Effects Of Estrogen Replacement Therapy Research Articles

Effect of oestrogen replacement therapy on idiopathic outflow tract ventricular arrhythmias in postmenopausal women

Sex hormones and gender differences are associated with the occurrence of ventricular arrhythmias. To investigate the relationship between sex hormones and idiopathic outflow tract ventricular arrhythmias (IOTVA), and the effect of oestrogen replacement therapy on IOTVA, in postmenopausal female patients. Plasma sex hormone concentrations and ventricular arrhythmia counts were estimated in postmenopausal patients with IOTVA and control postmenopausal women. The effect of oestrogen replacement therapy on IOTVA was observed in postmenopausal patients with IOTVA. The concentration of oestradiol in postmenopausal patients with IOTVA was significantly lower than that in control postmenopausal women (8.4 ± 3.4 vs 36.9 ± 12.8pg/mL, respectively; P<0.001). The ventricular arrhythmia count in postmenopausal patients with IOTVA was significantly higher than that in controls (10,171 ± 6091 vs 209 ± 468 counts/24 hours, respectively; P<0.001). After 3 months of oestrogen replacement therapy, the ventricular arrhythmia count was significantly lower than that before therapy (3958 ± 1972 vs 10171 ± 6091 counts/24 hours, respectively; P<0.001). This study showed that the concentration of oestradiol was lower in postmenopausal patients with IOTVA than in control postmenopausal women, and that oestrogen replacement therapy can inhibit effectively the genesis of IOTVA.

Effects of Estrogen Replacement Therapy to the Renal Function in Postmenopausal Women

Effects of Estrogen Replacement Therapy to the Renal Function in Postmenopausal Women

Effects of Estrogen Replacement Therapy with Vitamin E on Oxidative Stress in Hepatic and Pancreatic Tissues of Ovariectomized Diabetic Rats

Effects of Estrogen Replacement Therapy with Vitamin E on Oxidative Stress in Hepatic and Pancreatic Tissues of Ovariectomized Diabetic Rats

Physical inactivity as a global risk factor for chronic diseases in women

Social inequality, poverty and inequitable access to resources, including healthcare, result in a high burden of non-communicable diseases among women worldwide. Regular physical activity can improve women's health and help...

Hypothesis: Multiple factors are associated with the lack of any beneficial effects of oestrogen‐replacement therapy in the late postmenopausal stage

1. Epidemiological and clinical studies suggest that women may obtain cognitive benefits from oestrogen-replacement therapy (ERT) during menopause transition rather than in the post-menopausal stages. However, the underlying mechanisms remain to be determined. 2. We propose that long-term oestrogen deficiency may result in abnormal distribution and localization of brain oestrogen receptors, brain mitochondrial dysfunction, septohippocampal cholinergic degeneration and reactive gliosis. These multiple pathogenic factors may account for the lack of any beneficial effects of ERT in post-menopausal women with or without Alzheimer's disease.

Aldose reductase inhibition ameliorates the detrimental effect of estrogen replacement therapy on neuropathology in diabetic rats subjected to transient forebrain ischemia

