Response In Postmenopausal Women Research Articles

Circulating microRNA responses to acute whole-body vibration and resistance exercise in postmenopausal women

Evaluating alterations in circulating microRNA (c-miRNA) expression may provide deeper insight into the role of exercise in the attenuation of the negative effects of aging on musculoskeletal health. Currently, there are sparse data on c-miRNA responses to acute exercise in postmenopausal women. The purpose of this study was to characterize the effects of acute bouts of resistance exercise and whole-body vibration on expression of selected c-miRNAs in postmenopausal women aged 65-76 years (n=10). We also examined relationships between c-miRNAs and muscle strength and bone characteristics. This randomized crossover design study compared c-miRNA responses to a bout of resistance exercise (RE) (3 sets 10 reps 70% 1 repetition maximum (1RM), 5 exercises) and a bout of whole-body vibration (WBV) (5 sets 1min bouts 20Hz 3.38mm peak to peak displacement, Vibraflex vibration platform). DXA was used to measure body composition and areal bone mineral density (aBMD) of the total body, AP lumbar spine, and dual proximal femur. pQCT was used to measure tibia bone characteristics (4%, 38%, 66% sites). Blood samples were collected before exercise (Pre), immediately-post (IP), 60 minutes post (60P), 24 hours (24H), and 48 hours (48H) after exercise to measure serum miR-21-5p, -23a-3p, -133a-3p, -148a-3p (qPCR) and TRAP5b (ELISA). There was a significant modality × time interaction for c-miR-21-5p expression (p=0.019), which decreased from 60P to 24H after WBV only. TRAP5b serum concentrations significantly increased IP then decreased below Pre at 24H for both WBV and RE (p<0.01). Absolute changes in TRAP5b were negatively correlated with c-miR-21-5p fold changes (r= -0.642 to -0.724, p<0.05) for both exercise modalities. There were significant negative correlations between baseline c-miRNAs and bone status variables (r= -0.639 to -0.877, p<0.05). Our findings suggest that whole-body vibration is a sufficient mechanical stimulus for altering c-miR-21-5p expression, whereas a high intensity resistance exercise protocol did not elicit any c-miRNA responses in postmenopausal women. Increases in the bone resorption marker, TRAP5b, were associated with greater downregulation of c-miR-21-5p expression.

Cutaneous Microvascular Endothelial Function: Effects of Sex and Menopause Stage

BackgroundEndothelial dysfunction and increased arterial stiffness are both associated with increased risk of cardiovascular events and mortality.Vascular aging has been characterized by deteriorating endothelial function accompanied by increasing vascular stiffness that occurs with increasing chronological age, with the onset of these changes varying by sex. Deteriorating large artery vascular function has been reported across the menopause transition in women, but it is unclear if this relationship extends to the cutaneous microvasculature, which may have critical implications for both thermal regulation and general cardiovascular health.Purpose &amp; HypothesisThe primary purpose of this study was to determine the impact of sex and menopausal stage on cutaneous endothelial dependent (EDD) vasodilation. We hypothesized that cutaneous EDD vasodilation would decrease in women in a graded manner across the transition from pre, to peri, to postmenopause with differences compared to age matched men. Secondly, we hypothesized that there would be no differences in cutaneous EDD vasodilation between natural and surgical (i.e., hysterectomy) menopause.MethodsPremenopausal, (n=8, 44±5y), perimenopausal (n=6, 51±2y), and postmenopausal women (n=9, 60±7y) as well as men age matched to the postmenopausal group (n=6, 59±7y) volunteered for this study. Cutaneous EDD vasodilation was measured by local iontophoresis of Acetylcholine (Ach) administration into the forearm vasculature. Red blood cell flux was determined by laser Doppler flowmetry at baseline and after 200µL of Ach. CVC was calculated as the quotient of red blood cell flux and mean arterial pressure and expressed as the percentage increased from baseline (CVC%). Differences were determined using a 1‐way ANOVA. Data are presented as mean ± standard error.ResultsForearm microvascular CVC% was significantly different among groups (P=0.01) after Ach administration. Post hoc analyses revealed an attenuated CVC% response in postmenopausal women (691±150%; P=0.02) and men (733±127%; P=0.05) compared to premenopausal women (1398±247%). There were no differences detected between peri‐ and premenopausal women (1290±140% vs. 1398±247%; P=0.95). Further, we performed a subanalysis in our postmenopausal group which included surgical (n=3) and natural (n=8) postmenopausal women. No differences were present between surgical and natural postmenopausal women (P=0.87), while both the surgical (646±163%; P=0.08) and natural (713±221%; P=0.05) postmenopausal women appeared to have decreased CVC responses compared to premenopausal women (1398±247%).ConclusionsOur findings indicate that cutaneous EDD vasodilation decreases from pre‐ to postmenopause in healthy women. Our data suggests that decreases in microvascular function agrees with reported decrements in large vessel vascular function associated with the menopause transition.

Effects of light-emitting diode therapy on cardiovascular and salivary nitrite responses in postmenopausal women submitted to a single bout of high-intensity interval training.

