Postmenopausal Participants Research Articles

Factors associated with the CVD risk factors and body fat pattern of postmenopausal Hindu caste and Lodha tribal populations living in India: An exploratory study

BackgroundLoss in ovarian function during mid-life results in adverse changes in the cardiovascular profile of women. The association between CVD risk factors and menopause differ cross-culturally since several modifiable factors play significant roles in explaining CVD mortality in addition to differences in endogenous estrogen. Very few of the studies from the Indian subcontinent have been concerned with the menopause-specific CVD risk factors, particularly among the tribal groups. Thus, we intended to study the variations in body fat pattern and CVD risk factors between Hindu caste and Lodha tribal postmenopausal women and how these risk factors were associated with differential socio-economic, reproductive and menstrual characteristics and lifestyle variables. The Lodha tribal populations is considered a Particularly Vulnerable Group (PVTG) in this country.MethodsThis cross-sectional study was conducted among the Bengali Hindu caste and Lodha tribal populations of the State of West Bengal, India covering three districts namely Howrah, Jhargram and East Midnapure. A total of 197 postmenopausal participants were recruited for this study (urban caste 69, rural caste 65 and rural Lodha 63). Data on blood glucose and total cholesterol levels, blood pressure, muscle mass, body fat distribution and sociodemographic, reproductive and menstrual history and lifestyle variables were collected following standard protocols. Analysis of variance (ANOVA) was applied to compare blood glucose, total cholesterol and blood pressure levels and body fat measures across the three populations. Stepwise multiple linear regression analysis was performed to find out the factors associated with CVD risk factors. The data were analyzed with the Statistical Package for Social Science version 20.0(IBM corporation, 2011).ResultsThis cross-sectional comparison of women at midlife, though exploratory in nature showed significant differences in body fat pattern and CVD risk factors between caste and tribal groups owing to socioeconomic disparities and, differences in reproductive characteristics and lifestyle factors.ConclusionThe caste and tribal populations differed significantly in body fat pattern and CVD risk factors and in the factors associated with CVD risk suggesting interplay between menopause and modifiable factors in explaining CVD risk factors during mid-life.

Sex Hormones and Calcitonin Gene-Related Peptide in Women With Migraine: A Cross-sectional, Matched Cohort Study.

Sex hormones may modulate calcitonin gene-related peptide (CGRP) release in the trigeminovascular system. We studied CGRP concentrations in plasma and tear fluid in female participants with episodic migraine (EM) and a regular menstrual cycle (RMC), female participants with EM and combined oral contraception (COC), and female participants with EM in the postmenopause. For control, we analyzed 3 corresponding groups of age-matched female participants without EM. Participants with an RMC had 2 visits: during menstruation on menstrual cycle day 2 ± 2 and in the periovulatory period on day 13 ± 2. Participants with COC were examined at day 4 ± 2 of the hormone-free interval (HFI) and between days 7 and 14 of hormone intake (HI). Postmenopausal participants were assessed once at a random time point. Plasma and tear fluid samples were collected at each visit for determination of CGRP levels with an ELISA. A total of 180 female participants (n = 30 per group) completed the study. Participants with migraine and an RMC showed statistically significantly higher CGRP concentrations in plasma and tear fluid during menstruation compared with female participants without migraine (plasma: 5.95 pg/mL [IQR 4.37-10.44] vs 4.61 pg/mL [IQR 2.83-6.92], p = 0.020 [Mann-Whitney U test]; tear fluid: 1.20 ng/mL [IQR 0.36-2.52] vs 0.4 ng/mL [IQR 0.14-1.22], p = 0.005 [Mann-Whitney U test]). In contrast, female participants with COC and in the postmenopause had similar CGRP levels in the migraine and the control groups. In migraine participants with an RMC, tear fluid but not plasma CGRP concentrations during menstruation were statistically significantly higher compared with migraine participants under COC (p = 0.015 vs HFI and p = 0.029 vs HI, Mann-Whitney U test). Different sex hormone profiles may influence CGRP concentrations in people, with current or past capacity to menstruate, with migraine. Measurement of CGRP in tear fluid was feasible and warrants further investigation.

A multicenter, randomized, placebo-controlled study to select the minimum effective dose of estetrol in postmenopausal participants (E4Relief): part 2-vaginal cytology, genitourinary syndrome of menopause, and health-related quality of life.

