Dysfunction In Postmenopausal Women Research Articles

PP.08.20

Objective: Previous studies that indicate metabolic syndrome (MetS) might be at risk for left ventricular (LV) diastolic dysfunction. However, little is known about which metabolic factors contribute to the development of LV dysfunction in postmenopausal women without obesity or overweight, diabetes mellitus, and/or cardiovascular disease. Design and method: Participants aged over 60 years old without diabetes mellitus, systolic dysfunction, or other heart diseases underwent a thorough physical examination including tissue Doppler echocardiography. A peak early mitral annular velocity (e-prime) of < 5.0 was designated as indicating abnormal LV myocardial relaxation (LVMR). We performed single and multiple logistic regression analyses of e-prime and cardiovascular risk factors, including MetS factors and indicators of major organ dysfunction. Normal-weight subjects (body mass index < 25 kg/m2) were also analyzed. Results: A total of 269 postmenopausal women (mean age, 70 ± 7 years) participated, of which 29 (10.8%) had MetS and 67 (23.8%) had abnormal LVMR. Multiple logistic regression analysis revealed high diastolic blood pressure: DBP (odds ratio [OR] 5.3, 95% confidential interval [CI] 1.89 – 15.0, P < 0.01), abnormal waist circumference (OR 2.4, CI 1.15 – 5.01, P < 0.01) and age (OR 1.1, CI 1.05 – 1.16, P < 0.01) to be predictors of abnormal LVMR. In normal-weight subjects (n = 232), high DBP (OR 5.1, CI 1.65 – 15.89, P < 0.01), and aging (OR 1.1, CI 1.06 – 1.17, P < 0.01) were predictors of abnormal LVMR. Conclusions: In postmenopausal women, only diastolic blood pressure was the independent risk factors for abnormal LVMR in both normal-weight and over-weight individuals, and therefore might be useful for predicting diastolic heart failure during routine physical checkups.

Association of testosterone with estrogen abolishes the beneficial effects of estrogen treatment by increasing ROS generation in aorta endothelial cells.

Testosterone has been added to hormone replacement therapy to treat sexual dysfunction in postmenopausal women. Whereas estrogen has been associated with vascular protection, the vascular effects of testosterone are contradictory and the effects of its association with estrogen are largely unknown. In this study we determined the effects of testosterone associated with conjugated equine estrogen (CEE) on vascular function using a model of hypertensive postmenopausal female: ovariectomized spontaneously hypertensive rats. Female spontaneously hypertensive rats were divided into sham-operated, ovariectomized (OVX), and OVX treated for 15 days with either CEE alone (OVX+CEE) or associated with testosterone (OVX+CEE+T). Angiotensin II (ANG II)-induced contraction was markedly increased in aortic rings from OVX compared with sham-operated rats. CEE treatment restored ANG-II responses, a beneficial effect abrogated with CEE+T. CEE treatment also increased endothelium-dependent relaxation, which was impaired in OVX rats. This effect was lost by CEE+T. Treatment of aortas with losartan (ANG-II type-1 receptor antagonist) or apocynin (NADPH-oxidase inhibitor) restored the endothelium-dependent relaxation in OVX and CEE+T, establishing an interplay between ANG-II and endothelial dysfunction in OVX and CEE+T. The benefits by CEE were associated with downregulation of NADPH-oxidase subunits mRNA expression and decreased reactive oxygen species generation. The association of testosterone with CEE impairs the benefits of estrogen on OVX-associated endothelial dysfunction and reactive oxygen species generation in rat aorta by a mechanism that involves phosphorylation of the cytosolic NADPH-oxidase subunit p47(phox).

