Relations between bleeding pattern,endometrial histology,and oestrogen treatment in menopausal women

Vacuum curettage was performed on 348 women who had received various regimens of oestrogen treatment for an average of 9·7 months for climacteric symptoms. In 62 cases (18%) the specimens were unsatisfactory for histological assessment; among the remainder, however, they showed a normal endometrium in 257 cases (90%), cystic hyperplasia in 21 (7%), adenomatous hyperplasia in 7 (2%), and endometrial adenocarcinoma in one. Cyclical unopposed oral oestrogen treatment (98 cases) was associated with a 12% incidence of endometrial hyperplasia, but among those given an additional five-day course of progestogen in each cycle (37 cases) the incidence was only 8%. No case of hyperplasia occurred among 102 women taking regimens including 10 or 13 days of progestogen. Among women treated with subcutaneous oestradiol implants and monthly five-day courses of oral progestogen (50 cases) there was a 28% incidence of hyperplasia including the one case of carcinoma, though some of those with hyperplasia may not have taken the full course of progestogen. Regular withdrawal bleeding during treatment was associated with a lower incidence of endometrial hyperplasia (6%) than unscheduled breakthrough bleeding (28%), but the one patient with carcinoma had experienced regular bleeding only.The risk of developing endometrial carcinoma from oestrogen treatment may be reduced by avoiding the use of unopposed oestrogen regimens, the addition of more than five days'' treatment with a progestogen, and recognising that a regular bleeding response to oestrogen is no guarantee of a healthy endometrium.     

Influence of the level of trait anxiety on sleep EEG of men and women

Psychophysiological tests for identifying the level of trait anxiety and polysomnology have been used in this study. Gender differences in the organization of sleep phases during the first three cycles and the spectral density of sleep EEGs for persons with high and low levels of trait anxiety have been studied.     

Effects of "natural oestrogen" replacement therapy on menopausal symptoms and blood clotting.

In a double-blind study on the value of equine ("natural") oestrogens 30 patients presenting with menopausal symptoms in a group practice were monitored for possible adverse effects on blood clotting, weight, and blood pressure. The women were randomly allocated to two groups and given either three months'' hormone treatment followed by three months'' placebo or vice versa. An appreciable amelioration of all symptoms on placebo made it difficult to asses the genuine value of oestrogen treatment during the period of study. Both groups made a dramatic clinical improvement during the first three months. Nevertheless, the symptoms of the 15 women who received oestrogen first returned after the cross-over to placebo without any suggestion of a placebo response. In contrast, the other group who took placebo first did not deteriorate after changing to oestrogen. The menopausal index and the karyopyknotic index were not reliable guides to the need for oestrogen treatment. Hot flushes, however, were proportionately reduced on oestrogen and they seemed to be more readily eliminated in individual cases by oestrogen. The results of blood clotting studies indicated that natural oestrogen administration raised the levels of the extrinsic clotting factors VII and X and accelerated the prothrombin time. The findings were similar to those observed after three months synthetic oestrogen administration with oral contraception. Long-term studies and epidemiological surveys of the clinical incidence of thrombotic and other sequelae are needed before large-scale oestrogen replacement treatment can be recommended.     

Effect of testosterone on the apneic threshold in women during NREM sleep.

The hypocapnic apneic threshold (AT) is lower in women relative to men. To test the hypothesis that the gender difference in AT was due to testosterone, we determined the AT during non-rapid eye movement sleep in eight healthy, nonsnoring, premenopausal women before and after 10-12 days of transdermal testosterone. Hypocapnia was induced via nasal mechanical ventilation (MV) for 3 min with tidal volumes ranging from 175 to 215% above eupneic tidal volume and respiratory frequency matched to eupneic frequency. Cessation of MV resulted in hypocapnic central apnea or hypopnea depending on the magnitude of hypocapnia. Nadir minute ventilation as a percentage of control (%Ve) was plotted against the change in end-tidal CO(2) (Pet(CO(2))); %Ve was given a value of zero during central apnea. The AT was defined as the Pet(CO(2)) at which the apnea closest to the last hypopnea occurred; hypocapnic ventilatory response (HPVR) was defined as the slope of the linear regression Ve vs. Pet(CO(2)). Both the AT (39.5 +/- 2.9 vs. 42.1 +/- 3.0 Torr; P = 0.002) and HPVR (0.20 +/- 0.05 vs. 0.33 +/- 0.11%Ve/Torr; P = 0.016) increased with testosterone administration. We conclude that testosterone administration increases AT in premenopausal women, suggesting that the increased breathing instability during sleep in men is related to the presence of testosterone.     

