The impact of matching for reproductive status on the comparison of magnetic spectroscopic measurements of glutamate and gamma-aminobutyric acid + in the medial prefrontal cortex of women with major depression.

OBJECTIVES: The role played by medial prefrontal cortex (MPFC) glutamate (Glu) and gamma-aminobutyric acid (GABA) in the pathophysiology and the treatment of major depression (MD) is increasingly recognized. Although measurements of MPFC GABA and Glu have been shown to be sensitive to physiological fluctuations of female hormones, none of the magnetic resonance spectroscopy (MRS) investigations of MPFC Glu and GABA in MD have controlled for possible bias effect of the reproductive stage of the women included. METHODS: MPFC Glu and GABA+ (which include homocarnosine and macromolecules) referenced to creatine and phosphocreatine, were measured via magnetic resonance spectroscopy (MRS) using a 3-Tesla magnet in 24 women with MD and 24 healthy women paired for reproductive status. All participants were unmedicated. RESULTS: There were no statistical differences in either MPFC Glu [95 % CI: (-0.025, 0.034)] or MPFC GABA+ [95 % CI: (-0.005, 0.017)] between women with MD and healthy controls. CONCLUSIONS: Our investigation does not support abnormalities in measurement of MPFC Glu and GABA in MD women when stringent control for reproductive status is performed. As a result of the inherent limitations of MRS methodology, our results do not preclude glutamatergic and GABAergic dysregulations in the MPFC of women with MD.

Decreased GABA+ Levels in the Medial Prefrontal Cortex of Perimenopausal Women: A 3T 1H-MRS Study.

OBJECTIVE: Perimenopause is associated with an increased risk of developing a major depressive (MD) episode. A significant number of women develop their first MD episode during perimenopause, suggesting a unique pathophysiology of perimenopausal (PM) depression. Previous research has shown that depression is associated with decreased gamma-aminobutyric acid (GABA) levels in the medial prefrontal cortex (MPFC) of MD patients. The objective of this study was to compare MPFC GABA+ levels in healthy reproductive-aged (RD) and PM women. METHODS: A total of 18 healthy PM and 20 RD women were included in the study. MPFC GABA+ levels, which include homocarnosine and macromolecules, were measured via magnetic resonance spectroscopy using a 3 Tesla magnet. MPFC GABA+ levels were referenced to creatine + phosphocreatine (Cr+PCr). Absence of current or past psychiatric diagnosis was confirmed via a structured interview. RD participants were scanned during the early follicular phase of the menstrual cycle. PM women were scanned outside of ovulatory cycles. RESULTS: Mean MPFC GABA+ concentrations (relative to Cr+PCr) were decreased in the PM group compared with the RD group (PM mean = 0.08 ± 0.02, RD mean = 0.09 ± 0.02, t = -2.03, df = 36, P = .05) even after correcting for in percentage in gray matter (GM). Because PM women were inherently older than RD women (aged 48.8 ± 3.55 and 31.5 ± 9.66 years, respectively), the age difference between the 2 groups was statistically significant (P < .001). When age was treated as an independent covariate and included in the model, the difference in GABA+ between PM and RD women was no longer significant (P = .092). CONCLUSION: Perimenopause is associated with decreased MPFC GABA+/Cr+PCr levels, which may contribute to the increased risk of experiencing a MD episode during PM.

A comparative magnetic resonance spectroscopy study of GABA+ and glutamate referenced to creatine and phosphocreatine in the left dorsolateral prefrontal cortex of perimenopausal women and women of reproductive age.