A phase 2 study showed that 15 mg estetrol (E4) alleviates vasomotor symptoms (VMS). Here, we present the effects of E4 15 mg on vaginal cytology, genitourinary syndrome of menopause, and health-related quality of life. In a double-blind, placebo-controlled study, postmenopausal participants (n = 257, 40-65 y) were randomized to receive E4 2.5, 5, 10, or 15 mg or placebo once daily for 12 weeks. Outcomes were the vaginal maturation index and maturation value, genitourinary syndrome of menopause score, and the Menopause Rating Scale to assess health-related quality of life. We focused on E4 15 mg, the dose studied in ongoing phase 3 trials, and tested its effect versus placebo at 12 weeks using analysis of covariance. Least square (LS) mean percentages of parabasal and intermediate cells decreased, whereas superficial cells increased across E4 doses; for E4 15 mg, the respective changes were -10.81% (P = 0.0017), -20.96% (P = 0.0037), and +34.17% (P < 0.0001). E4 15 mg decreased LS mean intensity score for vaginal dryness and dyspareunia (-0.40, P = 0.03, and -0.47, P = 0.0006, respectively); symptom reporting decreased by 41% and 50%, respectively, and shifted to milder intensity categories. The overall Menopause Rating Scale score decreased with E4 15 mg (LS mean, -3.1; P = 0.069) and across doses was associated with a decreasing frequency and severity of VMS (r = 0.34 and r = 0.31, P < 0.001). E4 demonstrated estrogenic effects in the vagina and decreased signs of atrophy. E4 15 mg is a promising treatment option also for important menopausal symptoms other than VMS.

Lifetime Cumulative Effect of Reproductive Factors on Stroke and Its Subtypes in Postmenopausal Chinese Women: A Prospective Cohort Study.

Multiple reproductive factors are associated with stroke. Little is known about the cumulative effects of reproductive factors during a reproductive life course on stroke and its subtypes, especially among female Chinese individuals. The objective of this study was to assess the associations of lifetime cumulative estrogen exposure due to reproductive factors with stroke and its etiologic subtypes among postmenopausal Chinese women. Postmenopausal women without prior stroke at baseline (2004-2008) were selected from the China Kadoorie Biobank (CKB). Lifetime cumulative estrogen exposure due to reproductive factors was assessed using 3 composite indicators: reproductive lifespan (RLS), endogenous estrogen exposure (EEE), and total estrogen exposure (TEE). Stroke and its subtypes, ischemic stroke (IS), intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH), were identified through linkage to a disease registry system and health insurance data during follow-up (2004-2015). Multivariable-adjusted Cox proportional hazards regression models were applied to estimate the adjusted hazard ratio (aHR) and 95% CIs for the risk of stroke by quartiles of RLS, EEE, and TEE, respectively. A total of 122,939 postmenopausal participants aged 40-79 years without prior stroke at baseline were included. During a median follow-up period of 8.9 years, 15,139 cases with new-onset stroke were identified, including 12,853 cases with IS, 2,580 cases with ICH, and 269 cases with SAH. Compared with the lowest quartile (Q1) of RLS, the highest quartile (Q4) had a lower risk of total stroke (aHR: 0.95, 95% CI 0.92-0.98), IS (aHR: 0.95, 95% CI 0.92-0.98), and ICH (aHR: 0.87, 95% CI 0.81-0.94). Both EEE and TEE displayed a graded association with the subsequent descending risk of total stroke (aHR for Q4 vs Q1: EEE: 0.85, 95% CI 0.82-0.89; TEE: 0.87, 95% CI 0.84-0.90), IS (aHR for Q4 vs Q1: EEE: 0.86, 95% CI 0.83-0.90; TEE: 0.86, 95% CI 0.83-0.89), and ICH (EEE: 0.73, 95% CI 0.65-0.81; TEE: 0.83,95% CI 0.76-0.91), with a p for trend < 0.001 for all these associations. Individuals' cumulative estrogen exposure due to reproductive factors could potentially be a valuable indicator for risk stratification of stroke events after menopause.

Reproductive factors and metabolic syndrome among Chinese women aged 40 years and older.

The aim of this study is to explore the relationship between reproductive variables and the prevalence of metabolic syndrome (MetS) and its components among Chinese women aged 40 years and older. A cross-sectional study was conducted among 4453 women aged 40 years and older in Guangxi, China. The associations between women's reproductive factors and MetS were analyzed using a logistic regression model. The prevalence of MetS was 23.9% in this population. Women with MetS were mostly older, more likely to be postmenopausal, and had higher parity. Compared to women with one prior live birth, those with three or more live births had the highest odds of having MetS (odds ratio [OR]=1.56; 95% CI, 1.23-1.99). Similarly, compared to premenopausal women, postmenopausal participants had higher odds of having MetS (OR=1.86; 95% CI, 1.49-2.31). No associations were observed between MetS and abortion or with age at menarche. Our study suggests that multiparity and menopausal status may be associated with the development of MetS. The inconsistency seen in epidemiological research to date calls for further investigation.

The role of advanced glycation end products in fracture risk assessment in postmenopausal type 2 diabetic patients.

