimulates cardiac muscle protein synthesis via receptor-dependent pathway

OBJECTIVE: To examine the effect of ovarian hormones on the regulation of cardiac growth. DESIGN: Ovariectomized rat model with replacement of 17beta-estradiol (E(2)) and progesterone (P). SETTING: University research laboratory. PATIENT(S): Female Sprague-Dawley rats (7-8 weeks old). INTERVENTION(S): Rats were separated into five groups: [1] sham-operated (S; n = 6), [2] ovariectomized plus placebo (OVX; n = 8), [3] OVX plus 17beta-E(2) (OVX+E(2); n = 8), [4] OVX plus P (OVX+P; n = 8), and [5] OVX+E(2)+P (n = 7). MAIN OUTCOME MEASURE(S): Cardiac muscle protein synthesis rates, steroid hormone receptor protein expression, and plasma volume. RESULT(S): Cardiac protein synthesis was greater in OVX+P (mean +/- SE; 11.4 +/- 1.5% per day) rats compared with S (5.9 +/- 0.6%/day), OVX (6.9 +/- 0.5%/day), OVX+E(2) (5.2 +/- 0.4%/day), and OVX+E(2)+P (6.8 +/- 0.3%/day) groups. Treatment of OVX+P rats with the P receptor antagonist RU 486 (n = 9) reduced protein synthesis rates to control levels (7.5 +/- 0.5% per day), indicating that P regulates cardiac protein metabolism through a receptor-dependent pathway. Both P and estrogen receptors were found in cardiac tissue homogenates, suggesting the possibility of direct effects of ovarian hormones on the heart. Progesterone replacement had an additional effect of increasing plasma volume. Rats in the OVX+P group had a 20% greater plasma volume compared with animals in the S group (5.24 +/- 0.22 vs. 4.19 +/- 0.26 mL/100 g). This effect of P replacement to increase plasma volume was not blocked by RU 486 (5.01 +/- 0.24 mL/100 g), suggesting that volume expansion was not solely responsible for the effects of P on cardiac protein synthesis. CONCLUSION(S): Our findings indicate a role for ovarian hormones in the regulation of cardiac growth in female rats.     

The effect of carvacrol on the proinflammatory cytokines,histology, and fertility outcome of cisplatin-related ovarian change in a rat model

ObjectiveIn women, agents used in chemotherapy treatment have side effects such as accelerating follicular depletion and early menopause. Thus, cytotoxic treatments may cause various effects ranging from partial damage to the ovary to premature ovarian failure (POI) and infertility.This study aimed to investigate the protective effect of carvacrol on cisplatin (CIS)-induced reproductive toxicity in female rats.Materials and methodsThe animals were divided to four groups; a healthy group (HG), administered only cisplatin 2.5 mg/kg (CIS); cisplatin 2.5 mg/kg + carvacrol mg/kg (CC-50), and cisplatin 2.5 mg/kg + carvacrol 100 mg/kg (CC-100). In this study, the CC-50 and CC-100 groups were injected with carvacrol at 50 and 100 mg/kg intraperitoneally (IP). The CIS and HG groupswere administered normal saline as a solvent in the same way. One hour afterwardthe CC-50 and CC-100 groups were injected with cisplatin at 2.5 mg/kg IP. This procedure was continued once a day for 14 days. At the end of this period, six rats from each group were euthanized with high-dose anaesthesia. Biochemical (oxidant-antioxidant and proinflammatory cytokines) and histopathological examinations were performed on the right ovarian tissue removed from the dead rats. The remaining (n = 6 in each group) animals were kept in the laboratory with mature male rats for two months for breeding. Rats that didn't give birth within two months were considered infertile. A one-way ANOVA test was used for the biochemical analysis, the a Kruskal Wallis test was used for the histopathological analysis.ResultsIt has been observed that cisplatine causes oxidative stress and inflammatory damage in the ovarian tissue of animals and ultimately causes infertility due to this oxidative stress. While carvacrol significantly suppressed cisplatin-related oxidative stress in ovarian tissue at the 50 and 100 mg/kg doses, it could suppress proinflammatory cytokine increase only at thecytokine increase only at the 100 mg/kg dose. In addition, carvacrol significantly reduced the development of cisplatin-related infertility (from 0 to 83.3%) at a dose of 100 mg/kg.ConclusionThese findings suggest that carvacrol at high doses can reduce the harmful effects of cisplatin on the ovary and improve ovarian reserve in rats.     

