Perimenopausal Research Articles

Body composition, physical activity, and menopause symptoms: how do they relate?

This study characterized the impact of physical activity (light, moderate, and vigorous [VIG] active minutes per day) and body composition (percent body fat [%BF] and fat-free mass index) on total menopausal symptoms (TMSs) in 72 premenopausal, perimenopausal (PERI), or postmenopausal women. Activity minutes were collected from wearable fitness trackers. Body composition was evaluated using a whole-body dual-energy x-ray absorptiometry scan. TMSs were quantified using The North American Menopause Society Questionnaire. Significant associations were observed between TMSs and %BF ( r = 0.464, P < 0.001) and VIG ( r = -0.245, P = 0.038). %BF and VIG were significant predictors for TMSs across groups ( R2 = 0.146 and R2 = 0.092, respectively), but only %BF maintained for PERI ( R2 = 0.421, P < 0.001). %BF predicted nearly half of the variance in PERI TMSs, whereas VIG predicted 9% of the sample variance, demonstrating an important influence of body fat accumulation and intense physical activity in the menopause transition. High-intensity exercise interventions to alleviate body composition changes may also reduce menopausal-related symptoms for PERI women.

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.

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

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. 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. 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). Perimenopause is associated with decreased MPFC GABA+/Cr+PCr levels, which may contribute to the increased risk of experiencing a MD episode during PM.

Differences in strength, leg lean mass,and lifestyle factors between premenopausal and perimenopausal women.

Menopausal changes coupled with age-related reductions in muscle strength can impact functionality. To evaluate the differences in muscle strength, dominant leg lean mass (DLMleg ), relative protein intake (r_PRO)and physical activity (PA) between premenopausal (PRE) and perimenopausal (PERI) women. Twenty-fourPRE- (age = 39.8 ± 3.3 years; BMI: 25.3 ± 5.0 kg/m2 ) and 24 PERI-women (age = 50.0 ± 3.3 years; BMI: 26.5 ± 5.4 kg/m2 ) participated in leg extensor isometric peak force (PF), DLMleg , r_PROand PA. Independent samples t-tests and one-way analyses of covariance covaried for age and DLMleg were used to compare groups. The PRE group had significantly higher PF (mean difference ± standard error: 57.8 ± 28.0 N; p = 0.045) and DLMleg (0.7 ± 0.3 kg; p = 0.031) when compared to the PERI group. There were no significant differences in r_PRO, or PA between groups (p = 0.173-0.423). When covaried for age and DLMleg , there was no significant difference in PF (p = 0.982 and 0.405, respectively). Age and DLMleg may be important contributors to menopause-phase related differences in strength.

ET‐1 Receptor Function in Women of Different Reproductive Age but Similar Chronological Age