Association of morning illumination and window covering with mood and sleep among post-menopausal women

Sleep and Biological Rhythms - The antidepressant and sleep-promoting effects of light exposure might be useful for treating age-related mood and sleep disorders. In view of recent evidence...     

Subjective sleep characteristics in primary insomnia versus insomnia with comorbid anxiety or mood disorder

Sleep and Biological Rhythms - We assessed subjective sleep measures in a cohort of 146 patients with chronic insomnia and hypothesized that these measures may differ depending on the presence as...     

Impact of night-float rotation on sleep,mood, and alertness: the resident's perception

Night-float rotations were designed to alleviate the workload of residents on night call and thereby improve patient safety. However, the impact of the night float on residents is yet to be surveyed. We assessed the impact of the night-float rotation on pediatric residents using an anonymous questionnaire that covered topics, based on recall, about sleep, mood, alertness, adjustment, and others. The study was conducted in a major tertiary pediatric teaching hospital in the United States. Participants were pediatric residents who had completed one or two night-float rotations and were in active training at our teaching hospital at the time of the study. Fifty-two of 60 eligible residents (87%) responded. Sleep duration during the night-float rotation was shorter than during day-shift work in 24 residents (46%), longer in 20 (38%), and unchanged in eight (15%). A higher proportion of residents took longer to fall asleep, had more difficulty falling asleep, had more sleep interruptions, and felt less rested upon awakening. Twenty-four residents (46%) felt that their bodies never adjusted to the night shift. Also, 22 residents (43%) felt moody or depressed in contrast to seven (14%) who felt depressed during the daytime rotation (p=0.0001). Twenty-one residents (41%) felt they were slower in their thinking during the night float than daytime rotations. The results suggest that disturbances of sleep and mood and decreased alertness, typical of night shift, are present in the night-float rotation. Residency programs should monitor closely the impact of the night-float rotation on resident well being and patient safety. The impact of night-shift work should be considered in the design of night-float schedules, and teaching should be provided for residents to learn coping strategies for night-shift work.     

Skeletal effects of oral oestrogen compared with subcutaneous oestrogen and testosterone in postmenopausal women.

STUDY OBJECTIVE--To compare oral and implanted oestrogens for their effects in preventing postmenopausal osteoporosis. DESIGN--Non-randomised cohort study of postmenopausal women treated with oral or depot oestrogens and postmenopausal controls. SETTING--Gynaecological endocrine clinic in tertiary referral centre. PATIENTS--Oral treatment group of 37 postmenopausal women (mean age 57.5 years, median 8.75 years from last menstrual period), compared with 41 women given oestrogen implants (mean age 56.2 years, median 9.5 years from last menstrual period) and 36 controls (mean age 51.8 years, median 2.0 years from last menstrual period). Weight was not significantly different among the groups. INTERVENTIONS--Oral treatment group was given continuous treatment with cyclic oestrogen and progesterone preparations (Prempak C or Cycloprogynova) for a median of 8.0 years. Implant group was given subcutaneous implants of oestradiol 50 mg combined with testosterone 100 mg, on average six monthly for a median of 8.5 years. Controls were not treated. END POINT--Significant increase in bone density. MEASUREMENTS AND MAIN RESULTS--Bone density measured by dual beam photon absorptiometry was 1.02 (SD 0.13) g hydroxyapatite/cm2 in implant group versus 0.89 (0.11) in oral group (p less than 0.01) and 0.87 (0.14) in controls (p less than 0.01). Serum oestradiol concentration in implant group was (median) 725 pmol/l versus 170 pmol/l in oral group (p less than 0.01) and 99 pmol/l in controls (p less than 0.01). Serum follicular stimulating hormone was median 1 IU/l (range 1-11) in implant group (equivalent to premenopausal values) versus 43 (4-94) IU/l in oral group (p less than 0.01) and 72 (28-99) IU/l in controls (p less than 0.01). CONCLUSIONS--Subcutaneous oestrogen is more effective than oral oestrogen in preventing osteoporosis, probably owing to the more physiological (premenopausal) serum oestradiol concentrations achieved. It also avoids problems of compliance that occur with oral treatment.     

