Knowledge equity for systems change – Systems Week 2021
Skoll Centre for Social Entrepreneurship
More Women Affected by Perimenopause and Menopause at Younger Ages
The Centre for Longitudinal Studies presented findings from more than 50,000 women participating in nine studies worldwide. The results showed women who have never given birth or been pregnant have twice the odds of reaching menopause before the age of 40. They’re also 30 percent more likely to begin menopause between ages 40 and 44. In 2011, the average age for a woman to begin perimenopause—the up to 10-year-long estrogen drop that marks a decline in fertility—was 45 years old. But last year, a study of women experiencing perimenopause symptoms showed that from a group of 6,806 women, 1,822 were under the age of 40. And when perimenopause starts at an earlier age, menopause comes right after. Dealing with hormone imbalance and difficult menstrual cycles has been a constant battle for Misty Kaiser since her early 20s. It came as no surprise when perimenopause and symptoms of early menopause also arrived ahead of schedule. “Even just having to deal with it is exhausting,” Mrs. Kaiser told The Epoch Times. Before perimenopause symptoms started in her mid-to-late 30s, she struggled with menstrual challenges like irregular and painful periods. She described her normal cycle cramps as “the kind where you want to just roll up and die.” But perimenopause threw another wrench into her daily life. She said brain fog became an issue that quickly got “worse and worse. You just can’t focus.” Mrs. Kaiser has also dealt with a roller coaster of weight gain during the transition into perimenopause, especially around the time of her menstrual cycle. Yet her weight gain and loss in the early perimenopause phase has turned into just “packing on weight” now that she’s skipping menstrual cycles and shifting toward menopause. Additionally, Mrs. Kaiser said she has intense mood swings and sleep disturbances since the onset of perimenopause. She said she can usually fall asleep, but can’t stay asleep. “I’ll be awake in the middle of the night, sometimes for hours.” Overall, it’s taken a toll on her mental and physical health. Part of that is because she tries hard to keep her “hormonal hell” from affecting her family. “You get so caught up in trying to manage these symptoms so they don’t impact everyone else, you feel like you don’t have time to give anything to anyone else,” she said. Mrs. Kaiser largely blames this on the use of birth control, which marked the beginning of her hormone troubles. “Going on birth control was one of the worst things I could do for my body. As soon as I started it, my body was never able to readjust,” she said. Starting in her mid 20s, Mrs. Kaiser went on birth control pills to help regulate her menstrual cycle. After getting married and having children, she began using an IUD at age 35. Since beginning the use of hormone-altering birth control, she’s gained a total of 60 pounds that no amount of diet or exercise has been able to change. The only reason she stuck with birth control as long as she did was because doctors kept telling her it wasn’t the contraceptives. “I was told it wasn’t the contraception. I was told it must’ve been my diet. I was told it was because I had a sedentary desk job. Because studies show the contraceptive weight gain was a myth, so it had to be a slew of other factors under my control,” Mrs. Kaiser said. It’s part of a common narrative women have heard for decades: Hormone-based birth control helps balance hormones, end of story. For years, the pill has been used as a sort of catch-all women’s drug that was prescribed for everything from acne to regulating menstrual cycles. Yet a 2023 study revealed that hormone-based contraceptives actually disrupt hormone balance and facilitate artificial states of anovulation. Anovulation is a type of hormone imbalance and also a common source of infertility in women. Further, research shows that premenstrual disorders—like what Mrs. Kaiser dealt with before going on the pill in her 20s—are associated with an increased risk of early menopause. When Mrs. Kaiser stopped using the IUD at age 35, she began experiencing perimenopause symptoms almost immediately. Now, at 43, she’s had consecutive missed menstrual cycles, signaling her approach to menopause. She’s also experiencing new symptoms like severe joint pain and hot flashes. SOURCE
Using Copper to Improve the Well-Being of the Skin
