Changes In Hormonal Milieu Research Articles

Cognitive function with changing hormonal milieu across menopausal transition stages and related symptoms in midlife and beyond

ABSTRACT The menopausal transition is regarded as the critical window where midlife women experience various health challenges having debilitating impact on their wellbeing. The present cross-sectional study intends to assess cognitive outcome with changing hormonal milieu during menopausal transition and related symptoms in midlife and beyond. For this purpose, cognitive performance of women and menopausal symptoms were studied on the sample of 320 women ranging in age from 45 to 60 years. Data collection was carried out by purposive sampling method from rural areas of Haryana from March 2021 to January 2023. Findings of the study demonstrated a successive downward trend in the mean scores of orientation to time and place, registration, attention, recall, as well as language and visual spatial skills cognitive domain from premenopause to late postmenopause stage. Multivariate logistic regression analysis (adjusted for age and educational status) identified severe menopausal symptoms, i.e. heart beating quickly or strongly, difficulty in sleeping, feeling tired, feeling unhappy or depressed, and sexual dysfunction as the potential determinants of poor functioning of different cognitive domains among women transitioning menopause and beyond. Hence, it was observed that cognitive decline during menopause transition and beyond is sensitive to severe menopausal symptoms.

BENEFICIAL ROLE OF DIETARY CHANGES IN MENOPAUSE: IMPACT ON CARDIOVASCULAR RISK

Objective: The changing hormonal milieu in post-menopausal women (PMW) predisposes them to increase cardiovascular (CV) risk, due to a constellation of risk factors, such as visceral obesity, atherogenic dyslipidemia and arterial hypertension. Our ongoing study aims to evaluate the impact of dietary changes in CV risk in PMW. Design and method: For 1 year, 65 PMW with BMI 24-39 Kg/m2 and at least another CV risk factor were followed. Anthropometric parameters, plicometry and blood pressure (BP) were taken. Questionnaires on medical history, physical activity, and food frequency (FFQ) were administered. Balanced low-calorie dietary plan with quantitative advice were released. Repeated measures ANOVA at 1 year were performed. Results: We observed at 1 year significant reductions (p<0.01) in weight (δ=-4.5 Kg), BMI (δ=-1.7 Kg/m2), waist (δ=-4.3cm) and hips (δ=-3.1cm) circumferences, subscapular (δ=-5.8mm), suprailiac (δ=-3.3mm) and triceps (δ=-5.5mm) skinfolds, adipose area of the arm (AFA) (δ=-7.3cm2), and fat mass (δ=-4.5kg) without variation of the lean mass (δ=-0.1 kg, p=0.48). All those reductions were followed by change in the obesity prevalence (-21.1%), in the fat mass distribution with 10% reduction in abdominal and truncular obesity and 5.2% reduction on waist-to-height ratio, and in systolic (δ=-8.8 mmHg) and diastolic (δ=-4.3 mmHg) BP. Significant positive correlations (p<0.0001) were observed between weight reduction and the following variables: waist (r=0.61) and hip (r=0.77) circumferences, subscapularis (r=0.56) and triceps (r=0.66) skinfolds, and AFA (r=0.73). Significant reductions (p<0.05) were observed in daily caloric intake (δ=-99.8Kcal/day), due to the reduction in fat intake (36.6->33.6%), specially saturated fatty acids (12->10.8%) and cholesterol (δ=-23.1mg/day), with maintenance of the average level of physical activity and in agreement with a significant reductions in consumption of animal meats, visible fat, processed meats, olive oil, sweets and baked goods detected by FFQ. Conclusions: The study underlines the medium-term utility of a 1 year balanced low-calorie diet in PMW with elevated CV risk factors with a clear reduction in CV risk.