Effects of lifestyle, personality, symptoms of anxiety and depression, and genetic predisposition on subjective sleep disturbance and sleep pattern.

The effects on sleep pattern ('short-sleep' versus 'long-sleep') and subjective sleep disturbance of genotype, personality, symptoms of anxiety and depression, and lifestyle, were examined using survey data on a clinically unselected sample of adult Australian twin pairs, aged 17-88 years. When the effects of genotype, personality and symptoms were ignored, lifestyle variables appeared to account for roughly 4% of the variance in sleep disturbance, and 9% of the variance in sleep pattern. Significant genetic effects on sleep disturbance and sleep pattern were found, which were only partly explained by the effects of personality and symptoms of anxiety and depression. Much of the association between sleep disturbance and lifestyle appeared to be explained by separate effects of personality and symptoms of anxiety and depression on sleep and lifestyle ('genotype-risk-factor correlation'). There was little evidence for genetically determined differences in sensitivity to the lifestyle variables ('genotype x risk-factor interaction').     

Effect of HDL and LDL from pre and post menopausal women on prostacyclin synthesis

Earlier we found LDL and HDL to differentially affect the synthesis of PGI2 from PGH2 by pig aorta microsomes and that this depended on the gender of the lipoprotein donors. Here we report there are also differences in the effects of LDL and HDL from pre- and postmenopausal women. The influence of the lipoproteins from postmenopausal women on the PGI2 formation is similar to the action of lipoproteins from men. We suggest that endogenous PGI2 formation is regulated by the sex related composition of the lipoproteins.     

Prospective trial of oestrogen and calcium in postmenopausal women.

In a prospective trial in 72 postmenopausal women to compare the effects on bone loss of no treatment, treatment with oestrogen, and treatment with calcium the women were followed up for at least two years and examined densitometrically and morphometrically. Women in the untreated control group continued to lose bone during the two years, whereas the oestrogen-treated group lost none. Loss in the calcium-treated group was intermediate. Oestrogen appeared to inhibit endosteal bone resorption and may have stimulated subperiosteal bone apposition.     

Association of polyaminergic loci with anxiety, mood disorders, and attempted suicide

Background

The polyamine system has been implicated in a number of psychiatric conditions, which display both alterations in polyamine levels and altered expression of genes related to polyamine metabolism. Studies have identified associations between genetic variants in spermidine/spermine N1-acetyltransferase (SAT1) and both anxiety and suicide, and several polymorphisms appear to play important roles in determining gene expression.

Methodology/Principal Findings

We genotyped 63 polymorphisms, spread across four polyaminergic genes (SAT1, spermine synthase (SMS), spermine oxidase (SMOX), and ornithine aminotransferase like-1 (OATL1)), in 1255 French-Canadian individuals who have been followed longitudinally for 22 years. We assessed univariate associations with anxiety, mood disorders, and attempted suicide, as assessed during early adulthood. We also investigated the involvement of gene-environment interactions in terms of childhood abuse, and assessed internalizing and externalizing symptoms as endophenotypes mediating these interactions. Overall, each gene was associated with at least one main outcome: anxiety (SAT1, SMS), mood disorders (SAT1, SMOX), and suicide attempts (SAT1, OATL1). Several SAT1 polymorphisms displayed disease-specific risk alleles, and polymorphisms in this gene were involved in gene-gene interactions with SMS to confer risk for anxiety disorders, as well as gene-environment interactions between childhood physical abuse and mood disorders. Externalizing behaviors demonstrated significant mediation with regards to the association between OATL1 and attempted suicide, however there was no evidence that externalizing or internalizing behaviors were appropriate endophenotypes to explain the associations with mood or anxiety disorders. Finally, childhood sexual abuse did not demonstrate mediating influences on any of our outcomes.

Conclusions/Significance

These results demonstrate that genetic variants in polyaminergic genes are associated with psychiatric conditions, each of which involves a set of separate and distinct risk alleles. As several of these polymorphisms are associated with gene expression, these findings may provide mechanisms to explain the alterations in polyamine metabolism which have been observed in psychiatric disorders.     

