Effects Of Estrogen Deficiency Research Articles

Associations of vaginal microbiota with the onset, severity, and type of symptoms of genitourinary syndrome of menopause in women.

Genitourinary syndrome of menopause (GSM) describes the symptoms and signs resulting from the effect of estrogen deficiency on the female genitourinary tract, including genital, urinary, and sexual symptoms. However, besides estrogen deficiency, little is known about the etiology of GSM. The objective of this study was to investigate the effects of vaginal microbiota dysbiosis on the occurrence and development of GSM in perimenopausal and postmenopausal women. In total, 96 women were enrolled in this cross-sectional study and clinical data were collected. GSM symptoms were divided into three types: genital, urological, and sexual symptoms. Full-length 16S rRNA gene sequencing using the third-generation PacBio sequencing technology was performed to analyze the vaginal microbiome using vaginal swabs of non-GSM and GSM women with different types of GSM symptoms. Live Lactobacillus Capsule for Vaginal Use (LLCVU) treatment was used to verify the effects of Lactobacillus on GSM symptoms. We found that 83.58% (56/67) of women experienced GSM symptoms in the perimenopausal and postmenopausal stages. Among these women with GSM, 23.21% (13/56), 23.21% (13/56), and 53.57% (30/56) had one type, two types, and three types of GSM symptoms, respectively. The richness and diversity of vaginal microbiota gradually increased from reproductive to postmenopausal women. There were significant differences in vaginal microbial community among non-GSM women and GSM women with different types of symptoms. Lactobacillus was found to be negatively associated with the onset, severity, and type of GSM while some bacteria, such as Escherichia-shigella, Anaerococcus, Finegoldia, Enterococcus, Peptoniphilus_harei, and Streptococcus, were found to be positively associated with these aspects of GSM, and these bacteria were especially associated with the types of genital and sexual symptoms in GSM women. LLCVU significantly relieved genital symptoms and improved the sexual life of GSM women in shortterm observation. The onset, severity, and type of GSM symptoms may be associated with changes in vaginal microbiota in perimenopausal and postmenopausal women. Vaginal microbiota dysbiosis probably contributes to the occurrence and development of GSMsymptoms, especially vaginal and sexual symptoms. Lactobacillus used in the vagina may be a possible option for non-hormonal treatment of GSM women with genital and sexual symptoms. https://www.chictr.org.cn/indexEN.html, identifier ChiCTR2100044237.

Estrogen deficiency in the menopause and the role of hormone therapy: integrating the findings of basic science research with clinical trials.

Menopause, defined by the cessation of menstrual cycles after 12 months of amenorrhea not due to other causes, is associated with significant hormonal changes, primarily a decrease in estrogen, androgen, and progesterone levels. This review delves into the effects of estrogen deficiency during the perimenopausal transition and postmenopause, integrating the findings of basic science with clinical trials. Here, we first outline the variation in endogenous estrogens before and after menopause, exploring both genomic and nongenomic actions of estrogen and its estrogen receptors throughout the body. Next, we detail the spectrum of menopausal symptoms, from acute vasomotor, urogenital, and psychological issues during perimenopause to chronic reproductive, cardiovascular, neurological, skeletal, dermatologic, immune, and digestive changes postmenopause. Finally, we evaluate the role of hormone therapy in alleviating these symptoms, weighing its benefits against known risks. Publicizing these findings and an accurate representation of the risks and benefits of estrogen replacement to our aging patients is fundamental to improving their care, quality, and even quantity of life.

059 Effects of hormone replacement therapy on osteopenia or osteoporosis in adolescents and young women with hypogonadism: Comparison of oral and transdermal 17 β estradiol administration

Objective: The effect of estrogen deficiency on bone is one of the most clearly demonstrated adverse consequences of hypogonadism in women. Estrogen replacement is essential for maintaining bone health as well as managing low bone mineral density (BMD) and osteoporosis due to hypogonadism in adolescents and young women [1]. Although there is no agreed consensus on optimum hormone replacement regimens for this group of patients, 17 β estradiol (E2) appears to have a more beneficial effect on BMD compared to ethinylestradiol [2,3].