Endothelial dysfunction is a primary driver of hypertension and cardiovascular disease. Our lab has previously shown that endothelin-1 (ET-1), which contributes to endothelial dysfunction, is regulated by changes in ovarian hormones in premenopausal women (PRE). Additionally, while the ETB receptor mediates vasodilation in PRE, this effect is lost in postmenopausal women. However, the influence of reproductive aging, independent of chronological aging, on the function of the ETB receptor is unclear. Purpose The purpose of this study was to test the hypothesis that ETB-mediated vasodilation is progressively reduced with advancing reproductive age in women who are of similar chronological age. Methods We used the STRAW+10 staging criteria to classify women as PRE (n=4, 47±1 yrs, 26±1 kg/m2, 81±4 mmHg), early perimenopausal (PERI) (n=6, 49±1 yrs, 25±1 kg/m2, 79±3 mmHg), or late PERI (n=9, 49±1 yrs, 23±1 kg/m2, 81±3 mmHg). Cutaneous vasodilatory responses to local heating were measured using laser doppler flowmetry during microdialysis perfusions of lactated Ringer's (Control), ETB receptor blockade (BQ-788, 300nM), and ETA receptor blockade (BQ-123, 500nM). Cutaneous vascular conductance (CVC) was calculated during the plateau phase of local heating (42°C), and normalized to maximal vasodilation achieved by perfusion of sodium nitroprusside (28mM) and heating to 43°C. One-way ANOVAs were used to compare vasodilatory responses between groups with Tukey post-hoc tests. Data are presented as mean±SEM. Results By design, women were of similar chronological age (P=0.25) but at different reproductive stages. PRE showed the greatest cutaneous vasodilation in response to local heating (PRE: 93±4; early PERI: 80±2; late PERI: 90±3 %CVC max, P<0.05 vs early PERI). However, there were no differences in vasodilatory responses during ETB receptor blockade (PRE: 85±11; early PERI: 87±4; late PERI: 94±1 %CVC max, P=0.38) or ETA receptor blockade (PRE: 81±2; early PERI: 90±1; late PERI: 88±5 %CVC max, P=0.27) between groups. Conclusions These preliminary data suggest that microvascular endothelial function is reduced in early PERI, independent of chronological aging. Additionally, these preliminary comparisons suggest ETB-mediated vasodilation may not differ between PRE, early PERI, and late PERI. Still, future studies should repeat these measurements and correlate findings with concurrent measurements of ovarian hormones.

Comparison of performance and health indicators between perimenopausal and postmenopausal obese women: the effect of high-intensity interval training (HIIT).

This study examined the effects of 6 weeks of high-intensity interval training (HIIT) on performance and health indicators in obese perimenopausal (PERIM) women and similarly aged and older postmenopausal women (POSTM1 and POSTM2, respectively). Sixteen PERIM women (average age 49.6 y), 21 POSTM1 women (average age 50.6 y), and 19 POSTM2 women (average age 69.6 y) completed a 6-week HIIT intervention. Anthropometric parameters, mechanical efficiency (ME in %), lipid oxidation (LO in %), and low and high spectral frequencies (LF[ms2] and HF[ms2]) were computed pre- and postintervention. PERIM women showed a significantly higher VO2max preintervention compared to POSTM1 and 2 (P < 0.01). Moreover, HF, LF, and the LF/HF ratio differed significantly in PERIM women preintervention compared to POSTM1 and 2 (P < 0.01, respectively). After 6 weeks, a significant decrease in anthropometric variables was observed for all groups (P < 0.01). The VO2max in mL/kg/min increased for all groups (P < 0.01). Multiple linear regression analysis demonstrated that age contributed significantly to differences in VO2max values between groups preintervention (r = 0.72). This model accounted for 34% (r2 = 0.34) of the variation. On the other hand, menopause status was an independent predictor of LO, accounting for 38% of the variation, as well as of HF (33%), LF (29%), and the LF/HF ratio (24%). After HIIT, no age or menopause effect was detected for these independent variables. Maximal oxygen consumption, HF, LF, and the LF/HF ratio differ among women according to the menopausal status and age. A 6-week HIIT intervention improved many health and performance parameters and reduced the effects of menopause and age.

Australian women’s understanding of menopause and its consequences: a qualitative study

Background This study was undertaken to determine women’s knowledge of menopause and its consequences, and their menopause-related health-care experiences. Methods Participants were recruited to this cross-sectional qualitative study from a nationally, representative sample of Australian women. Recruitment was stratified by age to achieve groups of premenopausal (PRE), perimenopausal (PERI), early postmenopausal (E-POST), and late postmenopausal (L-POST) women. Results The 32 participants were aged 46–69 years: 10 PRE, three PERI, 11 E-POST and eight L-POST women. All understood that menopause meant the end of reproductive function and were aware of menopause-associated symptoms. Most PRE and E-POST women referred to lifestyle changes to optimize health, and self-help and complementary therapies to manage symptoms. E-POST and L-POST women were more likely to nominate seeing a doctor for overall health and symptom management. Menopausal hormone therapy (MHT) was viewed negatively, with shared perceptions of cancer risk and over-prescription. A strong theme was lack of knowledge of long-term menopause sequelae, with only four women nominating osteoporosis. Conclusions Our in-depth qualitative study would suggest that, while Australian midlife women have a good understanding of the immediate effects of menopause, their lack of knowledge of the long-term consequences is concerning. Despite the effectiveness and safety of MHT, the overall attitude to MHT remains negative.