The objective of this study was to analyze the quantitative association between advanced glycation end products (AGEs) and adjusted FRAX by rheumatoid arthritis (FRAX-RA) in postmenopausal type 2 diabetic (T2D) patients. The optimal cutoff value of AGEs was also explored, which was aimed at demonstrating the potential value of AGEs on evaluating osteoporotic fracture risk in postmenopausal T2D patients. We conducted a cross-sectional study including 366 postmenopausal participants (180 T2D patients [DM group] and 186 non-T2D individuals [NDM group]). All the subjects in each group were divided into three subgroups according to BMD. Physical examination, dual-energy x-ray absorptiometry (DXA), and serum indicators (including serum AGEs, glycemic parameters, bone turnover markers and inflammation factors) were examined. The relationship between FRAX-RA, serum laboratory variables, and AGEs were explored. The optimal cutoff value of AGEs to predict the risk of osteoporotic fracture was also investigated. Adjusting the FRAX values with rheumatoid arthritis (RA) of T2D patients reached a significantly increased MOF-RA and an increasing trend of HF-RA. AGEs level was higher in the DM group compared to the NDMs, and was positively correlated with MOF-RA (r=0.682, P<0.001) and HF-RA (r=0.677, P<0.001). The receiver operating characteristic curve analysis revealed that the area under the curve was 0.804 (P<0.001), and the optimal AGEs cut-off value was 4.156mmol/L. Subgroup analysis for T2D patients revealed an increase in TGF-β, IL-6 and SCTX in the osteoporosis group, while a decreased PINP in the osteoporosis group compared to the other two subgroups. AGEs were positively associated with FBG, HbA1c, HOMA-IR, S-CTX, IL-6 and TGF-β in T2D patients, and negatively associated with PINP. RA-adjusted FRAX is a relevant clinical tool in evaluating fracture risk of postmenopausal T2D patients. Our study analyzed the relationship between AGEs and FRAX-RA, and explored the threshold value of AGEs for predicting fracture risk in postmenopausal T2D patients. AGEs were also associated with serum bone turnover markers and inflammation factors, indicating that the increasing level of AGEs in postmenopausal T2D patients accelerated the expression of inflammatory factors, which led to bone metabolism disorders and a higher risk of osteoporotic fractures.

Improvements in skin quality parameters in postmenopausal participants after use of topical growth factor serum.

Photodamage can induce skin aging processes that can be particularly concerning for postmenopausal women. Growth factors from hypoxic human fibroblast-conditioned media have demonstrated improvements in skin quality parameters. The aim of the study was to assess efficacy and tolerability of topical combination-treatment hypoxic growth factor serum (TNS A+) in postmenopausal women with moderate to severe facial photodamage. In this 12-week, open-label, single-center study, participants used TNS A+ serum twice daily. Postmenopausal women (40-65 years of age) with Fitzpatrick skin types I-VI and modified Griffiths scale scores 4-9 were eligible. Clinical and participant-reported assessments were evaluated at Weeks 6 and 12. Statistical significance was defined as p≤ 0.05. There were 17 enrolled participants. TNS A+ treatment demonstrated significant improvements from baseline in fine lines and wrinkles in periocular, forehead, and cheek areas at Week 12 and the perioral area at Weeks 6 and 12. Significant improvements from baseline in coarse lines and wrinkles were observed for the perioral area at Week 12 and periocular and cheek areas at Weeks 6 and 12. Improvements in overall photodamage, skin tone evenness, and tactile roughness were significantly greater at Weeks 6 and 12 versus baseline. Most participants reported TNS A+ made their skin look and feel smooth, soft, and rejuvenated; improved skin radiance; made lines and wrinkles less apparent; and improved skin texture. No treatment-related adverse events were reported. The TNS A+ regimen was well tolerated and provided significant improvements in skin quality in postmenopausal women with moderate to severe facial photodamage.