Sleep pathology and use of anabolic androgen steroids among male weightlifters in Norway

Use of anabolic androgenic steroids (AAS) causes drastic changes in hormonal milieu and is associated with a range of medical and psychological consequences. Sleep pathology is a common side-effect of AAS use but few have studied these relations. This study examined the relationship between AAS use, psychological distress and sleep quality, and how phases of heavy use and abstinence influence sleep. The Pittsburgh-Sleep-Quality-Index (PSQI) and Jenkins Sleep Scale (JSS) were used to assess sleep quality, and psychological distress was measured with the Hopkins Symptoms Checklist (HSCL). Participants comprised men who have previous or current long-term use of AAS (n = 68) and non-using weightlifting controls (WLC) (n = 58), where a subgroup of participants (n = 22) was monitored over ~ 6 months during phases of AAS use and withdrawal. Group differences on PSQI and JSS were evaluated with Kruskal-Wallis H tests, and the mediating role of psychological distress was evaluated using structural equation modeling. Linear mixed models were used to assess the role of AAS use and withdrawal on sleep quality. Among the AAS group, 66% reported sleep problems as a side effect, and 38% had used sleep medication. PSQI scores showed significantly lower sleep quality in the AAS group compared to WLC (p < 0.001) on all subscales except “sleep latency”. Furthermore, sleep quality was significantly poorer during withdrawal-phases than periods with AAS use (p < .001). Our findings provide key insight into sleep disturbances among men who use AAS, suggesting a link between sleep disturbances and hormone levels that deviate from physiologically normal levels in both directions.

Use of High-Dose Androgens Is Associated with Reduced Brain-Derived Neurotrophic Factor in Male Weightlifters

Introduction: Use of high-dose androgens causes drastic changes in hormonal milieu and is associated with adverse medical, psychological, and cognitive effects. Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family of growth factors plays a critical role in neuroplasticity, with implications for cognitive function and mental health. The impact of long-term, high-dose androgen use on BDNF in a natural setting has not been investigated. This study examined the association between long-term androgen exposure and BDNF levels, and the links between BDNF, heavy resistance exercise, hormones, androgens, and mental health. Methods: We measured serum levels of BDNF and sex steroid hormones in male weightlifters (N = 141) with a history of current (n = 59), past (n = 29), or no (n = 52) androgen use. All participants completed questionnaires assessing maximum strength and measures of anxiety and depression. Group differences in BDNF were tested using general linear models adjusting for age and associations between BDNF and strength, anxiety, and depression using Pearson’s or Kendall’s correlations. Results: Both current (mean: 44.1 ng/mL [SD: 12.7]) and past (39.5 ng/mL [SD: 13.9]) androgen users showed lower serum BDNF levels compared to nonusing controls (51.5 [SD: 15.3], p < 0.001, ηp² = 0.10). BDNF levels were negatively related to maximal strength, and with hormonal status in past androgen users, but no significant associations were found with measures of depression and anxiety. Conclusion: Lower circulating BDNF concentrations in current and past androgen users suggest that high-dose androgen exposure triggers persistent changes in BDNF expression. Further studies are needed to verify the relationship and its potential clinical implications.

Menopause-associated risk of cardiovascular disease.

Cardiovascular disease (CVD) is of major concern in women entering menopause. The changing hormonal milieu predisposes them to increased CVD risk, due to a constellation of risk factors, such as visceral obesity, atherogenic dyslipidemia, dysregulation in glucose homeostasis, non-alcoholic fatty liver disease and arterial hypertension. However, an independent association of menopause per se with increased risk of CVD events has only been proven for early menopause (<45 years). Menopausal hormone therapy (MHT) ameliorates most of the CVD risk factors mentioned above. Transdermal estrogens are the preferable regimen, since they do not increase triglyceride concentrations and they are not associated with increased risk of venous thromboembolic events (VTE). Although administration of MHT should be considered on an individual basis, MHT may reduce CVD morbidity and mortality, if commenced during the early postmenopausal period (<60 years or within ten years since the last menstrual period). In women with premature ovarian insufficiency (POI), MHT should be administered at least until the average age of menopause (50–52 years). MHT is contraindicated in women with a history of VTE and is not currently recommended for the sole purpose of CVD prevention. The risk of breast cancer associated with MHT is generally low and is mainly conferred by the progestogen. Micronized progesterone and dydrogesterone are associated with lower risk compared to other progestogens.