A Double-Blind Placebo-Controlled Trial of Maca Root as Treatment for Antidepressant-Induced Sexual Dysfunction in Women

Objective. We sought to demonstrate that maca root may be an effective treatment for antidepressant-induced sexual dysfunction (AISD) in women. Method. We conducted a 12-week, double-blind, placebo-controlled trial of maca root (3.0 g/day) in 45 female outpatients (mean age of 41.5 ± 12.5 years) with SSRI/SNRI-induced sexual dysfunction whose depression remitted. Endpoints were improvement in sexual functioning as per the Arizona Sexual Experience Scale (ASEX) and the Massachusetts General Hospital Sexual Function Questionnaire (MGH-SFQ). Results. 45 of 57 consented females were randomized, and 42 (30 premenopausal and 12 postmenopausal women) were eligible for a modified intent-to-treat analysis based on having had at least one postmedication visit. Remission rates by the end of treatment were higher for the maca than the placebo group, based on attainment of an ASEX total score ≤ 10 (9.5% for maca versus 4.8% for placebo), attaining an MGH-SFQ score ≤ 12 (30.0% for maca versus 20.0% for placebo) and reaching an MGH-SFQ score ≤ 8 (9.5% for maca versus 5.0% for placebo). Higher remission rates for the maca versus placebo group were associated with postmenopausal status. Maca was well tolerated. Conclusion. Maca root may alleviate SSRI-induced sexual dysfunction in postmenopausal women. This trial is registered with NCT00568126.

Factors for remodeling and diastolic myocardial dysfunction in postmenopausal women with diabetes and hypertension

Factors for remodeling and diastolic myocardial dysfunction in postmenopausal women with diabetes and hypertension

Hyperuricemia is independently associated with endothelial dysfunction in postmenopausal women but not in premenopausal women

ObjectivesThe purpose of this study was to determine the relationships between uric acid, endothelial function and cardiovascular risk factors and to investigate whether menopausal status was associated with the relationship...

Omega-3 polyunsaturated fatty acids and left ventricular diastolic dysfunction in postmenopausal women

Purpose: To asses fatty acids composition of erythrocyte membrane lipids in postmenopausal women depending on left ventricular (LV) filling parameters. Methods: 203 postmenopausal women were included in the investigation: 142 women with surgical menopause (average age 44,3±5,4 years, menopause duration 3,8±2,4 years); and 61 women with natural menopause (average age 46,2±4,7 years, menopause duration 4,3±2,1 years). All patients underwent general clinical examination, echocardiographic examination with systolic and diastolic LV function assessment. Besides that we assessed the proportion of different fatty acids in lipids of erythrocyte membranes. Control group consisted of 27 healthy menstruating women (mean age 39,2±4,2). Statistical methods such as Cruskell-Walles criteria and τ Kendall statistics were used. Results: 117 (57.6%) postmenopausal women had LV diastolic function disturbance (1st group) and 86 women had no (2nd group). Nobody of included postmenopausal women had LV systolic function failure. All patients in menopause had significant changes in fatty acids composition of erythrocyte membrane lipids in comparison with healthy women: saturated acids relative content was increased, and unsaturated acids relative content was decreased, especially in women with LV diastolic dysfunction. The most serious changes concerned omega-3 polyunsaturated acids: relative contents of alpha-linoleic acid in patients of the 1st group was 3,1 times less than in control group (P<0.001); patients of the 2nd group demonstrated 2,7 times decrease of this index in comparison with healthy women (P<0.001). The content of eicosapentaenoic acid in the 1st and the 2nd groups was 1,7 and 1,4 times less than in control group, respectively (P<0.01). The same changes in the 1st and the 2nd groups concerned to docosapentaenoic and arachidonic acids: they were 2,1 – 3 times less and 2,4 – 2,8 times less than in healthy women, respectively (P<0.001). The presence of LV diastolic dysfunction correlated negatively with alpha-linoleic, eicosapentaenoic acid content and common polyunsaturated acids content (τ from –0.32 to –0.58, P<0.001) and positively – with saturated acids relative content (τ = 0.55, P<0.001). Conclusions: Thus, disturbances in fatty acids composition of erythrocyte membrane lipids may play role in left ventricular dysfunction formation in postmenopausal women.