Gastric responses to acute psychological stress in climacteric women: a pilot study.

Women exhibit reduced ovarian sex hormones during the menopausal period that result in well-known physical and psychological symptoms. However, symptoms related to gastric motility (GM) have not been thoroughly investigated. We hypothesized that stress response gastric motility (SRGM) is lower in postmenopausal (PM) and perimenopausal (PERIM) women than in premenopausal (PREM) women. Estrogenic decline leads to neuroendocrine changes in different areas of the brain. These changes can result in hypothalamic vasomotor symptoms, disorders in eating behaviours, and altered blood pressure, in addition to psychological disorders such as stress, anxiety, depression, and irritability related to alterations in the limbic system. In this pilot study, 55 PREM, PERIM, and PM women were clinically evaluated using the Nowack stress profile (SP) and State-Trait Anxiety Inventory (STAI). GM was assessed via electrical bioimpedance using two psychological stress tests (Stroop and Raven tests). Basal SP and STAI-anxiety test scores were similar among the three groups of women (P > 0.05). PERIM women had lower GM in the basal state (P < 0.05) than did other women. PREM and PM women had significantly decreased GM during the stress tests (P < 0.05). However, PERIM did not exhibit GM changes during stress tests (P > 0.05). Changes in sex hormones during PERIM may affect GM and SRGM.

Unveiling hidden knowledge: discovering the hygiene needs of perimenopausal women

The provision of adequate water, sanitation and hygiene (WASH) services to ensure good health and wellbeing for all is incorporated into the Sustainable Development Goals, with the aim to ‘leave no-one behind’. The WASH needs of perimenopausal (PM) women are largely absent from academic literature. These personal needs are hidden knowledge. However, this article demonstrates the use of participative methodologies to ‘unveil’ these. A UK-based phenomenological review set the research agenda using PM women’s narratives; this was later developed in urban Ghana using oral history interviews, participatory mapping and PhotoVoice. Allowing for some adaption of these tools to account for local taboos in the global South, issues were revealed that are invisible to many but still warrant attention. Moving beyond theoretical discourse, practical approaches identified infrastructural issues and ensured the inclusion of PM experience. Unveiling hidden knowledge in this way has wider implications for other issues in development agendas.

Increased Alzheimer's risk during the menopause transition: A 3-year longitudinal brain imaging study.

Two thirds of all persons with late-onset Alzheimer’s disease (AD) are women. Identification of sex-based molecular mechanisms underpinning the female-based prevalence of AD would advance development of therapeutic targets during the prodromal AD phase when prevention or delay in progression is most likely to be effective. This 3-year brain imaging study examines the impact of the menopausal transition on Alzheimer’s disease (AD) biomarker changes [brain β-amyloid load via 11C-PiB PET, and neurodegeneration via 18F-FDG PET and structural MRI] and cognitive performance in midlife. Fifty-nine 40–60 year-old cognitively normal participants with clinical, neuropsychological, and brain imaging exams at least 2 years apart were examined. These included 41 women [15 premenopausal controls (PRE), 14 perimenopausal (PERI), and 12 postmenopausal women (MENO)] and 18 men. We used targeted minimum loss-based estimation to evaluate AD biomarker and cognitive changes. Older age was associated with baseline Aβ and neurodegeneration markers, but not with rates of change in these biomarkers. APOE4 status influenced change in Aβ load, but not neurodegenerative changes. Longitudinally, MENO and PERI groups showed declines in estrogen-dependent memory tests as compared to men (p < .04). Adjusting for age, APOE4 status, and vascular risk confounds, the MENO and PERI groups exhibited higher rates of CMRglc decline as compared to males (p ≤ .015). The MENO group exhibited the highest rate of hippocampal volume loss (p’s ≤ .001), and higher rates of Aβ deposition than males (p < .01). CMRglc decline exceeded Aβ and atrophy changes in all female groups vs. men. These findings indicate emergence and progression of a female-specific hypometabolic AD-endophenotype during the menopausal transition. These findings suggest that the optimal window of opportunity for therapeutic intervention to prevent or delay progression of AD endophenotype in women is early in the endocrine aging process.