High Fat Diet (HFD)-Induced Obesity Augments the Deleterious Effects of Estrogen Deficiency on Bone: Evidence from ovariectomized Mice

High Fat Diet (HFD)-Induced Obesity Augments the Deleterious Effects of Estrogen Deficiency on Bone: Evidence from ovariectomized Mice

Dynamic Alteration of the Gut Microbiota Associated with Obesity and Intestinal Inflammation in Ovariectomy C57BL/6 Mice.

Objective Estrogen is a critical hormone that is mainly produced by the ovary in females. Estrogen deficiency leads to various syndromes and diseases, partly due to gut microbiota alterations. Previous studies have shown that estrogen deficiency affects the gut microbiota at 6–8 weeks after ovariectomy, but the immediate effect of estrogen deficiency on the gut microbiota remains poorly understood. Methods To investigate the short time and dynamic effects of decreased estrogen levels on the gut microbiota and their potential impact on estrogen deficiency-related diseases, we performed metagenomic sequencing of 260 fecal samples from 50 ovariectomy (OVX) and 15 control C57BL/6 female mice at four time points after surgery. Results We found that seven gut microbiota species, including E. coli, Parabacteroides unclassified, Lachnospiraceae bacterium 8_1_57FAA, Bacteroides uniformis, Veillonella unclassified, Bacteroides xylanisolvens, and Firmicutes bacterium M10_2, were abundant in OVX mice. The abundance of these species increased with time after OVX surgery. The relative abundance of the opportunistic pathogen E. coli and the Crohn's disease-related Veillonella spp. was significantly correlated with mouse weight gain in the OVX group. Butyrate production and the Entner–Doudoroff pathway were significantly enriched in the control mouse group, while the degradation of glutamic acid and aspartic acid was enriched in the OVX mouse group. As the time after OVX surgery increased, the bacterial species and metabolic pathways significantly changed and tended to suggest an inflammatory environment, indicating a subhealthy state of the gut microbiota in the OVX mouse group. Conclusions Taken together, our results show that the dynamic gut microbiota profile alteration caused by estrogen deficiency is related to obesity and inflammation, which may lead to immune and metabolic disorders. This study provides new clues for the treatment of estrogen deficiency-related diseases.

The effects of estrogen deficiency and aging on myocardial deformation and motion in normotensive female rats.

Estrogen deficiency is associated with left ventricular (LV) dysfunction in postmenopausal women and ovariectomized rats. Whether the relationship between estrogen deficiency and LV dysfunction is independent of cardiovascular disease (CVD) risk factors remains uncertain. This study assessed the effects of short-term and long-term estrogen deficiency on cardiac structure and function using conventional and speckle tracking echocardiography, independent of traditional CVD risk factors. Female Sprague-Dawley rats were divided into short-term (6 wks) ovariectomized (n = 9), short-term sham-operated (n = 10), long-term (6 mo) ovariectomized (n = 8), and long-term sham-operated (n = 9) groups. Cardiac geometry, systolic and diastolic function, and myocardial deformation and motion were measured using echocardiography. Ovariectomy had no effect on conventional echocardiography measures of cardiac structure or function. Compared with short-term, long-term groups had reduced LV internal diameter (false discovery rate [FDR] adjusted P = 0.05) and impaired relaxation (e'; FDR adjusted P = 0.0005) independent of body mass and blood pressure (BP). Global longitudinal strain was impaired in ovariectomized compared with sham-operated rats (FDR adjusted P = 0.05), but not after adjusting for body mass and BP (FDR adjusted P = 0.16). Global longitudinal strain (FDR adjusted P = 0.05), strain rate (FDR adjusted P = 0.002), and velocity (FDR adjusted P = 0.04) were impaired in long-term compared with short-term groups. Global longitudinal strain rate remained impaired after adjustments for body mass and BP (FDR adjusted P = 0.02). Estrogen deficiency does not independently cause cardiac remodeling, LV dysfunction, or impaired myocardial deformation. Traditional CVD risk factors accompanying estrogen deficiency may account for cardiac remodeling and dysfunction observed in postmenopausal women.