The impact of endocrine therapy on sexual dysfunction in postmenopausal women with early stage breast cancer: encouraging results from a prospective study

The goal of this project was to investigate the contentious issue of a possible effect of endocrine therapy (ET) on sexual dysfunction (SD) in postmenopausal early stage breast cancer survivors. To date, few studies have assessed sexual functioning prior to initiating ET and none have taken sexual distress into account when reporting the prevalence of ET-induced SD. We report the findings of a study on the change in SD (defined as experiencing sexual problems causing distress) during the first 6 months of ET usage. Between January 2009 and May 2011, 118 patients entered the study and 66 completed questionnaires prior to initiation of ET and after 6 months of use. Sexual functioning (SF) was evaluated with the female sexual function index while sexual distress was assessed with the female sexual distress scale (FSDS-R). Gynecological symptoms were measured with the FACT-B ES subscale. Over time, the level of gynecological symptoms increased (p < 0.001), whereas no decline in SF was observed. The percentage of women who reported experiencing at least one sexual problem (85 %) and the percentage who were sexually distressed (30 %) remained the same across time. Importantly, the change in the prevalence of SD between baseline (24 %) and 6 months (29 %) was not statistically significant. Women experiencing SD at baseline were more likely to experience SD after 6 months of ET usage (OR = 7.4, 95 % CI = 1.5-36.9) than women who had no SD prior to initiating ET. The observation that SF remained stable across time is encouraging news. However, longer follow-up and the inclusion of women who were premenopausal at diagnosis are needed to determine the potential influence of extended duration of ET (e.g., at least 5 years) on SD. Further studies, including assessing the impact of early identification of patients at risk of developing SD and timely intervention, are warranted.

Arterial stiffness, carotid atherosclerosis and left ventricular diastolic dysfunction in postmenopausal women

BackgroundPostmenopausal women have an increased cardiovascular morbidity that may be due to the increase in classical cardiovascular risk factors and also to the arterial structure and function alterations. The aim of our study was to evaluate the association of aortic pulse wave velocity (PWV), and carotid intima–media thickness (IMT), with left ventricular diastolic dysfunction (LVDD) in postmenopausal women. Patients and methodsIn 96 women without overt cardiovascular disease (age 62±7.7years), and with normal left ventricular systolic function, aortic PWV was assessed by using an oscillometric device, intima–media thickness was measured by B-mode ultrasonography and the parameters of left ventricular diastolic function were evaluated by a transthoracic echocardiographic study. ResultsLVDD, defined as an E/A ratio≤1 was found in 50 patients (52%). All of them had mild LVDD. In these patients we found significant increase in age (p<0.001), aortic PWV (p<0.001), carotid IMT (p=0.002) and plaque score (p=0.004) when compared with patients without LVDD. In a logistic regression analyzed, after adjusting for age, only aortic PWV was a significant predictor of LVDD (2.15, 95% CI 1.39–3.31, p=0.0006). ConclusionsThis study among postmenopausal women provides evidence that increased arterial stiffness as measured by aortic PWV and not carotid IMT may be a marker or a risk factor for LVDD, independent of other classical risk factors.

Pitavastatin Improves Endothelial Function and Glucose Metabolism in Ovariectomized Mice

Estrogen deficiency increases the cardiovascular risks and metabolic dysfunction in postmenopausal women. The potential effects of estrogen are partially related to its direct effects on the vascular wall, stimulating endotheliumderived NO synthesis (eNOS). HMG-CoA reductase inhibitors (statins) may also improve the endothelial function through upregulation of eNOS. In this study, we examined whether the treatment of pitavastatin for a short period (1 week) may improve the endothelial function or glucose metabolism under estrogen deficiency induced by ovariectmy. At 4 weeks after ovariectomy, hyperglycemia and hyperinsulinemia were observed in estrogen deficient mice as assessed by intraperitoneal glucose tolerance test, and endothelial dysfunction was also observed as assessed by the vasodilator response to acetylcholine. At 3 weeks after ovariectomy, we started to administer pitavastatin to ovariectomized mice for 1 week. Although the treatment of pitavastatin for a week did not affect obesity, the treatment of pitavastatin significantly attenutaed hyperglycemia and hyperinsulinemia as well as endothelial dysfunction induced by estrogen deficiency. These results demonstrated that treatment of pitavastatin rapidly improved glucose metabolism and endothelial function under estrogen deficiency. Keywords: Endothelial function, eNOS, estrogen, hyperglycemia, hyperinsulinemia, insulin resistance, IGF-1, menopause, ovariectomy, statins