RF34 | PMON202 The Human Metabolic Profile of Estetrol

Abstract Objectives Estetrol (E4), a native estrogen produced by the fetal human liver, has four hydroxyl-groups, making it structurally distinct from other estrogens. We determined the human metabolic profile of E4, which is recently marketed combined with drospirenone as a novel contraceptive and is currently in development for the relief of menopausal symptoms. Method: We studied the in vitro metabolism of E4 using human hepatocytes, human liver microsomes and recombinant CYP enzymes in reaction phenotyping studies to evaluate the role of human cytochrome P450 enzymes, UDP-glucuronosyltransferases (UGT) and sulfotransferases (SULT). Furthermore, we evaluated the in vivo metabolism of E4 in an open-label, non-randomised phase 1 human absorption, distribution, metabolism, and excretion study, in which six healthy postmenopausal participants received a single oral solution containing 15 mg [14C]-E4. We analysed blood (up to 240h), urine and faecal samples (up to 312h). Metabolite profiling and identification was performed using liquid chromatography with tandem mass spectrometry. Results The in vitro studies showed that E4 undergoes extensive phase 2 metabolism to form glucuronide and sulphate conjugates. UGT2B7 is the key enzyme catalysing the direct glucuronidation of E4 and SULT1E1 is the dominant sulfotransferase for sulphate conjugation in vitro. Unlike for other estrogens, oxidative phase 1 metabolism by P450 enzymes does not play a major role in the metabolism of E4. Following oral administration of E4 to humans, the major metabolites observed in human plasma were E4-16-glucuronide, E4-3-glucuronide and E4-glucuronide-sulfate (respectively 62%, 17% and 9% of radioactivity at the time of maximum plasma concentration [Tmax]). At Tmax, unchanged E4 accounts for only 7.5% of plasma radioactivity. Main metabolites quantified in urine during the first 6 hours after administration were E4-16-glucuronide and E4-3-glucuronide (respectively 77.4% and 16.5% of urine radioactivity). Approximately 69% of the total administered radioactivity was recovered in urine and 22% in faeces. Mass spectrometry showed that E4 was not present in urine but was detected in faeces and that E4 is not converted back into one of the other natural estrogens (estriol, estradiol, estrone). Conclusions Altogether, these data suggest that E4 has a unique metabolic profile. E4 is a terminal end-product of estrogen metabolism, which is not converted back, in vivo, into active metabolites like estriol, estradiol or estrone. Unlike for other estrogens, CYP450 enzymes do not play a major role in the metabolic pathway of E4. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m., Monday, June 13, 2022 12:48 p.m. - 12:53 p.m.

Racial differences in anthropometric measures as risk factors for triple-negative breast cancer.

The incidence of triple-negative breast cancer (TNBC) is higher in Black women compared to White women which is not explained by racial differences in body mass index (BMI). As BMI has limitations as an anthropometric measure, we used different anthropometric measures to examine associations with TNBC by race. Of 161,808 postmenopausal participants in Women's Health Initiative, eligible were a subsample of 121,744 White and Black postmenopausal women enrolled from 1993 to 1998, 50-79years of age with anthropometric measures who were followed for breast cancer incidence until March 2019. At entry, BMI, waist circumference (WC), and waist-hip ratio (WHR) were measured using standardized methods. Breast cancers were verified by central medical record review. Associations between anthropometric measures and triple-negative breast cancer risk were examined using Cox proportional hazards regression models. After 17.6years (median) follow-up, there were 87 Black women and 529 White women with incident triple-negative breast cancer. Overall, there were no significant associations between anthropometric measures and risk of triple-negative breast cancer. However, compared to White women with normal BMI, White women with obesity (BMI ≥ 30) (HR 0.76, 95% CI 0.60, 0.96) were significantly associated with a lower risk of triple-negative breast cancer. And larger waist circumference (HR per centimeter 0.99, 95% CI 0.99, 1.00) was significantly associated with a lower risk of triple-negative breast cancer among White women. Overall, among postmenopausal women, anthropometric measures were not associated with risk of TNBC. The association among White women with larger waist circumference and women with obesity with a lower risk of triple-negative breast cancer needs further confirmation.

Menopausal symptoms and hormone therapy in women with multiple sclerosis: A baseline-controlled study

BackgroundDepression, sleep disturbances, and cognitive difficulties impair the quality of life in people with multiple sclerosis (MS). Similar symptoms are also frequent during the menopausal transition. In clinical practice, it is important to consider the multifactorial causes of these overlapping symptoms and the potential benefits of menopausal hormone therapy (MHT). The objective of this study was to evaluate vasomotor symptoms (VMS), mood, sleep, and cognition of menopausal women with and without MS at baseline and during one year of MHT. MethodsIn this prospective baseline-controlled study, peri- and early postmenopausal participants with (n=14) and without (n=13) MS received MHT containing 1 or 2 mg of estradiol and cyclical 10 mg dydrogesterone for one year. VMS frequency, depressive symptoms (measured by Beck Depression Inventory), insomnia severity (Insomnia Severity Index), and cognitive performance (Paced Auditory Serial Addition Test; PASAT, Symbol Digit Modalities Test; SDMT) were evaluated at baseline and at 3 and 12 months of treatment. Differences in the outcome measures between groups at baseline were assessed using the Mann-Whitney U test. Changes during follow-up compared to baseline within groups were evaluated by Wilcoxon Signed Ranks Test. P < 0.05 was considered for statistical significance. MS activity was monitored by clinical assessment and brain MRI at baseline and at 12 months. ResultsDepressive symptoms were more common in MS group, while vasomotor and insomnia symptoms were equally common. During follow-up with MHT, VMS frequency decreased in both groups. Depressive symptoms decreased at 3 months (p = 0.031 with MS; p = 0.024 without MS) and the reduction was sustained at 12 months (p = 0.017; p = 0.042, respectively). Alleviation in insomnia symptoms was seen in participants without MS at 3 months (p = 0.029) and in those participants with MS suffering insomnia at baseline (p = 0.016 at 3 months; p = 0.047 at 12 months). Both groups improved their performance in PASAT, but no significant change was observed in SDMT. MS activity at baseline was mainly stable, and no increase in activity was detected during MHT. ConclusionImprovements in vasomotor, depressive, and insomnia symptoms observed during one year of MHT are encouraging and suggest that larger placebo-controlled studies of MHT in women with MS are warranted. Cognitive implications were inconclusive because the findings in PASAT likely result from practice effect. MHT did not show any adverse effect on MS activity and increasing safety data will hopefully facilitate patient recruitment for future studies.