Estrogen depletion alters osteogenic differentiation and matrix production by osteoblasts in vitro

Recent studies have revealed that the effects of estrogen deficiency are not restricted to osteoclasts and bone resorption, but that bone matrix composition is altered and osteoblasts exhibit an impaired response to mechanical stimulation. In this study, we test the hypothesis that estrogen depletion alters osteogenic differentiation and matrix production by mechanically stimulated osteoblasts in vitro. MC3T3-E1 cells were pre-treated with estrogen for 14 days, after which estrogen was withdrawn or inhibited with Fulvestrant up to 14 days. Fluid shear stress (FSS) was applied using an orbital shaker. Under estrogen depletion in static culture, osteogenic marker (ALP) and gene expression (Runx2) were decreased at 2 and after 7 days of estrogen depletion, respectively. In addition, up to 7 day the inhibition of the estrogen receptor significantly decreased fibronectin expression (FN1) under static conditions. Under estrogen depletion and daily mechanical stimulation, changes in expression of Runx2 occurred earlier (4 days) and by 14 days, changes in matrix production (Col1a1) were reported. We propose that changes in osteoblast differentiation and impaired matrix production during estrogen depletion may contribute to the altered quality of the bone and act as a contributing factor to increased bone fragility in postmenopausal osteoporosis.

MO476EFFECT OF ESTROGEN DEFICIENCY ON THE STATE OF BONE AND MINERAL METABOLISM IN WOMEN WITH STAGE III-V CHRONIC KIDNEY DISEASE

Abstract Background and Aims Clinical studies in recent years have revealed a close relationship between hormonal disorders in women with CKD and the duration and quality of life, bone mineral and related disorders of the cardiovascular system. In individual studies, there is a tendency to improve the indicators of mineral and bone metabolism and the state of the cardiovascular system in hormonal or other drug-induced correction of hormonal dysfunctions in women. - Aims to study the effect of estrogen deficiency on bone and mineral metabolism in a population of women suffering from CKD stages III-V Method The study included 52 women who met the clinical criteria for the possible appointment of hormone therapy (both replacement and combined oral contraceptives) for the purpose of a detailed examination of the state of their cardiovascular system and bone-mineral metabolism in dynamics (with an interval of 10-12 months) in order to assess the degree of influence of estrogen-deficient conditions on the course of such common complications of CKD as cardiovascular diseases and pathology of the bone system. The age of the patients ranged from 26 to 61 years (mean age-50.65±9.17 years). The duration of CPN averaged 77.02 months.. The stages of CKD were determined according to the K/DOQI (2012) criteria, and the glomerular filtration rate was calculated using the CKD-EPI formula. The following parameters were evaluated: the concentration of sclerostin, osteoprotegerin, fibroblast growth factor 23 (FGF-23), parathyroid hormone, total calcium, phosphorus, alkaline phosphatase, creatinine, and urea. Follicle-stimulating hormone( FSH), luteinizing hormone(LH) and estradiol were determined by solid-phase chemiluminescent enzyme immunoassay (commercial sets of Alkor-Bio, St. Petersburg). Serum concentrations of sclerostin, sRANKL (soluble RANKL), and osteoprotegerin were determined by the enzyme-linked immunoassay using Biomedica gruppe test systems. Results The examined patients showed hormonal dysfunctions (82%), accompanied by changes in the content of sex hormones: the concentration of estradiol was below normal: 123.4±72.5 pmol/l and 150.0-450.0 pmol/l, respectively, in patients and in normal (p<0.01), which confirms the presence of estrogen deficiency in the examined patients . Concentrations of FSH and LH exceeded the norm in the group of patients as a whole: 91.6±46.1 IU/l and 3.0-8.0 IU/l FSH content in patients and normal; 51.8±32.1 IU/l and 3.0-10.0 IU/l LH in patients and normal. In the group of patients as a whole, an increase in the level of sclerostin to 28.5 ± 9.2 pmol/l was detected ( norm 12±33.45 pmol/l), an increase in the level of osteoprotegerin to 6.9±0.4 pmol/l (norm 2.7 pmol/l). Positive and negative correlations were found between the levels of morphogenetic proteins, sex hormones, and characteristic parameters of hormonal dysfunctions Conclusion Pre-and postmenopausal women with CKD have hormonal dysfunctions, including disorders of sexual and reproductive function, menstrual cycle, decreased fertility, increased risks of miscarriage at its onset, the basis of hormonal dysfunctions is the absence of LH peaks and changes in the concentration of estradiol depending on the phase of the cycle, hypoestrogenemia. It is assumed that there is a pathogenetic link between hormonal dysfunctions and disorders in the system of bone metabolism regulatory proteins in patients with CKD.

