John Taffe

Hormones, mood, sexuality, and the menopausal transition

OBJECTIVE To determine the extent of changes in womens sexual functioning and well-being during the menopausal transition and the relationship to hormonal changes. DESIGN Prospective observational study. SETTING Population-based sample assessed at home. PATIENT(S) 438 Australian-born women 45-55 of years who were still menstruating at baseline. Of these, 226 were studied for effects of hormones on sexual functioning. MAIN OUTCOME MEASURE(S) Short Personal Experiences Questionnaire (SPEQ) and Affectometer 2 scores and annual blood sampling. RESULT(S) From the early to late menopausal transition, the percentage of women with SPEQ scores indicating sexual dysfunction increased from 42% to 88%. Mood scores did not change significantly. In the early menopausal transition, women with low total SPEQ scores had lower estradiol level but similar androgen levels to those with higher scores. Decreasing SPEQ scores correlated with decreasing estradiol level but not with androgen levels. Hormone levels were not related to mood scores. CONCLUSION(S) Female sexual functioning declines with the natural menopausal transition. This decline relates more to decreasing estradiol levels than to androgen levels.

Estrogen - a potential treatment for schizophrenia.

Estrogen has been shown in animal studies to modulate both the dopamine and serotonin neurotransmitter systems - the main neurotransmitters implicated in the pathogenesis of schizophrenia. A double blind, 28 day, placebo-controlled study was conducted with three groups of women of child-bearing age (N=12 in each group) who received standardized antipsychotic medication plus 50mcg transdermal estradiol or 100mcg transdermal estradiol or transdermal placebo. Analyses show that women receiving 100mcg of estradiol made greater improvements in the symptoms of schizophrenia than both the 50mcg estradiol and placebo groups. Women receiving 50mcg estradiol had more improvement in their symptoms compared with the placebo group. The 100mcg estradiol group had significantly lower mean lutenizing hormone (LH) and higher mean prolactin levels across the study period compared with both the 50mcg and placebo groups. The addition of 100mcg adjunctive transdermal estrogen significantly enhanced the treatment of acute, severe psychotic symptoms in women with schizophrenia. The differential response of adding 50mcg versus 100mcg estradiol on the types of symptom affected may be related to the estrogen effect on LH and prolactin. The positive impact of estrogen treatment on psychotic symptoms by a direct effect on dopamine and serotonin systems or via an indirect prolactin-mediated effect may be very useful in the overall treatment of women with schizophrenia.

The menopausal transition: a 9-year prospective population-based study. The Melbourne Women's Midlife Health Project

Objectives To describe the natural history of the menopause in Australian-born women. To determine the hormonal changes relating to the menopausal transition (MT) and how these affect quality of life, bone mineral density, body composition, cardiovascular disease (CVD) risk and memory. Design A 9-year prospective, observational study of a population-based sample of 438 Australian-born women aged 45–55 years at baseline. By the 9th year, the retention rate was 88%. Interviews, blood sampling, menstrual calendars, quality of life and physical measures were taken annually, and bone mineral density was measured bi-annually. Results The late MT coincides with changes in estradiol, follicle stimulating hormone, and free testosterone index, decreases in bone density and mastalgia, and increases in central adiposity, vasomotor symptoms, insomnia and vaginal dryness. Levels of total testosterone and dehydroepiandrosterone sulfate are unchanged by the MT. An increase in CVD risk was associated with increases in weight and free testosterone index and a decrease in estradiol. Depressed mood is increased by symptoms and by stressors occurring in the MT. Sexual functioning significantly deteriorates with the MT and aging, but relational factors have major effects. Menstrual cycles became more variable and longer closer to the final menstrual period. Conclusions As hormonal changes during the MT directly or indirectly adversely affect quality of life, body composition and CVD risk, maintenance of health parameters in the premenopausal years is crucial for a healthy postmenopause.

A clinical trial of the effects of estrogen in acutely psychotic women.

This study was a preliminary open clinical trial aimed at exploring the hypothesis that estrogen may provide protection against schizophrenia in women. Eleven women with acute psychotic symptoms, as scored on the BPRS, SAPS and SANS, had 0.02 mg estradiol added to neuroleptic treatment for eight weeks. Their response was compared to seven women with similar symptom severity receiving neuroleptic treatment alone. Both groups had baseline hormonal assays of estrogen, progesterone, LH and FSH and underwent regular psychopathology ratings during the eight weeks. The group receiving the estradiol adjunct showed more rapid improvement in psychotic symptoms compared with the group receiving neuroleptics only. This difference was not sustained for the entirety of the trial. Both groups reached similar levels of recovery by the eighth week. These results suggest that estradiol may have antipsychotic properties and/or act as a catalyst for neuroleptic responsiveness in women with schizophrenia.

Hot flushes during the menopause transition: a longitudinal study in Australian-born women.

Objective:To investigate factors associated with the presence, severity, and frequency of hot flushes. Design:A 9-year prospective study of 438 Australian-born women, aged 45 to 55 years and menstruating at baseline. Annual fasting blood collection, physical measurements, and interviews including questions about bothersome hot flushes in previous 2 weeks were performed. A “hot flush index” score was calculated from the product of the severity and frequency data. Data were analyzed using random-effects time-series regression models. Results:A total of 381 women supplied complete data over the follow-up years. A total of 350 women experienced the menopause transition, of whom 60 (17%) never reported bothersome hot flushes. At baseline, women who reported hot flushes were significantly more likely to have higher negative moods, not be in full- or part-time paid work, smoke, and not report exercising every day. Over the 9-year period of the study, variables significantly associated with reporting bothersome hot flushes were relatively young age (P < 0.001), low exercise levels (P < 0.05), low estradiol levels (P < 0.001), high follicle-stimulating hormone (FSH) levels (P < 0.001), smoking (P < 0.01), being in the late menopause transition (P < 0.001), or being postmenopausal (P < 0.001). In women reporting hot flushes, the hot flush index score increased as their FSH levels increased (P < 0.01), as they entered the late stage of the menopause transition (P < 0.001), and as they became postmenopausal (P < 0.05), and decreased with as their age (P < 0.001) and exercise level (P < 0.05) increased. Between-women analyses found that the hot flush index score was greater in women with higher average FSH levels over time (P < 0.05). Conclusion:Menopause status, FSH and estradiol levels, age, exercise level, and smoking status all contributed to the experience of bothersome hot flushes.