0343 Associations of Endogenous Hormones and Phthalate Exposure with Subjective and Objective Sleep Measures in Midlife Women

Abstract Introduction Impaired sleep during the menopausal transition reduces quality of life and increases risk of multiple diseases. The changing hormonal milieu during midlife is associated with impaired sleep. Endocrine disrupting chemicals, such as phthalates, may also contribute to the increased prevalence of sleep disturbances in midlife women. Phthalates are known to impact the endogenous hormones associated with sleep. However, the link between phthalate exposure and sleep quality remains unexplored. Methods We recruited 26 midlife women (median age 50 years) through the Carle Regional Sleep Disorders Center in Urbana, Illinois. Subjective sleep was assessed through the Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, and self-reported frequency of sleep disturbances, insomnia, and restless sleep. Objective sleep was measured using actigraphy and manual sleep logs (7-day average). Serum levels of follicle-stimulating hormone, estradiol, progesterone, testosterone, free estradiol, and free testosterone were quantified using ELISAs from a single sample from each participant. Phthalate metabolites were quantified from urine using high performance liquid chromatography-mass spectrometry (HPLC-MS). Covariates, including depression, hot flashes, quality of life, demographics, and lifestyle factors, were measured via surveys. Results Preliminary unadjusted logistic regression was used to determine the association between hormone values and subjective sleep quality binomial variables, including daytime sleepiness, sleep efficiency, sleep onset latency, sleep duration, number of sleep disturbances, and frequency of sleep disturbances. Each of these subjective sleep measures is significantly associated with one or more hormones. Conclusion Our results are consistent with literature identifying associations between hormones and subjective sleep in midlife women. Additional analyses will determine associations between hormones and objective sleep, and phthalates with both subjective and objective sleep measures. Excitingly, our study will be among the first to investigate the association between endocrine disruption and sleep quality in this population. Support Carle Illinois Seed Grant Program

Long-Term Metabolic Consequences of Intrauterine Growth Restriction

To summarize recent findings on the associations of intrauterine growth restriction (IUGR) and long-term metabolic consequences such as obesity, type 2 diabetes (T2D), and cardiovascular diseases and the underlying mechanisms. Recent evidence suggests that metabolic diseases such as obesity, T2D, hypertension, and coronary artery disease are related to developmental programming in fetal period and early childhood. Rapid postnatal catch-up growth is also an important factor that contributes to the development of these long-term metabolic complications. The underlying mechanisms include oxidative stress, changes in hormonal milieu, vascular endothelial dysfunction, epigenetic regulation, and the potential alteration of microbiome. Fetal and early life environment is an important determinant of long-term cardiometabolic risks. Children with IUGR need close follow-up for early detection of these complications.

The emerging risk of exposure to nano(micro)plastics on endocrine disturbance and reproductive toxicity: From a hypothetical scenario to a global public health challenge