The aim of the present study was to analyze the effects of light-emitting diode therapy (LEDT) on cardiovascular effort during a single bout of high-intensity interval training (HIIT) and on blood pressure (BP), salivary nitrite, and heart rate variability (HRV) responses after the exercise session in postmenopausal women. Sixteen postmenopausal women between 50 and 70years of age participated in the present study. The intervention comprised two sessions: placebo plus HIIT and LEDT plus HIIT, with a 14-day interval between sessions. The oxygen uptake (VO2), heart rate (HR), and rating of perceived exertion (RPE) were monitored throughout the HIIT sessions. Salivary samples were taken before, immediately post, and 30' and 60' post-HIIT sessions for nitric oxide (NO) analysis. In addition, HR and BP were checked before, 15min, 30min, 45min, and 60min post-HIIT sessions. HR data were used to calculate the HRV indices. Cardiovascular parameters during HIIT and BP, HRV, and NO responses were not different between placebo and LEDT conditions (p > 0.05). BP responses increased after compared to pre-exercise (p < 0.01). HRV was impaired post- compared to pre-exercise (p < 0.05). LEDT did not improve physiological performance during HIIT and did not accelerate the recovery of BP and autonomic modulation or change the NO release after exercise in postmenopausal women.

Effect of Regular Taekwondo Self-Defense Training on Oxidative Stress and Inflammation Markers in Postmenopausal Women

We aimed to investigate the effect of a 12-week Taekwondo self-defense training course on oxidative stress and inflammation in postmenopausal women. Sixteen middle-aged women participated and were randomized into two groups: a control group (CG, n = 8) and a Taekwondo self-defense training group (TSDG, n = 8). The TSDG was trained for 60 min, four times per week, for 12 weeks. Following the Taekwondo training intervention, side-step was significantly higher in the TSDG than in the CG (p < 0.001). Malondialdehyde levels were significantly lower after the intervention than before in the TSDG (p < 0.01). Superoxide dismutase (SOD) levels were also significantly higher after the intervention than before in the TSDG (p < 0.001). After the Taekwondo training intervention, SOD levels were significantly higher in the TSDG than in the CG (p < 0.01). Tumor necrosis factor α (TNF-α) levels were significantly lower after the intervention than before in the TSDG (p < 0.05). After the Taekwondo training intervention, TNF-α levels were significantly lower in the TSDG than in the CG (p < 0.05). The results of this study suggest that Taekwondo self-defense training is an effective exercise that improves agility, oxidative stress, and inflammatory responses in postmenopausal women.

Differential effects of estradiol on neural and emotional stress response in postmenopausal women with remitted Major Depressive Disorder

BackgroundEstrogen fluctuations throughout the lifespan may contribute to major depressive disorder (MDD) risk in women through effects on brain networks important in stress responding, and mood regulation. Although there is evidence to support ovarian hormone treatment for peri-menopausal depression, postmenopausal use has not been well examined. The objective of this study was to investigate whether estrogen modulation of the neural and emotional cognitive responses to stress differs between postmenopausal women with and without MDD history. Methods60 postmenopausal women completed an fMRI psychosocial stress task, after receiving no drug or 3 months of daily estradiol (E2). fMRI activity and subjective mood response were examined. ResultsIn women without a history of MDD, E2 was associated with a more negative mood response to stress and less activity in emotional regulation regions. In women with a history of MDD, E2 was associated with a less negative mood response to stress and less activity in emotion perception regions. LimitationsThis study was limited by open-label estradiol administration and inclusion of participants using antidepressants. ConclusionsThese results support a differential effect of estrogen on emotional and neural responses to psychosocial stress in postmenopausal women with MDD history and may reflect a shift in brain activity patterns related to emotion processing following menopause.

Differential effects of estradiol on neural and emotional stress response in postmenopausal women with remitted Major Depressive Disorder

<h3>Introduction</h3> Ovarian hormones can influence neural systems involved in mood regulation, suggesting a pathway explaining why women have a greater incidence of Major Depressive Disorder (MDD) than men primarily beginning at puberty. Estrogen fluctuations may contribute to MDD risk through effects on brain networks important in emotion processing, stress responding, and mood regulation. Although there is evidence to support the use of ovarian hormone treatment for peri-menopausal depression, postmenopausal use has not been as well examined. As the neural systems involved in emotional processing and stress response are altered in MDD, it is possible that the effect of estrogen treatment on these systems may differ between postmenopausal women with and without a history of MDD. The objective of this study was to investigate whether estrogen modulation of the neural and emotional cognitive responses to stress differs between postmenopausal women with and without MDD vulnerability. <h3>Methods</h3> 60 postmenopausal women completed this fMRI study including a psychosocial stress task, the Montreal Imaging Stress Task (MIST), after receiving no drug or 3 months of daily 2mg 17β estradiol (E2). Participants included women with no personal history of MDD by SCID interview and women with remitted MDD with at least one episode in the last ten years and no depressive episodes within the last year. There were 4 participant groups: 1) MDD+/E2+ (n=10), 2) MDD+/E2- (n=12), 3) MDD-/E2= (n=20), 4) MDD-/E2- (n=18). All groups were euthymic at the time of study with non-clinical scores on the Beck Depression and Anxiety Inventories. Subjective mood response to the MIST was assessed as change score on the Stress-Arousal Checklist (SACL stress) before and after the MIST. fMRI analyses examined activity differences between the "stress and "control" conditions of the MIST using SPM 12. Second level analyses included 2 × 2 interactions (MDD history X E2 administration), whole-brain (gray matter masked), and cluster threshold corrected for multiple comparisons (p<0.005, K >102, FDR<0.05) for differences in activity during the MIST between the 4 groups and the relationship between activity during the MIST and SACL stress score in each group. <h3>Results</h3> E2 administration was associated with different effects in post-menopausal women with or without a history of MDD. In accordance with our previous work, the MDD-/E2+ group had a more negative mood response (higher SACL stress score) to the stress task than the MDD-/E2- group. In contrast, this effect was reversed in women with a history of MDD, where the MDD+/E2+ group had a less negative mood response than the MDD+/E2- group. Additionally, both groups who exhibited more negative mood responses also showed greater activity in emotional perception areas (left inferior frontal and left angular gyri) during the stress condition of the task than the groups which showed less negative mood responses. Group differences were also observed on fMRI. Women who did not receive E2 showed a positive correlation between greater right inferior frontal activity and higher SACL stress score, while the MDD+/E2- group additionally showed a positive correlation between right insula activity and SACL score. The MDD+/E2+ group showed negative correlations between activity in each area and SACL stress score in both the "stress" and "control" conditions of the MIST, while the MDD-/E2+ did not show significant correlations between activity in any area and SACL stress Score. <h3>Conclusions</h3> These results support a differential effect of estrogen administration on emotional and neural responses to psychosocial stress in postmenopausal women with and without a history of MDD. We had previously show that in women without a history of MDD, E2 is associated with a more negative mood response to stress than placebo. The results of this study replicated those findings in women without a history of MDD and show that E2 is also associated with increased activity in brain areas involved in emotion perception and response. Additionally, the result of this study support that the effect of E2 is reversed in women with a history of MDD, such that E2 is associated with a less negative mood response to stress and a differential relationship between activity in brain areas involved in emotion response. This suggests that women with a history of MDD, even while currently euthymic, have both a different mood and neural response to psychosocial stress and may show a beneficial mood effect E2 that is not seen in women without a history of MDD. These results may provide a neurological basis for recurrence risk and the beneficial mood effects of post-menopausal hormone treatment in women with a history of MDD. <h3>Funding</h3> This work was supported by the National Institutes of Aging R01AG021476, the National Institutes of Mental Health H110598, and Vanderbilt CTSA grant UL1 TR002243 from National Center for Advancing Translational Sciences.

