Selective oestrogen receptor modulators - current and future brain and behaviour applications

Selective oestrogen receptor modulators (SERMs) are compounds that act as oestrogen agonists on selected targets while being oestrogen antagonists on others. The main targets of SERMs are oestrogen agonist activity on bone metabolism and several functions of the cardiovascular system, as well as oestrogen antagonism in the breast and uterus. They are indicated for the treatment and/or prevention of breast and endometrial cancer, osteoporosis and coronary heart disease. The extensive documentation of the multiple oestrogen effects on the CNS, greater understanding of the mechanisms of action, and especially the discovery of a second oestrogen receptor with differentiated distribution and mechanisms, have all led the way to the possibility of specific CNS-targeted SERMs. The demonstration that oestrogen selectively improves cognition, delays the appearance of Alzheimer’s dementia, improves the feeling of well-being, as well as the response to antidepressant medications, provides targeted CNS indications for SERMs. The CNS effects of the currently marketed SERMs are not sufficiently explored yet. However, in postmenopausal women, tamoxifen and raloxifene probably show the most oestrogen agonist CNS effects. In women of reproductive age, competition with oestrogen probably exists, resulting in antagonist effects. Activity in men is still mostly unknown. It is quite safe to predict that the recent accumulation of knowledge, combined with the large, thirsty anticipated market for these ‘designer oestrogens’, will lead to clinical trials of CNS-targeted SERMs in the very near future.     

Effects of DHA-Rich n-3 Fatty Acid Supplementation and/or Resistance Training on Body Composition and Cardiometabolic Biomarkers in Overweight and Obese Post-Menopausal Women

Resistance training (RT) and n-3 polyunsaturated fatty acids (n-3 PUFA) supplementation have emerged as strategies to improve muscle function in older adults. Overweight/obese postmenopausal women (55–70 years) were randomly allocated to one of four experimental groups, receiving placebo (olive oil) or docosahexaenoic acid (DHA)-rich n-3 PUFA supplementation alone or in combination with a supervised RT-program for 16 weeks. At baseline and at end of the trial, body composition, anthropometrical measures, blood pressure and serum glucose and lipid biomarkers were analyzed. Oral glucose tolerance tests (OGTT) and strength tests were also performed. All groups exhibit a similar moderate reduction in body weight and fat mass, but the RT-groups maintained bone mineral content, increased upper limbs lean mass, decreased lower limbs fat mass, and increased muscle strength and quality compared to untrained-groups. The RT-program also improved glucose tolerance (lowering the OGTT incremental area under the curve). The DHA-rich supplementation lowered diastolic blood pressure and circulating triglycerides and increased muscle quality in lower limbs. In conclusion, 16-week RT-program improved segmented body composition, bone mineral content, and glucose tolerance, while the DHA-rich supplement had beneficial effects on cardiovascular health markers in overweight/obese postmenopausal women. No synergistic effects were observed for DHA supplementation and RT-program combination.     

Relationship between the body iodine status and menopausal symptoms during postmenopausal period

Abstract

Aim: The aim of this study was to assess the effect of body iodine status on hot flashes and cardiovascular disease risk in postmenopausal women.

Methods: Two hundred and ten consecutive postmenopausal women without known any risk factor for cardiovascular disease risk or systemic disorder were recruited for the study. All participants underwent serum screening consisted of lipid profile including lipoprotein-a (Lp(a)) and urinary iodine excretion. Participants were also asked for the frequency and the duration of hotflashes. All parameters were assessed for the association between urine iodine excretion and other parameters.

Results: Urine spot iodine level was significantly correlated with Lp(a) (r?=??0.287, p?<?0.001), low-density lipoprotein cholesterol (LDL-C) (r?=??0.187, p?=?0.006), cholesterol level (r?=??0.573, p?<?0.001), TG level (r?=??0.211, p?=?0.02), frequency of hot flashes per a day (r?=??0.467, p?<?0.001), durations of hot flashes (r?=??0.424, p?<?0.001), fasting glucose level (r?=?0.331, p?<?0.001), and fT3 level (r?=?0.475, p?<?0.001). In multivariate analysis, Lp(a) levels were significantly associated with the urine iodine level (beta coefficient?=??0.342, p?<?0.001) after adjustment for LDL-C (beta coefficient?=?0.225, p?<?0.001), glucose (beta coefficient?=?0.303, p?<?0.001), and age (beta coefficient?=?0.146, p?<?0.017).

Conclusion: Body iodine status during postmenopausal period is associated with the menopausal symptoms and lipid profile including Lp(a).     

绝经后女性慢性肾脏病患者合并心力衰竭的相关研究进展

绝经后女性由于雌激素水平下降,心血管疾病的风险升高。慢性肾脏病(CKD)是随年龄增长发病率逐年上升的疾病之一,同样多见于绝经后的女性。若绝经后女性同时合并CKD将易出现心力衰竭(HF)。本文将从近年来临床及基础研究结果入手,深入分析绝经后女性CKD患者发生HF的相关机制,以期增进对绝经后女性CKD患者相关研究的了解,促进未来对该病新治疗靶点的识别与进一步研究。     

A positive association between interleukin-1 receptor antagonist and insulin resistance in postmenopausal women

Objective: The purpose of this study was to determine whether higher circulating interleukin-1 receptor antagonist (IL-1Ra), an anti-inflammatory cytokine, was associated with insulin resistance in postmenopausal women.