Humans are potentially exposed to nano(micro)plastics, however their interaction with tissues and cells in humans remains largely unknown. This premise is particularly notable with nano-sized plastic particulates, a potentially most pernicious form of plastic pollution. In this study, even in a hypothetical scenario in terms of dose (1, 3, 6 and 10 mg/kg-day) and exposure time (five weeks), the potential endocrine disturbances with particular reference to reproductive toxicity of polystyrene nanoplastics (PS NPs, average size = 38.92 nm) was studied in male rats considering biomarkers of semen quality, changes in hormonal milieu and molecular signatures of endocrine disruption. Sperm DNA integrity and its chromatin structure were also analyzed. There observed significant inverse associations between exposure to PS NPs and serum concentrations of testosterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Tissue and cell impairments were also noticed even at the lowest tested dosage, though the severity of lesions followed a clear dose-response pattern. DNA damage as well as alterations in sperm morphology and viability were evident, again proportionally with the amount of exposure dosage. RT-qPCR data were in accordance with the results of physio-histological alterations and fluorescence imaging, as significant down-regulation of PLZF, DAZL, FSH and LH gene expressions were noticed in the testis of exposed animals, suggesting that exposure interferes with spermatogenesis and also with HPT-axis. However, among those with highest exposure dosage, expressions of FSH and LH were significantly increased. ABP modulation further revealed evidence of a nonlinear dose response. The association between PS NPs exposure and GnRH was indeed in an unexpected positive direction, though these end-points were less sensitive at higher doses. Although additional evidence is warranted, the present work provides new insights into the possible risks of plastic nanoparticles exposure in humans, especially since the problem is growing and will persist for a long time.

A Prospective Study on the Incidence of Metabolic Syndrome in Premenopausal and Postmenopausal Women.

Background:Metabolic syndrome is defined as a state of metabolic dysregulation characterized by insulin resistance, a predisposition to Type 2 diabetes mellitus and atherosclerotic vascular disease. The changing hormonal milieu with altered estrogen and testosterone ratio is the cause of metabolic syndrome at menopausal transition.Aims and Objectives:This study was designed to determine the incidence of metabolic syndrome and its various components in premenopausal and postmenopausal women from Punjab.Materials and Methods:This study was conducted on 200 females in the age group of 45–60 years attending outpatient department over a period of 2 years in the Department of Obstetrics and Gynaecology, Bebe Nanki Mother and Child Care Centre, Government Medical College, Amritsar. A detailed history and physical examination were done and recorded on a pro forma. Biochemical assessment comprising fasting blood glucose, triglycerides, and cholesterol was done. Metabolic syndrome was assessed as per the modified NCEP ATP III criteria.Results:Twenty-nine percent women were found to have newly onset metabolic syndrome, the incidence in premenopausal group was 16%, and in postmenopausal group was 42%. Among the components, the incidence of hypertension (58%) was the highest followed by waist circumference (42%). Maximum correlation of metabolic syndrome was found with high-density lipoprotein (odds ratio - 7.250) followed by waist circumference (odds ratio - 7.111).Conclusion:The incidence of metabolic syndrome was found to be higher in postmenopausal women than in premenopausal women. Currently, the need of the hour is lifestyle modification to reduce the emergence of metabolic syndrome and cardiovascular diseases.

Endogenous sex hormones and memory performance in middle-aged Greek women with subjective memory complaints.

The changing hormonal milieu during the menopausal transition may contribute to the development of memory disorders. We aimed to assess the association of sex hormones with memory function in a sample of Greek middle-aged women. This pilot study included 44 women with subjective memory complaints. Memory performance was evaluated using the Hopkins Verbal Learning Test (HVLT), the Brief Visuospatial Memory test (BVMT), and the verbal digits backwards test (VSPAN), to assess verbal, visuospatial, and working memory performance, respectively. Menopausal symptoms were assessed using the Green Climacteric Scale. VSPAN backwards scores were positively associated with log-transformed free androgen index (logFAI), in models adjusted for age, education, log-transformed free estrogen index (logFEI), hypertension, and the intensity of menopausal symptoms. BVMT total scores were predicted by logFAI (b-coefficient = 0.424, p value = 0.002), education, and combined climacteric symptomatology, in a model adjusted for age, logFEI, and hypertension. Women with circulating estradiol above the median value of 10pg/mL had better total HTLV total scores compared to women with estradiol values below the median (HTLV total scores, estradiol ≤10pg/mL vs. >10pg/mL: 24.2±3.6 vs. 30.0±7.9, p value = 0.007 unadjusted). This association was affected by education and remained independent of menopausal symptoms and testosterone levels, education, and hypertension (model R 2 = 22.3%; b-coefficient = 0.318, p value = 0.024). Endogenous total estradiol is associated with verbal episodic memory, while logFAI is associated with working memory performance and visuospatial episodic memory in this sample of postmenopausal women. These associations were not influenced by age, education, or menopausal symptoms. Larger studies are necessary to evaluate the significance of our findings.