Abstract GS4-05: Neoadjuvant chemotherapy (NCT) response in postmenopausal women with clinical stage II or III estrogen receptor positive (ER+) and HER2 negative (HER2-) breast cancer (BC) resistant to endocrine therapy (ET) in the ALTERNATE trial (Alliance A011106)

Abstract Background: Ki67 values &amp;gt;10% 2-4 weeks (wks) after starting neoadjuvant ET (NET) indicates persistent cell proliferation, resistance to ET, and is associated with increased risk of recurrence. The ACOSOG Z1031 trial suggested that these tumors are also relatively chemotherapy (chemo) resistant with a low pathologic complete response (pCR) rate to NCT. The ALTERNATE trial (NCT01953588) is a randomized study of neoadjuvant anastrozole (ANA), fulvestrant (FUL), or ANA + FUL in postmenopausal patients (pt) with newly diagnosed clinical stage II or III ER+ (Allred score 6-8)/HER2- BC. Ki67 &amp;gt;10% at wk 4 or 12 after starting NET triggered triage to NCT of physician choice or weekly paclitaxel. Pts who refused protocol-directed therapy, were not candidates for NCT, or decided to undergo immediate surgery are being followed per protocol. Here we report the rates of pCR and residual cancer burden (RCB) following NCT for pts triaged to NCT due to Ki67 &amp;gt;10% at wk 4 or 12. Results: Of the 1,299 eligible pts randomized to receive ANA, FUL, or ANA + FUL, 286 (22%) had Ki67 &amp;gt;10% at wk 4 or 12. 168 of these 286 pts (58.7%) chose to switch to NCT, 32 went to surgery (11.2%), and 86 discontinued further protocol-directed therapy (30.1%). Among the 168 pts who underwent NCT, the presenting clinical T stages were cT2 (n=113; 67.26%), cT3 (n=47; 27.98%) and cT4 (n=8; 4.76%) and N stages were cN0 (n=82; 48.8%), cN1 (n=75; 44.6%), cN2/3 (n=9; 5.4%) and cNx (n=2; 1.2%). Central ER testing was performed on pre-treatment biopsies and confirmed ER Allred score 6-8 in 155 of 168 (92.2%) pts, with the rest being ER Allred score 4-5 (n=5; 3%), ER- (Allred score 0) (n=2; 1.2%), or not tested (n=6; 3.6%). Most (n=139; 82.7%) were ER+/PR+, while 17.3% (n=29) were ER+/PR-, and tumor grades were G1 (n=10; 6%), G2 (n=99; 58.9%), G3 (n=54; 32.1%), not reported (n=5; 3%). Baseline Ki67 levels prior to NET were &amp;gt;10% in 94% (n=158), ≤10% in 3% (n=5), and not done in 3% (n=5). NCT regimens administered included doxorubicin/cyclophosphamide (AC) followed by paclitaxel (T) (n=60; 35.71%); weekly paclitaxel (n=56; 33.33%), docetaxel/cyclophosphamide (TC) (n=33; 19.65%), other doxorubicin and/or taxane containing regimen (n=17; 10.12%), and cyclophosphamide/methotrexate/fluorouracil (CMF) (n=2; 1.19%). 35 (20.8%) pts did not complete planned course of NCT due to toxicity (n=27) or refusal (n=8). 154 NCT pts underwent surgery (mastectomy in 40.3%, and breast conserving surgery in 59.7%). The path ypT stages were Tis/0 (n=10; 6.5%), T1 (n=62; 40.3%), T2 (n=61; 39.6%), and T3/4 (n=21; 13.6%), and the ypN stages were N0 (n=66; 42.9%), N1 (n=57; 37%), N2/3 (n=30; 19.5%), and Nx (n=1; 0.6%). Among the 168 pts who started on NCT (intent to treat population), there were 8 pCRs (no invasive disease in the breast or lymph nodes) (4.8%; 95% CI: 2.1% to 9.2%). Residual Cancer Burden (RCB) categories include RCB 0 (n=8; 4.8%), RCB 1 (n=15; 8.9%), RCB 2 (n=82; 48.8%), RCB 3 (n=42; 25.0%), and not determined (n=21; 12.5%). Correlations of baseline pt and tumor characteristics with pathology response to NCT will also be presented. Conclusion: In pts with NET-resistant ER+/HER2- BC, salvage NCT is not likely to induce a complete or near complete response. More effective treatments are needed for this high-risk ER+/HER2- pt population. Support: U10CA180821, U10CA180882, U24CA196171, UG1CA189856, U10CA180868 (NRG); NCI BIQSFP, BCRF, Genentech, AstraZeneca. https://acknowledgments.alliancefound.org. Clinical Trials.gov Identifier: NCT01953588 Citation Format: Cynthia X Ma, Vera Suman, A. Marilyn Leitch, Souzan Sanati, Kiran Vij, Gary W Unzeitig, Jeremy Hoog, Mark Watson, Olwen Hahn, Joseph Guenther, Abigail Caudle, Erika Crouch, Horacio Maluf, Amy Tiersten, Monica Mita, Wajeeha Razaq, Tina J Hieken, Yang Wang, Travis Dockter, Jo Anne Zujewski, Anna Weiss, Kelly Hunt, Clifford Hudis, Eric P Winer, Matthew J Ellis, Lisa A Carey, Ann H Partridge. Neoadjuvant chemotherapy (NCT) response in postmenopausal women with clinical stage II or III estrogen receptor positive (ER+) and HER2 negative (HER2-) breast cancer (BC) resistant to endocrine therapy (ET) in the ALTERNATE trial (Alliance A011106) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr GS4-05.