Objective: The perimenopause is associated with an increased risk of developing a major depressive (MD) episode. The biological changes occurring during perimenopause responsible for this increased risk of depression remain to be elucidated. Postmortem and magnetic resonance spectroscopy (MRS) studies have revealed decreased gamma-aminobutyric acid (GABA) and glutamate (Glu) levels in the dorsolateral prefrontal cortex (DLPFC) of MD patients. The objective of this study was to compare LDLPFC GABA+ and Glu ratios (referenced to creatine and phosphocreatine) in healthy reproductive-aged (RD) and perimenopausal (PM) women. Materials and methods: Eighteen healthy PM and 20 RD women were included in the study. Our dependent variables, LDLPFC Glu and GABA+ ratios which include homocarnosine and macromolecules, were measured via MRS, using a 3 Tesla magnet. Absence of current or past psychiatric diagnosis was confirmed via a structured interview. RD participants were scanned during the early follicular phase of the menstrual cycle (MC). PM women were scanned outside of ovulatory cycles. Results: Mean LDLPFC GABA+ and Glu ratios were not statistically different between the PM group and RD group (PM mean = 0.10 ± 0.06, RD mean = 0.11 ± 0.04, t = -0.383, df = 36, d = -0.13, p = 0.70) (PM mean = 0.56 ± 0.06, RD mean = 0.57 ± 0.05, t = -0.794, df = 36, d = -0.26, p = 0.43), respectively. The perimenopause demarcates the end of the reproductive life. Unsurprisingly PM women were older than RD women (PM women: 48.8 ± 3.55 years, range 41-53 years old; RD women: 31.5 ± 9.66 years, range 18-47 years old) (p < 0.001). This inherent entanglement of group and age is a limitation of our study. Conclusion: Contrary to our previous findings of decreased GABA+ and Glu in the medial prefrontal cortex in perimenopausal women, the perimenopause is not associated with decreased GABA+ or Glu ratios in the LDLPFC. This suggests that brain areas playing a role in MD display different sensitivity to the female hormones fluctuations associated with perimenopause.

Decreased Medial Prefrontal Cortex Glutamate Levels in Perimenopausal Women.

Objective: There is an increased risk of experiencing depression during perimenopause (PM), a period of rapidly changing female hormone concentrations. Women at particular risk of developing major depression (MD) during PM are those with history of mood sensitivity to female hormone fluctuations i.e., women with a history of premenstrual dysphoric disorder (PMDD) and/or post-partum depression (PPD). Depressive symptomology has been associated with fluctuations of glutamate (Glu) levels in the medial prefrontal cortex (MPFC) in MD patients as well as PMDD and PPD patients. The objective of the study was to compare MPFC Glu levels in healthy perimenopausal and reproductive-aged (RD) women. Methods: Medial prefrontal cortex Glu levels in healthy perimenopausal (n = 15) and healthy RD women (n = 16) were compared via Magnetic Resonance Spectroscopy (MRS) scan using a 3 Tesla (T) magnet. Absence of depressive symptomology and psychiatric comorbidity was confirmed via semi-structured interview. Participants were scanned during the early follicular phase (FP) of the menstrual cycle (MC). Results: Mean MPFC Glu concentrations were decreased in the PM group compared to RD group (PM mean = 0.57 ± 0.03, RD mean = 0.63 ± 0.06, t = -3.84, df = 23.97, p = 0.001). Conclusion: Perimenopause is associated with decreases in MPFC Glu levels. This decrease may be contributing to the increased risk of experiencing depression during PM. Further research should assess MPFC Glu levels in perimenopausal women suffering from MD.

Walking together: women with the severe symptoms of menopause propose a platform for a walking program; outcome from focus groups.

BACKGROUND: Menopause and midlife are stages in a woman's life that can be marked by debilitating symptoms and increasing risks for cancer, cardiovascular, metabolic, and bone health issues. Walking represents a simple, low cost, and widely accessible activity with proven health benefits, though its therapeutic effect on alleviating menopause symptoms is not well characterized. Women are generally not opposed to exercise programs; however, increasing or maintaining exercise levels remains a challenge. We undertook a qualitative descriptive study to explore features of a walking program that would be conductive to menopausal women's participation, as well as to inform the development of such a program. METHODS: We conducted focus groups with women recruited from two menopause clinics and who suffered from moderate to severe menopause symptoms. The focus groups were audio recorded and transcribed. Women were prompted to talk about their menopause experience and exercise practice and how they would envision a walking exercise program that would keep them engaged. Qualitative content analysis was used to analyze the data and to identify characteristics of a walking exercise program. RESULTS: Twenty women participated in 5 focus groups. Women were very interested in trying walking as a means of staying healthy and possibly reducing menopause symptoms. Four major characteristics emerged as important for a walking program: (a) sensitivity to health realities of menopausal women, (b) inclusivity of various needs/levels of physical ability, (c) attentiveness to the need for mutual social support, (d) flexibility in planning of locations and scheduling. A restricted social network platform with features catering to women in menopause was suggested as suitable to initiate and sustain an adequate walking program. CONCLUSIONS: The findings of this study will be essential in designing a program that would be attractive for women to start and maintain a walking habit. The program would assist in elucidating whether walking is a useful and valuable alternative therapy for menopausal symptoms and, ultimately, might help women staying fit in midlife and postmenopausal.