Effects of Intrauterine Growth Restriction and Female Sex on Future Blood Pressure and Cardiovascular Disease.

It is well-established that the age-related increase in blood pressure is augmented after menopause. Yet, the prevalence of hypertension is enhanced in low birth weight women relative to normal birth weight counterparts by 60years of age suggesting that adverse influences during fetal life heighten cardiovascular risk in later life. A changing hormonal milieu may contribute to increased cardiovascular risk that occurs after the menopausal transition. Low birth weight is associated with early age at menopause. A recent study indicates that a shift towards testosterone excess following early reproductive senescence may contribute to the etiology of age-dependent increases in blood pressure in a rodent model of low birth weight. This review will highlight current findings related to postmenopausal hypertension and discuss potential mechanisms that may contribute to the enhanced cardiovascular risk that develops with age in low birth weight women.

Peri-ovulatory Phytoestrogen Improves Pregnancy Rate in Women with Polycystic OvarianSyndrome Receiving Ovulation Induction with Clomiphene Citrate

Background: PCOS is the most common ovarian factor of female infertility, in low resource countries clomiphene citrate is the most popular drug used for induction of ovulation as its price is affordable for most of patients with least side effects. Objective: Evaluate the effect of phytoestrogen in women receiving induction with clomiphene citrate when given peri ovulatory to oppose antiestrogenic effect of clomiphene citrate. Methodology: Prospective study conducted on 500 patients with PCOD who attended infertility clinic, patients were randomized into 2 groups both groups received traditional CC induction , group (1) 225 patients received phyto-estrogen, starting in the 7th day of the cycle till the day of HCG injection ,group(2) 225 patients received clomiphene citrate only. Endometrial thickness and follicular growth were assessed by transvaginal US. When follicles reached 18 mm, 10,000 IU HCG was administered together with timed intercourse. Both groups were compared as regard cumulative pregnancy rate, ovulation, endometrial thickness and change in hormonal milieu. Results: Midluteal serum progesterone was significantly higher in the study group as compared with the control group (15.93 ±1.8 versus 12.93 ± 1.8); endometrial thickness was also greater in the study group as compared with the control group, (10.3 ± 1.1 versus 8.2 ± 0.9). Ovulation in the three cycles was in favor of study group 82.5% versus 80.4% but not statistically significant. The CPR was significantly higher in the study group than in the control group (34.2% vs. 20.8%. P = 0.1). There were 6 cases of multiple pregnancy in the study group and 4 cases in the control group. Conclusion: Adding phytoestrogen to CC induction improve ovulation and pregnancy rate, it is a good option for patients with PCOS seeking for pregnancy treatment with affordable price and minimal side effects

Efeito do estresse pré-natal na regulação da inflamação alérgica pulmonar no modelo murino de asma experimental