Copper has two key properties that are being exploited in consumer and medical device products in the last decade. On the one hand, copper has potent biocidal properties. On the other hand, copper is involved in numerous physiological and metabolic processes critical for the appropriate functioning of almost all tissues in the human body. In the skin, copper is involved in the synthesis and stabilization of extracellular matrix skin proteins and angiogenesis. This manuscript reviews clinical studies that show that the use of textile consumer and medical device products, embedded with microscopic copper oxide particles, improve the well-being of the skin. These include studies showing a) cure of athlete’s foot infections and improvement in skin elasticity, especially important for individuals suffering from diabetes; b) reduction of facial fine line and wrinkles; and c) enhancement of wound healing; by copper oxide embedded socks, pillowcases and wound dressings, respectively. The manuscript also reviews and discusses the mechanisms by which the presence of copper in these products improves skin well-being. SOURCE
Impacts of Psychological Stress on Osteoporosis: Clinical Implications and Treatment Interactions
While osteoporosis and psychological stress occur via differing mechanisms, there are several potential molecular links that exist between a pathological response to stress and the development of bone disease. Although not a comprehensive list, these may include dysregulation of the HPA-axis and SAM pathway, inflammatory pathways, IGF signaling, estrogen, serotonin, GABA, and RANKL. SOURCE
Role of cortisol in the pathogenesis of postmenopausal osteoporosis: relationship to bone structure
Excess glucocorticoids are well recognised as a cause of osteoporosis; they inhibit osteoblast function and increase osteoblast and osteocyte apoptosis resulting in thinning of the trabeculae. The circadian rhythm of bone turnover, which is linked to cortisol rhythm, is abnormal in osteoporosis. Furthermore, some studies show abnormal cortisol metabolism in osteoporosis. The aim of our study was to evaluate the day–night rhythm of cortisol and to relate cortisol levels to bone micro-structure. Methods: Postmenopausal women with vertebral fractures and a hip or spine BMD T-score <−1.0 were recruited (Group 1, n=30) In addition, two sex-/age-matched control groups with i) BMD matched to those in Group 1 (Group 2, n=30), and ii) normal BMD (Group 3, n=30) were studied. Salivary cortisol was measured at 0900 and 2300 h. Lumbar spine and hip BMD were measured by DXA, prevalent vertebral fractures were identified by VFA, and bone micro-structure in the distal radius and tibia was examined by high resolution peripheral quantitative computed tomography (HR-pQCT). Vertebral fractures were confirmed on plain radiography using the algorithm-based qualitative method. Results: Between group differences in hip (P<0.001) and spine (P<0.001) T-scores were detected by ANOVA. Post-hocScheffe tests revealed that spine and hip T-scores for Groups 1 and 2 did not differ, whilst T-scores for Group 3 were higher (P<0.001). Mean (S.D.) 0900 h salivary cortisol was significantly elevated in the vertebral fracture group (9.2 (4.7), 6.6 (5.0)and 6.4 (4.1) nmol/l ANOVA by trend P=0.034) and this correlated significantly with radial total volumetric BMD (Spearman’s ρ−0.78; P=0.01) and trabecular thickness (Spearman’s ρ−0.73; P=0.026) in the vertebral fracture group. 2300 h salivary cortisol levels were not related to BMD or bone micro-structure. Conclusion: Our findings show that the diurnal cortisol rhythm may possibly be altered in those women with vertebral fractures. Higher morning cortisol could contribute to an increased risk of vertebral fractures through thinning of the trabeculae. SOURCE
Stress Factors Increase Osteoporosis: A ComparativeAssessment of Osteocalcin and Cortisol Levels in Menopausal Women
Osteoporosis, a consequence of menopause in the biological cycle of women, emerges with the conclusion of reproductive capabi lities.Hormonal changes during this phase contribute to the development of the disease. The study evaluated the relationship between stres s,salivary cortisol levels, and osteocalcin, in postmenopausal women with osteoporosis. The study involved a total of 30 postmenopausal volunteers diagnosed with osteoporosis. Stress levels were assessed using the NIHstress score system to evaluate cortisol levels. Saliva and blood samples were analyzed using the LC-MS/MS and ELISA methods.Samples were collected from the participants during the 1st week and in the 2nd week after they were informed about their diagnosis. Statistical analyses, including the Wilcoxon Signed Rank test, paired samples t-tests, and correlation analyses, were conducted using IBM SPSS Statistics 21.0. A significance level of p<0.05 was considered. In comparing stress scores between the first/second weeks, a statistically significant difference was observed (z=4.795,p<0.001),indicating a higher mean stress score in the second week. Cortisol levels showed a significant increase from the 1st week(27.58±3.97) tothe 2nd week (29.99±2.44)(t=4.412,p<0.001). Osteocalcin values exhibited a significant difference between the 1st week(21.04±0.98) andthe 2nd week (24.22±1.44)(t=9.656, p<0.001). Examining participant variations, the mean difference in stress scores was 7.73±2.23, themean difference in cortisol levels was 2.41±2.99, and the mean difference in osteocalcin levels was 3.18±1.81. A weak positivestatistically significant relationship was found between stress score difference and cortisol difference (r=0.363, p=0.049). In contrast, anintermediate-level positive statistically significant relationship was observed between osteocalcin difference and cortisol difference(r=0.586, p=0.001). Findings demonstrate the intricate relationships between stress, cortisol levels, and osteocalcin. Contrary to some existing findings, our study suggests that menopause, as a stress -inducing factor, leads to an increase in bonemetabolism markers, including cortisol. Insights contribute to a more comprehensive understanding of the interplay between stress,hormonal changes, and osteoporosis in postmenopausal women. SOURCE
Association of Menopausal Vasomotor Symptoms With Increased Bone Turnover During the Menopausal Transition
The purpose of this study was to determine the longitudinal association between menopausal vasomotor symptoms (VMS) and urinary N-telopeptide level (NTX) according to menopausal stage. We conclude that among early perimenopausal and late perimenopausal women, those with VMS had higher bone turnover than those without VMS. Prior to the final menstrual period, VMS may be a marker for risk of adverse bone health. …high bone turnover is associated with lower bone mineral density, faster bone loss, and poor bone microarchitecture both in the trabecular compartment (trabecular perforations, loss of trabeculae, poor trabecular connectivity) and in the cortical compartment (cortical thinning, increased porosity). SOURCE
Presence of vasomotor symptoms is associated with lower bone mineral density
Objective: To determine whether women with vasomotor symptoms (VMS) have lower bone mineral density (BMD) than women without VMS. Design We analyzed data from baseline to annual follow-up visit 5 for 2213 participants in the bone substudy of the Study of Women’s Health Across the Nation. At baseline, women were aged 42 to 52 years, had intact uterus and ≥1 ovary, were not using exogenous hormones, were not pregnant or lactating, and were pre- or early perimenopausal. Menopausal stage and VMS were assessed by annual questionnaire. Menopausal stages were premenopausal, early perimenopausal, late perimenopausal, and postmenopausal. Using repeated measures mixed models, we determined the association between VMS (any vs. none) and BMD (by dual x-ray absorptiometry) within each menopause status category. Results After controlling for age, time within each menopausal stage, race/ethnicity, study site, and baseline menopause stage, postmenopausal women with any VMS had lower lumbar (0.008g/cm2 lower, P=0.001) and lower total hip (0.005 g/cm2 lower, P=0.04) BMD than postmenopausal women without VMS. Compared to early perimenopausal women without VMS, early perimenopausal women with any VMS had lower femoral neck BMD (0.003g/cm2 lower, P=0.0001). Premenopausal women with any VMS had lower femoral neck BMD (0.003g/cm2 lower, P=0.03), compared to premenopausal women without VMS. Conclusions Even in the earliest menopause transition stages, women with VMS had lower BMD than women without VMS. Effects varied by anatomical site, being most evident in postmenopausal women at the lumbar spine and total hip, and among premenopausal and early perimenopausal women at the femoral neck. SOURCE
Endocrinal metabolic regulation on the skeletal system in post-menopausal women
Loss of estrogen results in reduced osteoblast mediated bone formation and enhanced osteoclastic resorption (Emmanuelle et al., 2021). Given the recent expansion of interest in understanding how these cellular processes are regulated via metabolic flux and bioenergetic capacity, there are several lines of indirect evidence that postmenopausal osteoporosis is a product of dysregulated intracellular metabolism in bone cells. Glucose metabolism Osteoblast metabolism has been generally well characterized by our lab and others. This includes the finding that bone formation by the osteoblast is viewed as an energy demanding process whereby extracellular matrix proteins are synthesized and secreted along with mineralization vesicles (Borle et al., 1960a; Borle et al., 1960b). Metabolic substrates capable of generating adenosine triphosphate (ATP), osteoblasts can utilize glucose, glutamine, and fatty acids (Karner et al., 2015; Wei et al., 2015; Kim et al., 2017). The ability for osteoblasts to utilize glucose as a substrate is widely accepted in the bone biology field (Esen et al., 2013; Wei et al., 2015). Relative to these findings, Wei et al. (2015) published data describing GLUT1’s (Slc2a1) as the primary glucose transporter on