Association of Vaginal Microbiota With Signs and Symptoms of the Genitourinary Syndrome of Menopause Across Reproductive Stages.

The genitourinary syndrome of menopause (GSM) describes signs and symptoms resulting from effects of estrogen deficiency on the female genitourinary tract, including the vagina, labia, urethra, and bladder. Signs/symptoms associated with GSM may occur during any reproductive stage from multiple etiologies but are most common during menopause due to low estrogen. Vaginal microbiota, particularly Lactobacillus spp., are beneficial to the female genital tract; however, their abundance declines during menopause. We aimed to longitudinally assess vaginal microbiota characterized by 16S rRNA gene amplicon sequencing and GSM-associated endpoints across reproductive stages. In a 2-year cohort study of 750 women aged 35-60 years at enrollment and 2 111 semiannual person-visits, low-Lactobacillus vaginal microbiota communities were observed at 21.2% (169/798), 22.9% (137/597), and 49.7% (356/716) of person-visits among pre-, peri-, and postmenopausal women, respectively (p < .001). Compared to communities that have high Gardnerella vaginalis relative abundance and diverse anaerobes, the following communities were associated with a lower covariate-adjusted odds of vaginal atrophy: L crispatus-dominated communities among postmenopausal women (odds ratio [OR] = 0.25; 95% confidence interval [CI]: 0.08, 0.81), L gasseri/L jensenii (OR = 0.21; 95% CI: 0.05, 0.94) and L iners (OR = 0.21; 95% CI: 0.05, 0.85) among perimenopausal women, and L iners-dominated communities (OR = 0.18; 95% CI: 0.04, 0.76) among premenopausal women. Postmenopausal women with L gasseri/L jensenii-dominated communities had the lowest odds of vaginal dryness (OR = 0.36; 95% CI: 0.12, 1.06) and low libido (OR = 0.28; 95% CI: 0.10, 0.74). Findings for urinary incontinence were inconsistent. Associations of vaginal microbiota with GSM signs/symptoms are most evident after menopause, suggesting an avenue for treatment and prevention.

Effects of estrogen deficiency during puberty on maxillary and mandibular growth and associated gene expression \u2013 an \u03bcCT study on rats

BackgroundEstrogen is a well-known and important hormone involved in skeletal homeostasis, which regulates genes involved in bone biology. Some studies support that estrogen is important for craniofacial growth and development. Therefore this in vivo animal study aimed to investigate, whether and in which way low estrogen levels in the prepubertal period affect craniofacial development in the postpubertal stage and to quantify the gene expression of RANK, RANKL and OPG in cranial growth sites in ovariectomized estrogen-deficient rats during puberty.MethodsControl (sham-operated, n = 18) and ovariectomy (OVX, n = 18) surgeries were performed on 21-days-old female Wistar rats. Animals euthanized at an age of 45 days (pubertal stage) were used for gene expression analyses (n = 6 per group) and immunohistochemistry of RANK, RANKL and OPG. Animals euthanized at 63 days of age (post-pubertal stage) were used for craniofacial two-dimensional and three-dimensional craniofacial measurements using μCT imaging (n = 12 per group).ResultsIn the μCT analysis of the mandible and maxilla many statistically significant differences between sham-operated and OVX groups were observed, such as increased maxillary and mandibular bone length in OVX animals (p < 0.05). Condylar volume was also significantly different between groups (p < 0.05). The sham-operated group showed a higher level of RANK expression in the midpalatal suture (p = 0.036) and the RANKL:OPG ratio levels were higher in the OVX group (p = 0.015).ConclusionsOur results suggest that estrogen deficiency during the prepubertal period is associated with alterations in the maxillary and mandibular bone length and condylar growth.

