Browsing by Subject "Postmenopause"
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Item Abdominal visceral and subcutaneous adipose tissue associations with postmenopausal breast cancer incidence(Oxford University Press, 2025) Bea, Jennifer W.; Ochs-Balcom, Heather M.; Valencia, Celina I.; Chen, Zhao; Blew, Robert M.; Lind, Kimberly E.; Caan, Bette J.; Roe, Denise J.; Rohan, Thomas E.; Reeves, Katherine W.; Manson, JoAnn E.; Ballinger, Tarah; Reding, Kerryn W.; Follis, Shawna; Ziller, Shelby G.; Odegaard, Andrew O.; Medicine, School of MedicineBackground: Obesity, classified by body mass index (BMI), is associated with higher postmenopausal breast cancer (BCa) risk. Yet, the associations between abdominal visceral (VAT) and subcutaneous adipose tissue (SAT) with BCa are unclear. Methods: We assessed BCa associations with abdominal VAT and SAT in a prospective cohort of postmenopausal women without a history of cancer and with 27 years follow-up (N = 9950), during which all new cancers were adjudicated. Dual-energy x-ray absorptiometry scans assessed adiposity at baseline, year 3, and year 6. Competing-risks multivariable sub-hazard ratios (SHR), with adjustments for sociodemographic, behavioral, reproductive, and anthropometric characteristics, were estimated for baseline and time-dependent associations between VAT, SAT, and incident BCa. Results: Participants averaged 63.3 ± 7.4 years of age and a BMI of 28.20 ± 5.72 kg/m2 at baseline. The models included 738 incident BCa case patients (N = 593 invasive; N = 145 in situ). Baseline VAT and SAT area were associated with statistically significantly increased BCa risk, by 36% and 19%, respectively. Increasing VAT/SAT ratio was associated with an 8% increase in incident BCa. Time-dependent models produced similar results. VAT and VAT/SAT associated BCa risk was highest for African American/Black women, although not statistically significantly different from other groups. Quartiles (Q) of VAT/SAT were also explored; the SHR for Q4 compared with Q1 was 1.49 (95% CI = 1.18 to 1.87). Conclusion: Higher abdominal VAT and SAT are associated with an increased risk of postmenopausal BCa, and VAT/SAT may provide a distinctive risk estimate. Potential racial and ethnic differences require replication in a larger sample.Item Estrogen receptor genotypes, menopausal status, and the effects of tamoxifen on lipid levels: revised and updated results.(Clinical pharmacology and therapeutics, 2010-11) Hayes, D.F.; Skaar, Todd C.; Rae, J.M.; Henry, N.L.; Nguyen, A.T.; Stearns, V.; Li, L.; Philips, S.; Desta, Z.; Flockhart, D.A.We previously reported that the ESR1 XbaI genotypes were associated with baseline and tamoxifen-induced serum lipid profiles. The analysis in that study was carried out by PCR followed by restriction-enzyme digestion. After reanalysis using more robust TaqMan assays, the findings related to ~10% of the genotypes for the ESR1 XbaI single-nucleotide polymorphism (SNP) were revised. For the other genotypes (i.e., ESR1 PvuII, ESR2, and CYP2D6), the results were nearly identical to those in the previous study. Upon reanalysis, previously reported associations between the ESR1 Xba1 genotypes and baseline triglyceride and low-density lipoprotein (LDL) cholesterol levels were no longer observed. Previously reported associations between the ESR1 XbaI genotypes and tamoxifen-induced changes in levels of total cholesterol, triglycerides, and high-density lipoprotein (HDL) cholesterol were also no longer observed. However, the following observations from the original report did not change: (i) the levels of circulating lipids are lower in women taking tamoxifen; (ii) there is an association between the ESR2-02 genotypes and changes in triglyceride levels; and (iii) neither ESR1 PvuII nor CYP2D6 is associated with any changes in serum lipid concentrations in patients receiving treatment with tamoxifen.Item Estrogens and their precursors in postmenopausal women with early breast cancer receiving anastrozole(Elsevier, 2015-07) Ingle, James N.; Kalari, K. R.; Buzdar, Aman U.; Robson, Mark E.; Goetz, Matthew P.; Desta, Zeruesenay; Barman, Poulami; Dudenkov, Tanda T.; Northfelt, Donald W.; Perez, Edith