Land vs. water HIIE effects on muscle oxygenation and physiological parameter responses in postmenopausal women

Muscle oxygenation (MO) status is the dynamic balance between O2 utilization and O2 delivery. Low-impact high-intensity interval exercise MO responses in the exercise and recovery stage are still unclear. We compared the differences in MO and physiological parameters between high-intensity interval water-based exercise (WHIIE) and high-intensity interval land bike ergonomic exercise (LBEHIIE) in postmenopausal women. Eleven postmenopausal women completed WHIIE or LBEHIIE in counter-balanced order. Eight sets were performed and each exercise set included high intensity with 80% heart rate reserve (HRR) in 30 s and dynamic recovery with 50% HRR in 90 s. Muscle tissue oxygen saturation index (TSI), total hemoglobin (tHb), oxy-hemoglobin (O2Hb), and deoxy-hemoglobin (HHb) were recorded. Blood lactate, heart rate and rating of perceived exertion (RPE) were measured at pre and post-exercise. Under similar exercise intensity, RPE in WHIIE was lower than that in LBEHIIE. The heart rate in WHIIE was lower than that in LBEHIIE at 1 and 2 min post-exercise. During the dynamic recovery, TSI, tHb, and O2Hb in water were higher than on land. A negative correlation was found between the change in TSI and lactate concentration (r = − 0.664). WHIIE produced greater muscle oxygenation during dynamic recovery. Muscle TSI% was inversely related to blood lactate concentration during exercise in water.

Habitual Exercise and ETB Receptor Responses in Postmenopausal Women

Age‐related declines in endothelial function can be reversed with habitual exercise (HEx) in older men by attenuating the vasoconstricting effects of endothelin‐1 (ET‐1), attributable in part by enhanced ETA receptor activity. Our laboratory has recently demonstrated that ET‐1 contributes to age‐related endothelial dysfunction in postmenopausal women (PMW) via the ETB receptor (ETBR). Although there is evidence for sex‐specific differences in ET‐1 receptor activity with aging, the impact of habitual exercise (HEx) on ET‐1 receptor responses in PMW has yet to be established.PURPOSETo test the hypothesis that ETBR responses would be attenuated in HEx PMW.METHODSIn a retrospective analysis, 30 PMW were grouped by self‐reported weekly exercise. We measured vasodilatory responses to local heating of the skin (laser Doppler flowmetry) during microdialysis perfusions of lactated Ringer’s (Control) and ETBR blockade (BQ‐788, 300nM) in 15 low (LEx: 2±2 d/wk, 57±4 yrs) and 15 high (HEx: 6±1 d/wk, 60±5 yrs) frequency exercisers. 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. We analyzed the impact of weekly exercise frequency on vasodilatory responses to ETBR blockade using a two‐way ANOVA. Data presented are mean ± standard deviation.RESULTSGroups were well‐matched for body mass index (BMI) (LEx: 25±4 vs HEx: 24±2 kg/m2, P=0.31), resting heart rate (LEx: 60±8 vs HEx: 54±9 bpm, P=0.14), and resting mean arterial pressure (LEx: 90±10 vs HEx: 90±8 mmHg, P=0.96). Microvascular endothelial function was similar between LEx (control: 87±9 %CVCmax) and HEx (control: 88±6 %CVCmax, P=0.86). ETBR blockade improved vasodilation in LEx (BQ‐788: 93±7 %CVCmax, P=0.01 vs. control) but not in HEx (BQ‐788: 91±7 %CVCmax, P=0.11). To account for differences in age and time since menopause, we performed a sub‐analysis of age and BMI‐matched early PMW (&lt;5 years since menopause) PMW (LEx, n=4: 53±2 yrs, 24±4 kg/m2; HEx, n=5: 53±3 yrs, 23±2 kg/m2). This sub‐analysis revealed a similar trend of enhanced vasodilation during ETBR blockade in LEx (control: 88±3 vs BQ‐788: 96±4 %CVCmax) but not HEx PMW (control: 87±6 vs BQ‐788: 85±13 %CVCmax; drug*exercise, P=0.07).CONCLUSIONBlocking ETBR improved microvascular endothelial function in LEx, indicating a removal of the vasoconstricting effects of ETBR in LEx but not HEx PMW. Therefore, these data suggest that exercise may attenuate ETBR‐mediated vasoconstriction in PMW. Additional data are needed to determine the impact of exercise on ETA receptor responses in PMW.Support or Funding InformationSupported by NIH R01 HL 146558, P20 GM 113125, AHA 16SDG30700015, and University of Delaware Research Foundation