Can walking exercise programs improve health for women in menopause transition and postmenopausal? Findings from a scoping review.

OBJECTIVE: Our goal was to explore the range and characteristics of published papers on therapeutic walking programs for menopausal women and to identify program features that resulted in successful outcomes including reduced symptoms and improved long-term wellness. METHODS: We searched biomedical and exercise-related databases for articles published up to June 1, 2017, using keywords related to menopause and walking. Data were collected into EndNote X8 reference manager to identify and remove duplicates. The final selection included all articles that studied walking as a health intervention for women in menopause transition or postmenopausal. RESULTS: A total of 3,244 papers were collected from the six databases. After removing duplicates and applying inclusion and exclusion criteria, 96 articles were charted, including 77 different walking programs. Walking interventions ranged from 4 weeks to 3 years with an average weekly frequency of 3.8 ±â€Š1.8 and were applied to a variety of symptoms and their biological markers and risk factors. Overall, 91% of the programs showed a beneficial outcome in at least one menopause-related medical issue. Information on menopause-specific symptoms, especially vasomotor symptoms and sleep problems, was scarce. CONCLUSION: The scoping review highlights the growing interest in walking programs as therapies for menopause and related symptoms and provides evidence of their possible benefit as a wellness option for women in menopause and beyond. Further research would be recommended to establish the therapeutic value of walking programs for women with specific focus on typical menopause symptoms at different stages of menopause. : Video Summary:http://links.lww.com/MENO/A587.

Video Summary:http://links.lww.com/MENO/A587.

Change over time in patient-reported symptoms and quality of life in Edmonton interdisciplinary menopause clinics: preliminary cohort study of clinic patients and waitlist patients.

OBJECTIVE: Specialized interdisciplinary menopause clinics in Edmonton provide care for women suffering from severe menopausal symptoms. Our objectives were to evaluate changes over time in patient-reported menopause symptoms and quality of life (QOL) in a cohort of clinic patients, compared to a cohort of women recruited from the clinic waitlists. METHODS: We conducted a prospective study of consecutive new patients in two clinics. Consenting women completed a generic menopause symptom severity questionnaire (MSSQ) and the menopause-specific quality of life (MENQOL) questionnaire at their first clinic and at a follow-up visit. Demographics, medical and obstetric histories, and medication use were extracted from patient charts. Women on the clinics' waitlists were enrolled as controls; corresponding data for baseline and follow-up were collected in mailed-in surveys. Descriptive and paired statistics were used for data analysis. Agreement plot was created to visualize the agreement between MSSQ and MENQOL scores. RESULTS: A total of 139 women were recruited: 98 attended the clinic and 41 were from the waitlist. Follow-up data were available for 99 women (71 clinic and 28 waitlist). There were no significant differences between clinic and waitlist patient characteristics. Women attending the clinics experienced significant reduction in symptom severity (mean MSSQ scores) and improvement in QOL (reduced MENQOL "bother" scores). Women on the clinic waitlist did not demonstrate significant changes over a similar timeframe. MENQOL correlated well with menopause symptom severity assessment. CONCLUSION: Women attending specialized menopause clinics experienced improvement in symptoms and QOL, whereas women on the waitlists did not experience these changes. : Video Summary: Supplemental Digital Content 1, http://links.lww.com/MENO/A418.

Perspectives and decision-making about menopausal therapies in women who had bilateral oophorectomy.

OBJECTIVE: The aim of the study was to explore the process of decision-making about menopausal treatments in women who have had surgical menopause as a result of bilateral oophorectomy (≤50 y). METHODS: We used a descriptive qualitative research design. Women who had a surgical menopause were purposefully selected from the Edmonton Menopause Clinics. Focus groups were held, each with six to nine participants. All sessions were audio-recorded and transcribed verbatim. Data were analyzed using qualitative content analysis. RESULTS: We conducted five focus groups from June 30 to July 21, 2016 (N = 37). One-third of the women had the surgery within the last 5 years. Almost all women had a concurrent hysterectomy (97%) and were current users of hormone therapy (70%). Four main themes identified were "perceptions of surgical menopause," "perceptions of received support," "being my own advocate," and "concept of adequate support." Women shared that the experience was worse than their expectations and did not believe they were given adequate support to prepare them to make therapy decisions. Women had to "be their own advocates" and seek support from within the healthcare system and outside to cope with their health issues. To make an informed decision about treatments postsurgery, women expressed a need to learn more about the symptoms of surgical menopause, treatment options, resources, avenues for support, and stories of similar experiences, preferably before the surgery. CONCLUSIONS: We identified several modifiable deterrents to decision-making in early surgical menopause which can help inform the development of a patient decision aid for this context.