A.; Flockhart, David A.; Williard, Clark V.; Wang, Liewei; Weinshilboum, Richard M.; Department of Medicine, IU School of MedicinePURPOSE: We determined hormone concentrations (estradiol [E2], estrone [E1], estrone conjugates [E1-C], androstenedione [A], testosterone [T]) before and on anastrozole therapy where we also determined plasma concentrations of anastrozole and its metabolites. EXPERIMENTAL: Postmenopausal women who were to receive adjuvant anastrozole for resected early breast cancer were studied. Pretreatment, blood samples were obtained for the acquisition of DNA and for plasma hormone measurements (E2, E1, E1-C, A, and T). A second blood draw was obtained at least 4 weeks after starting anastrozole for hormone, anastrozole and metabolite measurements. For hormone assays, a validated bioanalytical method using gas chromatography negative ionization tandem mass spectrometry was used. Anastrozole and metabolite assays involved extraction of plasma followed by LC/MS/MS assays. RESULTS: 649 patients were evaluable. Pretreatment and during anastrozole, there was large inter-individual variability in E2, E1, and E1-C as well as anastrozole and anastrozole metabolite concentrations. E2 and E1 concentrations were below the lower limits of quantitation in 79% and 70%, respectively, of patients on anastrozole therapy, but those with reliable concentrations had a broad range (0.627-234.0 pg/mL, 1.562-183.2 pg/mL, respectively). Considering E2, 8.9% had the same or higher concentration relative to baseline while on anastrozole, documented by the presence of drug. CONCLUSIONS: We demonstrated large inter-individual variability in anastrozole and anastrozole metabolite concentrations as well as E1, E2, E1-C, A, and T concentrations before and while on anastrozole. These findings suggest that the standard 1mg daily dose of anastrozole is not optimal for a substantial proportion of women with breast cancer.Item Hypnosis Intervention for Sleep Disturbance: Determination of Optimal Dose and Method of Delivery for Postmenopausal Women(T&F, 2021) Elkins, Gary; Otte, Julie; Carpenter, Janet S.; Roberts, Lynae; Jackson, Lea' S.; Kekecs, Zoltan; Patterson, Vicki; Keith, Timothy Z.; School of NursingSleep disturbances are a pervasive problem among postmenopausal women, with an estimated 40 to 64% reporting poor sleep. Hypnosis is a promising intervention for sleep disturbances. This study examined optimal dose and delivery for a manualized hypnosis intervention to improve sleep. Ninety postmenopausal women with poor sleep were randomized to 1 of 4 interventions: 5 in-person, 3 in-person, 5 phone, or 3 phone contacts. All received hypnosis audio recordings, with instructions for daily practice for 5 weeks. Feasibility measures included treatment satisfaction ratings and practice adherence. Sleep outcomes were sleep quality, objective and subjective duration, and bothersomeness of poor sleep. Results showed high treatment satisfaction, adherence, and clinically meaningful (≥ 0.5 SD) sleep improvement for all groups. Sleep quality significantly improved, p < .05, η2 = .70, with no significant differences between groups, with similar results for the other sleep outcomes across all treatment arms. Comparable results between phone and in-person groups suggest that a unique “dose” and delivery strategy is highly feasible and can have clinically meaningful impact. This study provides pilot evidence that an innovative hypnosis intervention for sleep (5 phone contacts with home practice) reduces the burden on participants while achieving maximum treatment benefit.Item Long-term cognitive effects of menopausal hormone therapy: Findings from the KEEPS Continuation Study(Public Library of Science, 2024-11-21) Gleason, Carey E.; Dowling, N. Maritza; Kara, Firat; James, Taryn T.; Salazar, Hector; Ferrer Simo, Carola A.; Harman, Sherman M.; Manson, JoAnn E.; Hammers, Dustin B.; Naftolin, Frederick N.; Pal, Lubna; Miller, Virginia M.; Cedars, Marcelle I.; Lobo, Rogerio A.; Malek-Ahmadi, Michael; Kantarci, Kejal; Neurology, School of MedicineBackground: Findings from Kronos Early Estrogen Prevention Study (KEEPS)-Cog trial suggested no cognitive benefit or harm after 48 months