Methods: We measured IL-1Ra concentrations in 160 naturally postmenopausal women without a history of diabetes mellitus. A Pearson coefficient was computed to assess the relationship between plasma IL-1Ra and homeostasis model assessment of insulin resistance (HOMA-IR). The association between HOMA-IR and IL-1Ra plasma level above the median was assessed by logistic regression. Linear regression was used to explore the determinants of IL-1Ra plasma levels.

Results: A significant positive correlation existed between IL-1Ra and HOMA-IR (r?=?0.42, p?p?=?.007).

Conclusions: Our results demonstrated a positive association between plasma IL-1Ra and insulin resistance in postmenopausal women. This analysis suggested that insulin resistance was an important determinant of circulating IL-1Ra for these women.     

Hypertension and the Risk of Breast Cancer in Chilean Women: a Case-control Study

Background: Breast cancer is the most common cancer in women worldwide. Although different metabolicfactors have been implicated in breast cancer development, the relationship between hypertension and breastcancer has not been elucidated. Aim: To evaluate hypertension as a risk factor for breast cancer in Chilean womenof low and middle socio-economic status. Methods: We conducted an age-matched (1:1) case-control study in 3hospitals in Santiago, Chile. Breast cancer cases (n=170) were histopathologically confirmed. Controls had beenclassified as Breast Imaging Reporting and Data System I (negative) or II (benign findings) within 6 months ofrecruitment. Blood pressure was measured using a mercury sphygmomanometer and standardized procedures.We used 2 hypertension cut-off points: blood pressures of ≥140/90 mmHg and ≥130/85 mmHg. Fasting insulin andglucose levels were assessed, and anthropometric, sociodemographic, and behavioral information were collected.Odds ratios and 95% confidence intervals were estimated for the entire sample and restricted to postmenopausalwomen using multivariable conditional logistic regression models. Results: Hypertension (≥140/90 mmHg) wassignificantly higher in cases (37.1%) than controls (17.1%) for the entire sample and in postmenopausal pairs(44.0% compared to 23.8%). In crude and adjusted models, hypertensive women had a 4-fold increased risk ofbreast cancer (adjusted odds ratio: 4.2; 95% confidence interval: 1.8; 9.6) compared to non-hypertensive womenin the entire sample. We found a similar association in the postmenopausal group (adjusted odds ratio: 2.8; 95%confidence interval: 1.1; 7.4). A significant effect was also observed when hypertension was defined as bloodpressure of ≥130/85 mmHg. Conclusion: A significant association was found between hypertension and breastcancer over the entire sample and when restricted to postmenopausal women. Hypertension is highly prevalentin Latin America and may be a modifiable risk factor for breast cancer; therefore, a small association betweenhypertension and breast cancer may have broad implications.     

A clinical trial on the effects of a combination of elcatonin (Carbocalcitonin) and conjugated estrogens on vertebral bone mass in early postmenopausal women

Summary The study was carried out to determine the effect of a combination regimen of a small dose of calcitonin added to conjugated estrogens with medroxyprogesterone acetate on vertebral bone mass in early postmenopausal women. Comparisons were made with groups of women on calcitonin alone, on conjugated estrogens with medroxyprogesterone acetate alone, or on no treatment. The study was carried out over a 2-year period. The results of the study suggest that the combined regimen of calcitonin and estrogens increased vertebral bone mass in early postmenopausal women to a greater extent than calcitonin alone or estrogen alone. Increases in vertebral bone mass of 11.2% after 1 year and 9.2% after 2 years were demonstrated using the combined regimen. Both estrogens alone and calcitonin alone were, however, very effective in preventing rapid bone loss in the postmenopausal women studied.     

Calcitonin reserve in healthy women and patients with postmenopausal osteoporosis

Summary A deficit of immunoreactive calcitonin (iCT) has been found in women with postmenopausal osteoporosis (PM-OP), however, recent studies assessing the monomeric fraction of calcitonin (exCT) do not seem to confirm these findings. We have measured serum levels of iCT by radioimmunoassay (RIA) and exCT (chromatography and RIA) at 0, 5, 10, and 20 minutes after the i.v. infusion of 2 mg calcium/kg body weight in four different groups of women: (1) 12 healthy premenopausal women (HPM), (2) 16 early postmenopausal women (EPM), (3) 16 postmenopausal women within more than 2 years of menopause (LPM), and (4) 24 women with PM-OP. In the HPM group, iCT levels increased significantly 5 and 10 minutes after finishing the calcium infusion (P<0.05); this did not occur in the other three groups. The exCT levels in the HPM and LPM groups showed a significantly greater increase than in the EPM and PM-OP groups at 5 minutes (P<0.05) and at 10 and 20 minutes (P<0.01) after infusion. The behavior of the PM-OP and EPM groups was similar throughout the study. We conclude that there is a calcitonin reserve deficiency in the first years after menopause, which recovers later. This hormone deficiency could explain the accelerated bone loss that takes place at this time of life. The patients with PM-OP also show this deficit, and this may play an ethiopathogenic role in the production of the disease.