Moderate-intensity exercise reduces activated and apoptotic endothelial microparticles in healthy midlife women.

Endothelial microparticles (EMPs) are related to cardiovascular disease (CVD) risk. Risk factors for CVD increase with menopause, and greater cardiorespiratory fitness is generally expected to reduce CVD risk. The effects of habitual physical activity on endothelial health may be due in part to the effect of acute exercise on circulating EMPs. This study was performed to evaluate the effect of an acute bout of exercise on CD62E+ and CD31+/42b- EMPs in healthy fit midlife women at different menopausal stages. Healthy, active premenopausal (PRE), perimenopausal (PERI), and postmenopausal (POST) women completed a single bout of moderate-intensity treadmill exercise. Activated (CD62E+) and apoptotic (CD31+/42b-) EMPs were evaluated before and 30 min after exercise by using fluorescent activated cell sorting. In an exploratory analysis, these results were compared with data from low-fit peri- and postmenopausal women. Differences by group and time point were evaluated with repeated-measure ANOVAs. There was a reduction in the number of total microparticles ( P < 0.001), CD62E+ ( P = 0.003), and CD31+/42b- ( P < 0.001) EMPs/μl plasma following acute exercise. The percentage of CD62E+ EMPs increased with acute exercise ( P < 0.001), whereas the percentage of CD31+/42b- EMPs did not change ( P = 0.40). There was no effect of menopausal status on CD62E+or CD31+/42b- EMPs, or on total microparticles (all P > 0.05). The exploratory analysis revealed that low-fit women had similar changes in EMPs with acute exercise. We concluded that acute moderate-intensity exercise reduces CD62E+and CD31+/42b- EMPs, as well as total microparticles, in healthy midlife women. These effects occurred despite differences in menopausal status and fitness. NEW & NOTEWORTHY This study demonstrates that acute moderate-intensity exercise reduces activated and apoptotic endothelial microparticles in healthy midlife women.

Comparative study between Manual Liquid Based Cervical Cytology and Conventional Smear in Peri Menopausal and Post Menopausal Women

Comparative study between Manual Liquid Based Cervical Cytology and Conventional Smear in Peri Menopausal and Post Menopausal Women

Clinico-Pathological Correlation of Hysterectomy Specimens for Abnormal Uterine Bleeding in Peri Menopausal Women

Clinico-Pathological Correlation of Hysterectomy Specimens for Abnormal Uterine Bleeding in Peri Menopausal Women

Endothelial and inflammatory responses to acute exercise in perimenopausal and late postmenopausal women.