A survey of medical cannabis use during perimenopause and postmenopause.

Expanding access to legal cannabis has dovetailed with increased interest in medical cannabis (MC) use; however, there is a paucity of research examining MC use to alleviate menopause-related symptoms. This survey study assessed patterns of MC use in perimenopausal and postmenopausal individuals. Participants (perimenopausal, n = 131; postmenopausal, n = 127) completed assessments of menopause-related symptomatology and cannabis use, including modes of use, type of use, and menopause-related symptoms addressed by MC use. Most participants reported current cannabis use (86.1%) and endorsed using MC for menopause-related symptoms (78.7%). The most common modes of use were smoking (84.3%) and edibles (78.3%), and the top menopause-related symptoms for MC use were sleep disturbance (67.4%) and mood/anxiety (46.1%). Relative to postmenopausal participants, perimenopausal participants reported significantly worse menopause-related symptomatology on the vasomotor and psychosocial subscales of the Menopause-Specific Quality of Life Questionnaire ( P s ≤ 0.04), including greater burden of anxiety ( P = 0.01) and hot flash ( P = 0.04) symptoms. In addition, perimenopausal participants reported higher incidence of depression ( P = 0.03) and anxiety diagnoses ( P < 0.01), as well as increased use of MC to treat menopause-related mood/anxiety symptoms relative to postmenopausal participants ( P = 0.01). Results suggest that many individuals are currently using MC as an adjunctive treatment for menopause-related symptoms, particularly sleep disturbance and mood/anxiety. Future research should examine the impact of different MC use characteristics (e.g., cannabinoid profiles) on the efficacy of MC use for menopause-related symptoms. Increased severity and prevalence of mood and anxiety symptoms in perimenopausal participants suggest promising targets for clinical trials of cannabinoid-based therapies.

Associations of coffee/caffeine consumption with postmenopausal breast cancer risk and their interactions with postmenopausal hormone use.

We investigated the association of coffee and caffeine with breast cancer (BCa) risk, overall and by ER/PR status. We also examined potential interactions of coffee and caffeine with postmenopausal hormone use. Our study included 77,688 postmenopausal participants from the Women's Health Initiative observational study cohort without a history of any cancer at baseline (except non-melanoma skin) and with valid Food Frequency Questionnaire data and complete data on dietary caffeine. Regular coffee (none, 1, 2-3, 4-5, and ≥ 6 cups/day) and caffeine (tertiles) were assessed at baseline. Information on BCa risk factors was collected at baseline. The associations were examined using survival analysis, accounting for death as a competing risk. The median follow-up time for our cohort was 18.3years. During the follow-up, 5005 women developed invasive breast cancer. In multivariable analysis, coffee was not associated with the overall invasive BCa risk. Higher caffeine intake was mildly associated with increased BCa risk (2nd vs. 1st tertile SHR = 1.10, 95% CI 1.03-1.18, 3rd vs. 1st tertile SHR-1.05, 95% CI 0.98-1.13, overall p = 0.03). We found no interaction of coffee/caffeine with postmenopausal hormone use (p interaction = 0.44 and 0.42, respectively). In the exploratory analysis by ER/PR status, we found a positive association of caffeine with ER+ /PR+ BCa (2nd vs. 1st tertile SHR = 1.17, 95% CI 1.07-1.28, 3rd vs. 1st tertile SHR = 1.13, 95% CI 1.03-1.24, overall p = 0.002); no associations were observed for ER-/PR- tumors. Coffee was not associated with the risk of ER+ /PR+ or ER-/PR- tumors. We found no associations of coffee with BCa risk, overall and for ER/PR-defined tumor subtypes. The higher caffeine consumption was mildly and positively associated with the overall BCa risk and with ER+ /PR+ tumors.

Anthropometric measures and breast cancer risk among Hispanic women in Puerto Rico.