Reproductive hormones: ageing and the perimenopause

This review explores the pituitary-ovarian hormones involved with ageing and the onset of menopause. The serum patterns of pituitary-ovarian hormones throughout the menstrual cycle alter as menopause approaches. The increase in follicular phase FSH prior to menopause is attributed to an early decline in the ovarian hormone, inhibin B, which negatively regulates follicle-stimulating hormone (FSH) secretion. Serum inhibin B is believed to reflect the age-related decrease in ovarian follicle reserve, which is the primary source of serum inhibin B. The later rise in serum luteinizing hormone (LH) during the menopause transition is due to a cessation of ovarian follicle development. Hormonal patterns during the luteal phase of the menstrual cycle also show changes with age but these changes are poorly understood.     

Sexuality in the middle years

Sexual function undergoes natural changes at menopause, reflecting the effects of ovarian hormones on the nervous and cardiovascular systems. Most studies indicate deterioration of function as the impact of the biological changes is compounded by psychological reactions and sociocultural influences. This article reviews studies of sex and menopause and discusses etiological considerations with regard to ovarian hormones and sexual dysfunction. The concluding section describes ways in which the clinician can help the menopausal woman and her partner understand and deal with sexual dysfunction.     

Protective effect of alpha-lipoic acid in methotrexate-induced ovarian oxidative injury and decreased ovarian reserve in rats

To determine whether the possible oxidative effect of methotrexate (Mtx) on ovary and to evaluate the effectiveness of alpha lipoic acid (ALA), which may be useful in many oxidative stress models.

Thirty-two female Wistar-albino rats were randomly divided into four groups; control group, alpha lipoic acid group (ALA 100?mg/kg, 10?days), multiple dose Mtx group (Mtx 1?mg/kg 1, 3, 5, 7?days) and Mtx and ALA group (Mtx 1?mg/kg 1, 3, 5, 7?days and ALA 100?mg/kg, 10?days). Serum total antioxidant status (TAS), total oxidant status (TOS) and oxidative stress index (OSI), tumor necrosis factor-alpha (TNF-α), tissue malondialdehyde (MDA) and activities of glutathione peroxidase (GSH-Px) and catalase (CAT) and anti-Mullerian hormone (AMH) and total ovarian follicle count were evaluated.

Mtx administration caused a significant decrease in TAS, a significant increase in TOS and OSI, a significant increase in MDA levels and a decrease in GSH-Px and CAT activity. Moreover the proinflammatory cytokine (TNF-α) was increased in the Mtx group. And AMH values and total follicle count were significantly decreased in Mtx group. However, ALA treatment reversed biochemical results and AMH levels and total follicle count.

Alpha lipoic acid ameliorates methotrexate induced oxidative damage of ovarian in rats.     

Endometriosis during postmenopausal period--probable causes for its origin and development

A very rare--casuistic--case of endometriosis is presented, which appeared ten years after surgical menopause (hysterectomy and ovariectomy) without concomitant use of hormone replacement therapy or phytoestrogens. The possibilities of endogenous production and exogenous supply of estrogens in the female organism are discussed as well as the possible causes of proliferation of endometrial lesions during postmenopausal period. When menopause is induced by surgery (a stress for the organism) without exogenous supply of estrogens (HRT, phytoestrogens, xenoestrogens) the production of suprarenal hormones, including androgens, increases. The peripheral conversion of androgens into estrogens in fat tissue is increased and implanted during hysterectomy endometrial lesions in vagina walls are stimulated.     

Hormone concentrations in the homogenates of ovarian tissue and blood serum in postmenopausal women not using hormone therapy

Ovaries in postmenopausal women synthesize steroids, mostly androgens. Removal of the ovaries after menopause may be reflected by menopausal symptoms and arterial hypertension observed during postoperative period, along with a significantly increased risk of death due to cardiovascular complications. It is not understood if the clinical consequences of gonad removal at different time points after menopause are similar. The aim of this study was to evaluate ovarian steroidogenesis and consequently to define the role of the ovaries in postmenopausal women depending on the time after menopause. Concentrations of hormones were determined in ovarian homogenates and serum of postmenopausal women. This study included 207 postmenopausal women. They were divided into groups depending on the time after menopause. All participants had laparotomic removal of the ovaries. Concentrations of estradiol, testosterone and androstenedione were measured in ovarian homogenate and serum. The study revealed that ovarian homogenate and serum concentrations of estradiol, testosterone and androstenedione were the highest in women up to 5 years after menopause and since then significantly decreased. This study showed that testosterone, androstenedione and estradiol are synthesized in the postmenopausal ovaries. The peak synthesis of these hormones occurs up to 5 years after menopause and significantly decreases thereafter.     