An overview of vulvovaginal atrophy-related sexual dysfunction in postmenopausal women

Menopause and the climacteric period are associated with adverse risk factors for the development of vulvovaginal atrophyrelated sexual dysfunction. Sexual dysfunction is a common problem in postmenopausal women, often underdiagnosed, inadequately treated, frequently overlooked, and most often impairing the quality of life of these women. To provide clinicians with current information on vulvovaginal atrophy‑related sexual dysfunction in postmenopausal women. This study is a literature review on vulvovaginal atrophy‑related sexual dysfunction in postmenopausal women. Relevant publications were identified through a search of PubMed and Medline, selected references, journals, and textbooks on this topic, and were included in the review. The prevalence of female sexual dysfunction increases with age. It is a common multidimensional problem for postmenopausal women that alter the physiological, biochemical, psychological, and sociocultural environment of a woman. Menopause‑related sexual dysfunction may not be reversible without therapy. Estrogen therapy is the most effective option and is the current standard of care for vulvovaginal atrophy‑related sexual dysfunction in postmenopausal women. Sexual dysfunction is a common multidimensional problem for postmenopausal women and often impairs the quality of life of these women. Estrogen preparations are the most effective treatment. Selective estrogen receptor modulators, vaginal dehydroepiandrostenedione, vaginal testosterone, and tissue‑selective estrogen complexes are promising therapies, but further studies are required to confirm their role, efficacy, and safety. Keywords: Estrogen, postmenopausal women, sexual dysfunction, vulvo‑vaginal

Management of vulvovaginal atrophy-related sexual dysfunction in postmenopausal women

Menopause and its transition represent significant risk factors for the development of vulvovaginal atrophy-related sexual dysfunction. The objective of this study was to review the hormonal and nonhormonal therapies available for postmenopausal women with vulvovaginal atrophy-related sexual dysfunction, focusing on practical recommendations through a literature review of the most relevant publications in this field. This study is a literature review. Available vaginal estrogen preparations are conjugated equine estrogens, estradiol vaginal cream, a sustained-release intravaginal estradiol ring, or a low-dose estradiol tablet. Vaginal estrogen preparations with the lowest systemic absorption rate may be preferred in women with history of breast cancer and severe vaginal atrophy. Vaginal lubricants and moisturizers applied on a regular basis have an efficacy comparable with that of local estrogen therapy and should be offered to women wishing to avoid the use of vaginal estrogens. Oral, transdermal, or vaginal estrogen preparations are the most effective treatment options for vulvovaginal atrophy-related sexual dysfunction. Selective estrogen receptor modulators such as lasofoxifene and ospemifene showed a positive impact on vaginal tissue in postmenopausal women. Vaginal dehydroepiandrostenedione, vaginal testosterone, and tissue selective estrogen complexes are also emerging as promising new therapies; however, further studies are warranted to confirm their efficacy and safety.

Effects of cigarette smoking, metabolic syndrome and dehydroepiandrosterone deficiency on intima-media thickness and endothelial function in hypertensive postmenopausal women

SummaryBackgroundCigarette smoking is a major risk factor of atherosclerosis. The aim of this study was to assess the relationship between smoking and arterial hypertension as well as endothelial dysfunction in postmenopausal women without clinically manifested symptoms of atherosclerosis.Material/MethodsThe study groups consisted of 35 current smokers and 45 nonsmokers. The thickness of intima-media complex (IMT), a marker of atherosclerosis, was measured in carotid arteries. Plasma concentrations of fasting glucose, insulin, lipoproteins, inflammatory markers (tumor necrosis factor-alpha, intercellular adhesion molecule-1), matrix metalloproteinases (metalloproteinase-9, tissue inhibitor of metalloproteinase-1), insulin, and dehydroepiandrosterone sulfate (DHEA-S) were measured.ResultsSmokers compared with nonsmokers showed lower fasting glucose levels in blood (87.0±10.9 and 93.2±13.6 mg/dl, p<0.05), higher mean systolic (131.1±15.9 vs. 123.0±10.9 mm Hg, p<0.05) and diastolic (81.7±11.4 vs. 75.2±9.2 mm Hg, p<0.05) blood pressure during daytime, and higher average heart rate during the daytime (78.2±9.3/min vs. 71.5±9.5/min, p<0.01) and at night (67.2±10.6/min vs. 61.7±7.7/min, p<0.05), respectively. The IMT in the right carotid artery was significantly higher in smokers than in nonsmokers (0.96±0.16 mm vs. 0.82±0.21, p<0.05) and was positively correlated with smoking intensity (R=0.36) and habit duration (R=0.35). The comparison of inflammatory markers, metalloproteinases, and DHEA-S concentrations in plasma did not reveal significant differences between the 2 groups. A significant negative correlation between DHEA-S concentration in plasma and IMT in right carotid artery was found in smokers.ConclusionsSmoking in hypertensive postmenopausal women is associated with lower fasting blood glucose and BMI values, but higher arterial pressure and heart rate, and increases in IMT in right carotid artery.