Increased risk of postmenopausal breast cancer associated with anthropometric measures including Body Mass Index (BMI), adult weight gain, and waist circumference has been observed in North American and European populations, but little evidence is available for Hispanic women. Breast cancer is the leading type of cancer, and leading cause of cancer-related deaths among Hispanic women in Puerto Rico (PR). However, compared with the United States, breast cancer incidence rates are lower but increasing more rapidly. To examine associations between anthropometric characteristics and breast cancer risk in Hispanic women in PR. Data from a population-based case-control study in the San Juan metropolitan region (cases = 315; controls = 348) were used to examine associations between anthropometric measures and breast cancer risk, also considering menopausal status and hormone therapy (HT). Among premenopausal participants, there was a significant trend for lower odds of breast cancer with higher BMI and borderline significant with higher waist to height ratio (WHtR). For postmenopausal participants, a significant trend for lower odds of breast cancer was observed with higher WHtR, and waist to hip ratio (WHR), borderline significant with higher BMI, and higher odds with height. Among postmenopausal participants using HT, a significant trend for lower odds of breast cancer was observed with higher waist circumference, WHtR, WHR, and body shape index. Our study provides evidence of anthropometric differences in relation to breast cancer risk in PR compared to previous studies. Future studies should include analyses of fat and lean mass distribution, and hormone receptor status to further understand anthropometry and breast cancer risk among Hispanic women.

Association of infertility with atherosclerotic cardiovascular disease among postmenopausal participants in the Women’s Health Initiative

To investigate the association of infertility with atherosclerotic cardiovascular disease (ASCVD) among postmenopausal participants in the Women's Health Initiative (WHI). We hypothesized that nulliparity and pregnancy loss may reveal more extreme phenotypes of infertility, enabling further understanding of the association of infertility with ASCVD. Prospective cohort study. Forty clinical centers in the United States. A total of 158,787 postmenopausal participants in the Women's Health Initiative cohort. Infertility, parity, and pregnancy loss. The primary outcome was risk of ASCVD among women with and without a history of infertility, stratified by history of live birth and pregnancy loss. Cox proportional-hazards models were adjusted for demographics and risk factors for ASCVD. Among 158,787 women, 25,933 (16.3%) reported a history of infertility; 20,427 (80%) had at least 1 live birth; and 9,062 (35%) had at least 1 pregnancy loss. There was a moderate overall association between infertility and ASCVD (adjusted hazard ratio, 1.02; 95% confidence interval [CI], 0.99-1.06) over 19 years of follow-up. Among nulliparous women, infertility was associated with a 13% higher risk of ASCVD (95% CI, 1.04-1.23). Among nulliparous women who had a pregnancy loss, infertility was associated with a 36% higher risk of ASCVD (95% CI, 1.09-1.71). Women with a history of infertility overall had a moderately higher risk of ASCVD compared with women without a history of infertility. Atherosclerotic cardiovascular disease risk was much higher among nulliparous infertile women and among nulliparous infertile women who also had a pregnancy loss, suggesting that in these more extreme phenotypes, infertility may be associated with ASCVD risk.

Relation of Menopause With Cardiovascular Risk Factors in South Asian American Women (from the MASALA Study)

The menopausal transition is a time of accelerating risk of cardiovascular disease (CVD), and promoting cardiovascular health during midlife is an important period of time to prevent CVD in women. The association of menopause with cardiovascular risk factors or subclinical atherosclerosis has not previously been evaluated in South Asian American women, a population with a disproportionately higher CVD burden compared with other race/ethnic groups. The objective of this study was to evaluate the association of menopause with CVD risk factors and subclinical cardiometabolic disease markers. We studied women aged 40 to 84 years from the Mediators of Atherosclerosis in South Asians Living in America study. The association of self-reported menopausal status with multiple demographic and clinical variables was assessed with linear and logistic regression adjusted for age and cardiovascular health behaviors. In a secondary ("age-restricted") analysis, postmenopausal participants outside the age range of premenopausal participants were excluded. In the age-restricted sample, menopause was associated with a higher adjusted odds of hypertension (odds ratio=1.19, 95% confidence interval [CI] 1.02 to 1.41), and higher systolic blood pressure (β=6.34, 95% CI 0.82 to 11.87), and significantly higher subcutaneous fat area (β=42.8, 95% CI 5.8 to 91.4). No significant associations between menopause and ectopic fat deposition, coronary artery calcium, or carotid intima-media thickness were observed. In South Asian American women in the Mediators of Atherosclerosis in South Asians Living in America study, menopause was associated with cardiovascular risk factors and higher subcutaneous fat deposition. Menopausal status is an important factor to examine and address CVD risk factors.

Association of dietary and plasma carotenoids with urinary F2-isoprostanes.