Effect of immune stress on body weight regulation is altered by ovariectomy in female rats

It has been suggested that obesity and loss of ovarian function alter the inflammatory response to immune stress. Ovariectomized (OVX) rats, which are used as a model of human menopause, exhibit both hyperphagia-induced obesity and gonadal steroid deficiency. To evaluate the effects of ovariectomy on inflammatory responses, we compared the anorectic response to LPS in OVX rats and gonad intact female rats. As leptin and hypothalamic interleukin-1β (IL1β) play pivotal roles in the anorectic response to immune stress, these factors were also measured. It was found that the OVX rats exhibited an increased anorectic response to LPS compared with the sham-operated rats. The OVX rats showed higher serum leptin concentrations and a greater increase in hypothalamic IL1β mRNA expression after LPS injection. In addition, in order to determine whether gonadal steroid deficiency contributes to the changes in the inflammatory responses of OVX rats, we compared responses between OVX rats treated with gonadal steroids and untreated OVX rats. There were no differences in appetite, the serum leptin level, and hypothalamic IL1β mRNA expression between the two groups after LPS injection. These findings suggest that the loss of ovarian function increases the induction of leptin and hypothalamic IL1β synthesis and consequently increases the anorectic response under immune stress conditions. It is possible that these alterations are caused by OVX-induced obesity rather than the direct effects of gonadal steroid deficiency.     

Use of thiamine pyrophosphate to prevent infertility developing in rats undergoing unilateral ovariectomy and with ischemia reperfusion induced in the contralateral ovary

Objective

To investigate whether thiamine pyrophosphate can prevent infertility developing in rats undergoing unilateral ovariectomy and with ischemia reperfusion induced in the contralateral ovary. Biochemical examinations of the ovaries were also performed.

Study design

Rats were divided into two main groups of three subgroups each. An ischemia reperfusion model was established in the first main group, while surgical unilateral ovariectomy was performed in the second. Thiamine pyrophosphate and melatonin were administered to the subgroups. No additional procedure was performed in the control groups. The rats were then left in laboratory environments and their fertility levels were determined. Malondialdehyde, total glutathione and DNA damage products were measured in those rats from which ovarian tissue was collected.

Results

The results showed that thiamine pyrophosphate prevented ischemia/reperfusion injury-related infertility, but melatonin did not provide adequate prevention. However, reproduction in healthy animals receiving melatonin began earlier compared to those receiving thiamine pyrophosphate. Melatonin suppressed oxidative stress caused by ischemia/reperfusion in ovarian tissue significantly better than did thiamine pyrophosphate.

Conclusions

We think that different mechanisms, in addition to antioxidant activity, are involved in the prevention of reperfusion-associated infertility after ischemia.     

Sleep disturbances, oxidative stress and cardiovascular risk parameters in postmenopausal women complaining of insomnia.

OBJECTIVE: The aim of this work was to investigate cardiovascular risk factors and oxidative stress parameters as well as sleep disturbances in polysomnography recordings of 38 postmenopausal women with insomnia. METHODS: Polysomnography recordings were performed on subjects for sleep analysis. Oxidative stress parameters were analyzed by measuring blood concentration of catalase, superoxide dismutase (SOD), thiobarbituric acid reactive substances (TBARS) and glutathione. For cardiovascular risk factors, we measured plasma levels of homocysteine, folic acid and vitamin B6. RESULTS: Findings of polysomnography recordings revealed: 68% experienced decreased sleep efficiency, 50% had apnea, 7.8% had periodic leg movements and 2.6% had bruxism (involuntary gnashing and grinding of the teeth during sleep). Our results showed that the majority of our subjects presented normal concentrations of the parameters studied according to standards reached in our laboratory. The only notable exception was TBARS. In this case, only 21% displayed normal values. We also found inverse correlations between SOD activity and both age and time of menopause. CONCLUSIONS: Although all women complained of insomnia, 50% of them demonstrated apnea during polysomnography recordings. Of the parameters measuring oxidative stress, only TBARS levels were increased in our sample. Some clinical data, such as time of onset of menopause, may be associated with the oxidative stress status of these women, probably due to the lack of estrogen and to sleep disturbances, such as apnea.     