Patient characteristics, menopause symptoms, and care provided at an interdisciplinary menopause clinic: retrospective chart review.

OBJECTIVE: The goal of this study was to describe the characteristics, menopause symptoms, and treatment progressions in women cared for at an interdisciplinary menopause clinic. METHODS: We conducted a retrospective review of patient charts from women attending a multidisciplinary menopause clinic. Data collected from the charts included patient demographics, menopause symptoms, other concurrent medical conditions, and treatment recommendations. Data were entered into Research Electronic Data Capture database and analyzed descriptively. Generic symptom severity questionnaires were used to compare severity scores from initial to follow-up visits. RESULTS: Among the 198 women (mean age 52.1 y [±SD 6.3], 63.6% postmenopausal), the most common moderate/severe menopause symptoms were as follows: difficulty staying asleep or waking frequently (76.3%), tiredness (73.7%), and lack of interest in sex (60.1%). Women tended to have complex chronic medical conditions, with 54.5% suffering from four or more concurrent medical conditions. The majority of women (70.2%) were recommended various forms of hormone therapy. Women with a follow-up visit at 3 to 4 months reported a reduction in symptom severity. CONCLUSIONS: Our study addresses a gap in published information on patient characteristics and treatment in menopause-specific interdisciplinary clinics. The chart review highlights the variety of symptom experience and complexity of care faced in a menopause clinic. Rigorous prospective studies including standardized data collection and follow-up are needed to help guide clinicians in managing complex menopause patients.

Assessment of the severity of hypoglycemia and glycemic lability in type 1 diabetic subjects undergoing islet transplantation.

Currently, the major indications for solitary islet transplantation are recurrent severe hypoglycemia and labile glucose control. Quantifying these problems remains subjective. We have developed a scoring system for both hypoglycemia and glycemic lability, established normative data, and used them in patients who have undergone islet transplantation. A composite hypoglycemic score (HYPO score) was devised based on the frequency, severity, and degree of unawareness of the hypoglycemia. In addition, using 4 weeks of glucose records, a lability index (LI) was calculated based on the change in glucose levels over time and compared with a clinical assessment of glycemic lability. A mean amplitude of glycemic excursions (MAGE) was also calculated based on 2 consecutive days of seven readings each day. These scores were determined in 100 randomly selected subjects with type 1 diabetes from our general clinic to serve as a control group and in patients before and after islet transplantation. The mean age of the control diabetic subjects was 38.4 +/- 1.3 years (+/-SE), with a duration of diabetes of 21.5 +/- 1.1 years. The median HYPO score in the control subjects was 143 (25th to 75th interquartile range: 46-423). The LI in the diabetic control subjects was 223 (25th to 75th interquartile range: 130-329 mmol/l(2)/h.week(-1)). The LI correlated much more closely than the MAGE with the clinical assessment of lability. A HYPO score of > or = 1,047 (90th percentile) or an LI > or = 433 mmol/l(2)/h.week(-1) (90th percentile) indicated serious problems with hypoglycemia or glycemic lability, respectively. The islet transplant patients (n = 51) were 42.1 +/- 1.4 years old, with a duration of diabetes of 25.7 +/- 1.4 years. Islet transplant patients had a mean HYPO score of 1,234 +/- 184 pretransplant, which was significantly higher than that of the control subjects (P < 0.001), which became negligible posttransplantation with the elimination of hypoglycemia. The median LI pretransplant was 497 mmol/l(2)/h.week(-1) (25th to 75th interquartile range: 330-692), significantly higher than that of control subjects (P < 0.001), and fell to 40 (25th to 75th interquartile range: 14-83) within a month after the final transplant. In those who had lost graft function, the LI rose again. The HYPO score and LI provide measures of the extent of problems with hypoglycemia and glycemic lability, respectively, complement the clinical assessment of the problems with glucose control before islet transplantation, and will allow comparison of selection of subjects for transplants between centers.