Carotenoids may protect against chronic diseases including cancer and cardiometabolic disease by mitigating oxidative stress and/or inflammation. We cross-sectionally evaluated associations between carotenoids and biomarkers of oxidative stress or inflammation. From 2003 to 2009, the Sister Study enrolled 50,884 breast cancer-free US women aged 35-74. Post-menopausal participants (n = 512) were randomly sampled to measure carotenoids and biomarkers of oxidative stress. Dietary carotenoid consumption was assessed using a validated 110-item Block 1998 food frequency questionnaire; use of β-carotene-containing supplements was also assessed. Plasma carotenoids were quantified, adjusting for batch. Urinary markers of lipid peroxidation, 8-iso-prostaglandin F2α (8-iso-PGF2α) and its metabolite (8-iso-PGF2α-M) were also measured. Since the biomarker 8-iso-PGF2α can reflect both oxidative stress and inflammation, we used a modeled 8-iso-PGF2α to prostaglandin F2α ratio approach to distinguish effects reflecting oxidative stress versus inflammation. Multivariable linear regression was used to assess the associations of dietary and plasma carotenoids with the estimated biomarker concentrations. Total plasma carotenoids were inversely associated with 8-iso-PGF2α-M concentrations (P for trend across quartiles = 0.009). Inverse trends associations were also seen for α-carotene and β-carotene. In contrast, lutein/zeaxanthin showed associations with both 8-iso-PGF2α and 8-iso-PGF2α-M concentrations. The inverse association for total carotenoids appeared to be specific for oxidative stress (chemical 8-iso-PGF2α; Phighest vs. lowest quartile = 0.04 and P for trend across quartiles = 0.02). The pattern was similar for α-carotene. However, lutein/zeaxanthin tended to have a stronger association with enzymatic 8-iso-PGF2α, suggesting an additional anti-inflammatory effect. Supplemental β-carotene was inversely associated with both 8-iso-PGF2α and 8-iso-PGF2α-M concentrations, as well as with both chemical and enzymatic 8-iso-PGF2α. Dietary carotenoids were not associated with either biomarker. Plasma carotenoids and supplemental β-carotene were associated with lower concentrations of 8-iso-PGF2α metabolite. Plasma carotenoids associations may reflect antioxidant effects.

Metabolic effects of menopause: a cross-sectional characterization of body composition and exercise metabolism.

To evaluate body composition, fat distribution, and metabolism at rest and during exercise in premenopausal, perimenopausal, and postmenopausal women. This cross-sectional study in 72 women ages 35 to 60 years evaluated body composition via a fourcompartment model, fat distribution using dual-energy x-ray absorptiometry-derived android to gynoid ratio, metabolic measures via indirect calorimetry, and lifestyle factors using surveys. One-way analyses of variance and one-way analyses of covariance covaried for age and hormone levels (estrogen and progesterone) were used to compare groups. Body fat percent was significantly lower in premenopausal than perimenopausal women (mean difference ± standard error: - 10.29 ± 2.73%, P = 0.026) despite similarities in fat mass and fat-free mass between groups (P≥0.217). Android to gynoid ratio was significantly lower in premenopausal than perimenopausal women (MD ± SE: -0.16 ± 0.05 a.u., P = 0.031). Resting energy expenditure was similar between groups (P = 0.999). Fat oxidation during moderate intensity cycle ergometer exercise was significantly greater in premenopausal than postmenopausal women (MD ± SE: 0.09 ± 0.03 g/min, P = 0.045). The change in respiratory exchange ratio between rest and moderate intensity exercise was significantly lower in premenopausal women than peri- (MD ± SE: -0.05 ± 0.03 a.u., P = 0.035) and postmenopausal women (MD ± SE: -0.06 ± 0.03 a.u., P = 0.040). Premenopausal women reported significantly fewer menopause symptoms than peri- (MD ± SE: -6.58 ± 1.52 symptoms, P = 0.002) and postmenopausal participants (MD ± SE: -4.63 ± 1.52 symptoms, P = 0.044), while similarities between groups were observed for lifestyle factors including diet and physical activity (P>0.999). Perimenopause may be the most opportune window for lifestyle intervention, as this group experienced the onset of unfavorable body composition and metabolic characteristics. http://links.lww.com/MENO/A932.