Menopause and autonomic control of heart

Menopause is associated with decreased heart rate variability, which is due to reduced parasympathetic or increased sympathetic outflow to the heart. Acute myocardial infarction may be accompanied by decreased heart rate variability. The causes of autonomic dysfunction in postmenopausal women may be multi-factorial i.e. , dyslipidemia, increased body fat percentage, aging and loss of female sex hormones. The cardiac vagotonic and sympatholytic effects of estrogen can explain, at least in part, why premenopausal women compared with postmenopausal women have a lower coronary heart disease incidence and mortality rate.

Identifying and Treating Sexual Dysfunction in Postmenopausal Women: The Role of Estrogen

Sexual dysfunction is a common, but frequently overlooked, problem in postmenopausal women. At menopause, dramatic decreases in circulating estrogen concentrations cause physiologic changes that may affect sexual function, most notably the development of vulvovaginal atrophy. Vulvovaginal atrophy often leads to vaginal dryness, itching, irritation, reduced lubrication, dyspareunia, and vaginal bleeding associated with sexual activity. Estrogen deficiency also can affect other aspects of sexual function, including reduced vaginal blood flow and a reduced capacity for arousal and orgasm. As estrogen loss is a significant cause of sexual dysfunction in menopausal women, estrogen therapy is a logical treatment option in this population. Although both systemic and local estrogen therapy improve vaginal health and sexual functioning, local vaginal therapy with estrogen creams, rings, or tablets may be more appropriate for women without other indications for systemic estrogen therapy. These therapies are highly effective in reversing vaginal atrophy, improving vaginal symptomatology, and reducing dyspareunia, and may have effects on other dimensions of sexual function. Emerging treatments, such as ultra-low-dose vaginal estradiol tablets, new selective estrogen receptor modulators (SERMs), and intravaginal dehydroepiandrosterone (DHEA) are other promising options for postmenopausal women with vaginal atrophy and sexual dysfunction.

Central Arterial Pressure, Carotid Atherosclerosis and Left Ventricular Dysfunction in Post-Menopausal Women