Estrogen replacement therapy (ERT) elicits a deleterious, instead of protective, effect on neuropathology in diabetic ovariectomized (OVX) rats subjected to cerebral ischemia. This transformation may be linked to an estrogen-associated increase in function of the receptor for advanced glycation end-products (RAGE). Moreover, under diabetic conditions, advanced glycation end-products (AGEs) are excessively generated through the aldose reductase (AR)-polyol pathway. As such, in diabetic rats given ERT, a RAGE-related exacerbation of post-ischemic brain injury can occur. Thus, in the present study, we evaluated the contribution of AR in estrogen's detrimental effect on diabetic animals subjected to transient forebrain ischemia (TFI). Streptozotocin- and 17-β estradiol-treated OVX female rats were divided into two groups, where AR activity was blocked using epalrestat; or AGEs production was restricted, via administrating the protein glycation crosslink breaker, ALT-711. In all animals, ERT was initiated ∼ 10 days before TFI. Pial venular leukocyte adhesion was evaluated over 10 h post-TFI using a cranial window/intravital microscopy technique. In vehicle-treated control groups, a significant increase in leukocyte adhesion was observed post-TFI. Leukocyte extravasation, starting at ∼ 6 h post-TFI, was detected in most of the control animals. Chronic administration of either epalrestat or ALT-711 was associated with a marked decrease in post-TFI leukocyte adhesion, and the complete prevention of leukocyte extravasation. Animals receiving either epalrestat or ALT-711 exhibited a significant improvement in neurologic function, at 72 h post-ischemia, compared to vehicle-treated controls. Post-ischemic (72 h) histopathology was significantly reduced by epalrestat. Compared to the non-diabetic (ND) controls, diabetic OVX rats in the absence or presence of ERT showed a significant 2-fold or 3-fold increase in cortical AR mRNA levels, respectively. In contrast, only a modest increase in AR protein expression, relative to ND control, was detected in the two diabetic groups. The present findings suggest that AR participates in estrogen's deleterious action on post-ischemic neuropathology in diabetics by promoting inflammation. Targeting the AR-controlled polyol pathway may be a clinically promising strategy to restore the neuroprotection of ERT in diabetic females.

Additive effects of estrogen replacement therapy and bisphosphonates on osseointegration of hydroxyapatite-coated titanium screws in ovariectomized rats

This study investigated the effect of locally immobilized bisphosphonates and systemic estrogen replacement therapy on fixation of hydroxyapatite-coated screws in ovariectomized rats. Twelve weeks after being ovariectomized, each of the 20 rats received 2 hydroxyapatite-coated screws in the proximal tibia, with or without immobilized bisphosphonates. Half of the animals also received subcutaneous injections of 17beta-estradiol. Thus, there were 4 groups: control, estrogen, bisphosphonates, and estrogen plus bisphosphonates. Tibiae with screws were measured by microscopic computerized tomography and push-out test 12 weeks after implantation. Combined treatment had the strongest effects, with the bone volume ratio around screws and the percentage of osteointegration significantly increased by 2.3-fold and 1.9-fold and the push-out force by 3.3-fold compared with untreated control samples. Monotherapy also enhanced the fixation of screws, although less. Systemic estrogen replacement therapy and locally immobilized bisphosphonates had additive effects on fixation of hydroxyapatite-coated screws in ovariectomized rats.

Effect of estrogen replacement therapy on lens epithelial cell apoptosis in an experimental rat model

Epidemiologic studies have revealed a higher incidence of cataracts in estrogen-deprived postmenopausal women, although the pathogenic mechanism has not yet been elucidated. Apoptosis of lens epithelial cells has been associated with cataractogenesis. The aim of the study reported here was to investigate the effect of estrogen replacement therapy (ERT) on lens epithelial cell apoptosis in an experimental rat model. Forty female Wistar rats were randomized into four groups: ERT (17beta-estradiol, 10 microg/kg/day) for 3 months without ovariectomy (group 1) and with ovariectomy (group 2); only ovariectomy (group 3); sham operated (group 4). At the end of the third month, all rats were sacrificed in estrous cycle, as determined by the vaginal smear test, and their right eyes were enucleated. Enucleated eyes were analyzed by immunohistochemical methods for the expression of terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end (TUNEL), caspase-3, and bcl-2 labeling. The TUNEL, caspase-3, and bcl-2 staining scores were found to increase in group 3 rats following the ovariectomy compared to the sham-operated group. The ERT decreased these scores in rats with or without the ovariectomy; however, these differences were not statistically significant. These data suggest that estrogen does not significantly affect lens epithelial cell apoptosis. Further studies are needed to gain a better understanding of the protective mechanism of estrogen and to provide new ideas for the treatment and prevention of cataract.