Devido ao seu rápido crescimento, o feto é particularmente vulnerável a insultos e modificações no millieu hormonal. Este fato sugere que situações adversas experimentadas pela mãe grávida podem alterar o desenvolvimento e a saúde da prole, explicado principalmente pela permeabilidade da barreira placentária a diversos hormônios e substâncias. O objetivo deste trabalho foi estudar o efeito do estresse pré-natal na regulação da inflamação alérgica pulmonar, empregando o modelo murino de asma experimental. Para este propósito foram utilizadas camundongas virgens da linhagem Swiss, com 50 dias de idade. Foi empregado o modelo de choque nas patas para promover o estresse pré-natal e o modelo do “metrô de Nova Efeito do estresse pré-natal na regulação da inflamação alérgica pulmonar no modelo murino de asma experimental 65 Iorque” para o estresse pós-natal. As fêmeas foram distribuídas em 4 grupos experimentais: CC: fêmeas não estressadas;CE: fêmeas estressadas pós-natalmente aos 60 dias de idade (PND60), EC: fêmeas nascidas de mães estressadas entre o dia 15 (GD15) e 18 de gestação (GD18); EE: fêmeas nascidas de mães estressadas entre o GD15 e GD18 e estressadas pós-natalmente aos PND60. A indução da inflamação alérgica pulmonar foi realizada através da sensibilização dos animais com solução de ovalbumina (OVA) 0,1 mg.Kg-1 sc para avaliação do leucograma, lavado broncoalveolar (BAL), celularidade hematopoiética medular e neuroquímica. Os experimentos foram realizados 24h após a última sessão de nebulização.O número de células do BAL foi significantemente maior nos animais do grupo EE, em relação àqueles dos grupos CC (P&lt;0.01), CE (P&lt;0.01) e EC (P&lt;0.001). Na contagem diferencial do BAL os linfócitos e macrófagos do grupo EE foram significantemente maiores que em os outros grupos avaliados (P&lt;0.05). Na contagem diferencial de células no sangue não foram observadas alterações (P&gt;0.05) para os linfócitos, neutrófilos, eosinófilos e monócitos; porém, observou-se diferenças significativas (P&lt;0.05) entre o número de bastonetes dos grupos, sendo maior nos animais do grupo CC em relação àquelesdo grupo EC. O número de células hematopoiéticas da medula óssea foi significantemente (P&lt;0.05) menor nos animais do grupo EE, em relação àqueles do grupo CC. No córtex pré-frontal, há diferenças significantes na relação Ácido Homovanílico/Dopamina (HVA/DA) (P&lt;0.05), sendo maior nos animais do grupo EC, em relação àqueles do grupo CE. Em conclusão,o estresse pré-natal levou a modulação de células do sistema imune (SI) dos neonatos, evidenciado após a exposição a estresse agudo pós-natal, amplificando a resposta alérgica pulmonar. Sugere-se que a maior susceptibilidade dos animais do grupo EE seja consequência de alterações induzidas pelo estresse pré-natal no eixo hipotálamo-pituitária-adrenal (HPA).

Depression in the menopause transition: risks in the changing hormone milieu as observed in the general population.

There is accumulating evidence but no definitive answers about the incidence of depressed mood in the menopause transition and its association with the changing hormonal milieu. While a changing hormonal milieu is the natural condition for all women, only a minority of mid-life women experience debilitating depressive symptoms or clinical depression. This review focuses on associations between depressed mood and the menopause transition, primarily as identified in longitudinal, population-based studies in the past decade. Further aims were to present reported associations between depressed mood and reproductive hormones in the menopause transition as evaluated in the general population and associations of depressive symptoms or clinical depression with menopausal hot flashes or poor sleep in perimenopausal women. There is evidence to support the role of the changing endocrine milieu in the development of depressed mood in the menopause transition, but the contribution of hormones as measured is small. Disentangling the numerous factors that are associated with depression in midlife women is a major challenge for research and for clinical care, where treatments are needed to improve the most distressing menopausal symptoms.

Progestogens’ effects and mechanisms for object recognition memory across the lifespan

This review explores the effects of female reproductive hormones, estrogens and progestogens, with a focus on progesterone and allopregnanolone, on object memory. Progesterone and its metabolites, in particular allopregnanolone, exert various effects on both cognitive and non-mnemonic functions in females. The well-known object recognition task is a valuable experimental paradigm that can be used to determine the effects and mechanisms of progestogens for mnemonic effects across the lifespan, which will be discussed herein. In this task there is little test-decay when different objects are used as targets and baseline valance for objects is controlled. This allows repeated testing, within-subjects designs, and longitudinal assessments, which aid understanding of changes in hormonal milieu. Objects are not aversive or food-based, which are hormone-sensitive factors. This review focuses on published data from our laboratory, and others, using the object recognition task in rodents to assess the role and mechanisms of progestogens throughout the lifespan. Improvements in object recognition performance of rodents are often associated with higher hormone levels in the hippocampus and prefrontal cortex during natural cycles, with hormone replacement following ovariectomy in young animals, or with aging. The capacity for reversal of age- and reproductive senescence-related decline in cognitive performance, and changes in neural plasticity that may be dissociated from peripheral effects with such decline, are discussed. The focus here will be on the effects of brain-derived factors, such as the neurosteroid, allopregnanolone, and other hormones, for enhancing object recognition across the lifespan.