Development of Aging Treatment Model to improve self-management of menopause women: An effort to achieve SDGS goal

Abstract Aging process in menopausal women is an effect of estrogen deficiency. It will cause physical changes in vasomotor instability such as hot flushes, decreased immune system, vertigo, nausea, insomnia, and palpitation. Sexual problems also occur during menopause, such as vaginal infection, dyspareunia, painful intercourse, and decreased libido. The psychological changes also reported in menopause women. They tend to have low self-esteem and decreased memory that affects their daily social interaction. The study explained a new concept, called Aging Treatment Model, for menopausal women so they can deal with physical, psychological and sexual changes during menopause. The Quasi-Experimental with pre and post-test design and control group used in this study. A total of 230 menopause women in 5 cities in Indonesia were recruited. The data analyzed by using Mc Nemar and Chi-Square test. The result showed that the Aging Treatment Model had a significant impact on self-management to solve physical (p

High fat diet (HFD)-induced obesity augments the deleterious effects of estrogen deficiency in bone. Evidence from post-menopausal mice

High fat diet (HFD)-induced obesity augments the deleterious effects of estrogen deficiency in bone. Evidence from post-menopausal mice

PRINCIPLES OF HORMONE REPLACEMENT THERAPY IN WOMEN DURING MENOPAUSE

One of the most pressing problems is the onset of menopause in the women over the age of 45 and the development of menopausal syndrome. Because a large number of women with severe menopausal symptoms does not receive adequate therapy and applies for the alternative ineffective ways to alleviate the condition, they should be informed about preventive measures and treatment of this syndrome. The paper describes in details the disorders that occur during menopause. Particular attention is paid to the examination of such women, the study of complaints related to the nervous and cardiovascular systems, urogenital tract, metabolic processes. In addition to the general examination, special methods are used as follows: ultrasound, cytological examination of secretions from the surface of the cervix, cervical canal. If necessary, in women with cyclic bleeding, an endometrial biopsy is performed with a biopsy. In recent years, hormone replacement therapy has been widely used to treat menopausal syndrome as the most effective way to prevent disorders (osteoporosis, atrophy of the urogenital tract, etc.). The purpose of its implementation is to maintain the function of hormone−producing organs in a normal state, reduce the expression of symptoms, prevention and treatment of osteoporosis. Treatment is usually performed on an outpatient basis. Only natural estrogens are used, which are chemically similar to those synthesized in the female body. In order to prevent the development of hyperplastic processes in the endometrium, the women are prescribed with progestins in a cyclic or continuous mode from several months to several years. Hormone replacement therapy will help a woman to avoid the negative effects of estrogen deficiency on the body, maintain bone density and cardiovascular health, as well as improve overall quality of life. Key words: menopause, menopausal syndrome, vascular disorders, hormone replacement therapy.

Effects of estrogen deficiency followed by streptozotocin-induced diabetes on periodontal tissues of female rats.

Although both estrogen deficiency and diabetes contribute to periodontal tissue deterioration, the combined effects of these conditions on periodontium is unknown. Thus, we analyzed the combined effects of ovariectomy followed by streptozotocin (STZ)-induced diabetes on periodontal tissues of rats. Twenty adult rats were ovariectomized (OVX) or SHAM-operated (SHAM). After 3weeks, the rats received an intraperitoneal injection of STZ (60mg/kg/body weight) to induce diabetes or vehicle (blank) solution. The groups were assigned as follows (n = 5): SHAM-vehicle (SHAM), OVX-vehicle (OVX), SHAM + STZ (SHAM-Di), and OVX + STZ (OVX-Di). Seven weeks post-diabetes induction, the rats were euthanized. Blood samples were collected for glucose measurements and maxillae were processed for paraffin embedding. Sections stained with hematoxylin/eosin, Masson's trichrome, and picrosirius-red were used for alveolar bone loss and collagen fiber analysis in the lamina propria. Immunohistochemistry was performed for runt-related transcription factor 2 (Runx2), matrix metalloproteinase 9 (MMP-9), and tryptase detection. Alveolar bone loss and fewer collagen fibers were observed in the OVX-Di group, collagen fibers with irregular organization, and MMP-9 immunoreactivity were more evident in diabetic groups, and MMP-9-positive osteoclasts on alveolar bone surface were noticed in all groups. The OVX-Di group showed lower Runx2 immunoreactivity (osteoblast formation marker), and more tryptase-positive cells (mast cell marker) in the alveolar bone marrow. Our results indicate that estrogen depletion, followed by STZ-induced diabetes, promotes periodontal tissue deterioration that is more evident than both interventions applied alone. Furthermore, our results points to a possible participation of bone-derived mast cells in this process.