Role of Estrogen and Endothelium in Migraine in Young Women

HomeStrokeVol. 40, No. 12Role of Estrogen and Endothelium in Migraine in Young Women Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBRole of Estrogen and Endothelium in Migraine in Young Women Kazushi Tsuda, MD, FAHA Kazushi TsudaKazushi Tsuda Cardiovascular and Metabolic Research Center, Kansai University of Health Sciences, Osaka, Japan Search for more papers by this author Originally published5 Nov 2009https://doi.org/10.1161/STROKEAHA.109.566489Stroke. 2009;40:e705Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: November 5, 2009: Previous Version 1 To the Editor:We read with great interest the recent article by Tietjen and colleagues1 dealing with migraine and endothelial activation in young women. The results of their study demonstrated a strong relation between migraine and endothelium-related biomarkers, including von Willebrand factor activity, high-sensitivity C-reactive protein, and total nitrite/nitrate concentration, in a young, relatively healthy cohort of women. The authors suggest that, in premenopausal women with migraine, there is evidence of increased endothelial activation, a component of endothelial dysfunction. They further propose that an understanding of the role of endothelium in migraine may provide a rationale for multiple avenues for stroke prevention in migraineurs.Numerous studies have shown that estrogen may have beneficial effects on cardiovascular functions. One of the mechanisms underlying the protective effect of estrogen may be the enhancement of nitric oxide production. There is evidence showing that vascular endothelial function is markedly influenced by estrogen and improved by hormone replacement therapy in postmenopausal women.2 In an in vitro study presented earlier, we demonstrated that 17β-estradiol increased membrane fluidity (a reciprocal value of membrane microviscosity) of erythrocytes and improved the rigidity of cell membranes in women through the nitric oxide- and cGMP-dependent mechanism.3 Because abnormalities in membrane microviscosity could cause a disturbance in rheological behavior and microcirculation, these findings indicate that estrogen deficiency might be involved in the pathophysiology of vascular complications in women. On the other hand, it has been demonstrated that endothelial function varied during the menstrual cycle in premenopausal women, suggesting that sex hormone status would have a crucial role in cardiovascular risk and other disease processes in premenopausal women.4 Kawano et al5 also demonstrated a menstrual cyclic variation of myocardial ischemia in premenopausal women. Therefore, we would like to know whether menstrual cycle-related endogenous estrogen status might be associated with the endothelial biomarker levels and the magnitudes of migraine in young women in the study of Tietjen and colleagues. It would be important to assess more precisely the relationships between estrogen status and endothelial function during the menstrual cycle and their contribution to the pathogenesis of migraine in young women.DisclosuresNone.1 Tietjen GE, Herial NA, White L, Utley C, Kosmyna JM, Khuder SA. Migraine and biomarkers of endothelial activation in young women. Stroke. 2009; 40: 2977–2982.LinkGoogle Scholar2 Higashi Y, Sanada M, Sasaki S, Nakagawa K, Goto C, Matsuura H, Ohama K, Chyayama K, Oshima T. Effects of estrogen replacement therapy on endothelial function in peripheral resistance arteries in normotensive and hypertensive postmenopausal women. Hypertension. 2001; 37: 651–657.CrossrefMedlineGoogle Scholar3 Tsuda K, Kinoshita Y, Kimura Y, Nishio I, Masuyama Y. Electron paramagnetic resonance investigation on modulatory effect of 17β-estradiol on membrane fluidity of erythrocytes in postmenopausal women. Arterioscler Thromb Vasc Biol. 2001; 21: 1306–1312.CrossrefMedlineGoogle Scholar4 Williams MR, Westerman RA, Kingwell BA, Paige J, Blombery PA, Sudhir K, Komesaroff PA. Variations in endothelial function and arterial compliance during the menstrual cycle. J Clin Endocrinol Metab. 2001; 86: 5389–5395.CrossrefMedlineGoogle Scholar5 Kawano H, Motoyama T, Ohgushi M, Kugiyama K, Ogawa H, Yasue H. Menstrual cyclic variation of myocardial ischemia in premenopausal women with variant angina. Ann Intern Med. 2001; 135: 977–981.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetails December 2009Vol 40, Issue 12 Advertisement Article InformationMetrics https://doi.org/10.1161/STROKEAHA.109.566489PMID: 19892993 Originally publishedNovember 5, 2009 PDF download Advertisement