PurposeMany recent data suggest that central arterial pressure is more relevant than peripheral blood pressure for the determination of cardiovascular risk assessment. We studied the association of central blood pressure with carotid intima-media thickness (IMT) and left ventricular diastolic function in postmenopausal women.Material & MethodsWe included in our study 96 women, mean age 62,3 years. Central aortic pressure was measured using an oscillometric device, Arteriograph (Tensio Med Ltd., Budapest, Hungary). We determined IMT of the common carotid artery by B-mode ultrasonography and cardiac diastolic function by echocardiography.ResultsAortic systolic blood pressure, aortic pulse pressure and aortic pulse wave velocity were associated with IMT and with parameters of left ventricular dysfunction, deceleration time and E/A ratio. Multivariate linear regression analysis, showed that central arterial pressure was correlated with IMT (Î2 = 0.46, p = 0.01) and with E/A ratio (Î2 = -0. 3, p = 0.03). From the whole study population, 24% had diabetes mellitus, 40% hypertension, 15% dyslipidemia.ConclusionOur study suggests that in postmenopausal women, central aortic pressure is correlated with carotid atherosclerosis and left ventricular dysfunction, and it may represent a marker for the increased cardiovascular risk in this population. PurposeMany recent data suggest that central arterial pressure is more relevant than peripheral blood pressure for the determination of cardiovascular risk assessment. We studied the association of central blood pressure with carotid intima-media thickness (IMT) and left ventricular diastolic function in postmenopausal women. Many recent data suggest that central arterial pressure is more relevant than peripheral blood pressure for the determination of cardiovascular risk assessment. We studied the association of central blood pressure with carotid intima-media thickness (IMT) and left ventricular diastolic function in postmenopausal women. Material & MethodsWe included in our study 96 women, mean age 62,3 years. Central aortic pressure was measured using an oscillometric device, Arteriograph (Tensio Med Ltd., Budapest, Hungary). We determined IMT of the common carotid artery by B-mode ultrasonography and cardiac diastolic function by echocardiography. We included in our study 96 women, mean age 62,3 years. Central aortic pressure was measured using an oscillometric device, Arteriograph (Tensio Med Ltd., Budapest, Hungary). We determined IMT of the common carotid artery by B-mode ultrasonography and cardiac diastolic function by echocardiography. ResultsAortic systolic blood pressure, aortic pulse pressure and aortic pulse wave velocity were associated with IMT and with parameters of left ventricular dysfunction, deceleration time and E/A ratio. Multivariate linear regression analysis, showed that central arterial pressure was correlated with IMT (Î2 = 0.46, p = 0.01) and with E/A ratio (Î2 = -0. 3, p = 0.03). From the whole study population, 24% had diabetes mellitus, 40% hypertension, 15% dyslipidemia. Aortic systolic blood pressure, aortic pulse pressure and aortic pulse wave velocity were associated with IMT and with parameters of left ventricular dysfunction, deceleration time and E/A ratio. Multivariate linear regression analysis, showed that central arterial pressure was correlated with IMT (Î2 = 0.46, p = 0.01) and with E/A ratio (Î2 = -0. 3, p = 0.03). From the whole study population, 24% had diabetes mellitus, 40% hypertension, 15% dyslipidemia. ConclusionOur study suggests that in postmenopausal women, central aortic pressure is correlated with carotid atherosclerosis and left ventricular dysfunction, and it may represent a marker for the increased cardiovascular risk in this population. Our study suggests that in postmenopausal women, central aortic pressure is correlated with carotid atherosclerosis and left ventricular dysfunction, and it may represent a marker for the increased cardiovascular risk in this population.

Does Estrogen Have Any Real Effect on Voiding Dysfunction in Women?

For many years, estrogen has been used to treat lower urinary tract dysfunction in postmenopausal women. The data supporting this practice vary. Large multi-institutional studies have shown little role for systemic estrogens in the treatment of urinary incontinence. Vaginal estrogen preparations show superiority to systemic estrogens for the treatment of irritative voiding symptoms in meta-analysis, but there is significant study heterogeneity and the practice remains debatable. Data from randomized controlled trials support estrogen use in the prevention of recurrent urinary tract infections. This article reviews the relevant literature addressing the role of estrogen therapy in urinary incontinence, irritative voiding symptoms, and recurrent urinary tract infections.

Exercise as a treatment of gait dysfunction in postmenopausal women

Exercise as a treatment of gait dysfunction in postmenopausal women

Tetrahydrobiopterin Restores Diastolic Function and Attenuates Superoxide Production in Ovariectomized mRen2.Lewis Rats