Interaction between reproductive hormones and physiological sleep in women.

The changing hormonal milieu around menopause is implicated in the development of sleep disturbances. No studies have assessed the association between concurrent physiological measures of sleep and serum hormone concentrations in perimenopausal women. This study aimed to assess the interaction between physiological sleep and reproductive hormone measures in perimenopausal women. This was a cross-sectional laboratory study of 33 perimenopausal women age 43-52 years (17 with no sleep complaints and 16 with a clinical diagnosis of insomnia). Eleven premenopausal women without sleep complaints (18-27 y), were included to determine whether hormone-sleep relationships differed depending on reproductive stage. Concurrent polysomnographic sleep indices and serum hormone levels (estradiol and follicle stimulating hormone [FSH]) were measured. FSH was positively associated with polysomnographic-defined wakefulness after sleep onset, and number of awakenings and arousals in perimenopausal women (P < .05) without sleep complaints independent of age, body mass index, and hot flashes. Similarly, FSH correlated with wakefulness after sleep onset and light N1 sleep in premenopausal women (P < .05). In contrast, in perimenopausal insomniacs amount of sleep correlated with anxiety and depression (P < .05) but not with FSH. Estradiol did not correlate with sleep in perimenopausal groups but correlated negatively with arousals in premenopausal women (P < .01). Our results suggest an interaction between the hypothalamic-pituitary-ovarian (HPO) axis and sleep-wake regulatory systems in pre- and peri-menopausal women without sleep complaints. There was no relationship between hormones and sleep in perimenopausal insomniacs, whose sleep may be influenced by other factors intrinsic to insomnia, such as hyperactivity, poor mood, and night-to-night variability.

Impaired enteroendocrine development in intestinal-specific Islet1 mouse mutants causes impaired glucose homeostasis.

Enteroendocrine cells secrete over a dozen different hormones responsible for coordinating digestion, absorption, metabolism, and gut motility. Loss of enteroendocrine cells is a known cause of severe congenital diarrhea. Furthermore, enteroendocrine cells regulate glucose metabolism, with the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) playing critical roles in stimulating insulin release by pancreatic β-cells. Islet1 (Isl1) is a LIM-homeodomain transcription factor expressed specifically in an array of intestinal endocrine cells, including incretin-expressing cells. To examine the impact of intestinal Isl1 on glycemic control, we set out to explore the role of intestinal Isl1 in hormone cell specification and organismal physiology. Mice with intestinal epithelial-specific ablation of Isl1 were obtained by crossing Villin-Cre transgenic animals with mice harboring a Isl1(loxP) allele (Isl1(int) model). Gene ablation of Isl1 in the intestine results in loss of GLP-1, GIP, cholecystokinin (CCK), and somatostatin-expressing cells and an increase in 5-HT (serotonin)-producing cells, while the chromogranin A population was unchanged. This dramatic change in hormonal milieu results in animals with lipid malabsorption and females smaller than their littermate controls. Interestingly, when challenged with oral, not intraperitoneal glucose, the Isl-1 intestinal-deficient animals (Isl1(int)) display impaired glucose tolerance, indicating loss of the incretin effect. Thus the Isl1(int) model confirms that intestinal biology is essential for organism physiology in glycemic control and susceptibility to diabetes.

Impact of breast cancer diagnosis and treatment on sexual dysfunction.