Effects of estrogen replacement therapy on estrogen receptor expression and immunoregulatory cytokine secretion in surgically induced menopausal women

To investigate the effect of oral and transdermal estrogen replacement therapy (ERT) on the expression of different estrogen receptor (ER) subtypes and the secretion of immunoregulatory cytokines, we performed a clinical investigation on previously healthy women who had undergone a total hysterectomy and bilateral salpingo-oopherectomy. These women were randomly distributed into two groups: an oral ERT group and transdermal ERT group. Before and after ERT, the serum levels of estradiol (E 2) and follicle stimulating hormone (FSH) were measured, ERα and ERβ expression of peripheral blood T lymphocytes was tested, and secretion of specific immunoregulatory cytokines (IFNγ, IL-2 and IL-4) by T lymphocytes was examined. Our results confirm that for both groups, the serum E 2 level was increased after ERT ( P < 0.01) and the serum FSH level was decreased after ERT ( P < 0.01), with no significant difference in hormone levels between the two groups. ERα expression by T lymphocytes was significantly higher after ERT than before ( P < 0.01) in both groups. Levels of type 1 cytokines (IL-2 and IFNγ), which were secreted by T helper 1 (Th1), after ERT were substantially decreased. The level of type 2 cytokine (IL-4), which were secreted by T helper 2 (Th2), was significantly increased after ERT ( P < 0.01 for the oral group and P < 0.05 for the transdermal group). In summary, both oral and transdermal ERT increased serum E 2 levels, decreased serum FSH levels and relieved the effects of peri-menopausal symptoms. These data suggest that both oral and transdermal ERT act to improve the balance of Th1/Th2 cytokines by the effects of estrogen potentially acting in T lymphocytes mainly through ERα.

THE EFFECTS OF ESTROGEN REPLACEMENT THERAPY ON SERUM LIPID PROFILE IN SURGICALLY MENOPAUSED WOMEN

Objectives: To evaluate short-term and long-term effects of estrogen replacement therapy (ERT) on lipid profile in surgically menopaused women. Methods: In this cross-sectional study, 120 surgically menopaused women after total hysterectomy and bilateral oophorectomy and 107 natural postmenopausal womenwere enrolled. After surgical menopause, 28 women received 0.625mg conjugated equine estrogen (CEE) and 32 women did not for 3months, 28women received and 32 women were did not for 1 year. Natural postmenopausal women received 0.625 mg conjugated equine estrogen (CEE) and 5 mg medroxyprogesterone acetate (MPA). The effects of hormone therapy on plasma levels of lipids were investigated. Results:During hormone therapy, total cholesterol and LDL cholesterol level decreased significantly for 3 months and 1 year in surgically menopaused women (P 0.05). Triglyceride level decreased in surgically menopaused women had not received ERT but there was no significant statistical difference (P>0.05). Conclusion:The results of our study results suggest that ERT had more beneficial effects on lipid profile in surgically menopaused women.