After oophorectomy, mRen2.Lewis rats exhibit diastolic dysfunction associated with elevated superoxide, increased cardiac neuronal nitric oxide synthase (nNOS) expression, and diminished myocardial tetrahydrobiopterin (BH₄) content, effects that are attenuated with selective nNOS inhibition. BH₄ is an essential cofactor of nNOS catalytic activity leading to nitric oxide production. Therefore, we assessed the effect of 4 wk BH₄ supplementation on diastolic function and left ventricular (LV) remodeling in oophorectomized mRen2.Lewis rats compared with sham-operated controls. Female mRen2.Lewis rats underwent either bilateral ovariectomy (OVX) (n = 19) or sham operation (n = 13) at 4 wk of age. Beginning at 11 wk of age, OVX rats were randomized to receive either BH₄ (10 mg/kg · d) or saline, whereas the sham rats received saline via sc mini-pumps. Loss of ovarian hormones reduced cardiac BH₄ when compared with control hearts; this was associated with impaired myocardial relaxation, augmented filling pressures, increased collagen deposition, and thickened LV walls. Additionally, superoxide production increased and nitric oxide decreased in hearts from OVX compared with sham rats. Chronic BH₄ supplementation after OVX improved diastolic function and attenuated LV remodeling while restoring myocardial nitric oxide release and preventing reactive oxygen species generation. These data indicate that BH₄ supplementation protects against the adverse effects of ovarian hormonal loss on diastolic function and cardiac structure in mRen2.Lewis rats by restoring myocardial NO release and mitigating myocardial O₂⁻ generation. Whether BH₄ supplementation is a therapeutic option for the management of diastolic dysfunction in postmenopausal women will require direct testing in humans.

Enhanced cardiac inflammation and fibrosis in ovariectomized hypertensive rats: a possible mechanism of diastolic dysfunction in postmenopausal women

Diastolic dysfunction is more prevalent in individuals with hypertension, particularly postmenopausal women; however, the pathogenesis of diastolic dysfunction remains unknown. Pressure overload activates cardiac inflammation, which induces myocardial fibrosis and diastolic dysfunction in rats with a suprarenal aortic constriction (AC). Therefore, we examined the effects of bilateral ovariectomy (OVX) on left ventricle (LV) remodeling, diastolic dysfunction and cardiac inflammation in hypertensive female rats. Rats were randomized to OVX+AC, OVX and AC groups as well as a Control group receiving sham operations for both the procedures. Rats underwent OVX at 6 weeks and AC at 10 weeks (Day 0). At Day 28, OVX did not appear to affect arterial pressure, cardiac hypertrophy or LV fractional shortening in AC rats. However, OVX increased myocardial fibrosis, elevated LV end-diastolic pressure and reduced the transmitral Doppler spectra early to late filling velocity ratio in AC rats. AC-induced transient myocardial monocyte chemoattractant protein-1 expression and macrophage infiltration, both of which peaked at Day 3 and were augmented and prolonged by OVX. At Day 28, dihydroethidium staining revealed superoxide generation in the intramyocardial arterioles in the OVX+AC group but not in the AC group. NOX1, a functional subunit of nicotinamide adenine dinucleotide phosphate oxidase, was upregulated only in the OVX+AC group at Day 28. Chronic 17β-estradiol replacement prevented the increases in macrophage infiltration, NOX1 upregulation, myocardial fibrosis and diastolic dysfunction in OVX+AC rats. In conclusion, we suggest that estrogen deficiency augments cardiac inflammation and oxidative stress and thereby aggravates myocardial fibrosis and diastolic dysfunction in hypertensive female rats. The findings provide insight into the mechanism underlying diastolic dysfunction in hypertensive postmenopausal women.

Amelioration of sexual adverse effects in the early breast cancer patient.

BackgroundAs the number of breast cancer survivors increases, the long term consequences of breast cancer treatment are gaining attention. Sexual dysfunction is a common complaint amongst breast cancer survivors, and there are few evidence based recommendations and even fewer well designed clinical trials to establish what treatments are safe or effective in this patient population.DesignWe conducted a PubMed search for articles published between 1995–2009 containing the terms breast cancer, sexual dysfunction, libido, vaginal dryness, testosterone, and vaginal estrogen. We initially reviewed articles focusing exclusively on sexual issues in breast cancer patients. Given the paucity of clinical trials addressing sexual issues in breast cancer patients, we also included studies evaluating both hormone and non-hormone based interventions for sexual dysfunction in post-menopausal women in general.ConclusionsAmong breast cancer survivors, vaginal dryness and loss of libido represent some of the most challenging long term side effects of breast cancer treatment. In the general post-menopausal population, topical preparations of estrogens and testosterone both appear to improve sexual function; however there are conflicting reports about the efficacy and safety of these interventions in women with a history of breast cancer, and further research is warranted.