Vaginal Estrogen Therapy Is Associated With Decreased Inflammatory Response in Postmenopausal Women With Recurrent Urinary Tract Infections.

Vaginal estrogen therapy (VET) has been shown to decrease the risk of recurrent urinary tract infections (UTIs) in postmenopausal women, but the mechanism of action has not been fully described. Our objectives were to assess whether the postmenopausal urine inflammatory profile changes in response to VET. We prospectively enrolled postmenopausal patients into 3 groups: (1) currently using VET without a history of recurrent UTIs (rUTIs); (2) history of UTIs, currently using VET; and (3) history of rUTIs, not using VET but willing to start. We followed patients over 6 to 19 months and collected urine samples at 3 time points. We performed comprehensive cytopathologic analysis, quantitative urine inflammatory scoring, and enzyme-linked immunosorbent assay for interleukin 6. Seventy patients were recruited (group 1, n = 30; group 2, n = 20; group 3, n = 20). Urine from patients in groups 2 and 3 demonstrated increased inflammatory cells, debris, and exfoliated urothelial cells. Quantitative urine inflammatory scores and interleukin 6 were significantly higher in postmenopausal patients with rUTIs not on VET (0.12 vs 0.93, P < 0.05) and decreased significantly after initiating VET (0.93 vs 0.38, P < 0.05). Postmenopausal women with rUTIs on VET demonstrate decreased cell shedding, reduced urine inflammatory scores, and decreased urine interleukin 6. Modulation of the genitourinary inflammatory profile may represent one mechanism through which VET helps prevent rUTIs in postmenopausal women.

Risk factors related to acupuncture response in postmenopausal women with stress urinary incontinence: Secondary analysis of a randomized controlled trial.

Postmenopausal women are at a higher risk of stress urinary incontinence (SUI). In a previous trial, electroacupuncture (EA) was shown to be an effective treatment for women with SUI. Here we present a secondary analysis to investigate the specific factors associated with response to acupuncture therapy among postmenopausal women with SUI.We conducted secondary analysis of data from a multicenter randomized controlled trial. This trial included a baseline period of 1 week and a treatment period of 6 weeks with electroacupuncture (EA) or sham electroacupuncture (SA). The patients were randomly assigned to 2 groups (EA group or SA group). Participants who showed a decrease in urine leakage by at least 50% from baseline level, as measured by 1-hour pad at week 6, were defined as responders. Baseline characteristics associated with response to acupuncture therapy (e.g., demographic, comorbidities, and lifestyle-related factors) were identified by logistic regression analysis and the interactions between treatment assignment and baseline characteristics assessed.This analysis included a total of 349 postmenopausal women, of whom 137 (39.3%) were classified as responders. Response rate in the EA group was significantly higher than that in the SA group (60.9% vs 18.9%, respectively; P < .001). On multivariable logistic regression analysis, only "mean number of urine pads used before treatment" remained a significant predictor of response to therapy (EA or SA). Greater weekly mean number of urine pads used before treatment showed a correlation with non-response to therapy, as the likelihood of clinical response reduced by 5.26% with increase in the weekly mean number of urine pads used (odds ratio 0.947, 95% confidence interval 0.902-0.993; P = .020). The interaction terms were not statistically significant.Postmenopausal women with SUI who used fewer number of pads per week before treatment were more likely to respond to therapy. This study provides valuable insights for pretreatment selection of women with SUI. Specific factors related to the therapeutic effects of acupuncture were not identified and need to be explored in future studies.Trial registration: Clinical Trials.gov: NCT01784172.

