Autonomic nervous system dysfunction throughout menopausal transition: A potential mechanism underpinning cardiovascular and cognitive alterations during female ageing.

Cardiovascular diseases (CVD) and neurodegenerative disorders, such as Alzheimer's disease (AD), are highly prevalent conditions in middle-aged women that severely impair quality of life. Recent evidence suggests the existence of an intimate cross-talk between the heart and the brain, resulting from a complex network of neurohumoral circuits. From a pathophysiological perspective, the higher prevalence of AD in women may be explained, at least in part, by sex-related differences in the incidence/prevalence of CVD. Notably, the autonomic nervous system, the main heart-brain axis physiological orchestrator, has been suggested to play a role in the incidence of adverse cardiovascular events in middle-aged women because of decreases in oestrogen-related signalling during transition into menopause. Despite its overt relevance for public health, this hypothesis has not been thoroughly tested. Accordingly, in this review, we aim to provide up to date evidence supporting how changes in circulating oestrogen levels during transition to menopause may trigger autonomic dysfunction, thus promoting cardiovascular and cognitive decline in women. A main focus on the effects of oestrogen-mediated signalling at CNS structures related to autonomic regulation is provided, particularly on the role of oestrogens in sympathoexcitation. Improving the understanding of the contribution of the autonomic nervous system on the development, maintenance and/or progression of both cardiovascular and cognitive dysfunction during the transition to menopause should help improve the clinical management of elderly women, with the outcome being an improved life quality during the natural ageing process.

Menopause and development of Alzheimer's disease: Roles of neural glucose metabolism and Wnt signaling.

Late onset Alzheimer´s disease (AD) is a neurodegenerative disease with gender differences in its onset and progression, being the prevalence predominant in women and at an earlier age than in men. The pathophysiology of the menopausal condition has been associated to this dementia, playing major roles regarding both endocrine and glucose metabolism changes, amongst other mechanisms. In the current review we address the role of estrogen deficiency in the processes involved in the development of AD, including amyloid precursor protein (APP) processing to form senile plaques, Tau phosphorylation forming neurofibrillary tangles, Wnt signaling and AD neuropathology, the role of glucose brain metabolism, Wnt signaling and glucose transport in the brain, and our research contribution to these topics.

Neurodevelopmental impact of the offspring by thyroid hormone system-disrupting environmental chemicals during pregnancy.

Everyday use chemicals have been demonstrated to be endocrine disruptors. Since normal thyroid function during pregnancy is transcendental for the neurodevelopment of the offspring, knowledge of endocrine disrupting chemicals (EDC) is of main importance. The aim of our study is to recognize and describe EDC actions in pregnant women and focus on neurodevelopmental processes that can lead to neurotransmitter imbalance and cognitive impairment, and the possible clinical outcomes in the newborn and child. We searched PubMed databases for animal studies and clinical trials evaluating chemicals recognized as thyroid disruptors -perchlorate, phthalates, bisphenol A-, as well as chemicals with potential thyroid disruption activity -parabens, pesticides and persistent organic pollutants, on thyroid hormones (THs) levels and their bioavailability during pregnancy, and the outcome in newborns, infants and children. We also exhibit evidence from worldwide cohort studies to this regard. The publications reviewed show: 1) known endocrine disruptors have an association with hormonal thyroid levels, where an effect of increase or decrease in TH concentrations has been reported depending on the chemical exposed 2) associations between TH, EDCs and neurocognitive disorders have been addressed, such as ADHD, though no conclusive impact on potential related disorders as autism has been established, 3) perchlorate has demonstrated effects on thyroid levels on iodine uptake. In conclusion, detrimental risks and long-term consequences after in-utero exposure to EDCs are being reported in several cohort studies and further research must be conducted to establish a well-known cause-effect association.

An individualized approach to the management of vaginal atrophy in Latin America.