Estrogen replacement therapy decreases plasma adiponectin but not resistin in postmenopausal women

The effects of estrogen replacement therapy (ERT) to cardiovascular disease risk are still unclear. Low adiponectin and high resistin plasma concentrations are reported to be associated with atherosclerosis. However, it is not known how ERT affects plasma adiponectin and resistin concentrations. Seventy-three hysterectomized, nondiabetic, postmenopausal women were randomized in a double-blind, double-dummy study to receive either peroral estradiol valerate or transdermal 17 β-estradiol gel for 6 months. Biochemical measurements were determined from samples taken before and after the therapy. Peroral estradiol valerate therapy decreased adiponectin concentrations from 13.6 to 11.6 mg/L ( P = .008), whereas transdermal 17 β-estradiol gel had no effect (12.7 vs 12.2 mg/L). Neither treatment changed the resistin concentrations significantly. Plasma concentrations of estradiol and estrone did not correlate with adiponectin or resistin concentrations before or after therapy. The change in adiponectin concentration correlated significantly with the changes in waist-hip ratio, very low-density lipoprotein triglycerides, and insulin-like growth factor 1 in the peroral estradiol valerate group. The changes in these variables and the change in estradiol concentration explained 43.1% ( P = .001) of the variability in the change of plasma adiponectin, the change in very low-density lipoprotein triglycerides being the strongest determinant ( β = −.407, P = .011). The results show that peroral ERT can decrease plasma adiponectin levels. However, ERT does not seem to influence plasma resistin concentrations.

The reduction in visceral fat mass in response to growth hormone is more marked in men than in oestrogen-deficient women

Context Women with severe growth hormone (GH) deficiency have a less marked response to GH replacement than men. This has mostly been attributed to the attenuating effects of oestrogen replacement therapy. Objective To study gender related differences in the response to GH treatment in men and postmenopausal women. Methods Fifteen men and 15 age- and BMI-matched women with abdominal obesity (mean age: 58; range 51–64 years) were treated for one year with similar doses (0.47 vs. 0.51 mg/day) of GH. All women were postmenopausal not receiving oestrogen treatment. Insulin sensitivity was assessed using a hyperinsulinemic euglycemic clamp and body composition by computed tomography (CT) scans and from total body potassium, K 40. Results Men and women were comparable at baseline in terms of waist circumference, IGF-1 and lipid levels. After one year of GH treatment, there was a 18% reduction in visceral adipose tissue (VAT) in men and a 5% reduction in women ( P = 0.0001 men vs. women). Although the magnitude of the difference was small, men increased more in thigh muscle mass ( P < 0.0001 vs. women). A reduction in thigh intermuscular adipose tissue (IMAT) and diastolic blood pressure was seen only in men (both p < 0.05 vs. baseline). A decrease in LDL cholesterol, and an increase in serum insulin, was observed only in women (both p < 0.05 vs. baseline). Conclusion Low dose GH treatment reduced VAT more markedly in men as compared with women. As all women were postmenopausal and oestrogen-deficient, this gender difference in responsiveness was not due to an antagonistic effect of oestrogen on peripheral GH action.

Estrogen reduces inflammation of asthmatic airways by inhibiting pathways leading to oxidant stress.

We have previously reported that estrogen replacement therapy reduces inflammation in a murine model of allergic asthma. We now studied the mechanisms responsible for this protective effect. Female C57/Bl6 mice were ovariectomized, implanted with subcutaneous osmotic minipumps releasing either vehicle or estrogen and subjected to a 25‐day regimen of ovalbumin sensitization. On day 26, animals were sacrificed and lung tissue was analyzed as described below. Asthmatic, vehicle‐treated mice exhibited strong oxidant stress, as revealed by immunohistological staining of lung tissue for 8‐hydroxy‐2‐deoxyguanosine (8‐OHdG), an indicator of oxidative DNA damage; 8‐OHdG staining was significantly reduced in asthmatic, estrogen‐treated mice and resembled that in non‐asthmatic controls. Furthermore, asthmatic, vehicle treated animals demonstrated increased Akt phosphorylation, and Rac‐1 activation, suggesting that NADPH oxidase may be an important contributor to the observed oxidant stress in asthmatic animals. Akt phosphorylation and Rac‐1 activation were profoundly inhibited in estrogen‐treated asthmatic mice, to levels resembling those on non‐asthmatic controls. These data suggest that the protective effects of estrogen replacement therapy may include inhibition of pathways leading to increased oxidant stress.