Hormontherapie bei POF-Syndrom

Premature ovarian failure refers to ovarian insufficiency with early estrogen depletion before the age of 40. Long-term risks of estrogen deficiency outweigh the risks of hormone therapy by far. Therefore, guidelines generally recommend hormonal therapy until the age of normal menopause at 51?years. Hormonal treatment can be administered as estradiol preparations with progestagens or oral contraceptive pills. Spontaneous pregnancies are rare, reported in approximately 5% of cases. No specific infertility treatment is available.     

Effects of dehydroepiandrosterone on ovarian cystogenesis and immune function

The purpose of the present report was to study the possible relationship between ovarian functionality and the immune response during cystogenesis induced by androgenization with dehydroepiandrosterone (DHEA). Daily injection of DHEA (6 mg/kg body weight) for 20 consecutive days induced ovarian cysts in BALB/c mice. As markers of ovarian function, serum estradiol (E) and progesterone (P) and the ovarian inmunomodulator prostaglandin E (PGE) were analyzed. In order to know how the integrity of the tissue was altered after induction of cystogenesis, the oxidative status was also evaluated. Serum E and P levels, and ovarian PGE concentration, were increased in animals with cysts compared with healthy controls. The oxidant status (quantified by malondialdehyde (MDA) formed after the breakdown of the cellular membrane by free radical mechanisms) was augmented, meanwhile the antioxidant (evaluated by the glutathione (GSH) content) diminished during the induction of cystogenesis. Both immunohistochemical and flow cytometry assays demonstrated that DHEA treatment increased the number of T lymphocytes infiltrating ovarian tissue. Therefore, while ovarian controls showed equivalent expression of CD4+ and CD8+ T cell subsets, injection of DHEA yielded a selective ovarian T cell infiltration as demonstrated by enhanced CD8+ and diminished CD4+ T lymphocyte expression. These results show that the development of cysts involves changes in ovarian function and an imbalance in the oxidant-antioxidant equilibrium. We observed also both an increased and selective T lymphocyte infiltration.     

Long-term effect of bilateral ovariectomy on endothelial function in aortic rings of spontaneously hypertensive rats: role of nitric oxide.

Endothelial dysfunction associated with both menopause and hypertension could be one of the possible explanations for increased cardiovascular morbidity and mortality in hypertensive postmenopausal women. The aim of the present study was to investigate the long-term effect of menopause (bilateral ovariectomy) on endothelial function in isolated aortic rings of spontaneously hypertensive rats (SHR). Aortic rings were suspended in organ chambers filled with physiological salt solution (95% O2, 5% CO2, 37 degrees C), and isometric tension was measured. In studies designed to assess the tone-related release of nitric oxide (NO) from phenylephrine-precontracted aortic rings, we found that vasoconstriction induced by L-NAME was greater in aortic rings from sham-ovariectomized SHR (SHAM SHR) than in those obtained from ovariectomized SHR (OVX SHR). Concentration-related relaxant responses to superoxide dismutase were significantly greater in the SHAM SHR than in the OVX SHR. In contrast, receptor-mediated release of NO was not altered by ovariectomy, as deduced from acetylcholine (ACh) concentration-responses curves. Responses to the exogenous NO donor sodium nitroprusside (SNP) were also identical in both ovariectomized and sham-ovariectomized groups, ruling out differences in smooth muscle reactivity to NO. These results show that NO release is impaired in OVX SHR, an animal model of simultaneous hypertension and menopause.     

Differential effects of aging on activin A and its binding protein, follistatin, across the menopause transition

To assess the involvement of ovarian-derived regulatory proteins in FSH modulation, we compared FSH, inhibin A, inhibin B, activin A, and follistatin (FS) in 79 women from the following five groups: young cycling, older cycling, perimenopause (PERI), spontaneous menopause (PM), and surgical menopause receiving estrogen (OVX+ET). Although inhibin B varied as expected by ovarian function, no group differences were observed in activin A, barring a tendency for an increase in PERI, while FS 288 was lower in the PERI, PM, and OVX+ET groups and negatively correlated with advancing age.     