125 Background: Sexual dysfunction is a common and under acknowledged disorder in women with breast cancer. Sexual dysfunction in this scenario may be related to multiple factors: psychological distress due to diagnosis, physical decline due to treatment, change in hormonal milieu and/or poor body image. Methods: We assessed the changes in sexual activity after breast cancer diagnosis and treatment in 45 women using an anonymous questionnaire. Data was analyzed via descriptive statistics and paired sample t-test. Results: The age of women in our study ranged between 33-73 years with an average age of 51.6 years. Most of the subjects (89%) had completed chemotherapy and/or radiation therapy however 52% were still on hormonal treatment. Women who were more sexually active prior to breast cancer diagnosis were more likely to experience sexual dysfunction (p = 0.001). Overall, 45% of the women with breast cancer experienced a decline in their sexual health. A greater decline occurred after breast cancer treatment (chemotherapy and/or hormonal therapy) than after diagnosis (p &lt; 0.05). Fifty percent had a decrease in libido and sexual arousal, 40.5% had difficulty in reaching sexual orgasm, and 29% had dyspareunia. Sexual difficulties were addressed by the treating oncologist in 3 out of the 45 women. Conclusions: The data reveals that sexual dysfunction is prevalent in breast cancer survivors. Its onset in concomitance with the diagnosis of breast cancer reflects the psychosocial impact of such a diagnosis. The further decline in sexual health after treatment emphasizes the important adverse effects of chemotherapy and hormone therapy in terms of vaginal dryness, dysparunia and sexual well-being. Despite its prevalence, sexual dysfunction is not commonly addressed in women with breast cancer. [Table: see text]

Cognitive Effects of Cancer and Its Treatments at the Intersection of Aging: What Do We Know; What Do We Need to Know?

There is a fairly consistent, albeit non-universal body of research documenting cognitive declines after cancer and its treatments. While few of these studies have included subjects aged 65 years and older, it is logical to expect that older patients are at risk of cognitive decline.Here, we use breast cancer as an exemplar disease for inquiry into the intersection of aging and cognitive effects of cancer and its therapies. There are a striking number of common underlying potential biological risks and pathways for the development of cancer, cancer-related cognitive declines, and aging processes, including the development of a frail phenotype. Candidate shared pathways include changes in hormonal milieu, inflammation, oxidative stress, DNA damage and compromised DNA repair, genetic susceptibility, decreased brain blood flow or disruption of the blood-brain barrier, direct neurotoxicity, decreased telomere length, and cell senescence. There also are similar structure and functional changes seen in brain imaging studies of cancer patients and those seen with "normal" aging and Alzheimer's disease. Disentangling the role of these overlapping processes is difficult since they require aged animal models and large samples of older human subjects. From what we do know, frailty and its low cognitive reserve seem to be a clinically useful marker of risk for cognitive decline after cancer and its treatments. This and other results from this review suggest the value of geriatric assessments to identify older patients at the highest risk of cognitive decline. Further research is needed to understand the interactions between aging, genetic predisposition, lifestyle factors, and frailty phenotypes to best identify the subgroups of older patients at greatest risk for decline and to develop behavioral and pharmacological interventions targeting this group. We recommend that basic science and population trials be developed specifically for older hosts with intermediate endpoints of relevance to this group, including cognitive function and trajectories of frailty. Clinicians and their older patients can advance the field by active encouragement of and participation in research designed to improve the care and outcomes of the growing population of older cancer patients.

Associations between levels of sex steroid hormones and inflammatory cytokines by hormone replacement therapy (HRT) status in ethnic minority postmenopausal women

Elevated levels of inflammatory markers have been associated with metabolic diseases such as type 2 diabetes (DM) and cardiovascular disease. Inflammation associated with aging may be mediated by changes in hormonal milieu, as seen with menopause. Whether HRT modifies the relationships between levels of sex hormones and inflammatory cytokines is largely unknown, especially in minority women.