OBJECTIVE: In the absence of guidelines specific for Latin America, a region where the impact of menopause is becoming increasingly important, an evidence-based specialist opinion on management of vaginal atrophy will help improve outcomes. METHODS: An advisory board meeting was convened in São Paulo, Brazil, to discuss practical recommendations for managing vaginal atrophy in women in Latin America. Before the meeting, physicians considered various aspects of the condition, summarizing information accordingly. This information was discussed during the meeting. The expert consensus is now summarized. RESULTS: In Latin America, given the relatively early age of menopause, it will be beneficial to raise awareness of vaginal atrophy among women before they enter menopause, considering cultural attitudes and involving partners as appropriate. Women should be advised about lifestyle modifications, including attention to genital hygiene, clothing, and sexual activity, and encouraged to seek help as soon as they experience vaginal discomfort. Although treatment can be started at any time, prompt treatment is preferable. A range of treatments is available. By addressing the underlying pathology, local estrogen therapy can provide effective symptom relief, with choice of preparation guided by patient preference. An individualized treatment approach should be considered, giving attention to patients' specific situations. CONCLUSIONS: It is critical that women are empowered to understand vaginal atrophy. Educating women and healthcare providers to engage in open dialogue will facilitate appreciation of the benefits and means of maintaining urogenital health, helping to improve outcomes in middle age and beyond. Women should receive this education before menopause.

[Second Consensus of the Chilean Society of Endocrinology and Diabetes about insulin resistance]. / II Consenso de la Sociedad Chilena de Endocrinología y Diabetes sobre resistencia a la insulina.

Insulin resistance is a prevalent condition commonly associated with unhealthy lifestyles. It affects several metabolic pathways, increasing risk of abnormalities at different organ levels. Thus, diverse medical specialties should be involved in its diagnosis and treatment. With the purpose of unifying criteria about this condition, a scientific-based consensus was elaborated. A questionnaire including the most important topics such as cardio-metabolic risk, non-alcoholic fatty liver disease and polycystic ovary syndrome, was designed and sent to national experts. When no agreement among them was achieved, the Delphi methodology was applied. The main conclusions reached are that clinical findings are critical for the diagnosis of insulin resistance, not being necessary blood testing. Acquisition of a healthy lifestyle is the most important therapeutic tool. Insulin-sensitizing drugs should be prescribed to individuals at high risk of disease according to clinically validated outcomes. There are specific recommendations for pregnant women, children, adolescents and older people.

II Consenso de la Sociedad Chilena de Endocrinología y Diabetes sobre resistencia a la insulina

Insulin resistance is a prevalent condition commonly associated with unhealthy lifestyles. It affects several metabolic pathways, increasing risk of abnormalities at different organ levels. Thus, diverse medical specialties should be involved in its diagnosis and treatment. With the purpose of unifying criteria about this condition, a scientific-based consensus was elaborated. A questionnaire including the most important topics such as cardio-metabolic risk, non-alcoholic fatty liver disease and polycystic ovary syndrome, was designed and sent to national experts. When no agreement among them was achieved, the Delphi methodology was applied. The main conclusions reached are that clinical findings are critical for the diagnosis of insulin resistance, not being necessary blood testing. Acquisition of a healthy lifestyle is the most important therapeutic tool. Insulin-sensitizing drugs should be prescribed to individuals at high risk of disease according to clinically validated outcomes. There are specific recommendations for pregnant women, children, adolescents and older people.

Tumor de células de la granulosa asociado a hiperandrogenismo femenino rápidamente progresivo / Granulosa cell tumour associated with rapidly progressive female hyperandrogenism

Reportamos el caso de una mujer de 21 años con hiperandrogenismo rápidamente progresivo de origen tumoral ovárico. La biopsia informó tumor de células de la granulosa y la resección fue curativa. Se analizan los posibles mecanismos por los que un tumor de origen en células de la granulosa pueda sintetizar andrógenos.

We report a 21 year old woman with rapidly progressive hyperandrogenism of ovaric tumoral origin. The biopsy of the tumor reported a granulosa cell tumor and the surgery was curative. We analyze the possible mechanisms implied in the androgen production in the granulosa cells of the tumor.

Nonalcoholic fatty liver disease in women with polycystic ovary syndrome.