Menopause: evidence-based practice

Menopause is a physiologic transition and is assuming an increasing importance as the demographic bulge moves through this phase. The transition takes place over several years. It is characterized by depletion of the ovarian follicles, decreasing inhibin leading to increases in follicle-stimulating hormone and loss of the menstrual cycle, accompanied by decreased estradiol production and typical symptoms. The role of hormone therapy in menopause has shifted from preventive use to a limited role in symptom management, for which it remains the most effective intervention. There is good evidence from observational and randomized trials of an increased risk of breast cancer in women on estrogen plus a progestin, compared with those on estrogen alone. There are insufficient data to be able to determine if there are clinically important differences between various progestins and progesterone with respect to breast cancer risk, nor between different regimens. Even relatively short-term exposure to unopposed estrogen will increase the risk of atypical endometrial hyperplasia or cancer; women who have their uterus should be using a progestational agent. Lifestyle changes at menopause are important and effective for preventive health. Recent evidence suggests that the discordance between epidemiologic studies with respect to cardiovascular outcomes and the Women's Health Initiative randomized controlled trial (WHI RCT) data might be attributable in large part to the older age of women enrolled in the WHI.     

Long-term effect of bilateral ovariectomy on endothelial function in aortic rings of spontaneously hypertensive rats: role of nitric oxide

Endothelial dysfunction associated with both menopause and hypertension could be one of the possible explanations for increased cardiovascular morbidity and mortality in hypertensive postmenopausal women. The aim of the present study was to investigate the long-term effect of menopause (bilateral ovariectomy) on endothelial function in isolated aortic rings of spontaneously hypertensive rats (SHR). Aortic rings were suspended in organ chambers filled with physiological salt solution (95% O₂ ,5% CO₂ ,37°C) ,and isometric tension was measured. In studies designed to assess the tone-related release of nitric oxide (NO) from phenylephrine-precontracted aortic rings ,we found that vasoconstriction induced by L-NAME was greater in aortic rings from sham-ovariectomized SHR (SHAM SHR) than in those obtained from ovariectomized SHR (OVX SHR). Concentration-related relaxant responses to superoxide dismutase were significantly greater in the SHAM SHR than in the OVX SHR. In contrast ,receptor-mediated release of NO was not altered by ovariectomy ,as deduced from acetylcholine (ACh) concentration-responses curves. Responses to the exogenous NO donor sodium nitroprusside (SNP) were also identical in both ovariectomized and sham-ovariectomized groups ,ruling out differences in smooth muscle reactivity to NO. These results show that NO release is impaired in OVX SHR ,an animal model of simultaneous hypertension and menopause.     

Cardiovascular disease as a current threat of older women. Relation to estrogens

Cardiovascular disease (CVD) is the leading cause of death in women around the world. Cardiovascular disease risk increases after the menopause which may be related to metabolic and hormonal changes. The decline in ovarian function with menopause is associated with spontaneous increases in proinflammatory cytokines. Chronic inflammation is a major factor that drives the progression of atherosclerosis and atherothrombosis. Measurement of the inflammatory markers has been postulated as a method of determining increased risk of cardiovascular disease in apparently healthy older women. Endogenous estrogen appears to be cardioprotective and several observational epidemiological studies have suggested that hormone therapy reduces the risk of coronary events in healthy postmenopausal women. However, recent clinical studies failed to show such beneficial effect. Among the mechanism that may account for the effects of hormone therapy on cardiovascular disease is inflammation.     

Postmenopausal hormone replacement and cardiovascular disease: incorporating research into practice

The long-standing practice of prescribing hormones to postmenopausal women was based in part on the observation that following menopause, women's incidence of cardiovascular diseases such as atherosclerosis, myocardial infarction, and cerebral vascular accident increased. Recent large-scale research has shown an increase in cardiovascular events for postmenopausal women receiving estrogen replacement in oral form. This article examines research on positive effects of hormone replacement therapy, discusses what is known about the development of cardiovascular disease in women, and evaluates recent research that has shown increased cardiovascular risk in women receiving hormone replacement. It concludes with recommendations for preventing cardiovascular disease in women. This is essential information for nurses, who need to be informed of ways to maintain their own health while serving as sources of health information for the public at large.     

The SWAN song: Study of Women's Health Across the Nation's recurring themes

Reproductive health can be a reflection of overall health. It follows that abnormalities of reproductive milestones may be a manifestation of unhealthy aging. Since 1994, the Study of Women's Health Across the Nation (SWAN) has assessed how menopause and the process of that transition may affect future health. Themes have emerged from SWAN associating patterns of hormones and symptoms with metabolic status.The nature of these relationships vary as women traverse the menopause and ovarian hormone production ceases. This review describes these cross-cutting themes and their possible meaning for the health of the mid-life woman.