Acute physiological and affective responses in postmenopausal women during prescribed and self-selected aerobic exercise:

Few elderly meet current physical activity (PA) guidelines. The limitations for PA adherence is due the barriers found such as displeasure, discomfort, pain and sense of exhaustion. Self-selected exercise has been strategy for PA adherence, due greatest tolerance by aerobic exercise practitioners. The aim of this study was investigate physiological and psychological responses in prescribed and self-selected sessions in postmenopausal women. It was recruited 27 women active. The study consisted 3 moments: familiarization, self-selected, prescribed sessions. The intensity of self-selected session was replicated in prescribed session. There was significant main effect of the time for HR (p=0,047), FS (p=0,009) and Borg scale (p=0,012). Session by time interaction the significant main effect in HR (p&lt;0,001). Significant mean difference was observed for psychological variables FS (p= 0,011), Borg scale (p= 0,016) and ITL (p&lt;0,001). This study demonstrates the self-selected session relationship with greatest affection and low perceived effort exercise when compared to prescribed exercise

Abstract P4-14-15: Prospective study analyzing value of breast Density change predicting ENdocrine therapy response in postmenopausal women taking adjuvant ARomatase inhibitor [DEAR study] (interim analysis)

Abstract Objective : To evaluate the value of breast density change of mammography and breast MRI as a predictive marker for a response to postoperative anti-hormone therapy by targeting ER-positive postmenopausal breast cancer patient Methods : Density change of mammography, breast MRI density being taken just before start of anti-hormone therapy, mammography being performed after 6 months, 1 year, 2 years thereafter and breast MRI being performed 1 year after start of therapy will be measured by volpara and 3D-MR method. Molecular profile including ER expression level that has a relation with response rate to anti-hormone therapy will be analyzed and outcome will be evaluated based on disease free survival and overall survival. Recurrence rate of each group was estimated based on the data of the patients in breast center of Seoul National University Hospital, 2006-2011, who underwent surgery of ER-positive breast cancer. Among 1065 persons, 7.5% (80/1065) showed recurrence rate and among these, recurrence rate of patients who took AI was 6.9% (12/175). Among these, based on MDR 5% cutoff, 1.6% vs 9.8% was represented. By designating recurrence rate as 1.5%, 9.5% and assuming dropout rate by refusal to clinical test as 10%, registration goal was set at total 411 persons based on each 137, 274 persons per each group. Results : (this is interim analysis) From 2012, total 156 patients are enrolled, among them, 32 patients were eliminated (affirmative consent, switched to Tamoxifen, recurrence and etc). From now total 124 patients are on-going to this study. Compare with Non AI group, breast density change of AI group is much decreased from base line study and it is statistically significant. (1 year follow up – base line, 2 year follow up– base line ; -12.2%, - 18.6% vs - 7.6%, -15.3% P-value 0.002, 0.009 respectively) Only one patient was relapsed within 5 year and there were no death. Psychological anxiety, medication compliance and side effects analysis were done. Psychological anxiety about disease and medication were improved as time goes by (p&amp;lt;0.001). But medication compliance and side effects of AI were worsen. (p = 0.178, 0.015 respectively) Other topics will analyze. (DFS and OS, etc.) Discussion : 70% of breast cancer is ER-positive breast cancer. Endocrine therapy (ET) has been clarified as an effective target therapy in large scale, prospective randomized trial and up to the present, it has been settled down as a standard therapeutic method of ER-positive breast cancer. As a result of 20 years' follow-up after intake of AI (aromatase inhibitor) and 20 years' follow-up after intake of tamoxifen, recurrence was represented as 2-2.5% and at present, clear mechanism of such resistance and predictive biomarker have not been clarified. Due to this resistance, all the ER-positive breast cancer patients are forced to receive anti-hormone therapy for 5 years or 10 years. According to the taking AI, breast density is significantly decreased compare Non AI group. Of course need more follow up data and analysis, but we can confirm a meaning of endocrine responsiveness of breast density change being measured after anti-hormone therapy as predictive surrogate. Citation Format: Kim Y, Lee E, Lee H-B, Kim KE, Ju YW, Jung JG, Moon H-G, Noh D-Y, Han W. Prospective study analyzing value of breast Density change predicting ENdocrine therapy response in postmenopausal women taking adjuvant ARomatase inhibitor [DEAR study] (interim analysis) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-14-15.

Progestin enhances vasoconstrictor responses in postmenopausal women receiving estrogen replacement therapy.

Clinical and experimental evidence suggests that the cardioprotective effect of estrogen replacement is due to effects both on scrum lipids and on blood vessels. Current practice includes the use of a progestin in combination with estrogen if the patient still has her uterus: however, little is known about the effects of combination therapy on vascular reactivity. We therefore studied the effects of estrogen alone and with added progestin on forearm vascular resistance at rest, during reactive hyperemia, and after cold pressor stimulation using plethysmography in six healthy, postmenopausal women. Measurements were made before therapy: after giving conjugated estrogen i.v.; followed by a daily oral dose of 0.625 mg for 21 days; and sequentially after the addition of 10 mg of medroxyprogesterone acetate (MPA) for 10 days. Mean blood pressure did not change significantly. After 21 days of estrogen therapy, forearm blood flow, resting vascular resistance, and resistance after cold pressor stimulation did not change significantly. However, after addition of MPA, resting forearm vascular resistance rose significantly from baseline: 25.7 ± 2.7 U (SE) versus 38.3 ± 2.5 (p = 0.004). In addition, forearm vascular resistance rose to a higher level after cold pressor stimulus during combination therapy (32.3 ± 5.9 vs. 58.4 ± 5.7; p = 0.0057) than after estrogen replacement alone (32.3 ± 5.9 vs. 37.7 ± 5.3; p = NS). We conclude that combination hormone replacement therapy results in higher resting vascular resistance and increased pressor responsiveness than does estrogen replacement therapy alone.