Timing of estrogen replacement influences atherosclerosis progression and plaque leukocyte populations in ApoE−/− mice

Studies of the effects of estrogen replacement therapy on coronary heart disease risk have produced conflicting results. We hypothesize that this may be explained by differences in the length of estrogen deficiency prior to initiation of treatment and associated variation in plaque inflammation or stage of progression. The goal of this study was to determine whether estrogen administered after a period of deficiency affects plaque progression and leukocyte populations. Ovariectomized ApoE−/− mice were treated as follows: group 1: continuous estrogen for 90 days (E+/+); group 2: placebo for 45 days followed by estrogen for 45 days (E−/+); group 3: estrogen for 45 days followed by placebo for 45 days (E+/−); and group 4: placebo for 90 days (E−/−). Serum lipoprotein concentrations, plaque size and inflammatory cell (macrophage, CD3+, CD4+, CD8+, dendritic cell, and NK cell) densities were quantified. Plaque size was smaller in groups receiving early estrogen therapy. CD3+ and total inflammatory cell densities were lower in late estrogen therapy groups. The CD8 to dendritic cell ratio was significantly lower in the E−/+ group only. These results suggest that a period of estrogen deficiency followed by reintroduction alters the immunologic environment of atherosclerotic lesions as well as plaque progression.

Effect of estrogen replacement therapy on arthritis and bone mineral density in estrogen-replete rats with collagen-induced arthritis

The influence of estrogen therapy on changes in arthritis and bone mineral density (BMD) was evaluated using an estrogen-replete collagen-induced arthritis (CIA) rat model. Seven-month-old female Sprague–Dawley rats (n = 30) were divided into the three groups; control (CONT), collagen sensitization (CIA), and CIA + 17β-estradiol administration for 7 weeks (CIA + E). BMD was measured by peripheral quantitative computed tomography in the proximal tibia every 2 weeks. Eight weeks after the initial sensitization the rats were killed and histomorphometry of tibia was performed. The hind paw thickness increased with time in CIA rats and there was a significant difference between CONT and CIA at 8 weeks after the initial sensitization. Estrogen tended to make the development of arthritis milder. In CIA, BMD at metaphyseal cancellous bone began to decrease with the onset of arthritis and became significantly lower than in CONT after 8 weeks. Compared with the CIA, the deterioration in BMD was inhibited in CIA + E. Histomorphometrical parameters of bone resorption were increased in CIA compared with CONT, and those elevations were reduced by estrogen treatment, but estrogen had no effect on bone formation parameters. In conclusion, estrogen could partially suppress arthritis and bone loss in estrogen-replete rats as well as estrogen-deplete ones.

Effect of estrogen replacement therapy on arthritis and bone mineral density in estrogen-replete rats with collagen-induced arthritis

The influence of estrogen therapy on changes in arthritis and bone mineral density (BMD) was evaluated using an estrogen-replete collagen-induced arthritis (CIA) rat model. Seven-month-old female Sprague-Dawley rats (n = 30) were divided into the three groups; control (CONT), collagen sensitization (CIA), and CIA + 17beta-estradiol administration for 7 weeks (CIA + E). BMD was measured by peripheral quantitative computed tomography in the proximal tibia every 2 weeks. Eight weeks after the initial sensitization the rats were killed and histomorphometry of tibia was performed. The hind paw thickness increased with time in CIA rats and there was a significant difference between CONT and CIA at 8 weeks after the initial sensitization. Estrogen tended to make the development of arthritis milder. In CIA, BMD at metaphyseal cancellous bone began to decrease with the onset of arthritis and became significantly lower than in CONT after 8 weeks. Compared with the CIA, the deterioration in BMD was inhibited in CIA + E. Histomorphometrical parameters of bone resorption were increased in CIA compared with CONT, and those elevations were reduced by estrogen treatment, but estrogen had no effect on bone formation parameters. In conclusion, estrogen could partially suppress arthritis and bone loss in estrogen-replete rats as well as estrogen-deplete ones.