osteoblasts, whereas data exists that both GLUT3 and GLUT4 are also expressed (Thomas et al., 1996; Zoch et al., 2016). To this end, mature osteoblasts generate ATP via glucose substrates using aerobic glycolysis (Jayapalan et al., 2022). In fact, cellular metabolic programming has been suggested to be the determining factor in deciding the lineage fate of the stromal cells in mice (Tencerova et al., 2019a). Adipo-progenitor cells have been shown to be more responsive to insulin and dependent on oxidative phosphorylation whereas the osteo-progenitor cells are more glycolytic. Interestingly, up-regulating glycolysis in adipo-progenitor cells by treating them with parathyroid hormone (PTH) decreases their adipogenic potential (Tencerova et al., 2019a). Even mesenchymal stromal cells from obese human have been shown to exhibit higher oxidative phosphorylation tendency and higher adipogenic potential (Tencerova et al., 2019b). While it has yet to be studied directly, it is plausible estrogen, or lack thereof in menopause, could regulate osteoblast glucose metabolism. For example, estrogen has been shown to activate GLUT4 in the intestine and GLUT1 in the brain (Gregorio et al., 2021). Estrogens have also been demonstrated to enhance glycolysis via intermediate metabolite regulation of phosphofructokinase (Alemany, 2021). Taken together, it is possible that similar pathways are also altered in osteoblasts given overlap in machinery. If this were the case, loss of estrogen as in menopause, would be expected to downregulate glucose transporters on osteoblasts and glycolysis, thereby reducing osteoblast activity. Microbiome/Ketones – Short chain fatty acids Estrogen modulates the intestinal microbiome in an interplay tailored to enhance the proliferation of beneficial bugs (Chen and Madak-Erdogan, 2016) Estrogen activates regulatory T-cells (Tregs), that prevents osteoclastogenesis and promote bone mass. Clostridia are well known producers of SCFAs, including butyrate. Butyrate maintains gut epithelial barrier, demonstrate immunomodulatory characteristics, and thus activates regulatory T cells (Furusawa et al., 2013). Another study done by Attarshi et al. reported that human Clostridia induce Tregs activity and contribute to systemic skeletal homeostasis (Atarashi et al., 2013). Lucas et al. performed a study comparing mice fed with short chain fatty acids (SCFAs) or high fiber diet and found a considerable increase in bone mass preventing postmenopausal and inflammatory bone loss (Lucas et al., 2018). Moreover, the SCFAs propionate (C3) and butyrate inhibit osteoclast differentiation and limits bone resorption in vitro and in vivo (Wallimann et al., 2021). Even more significantly, these two SCFAs incite osteoclast metabolism resulting in increased glycolysis at the expense of oxidative phosphorylation and thus downregulates osteoclast genes such as TRAF6 (TNF Receptor Associated Factor 6) and NFATc1 (Nuclear Factor of Activated T Cells 1) (Lucas et al., 2018). SOURCE
Osteocalcin, a promising marker of osteoporosis: evaluation in post-menopausal females with osteoporosis
Background: Osteocalcin, has high affinity for calcium. In osteoporotic women, deficiency of calcium may lead to lowering of the formation of hydroxyapatite crystals. Thus, in the state of hypo mineralization, free osteocalcin available in the circulation. Therefore, present study was designed to evaluate significance of serum osteocalcin in diagnosis of osteoporosis, and relationship between Serum Osteocalcin and BMD (Bone mineral Density) in post-menopausal females with osteoporosis and without osteoporosis. Methods: One hundred and forty seven post-menopausal women between age 45 to 80 years attending the hospital OPD were studied. To be eligible for the study they had to have been postmenopausal for at least one year. The diagnosis of osteoporosis was made based on T-Scores (BMD) at the lumber spine (L1 to L4 and femaral neck) by DEXA (GE lunar Densitometer). Serum osteocalcin level was estimated by LIAISON osteocalcin assay. Patients with chronic conditions affecting skeletal health and patients on drugs affecting the skeleton were excluded from the study. Results: Serum osteocalcin level in post-menopausal female without osteoporosis was 9.87±1.04ng/ml, while post-menopausal female with osteoporosis had 22.62±2.25ng/ml suggesting significant increase in bone marker level in osteoporotic females (p<0.05.) Correlation study between BMD and osteocalcin showed strong Negative Correlation (r=-0.77, p<0.05). Conclusions: Serum osteocalcin can be considered as a specific marker of osteoblast function as its levels have been shown to correlate with bone formation rates. Thus, serum osteocalcin can be used for diagnosis and monitoring of response to therapy and this may be the better predictor than BMD. SOURCE
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