Signs of mood and anxiety disorders in chimpanzees

Background

In humans, traumatic experiences are sometimes followed by psychiatric disorders. In chimpanzees, studies have demonstrated an association between traumatic events and the emergence of behavioral disturbances resembling posttraumatic stress disorder (PTSD) and depression. We addressed the following central question: Do chimpanzees develop posttraumatic symptoms, in the form of abnormal behaviors, which cluster into syndromes similar to those described in human mood and anxiety disorders?

Methodology/Principal Findings

In phase 1 of this study, we accessed case reports of chimpanzees who had been reportedly subjected to traumatic events, such as maternal separation, social isolation, experimentation, or similar experiences. We applied and tested DSM-IV criteria for PTSD and major depression to published case reports of 20 chimpanzees identified through PrimateLit. Additionally, using the DSM-IV criteria and ethograms as guides, we developed behaviorally anchored alternative criteria that were applied to the case reports. A small number of chimpanzees in the case studies met DSM-IV criteria for PTSD and depression. Measures of inter-rater reliability, including Fleiss'' kappa and percentage agreement, were higher with use of the alternative criteria for PTSD and depression. In phase 2, the alternative criteria were applied to chimpanzees living in wild sites in Africa (n = 196) and chimpanzees living in sanctuaries with prior histories of experimentation, orphanage, illegal seizure, or violent human conflict (n = 168). In phase 2, 58% of chimpanzees living in sanctuaries met the set of alternative criteria for depression, compared with 3% of chimpanzees in the wild (p = 0.04), and 44% of chimpanzees in sanctuaries met the set of alternative criteria for PTSD, compared with 0.5% of chimpanzees in the wild (p = 0.04).

Conclusions/Significance

Chimpanzees display behavioral clusters similar to PTSD and depression in their key diagnostic criteria, underscoring the importance of ethical considerations regarding the use of chimpanzees in experimentation and other captive settings.     

Effects of sleep disruption on cognitive performance and mood in medical house officers.

Twelve medical house officers were tested on a battery of memory, concentration, and work related tasks after three conditions: a night spent off duty; a night spent on call; and a night spent admitting emergency cases. Short term recall, but not digit span, concentration, or work related abilities, was impaired after a night of emergency admissions. A night spent on call had no effect on cognitive performance. Self reported mood scores showed that house officers were more deactivated (indicating a lack of vigour and drive) after nights of emergency admissions but not after nights on call. Significant between subject differences were found for five of the eight cognitive tests. Though loss of sleep and long hours of work have an effect on memory and mood, the individual differences among doctors are the main source of the variance in performance of tasks.     

Dose dependent response of symptoms,pituitary, and bone to transdermal oestrogen in postmenopausal women.

The effect of the plasma oestradiol concentration on climacteric symptoms, gonadotrophin release, and bone resorption was studied in three groups of postmenopausal women given 0.025 mg, 0.05 mg, or 0.1 mg transdermal oestradiol daily. There was a dose related reduction in symptoms, plasma follicle stimulating hormone concentration, and urinary calcium and hydroxyproline excretion. The relation of the response to plasma oestradiol values was similar for each variable with an initial large reduction and little change in response to increases in the plasma oestradiol concentration above 150 pmol/l (41 pg/ml). Hormone replacement therapy producing an effect equivalent to higher oestradiol concentrations is likely to increase the risk of side effects without conferring any additional benefit.     

Local oestrogen therapy modulates extracellular matrix and immune response in the vaginal tissue of post‐menopausal women with severe pelvic organ prolapse