Endothelial dysfunction and inflammation are characteristics of subclinical atherosclerosis and may increase through progressive menopausal stages. Evaluating endothelial responses to acute exercise can reveal underlying dysfunction not apparent in resting conditions. The purpose of this study was to investigate markers of endothelial function and inflammation before and after acute exercise in healthy low-active perimenopausal (PERI) and late postmenopausal (POST) women. Flow-mediated dilation (FMD), CD31+/CD42b- and CD62E+ endothelial microparticles (EMPs), and the circulating inflammatory factors monocyte chemoattractant protein 1 (MCP-1), interleukin 8 (IL-8), and tumor necrosis factor-α (TNF-α) were measured before and 30 min after acute exercise. Before exercise, FMD was not different between groups (PERI: 6.4 ± 0.9% vs. POST: 6.5 ± 0.8%, P = 0.97); however, after acute exercise PERI tended to improve FMD (8.5 ± 0.9%, P = 0.09), whereas POST did not (6.2 ± 0.8%, P = 0.77). Independent of exercise, we observed transient endothelial dysfunction in POST with repeated FMD measures. There was a group × exercise interaction for CD31+/CD42b- EMPs (P = 0.04), where CD31+/CD42b- EMPs were similar before exercise (PERI: 57.0 ± 6.7 EMPs/μl vs. POST: 58.5 ± 5.3 EMPs/μl, P = 0.86) but were higher in POST following exercise (PERI: 48.2 ± 6.7 EMPs/μl vs. POST: 69.4 ± 5.3 EMPs/μl, P = 0.023). CD62E+ EMPs were lower in PERI compared with POST before exercise (P < 0.001) and increased in PERI (P = 0.04) but did not change in POST (P = 0.68) in response to acute exercise. After acute exercise, MCP-1 (P = 0.055), TNF-α (P = 0.02), and IL-8 (P < 0.001) were lower in PERI but only IL-8 decreased in POST (P < 0.001). Overall, these data suggest that perimenopausal and late postmenopausal women display different endothelial and inflammatory responses to acute exercise.

Cervical cytology in patients with postmenopausal bleeding

In this study, the role of cervical cytology in the diagnosis of post or perimenopausal (PM) bleeding was explored. A total of 135 patients with PM bleeding were selected. In all these cases both conventional cervical cytology and histopathology follow up were available. The commonest causes of postmenopausal (PM) bleeding with abnormal histopathology were squamous cell carcinoma of cervix (14), endocervical polyp (13), endometrial adenocarcinomas (13) and simple hyperplasia without atypia (13). There were a total 13 cases of endometrial adenocarcinoma and cervical smears of these cases were reported as high grade squamous intra epithelial lesion (1), presence of endometrial cells (4), unsatisfactory due to low cellularity (2), and within normal limit (6). In brief, endometrial carcinoma and hyperplasia are the predominant causes of PM bleeding due to endometrial pathology. The presence of benign looking endometrial cells with PM bleeding always indicates a careful work upto exclude endometrial pathology.

The Enhancement of Female Sexual Function with ArginMax, a Nutritional Supplement, Among Women Differing in Menopausal Status

We conducted a double-blind, placebo-controlled study to determine the role of dietary supplementation on sexual function in women of differing menopausal status. One hundred eight (108) women, age 22–73 years, who reported a lack of sexual desire, enrolled as participants. Of these, 55 received ArginMax for women and 53 received placebo. ArginMax for women contains L-arginine, ginseng, ginkgo, damiana, multivitamins, and minerals. The 108 women, given definitions, self-reported as 59 premenopausal (PRE); 20 perimenopausal (PERI), and 29 postmenopausal (POST). After 4 weeks, PRE women on ArginMax primarily reported significant improvement in level of sexual desire (72%; p = 0.03) and satisfaction with overall sex life (68%; p = 0.007), compared with placebo group, according to the Female Sexual Function Index (FSFI; Kaplan et al., 1999) scales. Frequency of sexual desire (60%; p = 0.05) and frequency of intercourse (56% p = 0.01) also increased among the PRE women. In contrast, among PERI women, primary improvements were reported for frequency of intercourse (86%; p = 0.002), satisfaction with sexual relationship (79%; p = 0.03), and vaginal dryness (64%; p = 0.03) compared with placebo group. POST women primarily showed an increased in level of sexual desire, with 51% showing improvement, compared with only 8% in the placebo group (p = 0.008). Nutritional intervention plays an important role in women's sexual health, but issues and areas of greatest improvement differ among women of different menopausal states. The largest number of attribute improvements were seen in PRE and PERI women, although attribute types vary among these groups. Level of desire was shown to increase significantly in POST women. Since ArginMax for women has been shown to exhibit no estrogen activity, it may be desirable alternative to hormone therapy for sexual concerns.