21-Gene Assay to Inform Chemotherapy Benefit in Node-Positive Breast Cancer

BackgroundThe recurrence score based on the 21-gene breast-cancer assay has been clinically useful in predicting a chemotherapy benefit in hormone-receptor–positive, human epidermal growth factor receptor 2 (HER2)–negative, axillary lymph-node–negative breast cancer. In women with positive lymph-node disease, the role of the recurrence score with respect to predicting a benefit of adjuvant chemotherapy is unclear.MethodsIn a prospective trial, we randomly assigned women with hormone-receptor–positive, HER2-negative breast cancer, one to three positive axillary lymph nodes, and a recurrence score of 25 or lower (scores range from 0 to 100, with higher scores indicating a worse prognosis) to endocrine therapy only or to chemotherapy plus endocrine (chemoendocrine) therapy. The primary objective was to determine the effect of chemotherapy on invasive disease–free survival and whether the effect was influenced by the recurrence score. Secondary end points included distant relapse–free survival.ResultsA total of 5083 women (33.2% premenopausal and 66.8% postmenopausal) underwent randomization, and 5018 participated in the trial. At the prespecified third interim analysis, the chemotherapy benefit with respect to increasing invasive disease–free survival differed according to menopausal status (P=0.008 for the comparison of chemotherapy benefit in premenopausal and postmenopausal participants), and separate prespecified analyses were conducted. Among postmenopausal women, invasive disease–free survival at 5 years was 91.9% in the endocrine-only group and 91.3% in the chemoendocrine group, with no chemotherapy benefit (hazard ratio for invasive disease recurrence, new primary cancer [breast cancer or another type], or death, 1.02; 95% confidence interval [CI], 0.82 to 1.26; P=0.89). Among premenopausal women, invasive disease–free survival at 5 years was 89.0% with endocrine-only therapy and 93.9% with chemoendocrine therapy (hazard ratio, 0.60; 95% CI, 0.43 to 0.83; P=0.002), with a similar increase in distant relapse–free survival (hazard ratio, 0.58; 95% CI, 0.39 to 0.87; P=0.009). The relative chemotherapy benefit did not increase as the recurrence score increased.ConclusionsAmong premenopausal women with one to three positive lymph nodes and a recurrence score of 25 or lower, those who received chemoendocrine therapy had longer invasive disease–free survival and distant relapse–free survival than those who received endocrine-only therapy, whereas postmenopausal women with similar characteristics did not benefit from adjuvant chemotherapy. (Funded by the National Cancer Institute and others; RxPONDER ClinicalTrials.gov number, NCT01272037.)

Low-Intensity Extracorporeal Shock Wave Therapy Promotes Bladder Regeneration and Improves Overactive Bladder Induced by Ovarian Hormone Deficiency from Rat Animal Model to Human Clinical Trial.

Postmenopausal women with ovary hormone deficiency (OHD) are subject to overactive bladder (OAB) symptoms. The present study attempted to elucidate whether low-intensity extracorporeal shock wave therapy (LiESWT) alters bladder angiogenesis, decreases inflammatory response, and ameliorates bladder hyperactivity to influence bladder function in OHD-induced OAB in human clinical trial and rat model. The ovariectomized (OVX) for 12 months Sprague–Dawley rat model mimicking the physiological condition of menopause was utilized to induce OAB and assess the potential therapeutic mechanism of LiESWT (0.12 mJ/mm2, 300 pulses, and 3 pulses/second). The randomized, single-blinded clinical trial was enrolled 58 participants to investigate the therapeutic efficacy of LiESWT (0.25 mJ/mm2, 3000 pulses, 3 pulses/second) on postmenopausal women with OAB. The results revealed that 8 weeks’ LiESWT inhibited interstitial fibrosis, promoted cell proliferation, enhanced angiogenesis protein expression, and elevated the protein phosphorylation of ErK1/2, P38, and Akt, leading to decreased urinary frequency, nocturia, urgency, urgency incontinence, and post-voided residual urine volume, but increased voided urine volume and the maximal flow rate of postmenopausal participants. In conclusion, LiESWT attenuated inflammatory responses, increased angiogenesis, and promoted proliferation and differentiation, thereby improved OAB symptoms, thereafter promoting social activity and the quality of life of postmenopausal participants.

Dance practice modifies functional fitness, lipid profile, and self-image in postmenopausal women.

The aim of the present study was to analyze the effects of dance practice on body composition, metabolic profile, functional fitness, and self-image/self-esteem in postmenopausal women. A total of 36 postmenopausal participants (mean age 57 years) danced three times per week for 90 minutes each day and were evaluated before and after 16 weeks. The parameters evaluated were body composition (body fat and lean mass), blood lipids, functional fitness, self-image, and self-esteem. Statistical analysis was done using Student t test for paired samples and the Wilcoxon test with P values less than 0.05 considered statistically significant. Lower triglycerides (baseline = 156.5 ± 17.0 mg/dL; after 16-weeks = 131.5 ± 12.9 mg/dL; P < 0.01), higher high-density lipoprotein cholesterol (baseline = 55.4 ± 15.9 mg/dL; after 16 weeks = 60.0 ± 15.4 mg/dL; P < 0.001), and higher total cholesterol (baseline = 199.5 ± 26.8 mg/dL; after 16 weeks = 211.8 ± 35.7 mg/dL; P < 0.01) levels were observed in postmenopausal women. Dance intervention improved coordination (baseline = 8.6 ± 2.6; after 16 weeks = 6.7 ± 1.6; P < 0.001), agility (baseline = 55.9 ± 8.8; after 16 weeks = 64.1 ± 8.3; P < 0.001), and aerobic capability (baseline = 446.8 ± 63.4; after 16 weeks = 377.4 ± 53.8; P < 0.001). Classification of general function fitness index (GFFI) was considered regular at baseline (GFFI of 200-299), but improved after 16 weeks of dance practice (GFFI of 300-399, P < 0.001). The 16-week dance intervention was effective in improving not only the lipid profile and functional fitness of postmenopausal women, but also self-image and self-esteem.