Effects of estrogen deficiency on liver function and uterine development: assessments of Medicago sativa's activities as estrogenic, anti-lipidemic, and antioxidant agents using an ovariectomized mouse model

We investigated the effects of Medicago sativa supplementation on the lipid profiles and antioxidant capacities of ovariectomized mice. The study was performed on white Swiss female mice that were divided into five groups: control, treated with Medicago sativa (0.75 g/kg/day), ovariectomized, ovariectomized treated with β-estradiol (1 μg/day) or with Medicago sativa. The mice were sacrificed after 3 and 8 weeks of treatment. Ovariectomy induced a decrease in overall growth, uterine atrophy, and hyperlipidemia demonstrated by increased cholesterol, triglycerides, and decreased HDL. We have shown the involvement of oxidative stress in this hepatic lesion proven by increased levels of TBARS, GPX, and GSH, and decreased levels of SOD and catalase. Treatment with Medicago sativa restores lipid balance, the activity of antioxidant enzymes and improves lipid peroxidation. This is probably due to the richness of this plant in polyphenols and flavonoids considered as an antioxidant and phytoestrogenic elements.

The effect of estrogen deficiency and its combination with chronic stress on the condition of periodontal in old rats

The aim of the study was to investigate the effect of ovariectomy and its combination with stress (femoral fracture) on the periodontal condition in old rats. Materials and methods. A total of 24 white female rats were used in the experiment. The first group consisted of intact rats. Rats of the second group were subjected to an ovariectomy (OE) at the age of 2 months. Rats of the third group underwent a fracture of the one femur 1 month before they were euthanized. The animals were sacrificed at 15 months of age. Results. The level of LPO was increased in the liver, salivary glands and alveolar bone process after experimental ovariectomy; the recession defects on molars were significantly increased. Stress (femoral fracture) aggravated the intensification of peroxidation processes in the salivary glands and liver of rats. The levels of nucleic and higher polyene fatty acids in the liver lipids were decreased in the combination of ovariectomy and stress. The level of LPO in the alveolar bone process was not changed significantly. Histomorphometric study of periodontium in rats revealed a decrease in the upper margin of epithelial attachment. Conclusions. Experimental estrogen deficiency caused the most significant pathogenic effect on the periodontium in old rats. The obtained data demonstrate that female sex hormone deficiency is one of the mechanisms in periodontitis pathogenesis.

Influence of estrogen deficiency on guided bone augmentation: investigation of rat calvarial model and osteoblast-like MC3T3-E1 cells.

The effect of estrogen deficiency in bone augmentation, and the mechanisms by which estrogen deficiency impedes osteoblast differentiation and collagen matrix production, were examined. Twenty female Jcl:Wistar rats were divided into two groups: ovariectomized rats; and control rats. Guided bone augmentation was performed by positioning plastic caps in the calvarium of all animals at 8 wk after ovariectomy or sham surgery. Micro-computed tomography and histological sections were used to determine the amount of bone augmentation within the plastic caps. At 8 wk, there was statistically significantly less newly formed bone volume in ovariectomized rats. Immunohistological staining revealed the rare alignment of runt-related transcription factor 2-positive osteoblast-like cells and collagen I-positive bundle fibers in ovariectomized rats. In cell culture experiments, pre-osteoblast-like cells, MC3T3-E1, were treated with the estrogen receptor antagonist, fulvestrant. In treated cells, alkaline phosphatase activity remained high, whereas Alizarin Red staining was completely inhibited. Extracellular staining intensity of collagen I was decreased after fulvestrant treatment. Consistent with these observations, gene-expression analysis confirmed that fulvestrant treatment led to weaker expression of mRNA for osteogenic transcription factors and bone matrix protein-related genes. The results demonstrate that estrogen deficiency suppresses osteoblast differentiation and collagen matrix production in bone augmentation.