BACKGROUND/AIMS: Insulin resistance is a common feature of both nonalcoholic fatty liver disease (NAFLD) and polycystic ovary syndrome (PCOS), therefore, we hypothesize that PCOS and NAFLD may coexist. The aim of the present study was to determine the frequency and characteristics of NAFLD in women with PCOS. METHODS: A prospective study of patients with PCOS and no current pharmacological treatment was conducted. NAFLD was diagnosed by abdominal ultrasound following exclusion of alcohol consumption, viral, or autoimmune liver disease. Anthropometric variables, serum levels of glucose, insulin, lipids and aminotransferases, and HOMA index were determined. RESULTS: Forty-one PCOS patients (mean age: 24.6+/-7.2yr, mean body mass index [BMI]: 30.3+/-7.0kg/m(2)) were included; 26 of 41 PCOS patients (63.4%) had insulin resistance and 17 (41.5%) had NAFLD. Nine of the NAFLD patients (64%) also had abnormal aminotransferases. Women with NAFLD and PCOS had a higher HOMA index and a higher waist-hip ratio than those with normal ultrasound. Patients with PCOS showed a higher frequency of NAFLD (41% vs. 19%) and insulin resistance (63% vs. 35.5%) than a control group. CONCLUSIONS: NAFLD is frequent in patients with PCOS confirming a relevant clinical association between these two conditions. Women with PCOS should be screened for liver disease.

Bilateral oophorectomy in a pregnant woman: hormonal profile from late gestation to post-partum: case report.

BACKGROUND: A 16 week pregnant woman presented with massive theca-lutein cysts requiring bilateral oophorectomy. Pregnancy progressed uneventfully and spontaneous lactation ensued after delivery. METHODS: To study the role of the ovary on the hormonal profile at the end of gestation and in post-partum, we measured FSH, estradiol (E2), unconjugated estrone (E1), unconjugated estriol (E3), sex hormone-binding globulin, progesterone, dehydroepiandrosterone sulphate and prolactin at 37 weeks gestation and at 8 h, 4 days, 5 weeks, and 2 months post-partum. RESULTS: These hormones were within the range expected for ovary-intact pregnant and puerperal women until 4 days post-partum. At 5 weeks post-partum, FSH increased to a peri-menopausal range (31.4 IU/l) while estrogens remained within the normal puerperal range (E2=239 pmol/l; E1=102 pmol/l), contrasting with their rapid changes in non-pregnant women after bilateral oophorectomy. At 2 months, while partially breastfeeding, FSH, E2 and E1 were closer to menopausal range (68 IU/l, 136 and 70.2 pmol/l respectively), and hormone replacement was started. CONCLUSIONS: We conclude that the ovary is not required to maintain a normal hormonal profile in late pregnancy and early puerperium. However, the increase in FSH to peri-menopausal levels at 5 weeks post-partum, despite breastfeeding, suggests that the ovary is needed to maintain low FSH concentrations during lactation.

Raloxifene is a better antioxidant of low-density lipoprotein than estradiol or tamoxifen in postmenopausal women in vitro.

OBJECTIVE: The oxidation of low-density lipoprotein (LDL) is an important factor in the development of atherosclerosis. The antioxidant activity of some compounds buffers the free radicals generated either endogenously or exogenously, thus decreasing the potential damage mediated by oxidation. Estrogens are potent antioxidants of LDL, in vitro and in vivo, a mechanism that could probably influence the cardioprotection associated with hormone replacement therapy in postmenopause. We conducted an in vitro study of the antioxidant effect on LDL of two selective estrogen receptor modulators, raloxifene (RLX) and tamoxifen (TMX), comparing them with the known antioxidant effect of estradiol (E2 ). DESIGN: LDL was isolated by ultracentrifugation from plasma obtained from 12 healthy, untreated, postmenopausal women. Aliquots containing 0.5 mg of LDL protein were incubated for 4 h with CuSO4 (15 micro M) to induce oxidative stress and with one of the three compounds studied: RLX, TMX, or E2 at doses of 0, 1, 2, 3, 5, 15, 50, and 500 micro M, and 1 and 2 mM. Malonaldehyde (MDA, nmol/mg protein) was measured as a marker of LDL oxidation. RESULTS: E2 induced a dose-dependent decrease in MDA concentration. MDA values decreased significantly, as compared with baseline, starting at a concentration of 2 micro M for RLX and 3 micro M for both, TMX, or E2. The dose necessary to reduce the generation of MDA by 50% was significantly lower for RLX (3.3 micro M, < 0.001) than for E2 (24.6 micro M ) or TMX (35.3 micro M). The area under the curve also showed a higher antioxidant activity for RLX compared with TMX or E2 ( < 0.001). CONCLUSIONS: The in vitro antioxidant activity of RLX is substantially more potent than TMX or E2. This finding, added to the other beneficial effects of the drug in the cardiovascular system, could imply some cardioprotector effect.