Abstract P175: Influence of Age and Estradiol on Blood Pressure Responses to Exercise

An exaggerated pressor response to exercise is associated with increased risk of cardiovascular events. The exercise pressor reflex, comprised of metabolic and mechanically sensitive skeletal muscle afferents, contributes importantly to blood pressure control during exercise. Data in preclinical animal models suggest that estradiol (E2) attenuates the pressor responses to exercise pressor reflex activation, yet it remains unclear if these findings translate to humans. Accordingly, we tested the hypothesis that pressor responses during exercise are augmented in post-menopausal women (PMW) compared to young women (YW), and that E2 administration will attenuate these responses in PMW. Methods: Mean arterial pressure (MAP, Finometer) and heart rate (ECG) were continuously measured in 12 PMW (age 59±2 years) and 16 YW (age 22±1 years) during 2-min of isometric handgrip performed at 30% of maximal voluntary contraction (MVC). Handgrip was immediately followed by 3-min of post-exercise ischemia (PEI), which isolates the muscle metaboreflex. Separately, BP responses during isometric handgrip at 35% MVC and PEI were measured in 6 PMW (age 53±1 years) before and after 1 month of transdermal E2 administration (100 μg/day). Results: Resting MAP was similar between PMW (77±3 mmHg) and YW (80±3 mmHg; P &gt;0.05). During handgrip, the increase in MAP was greater in PMW (Δ20±2mmHg) compared to YW (Δ12±1 mmHg; P &lt;0.05), and this was maintained during PEI (Δ14±1 mmHg PMW vs. Δ9±1 mmHg YW; P &lt;0.05). Estradiol administration decreased resting BP in PMW (MAP 93±3 mmHg vs. 89±3 mmHg; P &lt;0.05). Moreover, the increase in MAP during exercise in PMW was attenuated following estradiol administration (Δ31±8 mmHg vs. Δ20±6 mmHg; P &lt;0.05). There was also a tendency for this reduction in MAP during PEI (Δ22±6 mmHg vs. Δ18±7 mmHg; P =0.08). Conclusions: These preliminary data suggest that PMW exhibit an exaggerated BP response to isometric exercise, due in part to heightened metaboreflex activation, and that estradiol administration can attenuate such responses.

Effect of high complex carbohydrate diet on weight reduction and the metabolic and inflammatory markers in postmenopausal women

Aim: There is evidence of increasing rate of obesity, sub-clinical low-grade inflammation, pre-diabetes and diabetes in postmenopausal women. As obesity and metabolic syndrome are among the major risk factors for cardiovascular diseases, dietary changes can be beneficial for reducing the acute phase inflammatory response and rate of diabetes and pre-diabetes. The aim of this research was to evaluate the effect of high complex carbohydrate diet (HCCD) in treating obesity and in attenuating inflammatory and metabolic responses in postmenopausal women.

Skeletal response to treatment with teriparatide (TPD) after bisphosphonate in post-menopausal women with osteoporosis and a high prevalence of secondary risk factors in real-life setting of a metabolic bone clinic; effect of age and vitamin D status

ABSTRACTPurpose: Teriparatide (TPD) is a skeletal anabolic agent used in patients with severe post-menopausal osteoporosis (PMO) and steroid-induced osteoporosis who are at hish risk of fracture. Predictors of therapeutic response to teriparatide in real-life setting are not well characterised. We investigated potential factors associated with teriparatide response in post-menopausal women with established osteoporosis.Methods: We carried out a retrospective survey of 48 women, aged 73.2 [7.5] years with severe osteoporosis and prevalent fractures treated with TPD according to the NICE criteria. BMD was measured at baseline, 6-12 and 18-24 months at the lumbar spine (LS), total hip (TH) and femoral neck (FN). Bone turnover markers, serum 25 (OH)vitamin D were determined at 3-12 and 12-24 months.Results: BMD increased at 6-12 months (% change mean [SEM] 6.5 [1.1] p = 0.004) and 18-24 months (8.45 % [1.2] p<0.001) at the LS. A significant increase in BMD was observed at FN (3.1 [1.3] % p = 0.02). Changes in BMD at the TH was higher in patients younger than 73 years compared to older women (% change in BMD 4.13 [1.64] % v/s -1.7 [1.1] p = 0.007). Baseline 25 (OH) vitamin D correlated with change in P1NP at 3-12 months (r = 0.45 p = 0.049).Conclusions: TPD-induced changes in BMD at the TH appears may be dependent on age. Vitamin D status may influence the early anabolic effect to TPD. Our data suggest that these factors may be important considerations when initiating and optimising treatment with TPD, although further larger studies are needed to confirm these findings.

Acute Estrogen Does Not Augment the β2 ‐ Adrenergic Receptor Mediated Vasodilation in Postmenopausal Women