This study investigates the effect of local oestrogen therapy (LET) on the expression of proteins participating in collagen/elastin biogenesis and immune markers in vaginal tissues of post‐menopausal women with severe pelvic organ prolapse (POP). Vaginal biopsies were collected from the anterior vaginal wall of informed and consented 52 post‐menopausal women with severe POP undergoing total hysterectomy. Twenty‐nine of the 52 women were treated with LET (in the form of vaginal oestrogen cream or tablet), while the remaining 23 untreated patients served as the controls. This study was approved by Sinai Health System REB. Vaginal tissue specimens were analysed for gene and protein expression using real‐time RT‐PCR and Luminex assays, protein localization and immune cell infiltration were assessed by immunohistochemistry. Forty‐four cytokines were detected. We found that LET application: (a) significantly increased (P < 0.05) gene and protein expression levels of extracellular matrix (ECM) structural proteins, collagen and elastin, as well as the expression of ECM maturation enzyme BMP1; (b) decreased protein expression level of ECM degradation enzymes MMP1, MMP2 and MMP3 accompanied by an increase in their tissue inhibitors, TIMP1 and TIMP4; (c) significantly increased (P < 0.05) the gene and protein expression levels of 14 vaginal cytokines involved in leucocyte infiltration, which was confirmed by immunohistochemistry. Our results indicate that LET plays an important role in the activation of immune system within the local vaginal environment, limiting the undesirable ECM degradation, which supports the strengthening of vaginal ECM in post‐menopausal women, therefore resisting menopause/age‐related changes and inducing urogenital tract tissue regeneration.     

Relation between plasma hormone profiles,symptoms, and response to oestrogen treatment in women approaching the menopause.

Out of a consecutive series of 300 patients seen at a menopause clinic, 82 complained of symptoms generally associated with the climacteric, although they were still menstruating. Vasomotor disturbances were absent in 42 of these patients (group 1) and present in 40 (group 2). Headaches, insomnia, and dyspareunia were the most common complaints among the women with vasomotor symptoms, whereas loss of libido and depression predominated in those without. Conjugated equine oestrogens (Premarin) 1.25 mg daily given for three weeks out of four relieved nearly all symptoms in group 2, but in group 1 the response was disappointing. The mean plasma oestradiol concentration in women with vasomotor symptoms was significantly lower than that observed during days 1-10 of the menstrual cycle, but plasma testosterone values were not significantly different from those observed in younger women. Plasma follicle-stimulating hormone (FSH) and luteinising hormone (LH) concentrations were similar to those seen after the menopause. Concentrations of these hormones in the women without vasomotor symptoms were similar to those in the younger, regularly menstruating women. After six months of oestrogen treatment patients in group 2 had a 2.1-fold increase in mean plasma oestradiol concentration, and plasma FSH and LH concentrations were reduced to 39% and 66% of their pretreatment values respectively; in group 1, however, no such pronounced changes occurred. High concentrations of FSH were present in patients with oestrogen-responsive symptoms, 15 U/1 being the diagnostic cut-off point. This measurement in the presence of characteristic symptoms therefore constitutes the best method of selecting patients for oestrogen-replacement therapy.     

A psychometric investigation of the sleep,circadian rhythms,and mood (SCRAM) questionnaire

The sleep, circadian rhythms, and mood (SCRAM) questionnaire (Byrne, Bullock et al., 2017) was designed to concurrently measure individual differences in three clinically important functions: diurnal preference, sleep quality, and mood. The 15-item questionnaire consists of three 5-item scales named Morningness, Good Sleep, and Depressed Mood. The overarching aim of the current project was to investigate the validity and reliability of the questionnaire. Here, we report on associations investigated in three data sets. Study 1 (N = 70, 80% females) was used to examine the test–retest reliability of the questionnaire, finding strong test–retest reliability of the three scales over a 2-week period (r’s ranging from 0.73 to 0.86). Study 2 (N = 183, 80% females) enabled us to examine the construct validity of the SCRAM scales against well-validated self-report measures of diurnal preference, sleep quality, and depression. Strong correlations were found between each SCRAM scale and their respective measure in bivariate analyses, and associations were robust after the inclusion of the remaining two SCRAM scales as predictors in regression analyses. Data from Study 3 (N = 42, 100% males) were used to measure the extent to which SCRAM scores correlated with objective measures of sleep–wake behavior using actigraphy. Morningness was found to be related to earlier sleep onset and offset times, and Good Sleep was related to higher sleep efficiency but to no other measures of sleep quality; Depressed Mood was not related to actigraphy measures. The findings provide provisional support for construct validity and reliability of the SCRAM questionnaire as a measure of diurnal preference, sleep quality, and depressed mood. Future research into the psychometrics of SCRAM should test the questionnaire’s discriminant and predictive validity in clinical samples.