Hormone replacement therapy and cardiovascular disease: the case for a randomized controlled trial.

The menopause is associated with an increased risk of developing cardiovascular disease. Oestrogen may influence various metabolic pathways which contribute to the pathogenesis of cardiovascular disease, and observational studies suggest that in postmenopausal women oral oestrogen replacement therapy confers some protection against coronary heart disease and to a lesser extent against stroke. What is not clear is the magnitude of the cardioprotective effect and the overall balance of long-term benefits and hazards. Research is also required to establish the relative effects of oestrogen replacement therapy and combined or opposed hormone replacement therapy (HRT) where progestogen is added to counter the proliferative action of oestrogen on the endometrium. A large randomized controlled trial is the only way to provide accurate estimates of the cardioprotective effect of HRT and of other long-term benefits and hazards. Feasibility studies undertaken through the UK Medical Research Council (MRC) General Practice Research Framework show that such a trial is acceptable to patients and their doctors. Recruitment and withdrawal rates indicate that a trial of sufficient size to show a 25% reduction in cardiovascular disease with 90% power at the 1% level would be feasible. The full trial is costly and it is proposed that the UK collaborates with other countries in a major international trial to complement the Women's Health Initiative trial in the USA. Feasibility studies in Europe are underway, the design and scientific rationale for the trial have been approved by the UK MRC and it is hoped that recruitment to the full-scale trial can begin soon.

Hormone replacement Up-to-date. Effects of estrogen replacement therapy on lipid metabolism

Postmenopausal hormone replacement therapy (HRT) has favorable effects on lipids and decreases the risk of cardiovascular disease (CVD). Since Women's Health Initiative (WHI) has demonstrated that HRT increases the risk of CVD, indications of HRT use have been limited. Oral estrogen has several adverse effects on the risk of CVD. Oral estrogen increases the plasma triglyceride concentrations that decrease the size of LDL particles. Synthetic progestagens such as medroxyprogesterone acetate (MPA) decreases the plasma concentrations of high-density lipoprotein cholesterol. In contrast, recent studies demonstrated that transdermal estrogen or low dose oral estrogen administration, and the use of natural progestagen can protect against adverse effects of oral estrogen. Further studies are needed to investigate whether transdermal or low dose of estrogen administration and the use of natural progestagens can decrease the risk of CVD.

Non-hormonal therapy of post-menopausal vasomotor symptoms: a structured evidence-based review

Interest in non-hormonal therapies for the treatment of menopausal symptoms has increased since the publication of adverse effects of estrogen replacement therapy. To provide information on the efficacy of non-hormonal therapies for menopausal vasomotor symptoms based on evidence from published randomised controlled studies. The Cochrane Database of Systematic Reviews (CDSR), MEDLINE, Alternative Therapies in Health and Medicine database (ATHMD) and Allied and Complementary Medicine database (AMED) were searched for randomised controlled trials in the English language reporting data on treatment of menopausal vasomotor symptoms. Trials including cancer breast patients were included. Our search identified 58 randomised controlled trials of which 11 involved the use of clonidine, six for SSRIs, four for gabapentin, seven for black cohosh, seven for red clover, 18 for phytoestrogens, two for ginseng, one for evening primrose, one for dong quai and one for vitamin E. Most trials had methodological deficiencies. There is evidence that clonidine, paroxetine, venlafaxine, gabapentin and black cohosh may be beneficial in the treatment of menopausal vasomotor symptoms in some women. Current evidence does not support the use of fluoxetine, red clover, phytoestrogens, Ginseng, evening primrose, dong quai and vitamin E. The side effects profile of these therapies should be considered.