Reduced Lean Mass and Fat Mass Exacerbate Effects of Estrogen Deficiency on Bone

Lean mass is a stronger predictor of bone geometry in loaded limbs than fat mass in exercising women; however, estrogen exposure likely modulates the relationship between lean/fat mass and bone. We recently demonstrated that energy and estrogen status interact to impact vBMD, bone geometry and estimated bone strength (eBS) but that energy deficiency was often only detrimental in the presence of estrogen deficiency. This suggests that estrogen deficiency increases the vulnerability of bone to metabolic disruptions that accompany energy deficiency. We hypothesize that the impact of lean/fat mass on bone is dependent on estrogen status. PURPOSE: To compare the predictive value of lean mass index (LMI, kg*m-2) and fat mass index (FMI, kg*m-2) on vBMD, geometry, and eBS in the tibia in estrogen replete and estrogen deficient women. METHODS: Exercising women (n=60, 18-30 yrs) were grouped by 1) Estrogen deficient (E2D, n=27): oligo/amenorrheic <6 cycles/12 mo, and 2) Estrogen replete (E2R, n=33): eu/oligomenorrheic ≥6 cycles/12 mo. Body composition was assessed via DXA. vBMD, bone geometry, and eBS were assessed at the 4% (distal) and 66% (proximal) tibia via pQCT. Multivariate stepwise regression determined predictors of bone outcomes. RESULTS: LMI was a positive predictor of distal tibia total, trabecular, and cortical vBMD in E2D women only, accounting for 28-36% of the variance (p<0.004). LMI was a positive predictor of distal tibia cortical area in E2R women (R2=0.137, p=0.037). FMI was not predictive of bone outcomes in E2R women but was a positive predictor of cortical area at the distal tibia in E2D women (R2=0.162, p=0.038). At the proximal tibia, FMI and LMI were positive predictors of total vBMD (R2=0.494) and cortical thickness (R2=0.571) in E2D women only (p<0.015). LMI was a positive predictor of total area (R2=0.353) and negative predictor of cortical vBMD (R2=0.141) in E2R women only (p<0.044). FMI and LMI were positive predictors of distal tibia BSI in E2D women (R2=0.435, p<0.029). LMI positively predicted BSI in E2R women but explained less variance (R2=0.152, p=0.027). CONCLUSIONS: In the absence of adequate estrogen exposure, reduced fat or lean mass results in significant detriments to bone health in exercising women. It appears that in the face of reduced fat or lean mass, estrogen may be protective to bone.

Estrogen deficiency attenuates fluid flow-induced [Ca2+]i oscillations and mechanoresponsiveness of MLO-Y4 osteocytes.

It has been proposed that estrogen regulates the mechanosensitivity of osteocytes; however, the effects of estrogen deficiency that arises during postmenopausal osteoporosis on mechanical stimulation-induced calcium signaling in osteocytes remain elusive. Here, we pretreated MLO-Y4 osteocytes with 10 nM E2 for 2, 3 and 5 d, then simulated postmenopausal conditions either by estrogen withdrawal (EW) from culture medium, or by inhibiting the estrogen receptor by using fulvestrant and estrogen (FE; ICI 182,780) in vitro We investigated [Ca2+]i oscillations and mechanobiologic responses of osteocytes (EW and FE) that were exposed to oscillatory fluid flow (OFF; 1 Pa, 0.5 Hz). We demonstrated that estrogen treatment enhanced OFF-induced [Ca2+]i oscillations and that this effect was abrogated both by FE and EW. Moreover, osteocytes in both estrogen-depleted groups (EW and FE) had reduced levels of NO and prostaglandin E2 release, down-regulated dentin matrix protein-1, sclerostin, osteopontin, osteocalcin, and alkaline phosphatase mRNA expression, and reduced F-actin fiber formation after OFF stimulation compared with estrogen-treated cells. We propose a link between estrogen deficiency and alterations in [Ca2+]i-mediated mechanosensitivity of osteocytes, which ultimately alter osteocyte function and differentiation.-Deepak, V., Kayastha, P., McNamara, L. M. Estrogen deficiency attenuates fluid flow-induced [Ca2+]i oscillations and mechanoresponsiveness of MLO-Y4 osteocytes.

What Does the Data Show for Primary Ovarian Insufficiency?

Purpose of Review Primary ovarian insufficiency (POI), a clinical syndrome, is defined by the exhaustion of the functional potential of ovaries prior to 40 years. The consequences of POI are potentially serious for long-term fertility, reproductive health, and general health because of early menopause. This article provides an updated review of different etiologic factors and pathogenic mechanisms that lie behind POI as well as current and novel strategies for the management of this challenging disease aimed at the primary prevention of the adverse effects of estrogen deficiency and infertility related to the early loss of ovarian function.