The Emotion Regulation Questionnaire for Children and Adolescents (ERQ-CA): A Psychometric Evaluation.

Despite the recognized importance of emotion regulation (ER) for healthy psychological development, ER research has focused predominantly on the developmental periods of infancy, early childhood, and adulthood, while the middle childhood to adolescence years have been relatively neglected. An obstacle to ER research during these periods is the paucity of valid age-appropriate measures. This study reports on the psychometric evaluation of the Emotion Regulation Questionnaire for Children and Adolescents (ERQ-CA), a revision of the adult measure. The ERQ-CA was evaluated with a sample of 827 participants aged between 10 and 18 years. Results indicate sound internal consistency as well as stability over a 12-month period. Sound construct and convergent validity are also demonstrated. It is concluded that the ERQ-CA is a valid age-appropriate measure for investigating the use of 2 specific strategies of ER during the childhood and adolescence developmental periods.

Mortality in prader-willi syndrome

Persons with Prader-Willi syndrome have been known to have a high mortality rate. However, intellectual disability, which usually accompanies Prader-Willi syndrome, is also associated with a higher mortality rate than in the general population. In this study, the death rates in a longitudinal cohort of people with Prader-Willi syndrome are compared with those for an epidemiologically derived control sample of people with intellectual disability from other causes. We found that those with Prader-Willi syndrome had a higher mortality rate than did controls. After the protective effect of mild intellectual disability or average intellectual function was accounted for, the hazard ratio for Prader-Willi syndrome versus controls was 6.07. Obesity and its complications were factors contributing to the mortality identified in this study.

Mirror Neuron Activity Associated with Social Impairments but not Age in Autism Spectrum Disorder

BACKGROUND The neurobiology of autism spectrum disorder (ASD) is not particularly well understood, and biomedical treatment approaches are therefore extremely limited. A prominent explanatory model suggests that social-relating symptoms may arise from dysfunction within the mirror neuron system, while a recent neuroimaging study suggests that these impairments in ASD might reduce with age. METHODS Participants with autism spectrum disorder (i.e., DSM-IV autistic disorder or Aspergers disorder) (n = 34) and matched control subjects (n = 36) completed a transcranial magnetic stimulation study in which corticospinal excitability was assessed during the observation of hand gestures. RESULTS Regression analyses revealed that the ASD group presented with significantly reduced corticospinal excitability during the observation of a transitive hand gesture (relative to observation of a static hand) (p < .05), which indicates reduced putative mirror neuron system activity within ventral premotor cortex/inferior frontal gyrus. Among the ASD group, there was also a negative association between putative mirror neuron activity and self-reported social-relating impairments, but there was no indication that mirror neuron impairments in ASD decrease with age. CONCLUSIONS These data provide general support for the mirror neuron hypothesis of autism; researchers now must clarify the precise functional significance of mirror neurons to truly understand their role in the neuropathophysiology of ASD and to determine whether they should be used as targets for the treatment of ASD.

Menstrual patterns leading to the final menstrual period.

ObjectiveTo characterize premenopausal menstrual regularity and the patterns of divergence from regularity associated with the approach of the final menstrual period. DesignTwo samples of individual cycle length sequences contributed by participants in a population-based longitudinal study of the menopausal transition were examined. The first sample, of “early” sequences, is used to characterize menstrual regularity. The second shows how cycle length patterns change as the final menstrual period (FMP) is approached. Regression slopes are used to measure trend in cycle length, and changes in cycle length variability are registered by a simply calculated measure, the “running range.” ResultsSequences in the early cycles sample rarely varied outside the 21–35 day range and did not show a rising or falling trend. In contrast, pre-FMP sequences generally became increasingly variable in length, while rising above 35 days in mean during the last 10 cycles. The variability measure remained below 40 days throughout the early sequences, but characteristically rose above 42 days during sequences including the last 20 pre-FMP cycles. In early sequences, but not in pre-FMP sequences, long and short cycles tended to alternate. ConclusionsIncreased variability is the dominant feature of cycle length pattern for most women as their final menstrual period approaches. Underlying this is a steady trend toward mean cycle lengths above 35 days. An indicator of the approach of menopause is a rise in running range of cycle lengths to 42 days.

Trajectory of Behavior and Emotional Problems in Autism

High rates of behavior and emotional problems have been consistently reported in children and adolescents with autism. Elevated rates of mental health problems have also been reported in adults with autism. Little is known, however, about the longitudinal development of behavior and emotional problems in autism. This study followed a cohort of children and adolescents over 18 years. Outcomes were evaluated in terms of behavior and emotional problems and autism symptomatology. The role of childhood factors (age, gender, IQ, behavior, and emotional problems) and the environment (socioeconomic disadvantage) were considered in terms of adult outcomes. Overall, improvements in comorbid behavior and emotional problems and autism symptomatology were observed. However, rates of comorbid behavior and emotional problems in adulthood remained high.