IntroductionAcute estrogen infusion augments β2 ‐adrenergic receptor responsiveness in premenopausal women. This suggests an influential role of estrogen in controlling the vasodilator responsiveness via β2 ‐adrenergic receptors in premenopausal women. Postmenopausal women present with a reduced β2 ‐adrenergic receptor responsiveness as compared to premenopausal women. This divergent finding in β2 ‐adrenergic receptor responsiveness could be due to loss of endogenous estrogen postmenopause.ObjectiveHence, the objective of the study was to compare the β2 ‐adrenergic vasodilator responses with and without estrogen in postmenopausal women. We hypothesized that the vasodilator effects during endothelial dependent, independent and during β2 ‐adrenergic agonist infusion would be significantly greater with acute, local estrogen administration.MethodsVenous occlusion plethysmography was used to measure forearm blood flow (FBF) in 8 older (age = 59 ± 1 years) healthy, non‐obese (BMI = 23 ± 1 kg/m2) women. FBF was measured at baseline and during an intra‐arterial infusion of acetylecholine (ACH) at 1.0, 2.0, 4.0, and 8.0 μg/100 ml tissue/min, sodium nitroprusside (NTP) at 0.25, 0.5, 1.0 and 2.0 ug/100 ml tissue/min and terbutaline (β2 agonist) at 0.1, 0.5, 1.0, 2.0 μg/100 ml tissue/min before (with dextrose co‐infusion) and during acute, local intra‐arterial infusion of estrogen (20 ηg/mL at 1 mL/min). Forearm vascular conductance (FVC) was calculated as FBF divided by mean arterial pressure. Area under the curve (AUC) was calculated for the absolute FVC and percent baseline FVC of ACH, NTP and terbutaline.ResultsThere were no significant differences in FVC with estrogen infusion as compared to control during ACH, NTP and all terbutaline doses except dose 2 of ACH (Table 1). The AUC are not significantly different during estrogen (p&gt;0.05) as compared to control for ACH, NTP and terbutaline (figure 1).ConclusionsThese data suggest that acute administration of estrogen, which corresponds to the endogenous levels of estrogen seen in premenopausal women during mid‐cycle, does not augment the β2 ‐adrenergic vasodilator responses in postmenopausal women. Additionally, these data suggest that estrogen infusion does not increase the endothelial dependent and independent vasodilatory capacity in postmenopausal women.Support or Funding InformationHL83947 (MJJ) and Mayo Clinic Women's Health Scholarship (K12 HD065987).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Brachial and Cerebrovascular Functions Are Enhanced in Postmenopausal Women after Ingestion of Chocolate with a High Concentration of Cocoa

Background: Cocoa contains polyphenols that are thought to be beneficial for vascular health.Objective: We assessed the impact of chocolate containing distinct concentrations of cocoa on cerebrovascular function and cognition.Methods: Using a counterbalanced within-subject design, we compared the acute impact of consumption of energy-matched chocolate containing 80%, 35%, and 0% single-origin cacao on vascular endothelial function, cognition, and cerebrovascular function in 12 healthy postmenopausal women (mean ± SD age: 57.3 ± 5.3 y). Participants attended a familiarization session, followed by 3 experimental trials, each separated by 1 wk. Outcome measures included cerebral blood flow velocity (CBFv) responses, recorded before and during completion of a computerized cognitive assessment battery (CogState); brachial artery flow-mediated dilation (FMD); and hemodynamic responses (heart rate and blood pressure).Results: When CBFv data before and after chocolate intake were compared between conditions through the use of 2-factor ANOVA, an interaction effect (P = 0.003) and main effects for chocolate (P = 0.043) and time (P = 0.001) were evident. Post hoc analysis revealed that both milk chocolate (MC; 35% cocoa; P = 0.02) and dark chocolate (DC; 80% cocoa; P = 0.003) induced significantly lower cerebral blood flow responses during the cognitive tasks, after normalizing for changes in arterial pressure. DC consumption also increased brachial FMD compared with the baseline value before chocolate consumption (P = 0.002), whereas MC and white chocolate (0% cocoa) caused no change (P-interaction between conditions = 0.034).Conclusions: Consumption of chocolate containing high concentrations of cocoa enhanced vascular endothelial function, which was reflected by improvements in FMD. Cognitive function outcomes did not differ between conditions; however, cerebral blood flow responses during these cognitive tasks were lower in those consuming MC and DC. These findings suggest that chocolate containing high concentrations of cocoa may modify the relation between cerebral metabolism and blood flow responses in postmenopausal women. This trial was registered at www.ANZCTR.orgau as ACTRN12616000990426.

177 - Non-Enzymatic Antioxidant Response in Postmenopausal Women with Decreased Muscle Strength

Background Menopause is the beginning of aging in woman due to loss of ovarian follicular function that produces an abrupt drop in estrogen levels as well as body and biochemical changes like muscle strength loss and oxidative stress (OS). Objective To determinate OS biomarkers in postmenopausal women with low muscle strength. Methods We carried out a cross-sectional study with 42 premenopausal [PRE] (47.8±1.9 years) and 48 postmenopausal [POS] women (53.9±2.3 years) from Mexico City. We measured as OS biomarkers: plasma lipoperoxides (LPO) by the TBARS assay, serum uric acid (UA) using a Cobas© C111 analyzer, erythrocyte superoxide dismutase (SOD) and glutathione peroxidase (GPx), and total plasma antioxidant status (TAS) with Randox kits, and we calculated SOD/GPx ratio and antioxidant gap. Handgrip strength was measured with a dynamometer; also we measured weight and height and we calculated the body mass index (BMI). An alternative cut-off value of handgrip strength <20 kg was defined according the Sarcopenia European consensus. Results We found that PRE women had good strength and 20 (42%) of the POS women had low handgrip strength; 83 (92%) of the all women were obese (BMI >25 kg/m2). LPO levels were higher, and SOD and GPx activities were lower in POS women with low muscle strength compared with PRE women (control group), although only GPx had low activity statistically significant (58.6±2.9 vs. 69.2±.1 U/gHb, p<0.05). Non-enzymatic antioxidants were statistically higher (p<0.05) in POS women with low muscle strength than control group: TAS 1262±48.2 vs. 1147±29.9 μmol/L, UA 296±21.8 vs. 265±9.5 μmol/L, and GAP 502±46.1 vs. 395±28.4 μmol/L. Conclusion Our findings suggest that there is a non-enzymatic antioxidant response in postmenopausal women with decreased muscle strength. This work was supported by grant UNAM-IN224115.