of menopausal hormone therapy (mHT) initiated within 3 years of final menstrual period. To clarify the long-term effects of mHT initiated in early postmenopause, the observational KEEPS Continuation Study reevaluated cognition, mood, and neuroimaging effects in participants enrolled in the KEEPS-Cog and its parent study the KEEPS approximately 10 years after trial completion. We hypothesized that women randomized to transdermal estradiol (tE2) during early postmenopause would show cognitive benefits, while oral conjugated equine estrogens (oCEE) would show no effect, compared to placebo over the 10 years following randomization in the KEEPS trial. Methods and findings: The KEEPS-Cog (2005-2008) was an ancillary study to the KEEPS (NCT00154180), in which participants were randomized into 3 groups: oCEE (Premarin, 0.45 mg/d), tE2 (Climara, 50 μg/d) both with micronized progesterone (Prometrium, 200 mg/d for 12 d/mo) or placebo pills and patch for 48 months. KEEPS Continuation (2017-2022), an observational, longitudinal cohort study of KEEPS clinical trial, involved recontacting KEEPS participants approximately 10 years after the completion of the 4-year clinical trial to attend in-person research visits. Seven of the original 9 sites participated in the KEEPS Continuation, resulting in 622 women of original 727 being invited to return for a visit, with 299 enrolling across the 7 sites. KEEPS Continuation participants repeated the original KEEPS-Cog test battery which was analyzed using 4 cognitive factor scores and a global cognitive score. Cognitive data from both KEEPS and KEEPS Continuation were available for 275 participants. Latent growth models (LGMs) assessed whether baseline cognition and cognitive changes during KEEPS predicted cognitive performance at follow-up, and whether mHT randomization modified these relationships, adjusting for covariates. Similar health characteristics were observed at KEEPS randomization for KEEPS Continuation participants and nonparticipants (i.e., women not returning for the KEEPS Continuation). The LGM revealed significant associations between intercepts and slopes for cognitive performance across almost all domains, indicating that cognitive factor scores changed over time. Tests assessing the effects of mHT allocation on cognitive slopes during the KEEPS and across all years of follow-up including the KEEPS Continuation visit were all statistically nonsignificant. The KEEPS Continuation study found no long-term cognitive effects of mHT, with baseline cognition and changes during KEEPS being the strongest predictors of later performance. Cross-sectional comparisons confirmed that participants assigned to mHT in KEEPS (oCEE and tE2 groups) performed similarly on cognitive measures to those randomized to placebo, approximately 10 years after completion of the randomized treatments. These findings suggest that mHT poses no long-term cognitive harm; conversely, it provides no cognitive benefit or protective effects against cognitive decline. Conclusions: In these KEEPS Continuation analyses, there were no long-term cognitive effects of short-term exposure to mHT started in early menopause versus placebo. These data provide reassurance about the long-term neurocognitive safety of mHT for symptom management in healthy, recently postmenopausal women, while also suggesting that mHT does not improve or preserve cognitive function in this population.Item Palpitations Across the Menopause Transition in SWAN: Trajectories, Characteristics, and Associations with Subclinical CVD(Wolters Kluwer, 2023) Carpenter, Janet S.; Cortés, Yamnia I.; Tisdale, James E.; Sheng, Ying; Jackson, Elizabeth A.; Barinas-Mitchell, Emma; Thurston, Rebecca C.; School of NursingObjective: Our objectives were to identify trajectories of palpitations over the menopause transition, characterize them, and examine associations with subclinical cardiovascular disease (CVD). Methods: We analyzed the following data from the multisite, multiethnic SWAN (Study of Women Across the Nation): reported palpitations occurrence over time; baseline sociodemographic, reproductive, medication, and health-related factors; and follow-up visit subclinical CVD (carotid atherosclerosis, vascular stiffness). Trajectories of palpitations (n = 3,276), their characteristics, and their associations with subclinical CVD (n = 1,559) were identified using group-based trajectory modeling and linear and logistic regression models. Results: Three trajectories emerged: high probability of palpitations in perimenopause to early postmenopause diminishing in late postmenopause (15.9% of women), moderate probability of palpitations in perimenopause to early postmenopause diminishing in late postmenopause (34.3%), and sustained low probability of palpitations (49.8%). In the fully adjusted multivariable model, the high probability group had a more adverse reproductive and health-related profile at baseline (higher gravidity, early perimenopause, vasomotor symptoms, poorer overall health, higher depressive symptoms, higher perceived stress, greater sleep problems, higher blood pressure). In fully adjusted multivariable models, palpitation trajectories were not related to atherosclerosis or arterial stiffness. Conclusions: Distinct patterns of palpitations emerged, with a substantial portion of women having palpitations during the perimenopause and early postmenopause. Palpitations were not associated with subclinical CVD. Findings can help identify women at risk of palpitations during the menopause transition who may need symptom relief.Item “Quick Flutter Skip”: Midlife Women’s Descriptions of Palpitations(Wolters Kluwer, 2023) Carpenter, Janet S.; Fagan, Rileigh; Alzahrani, Mofareh A.; Jaynes, Heather A.; Tisdale, James E.; Kovacs, Richard J.; Chen, Chen X.; Draucker, Claire B.; School of NursingObjective: The objective of this study is to describe peri- and postmenopausal women's experiences of palpitations (quality, frequency, severity, distress, duration and temporal pattern, aura, associated symptoms, and aggravating/alleviating factors) and related healthcare experiences. Methods: Qualitative descriptive methods were used. Semistructured interviews were conducted with women who reported palpitations and were enrolled in a larger case-control pilot study comparing electrocardiographic results between women with and without palpitations. Authors analyzed women's narratives using standard content analytic procedures. Results: Fourteen participants (mean age, 54.5 y [SD = 4.8 y]; range, 46-62 y; 79% postmenopausal) completed interviews. The interviews revealed that women (a) often had difficulty describing their palpitations until prompted by the interviewer; (b) experienced noteworthy variations in the quality and other dimensions of their palpitations; (c) had a wide variety of healthcare experiences related to their palpitations, including not reporting their symptoms to providers, having providers dismiss their symptoms, and having providers be aware of their symptoms and provide diagnostic tests; and (d) at times, created worst case scenarios (downward shifts) under which they would seek treatment for their palpitations, thus enabling them to minimize their symptoms and avoid healthcare. Conclusion: This study advances understanding of how women describe their palpitations and related healthcare experiences. Findings could have implications for building research and clinical tools to guide assessment, communication, and/or education for patients and/or providers about palpitations and for developing and testing behavioral interventions to address this poorly understood symptom in peri- and postmenopausal women.Item Toward a Better Measure of Midlife Sexual Function: Pooled Analyses in Nearly 1000 Women Participating in MsFLASH Randomized Trials(Wolters Kluwer, 2022-01-31) Reed, Susan D.; Carpenter, Janet S.; Larson, Joseph; Mitchell, Caroline M.; Shifren, Jan; Heiman, Julia; Fugate Woods, Nancy; Tessler Lindau, Stacy; LaCroix, Andrea Z.; Guthrie, Katherine A.; School of NursingObjective: Evaluate appropriateness of the current Female Sexual Function Index (FSFI)-19 value of <26.6 to designate female sexual dysfunction (FSD) in postmenopausal women, using the Female Sexual Distress-Revised (FSDS-R) scale to measure distress. Methods: Participant-level data containing standardized measures from five completed Menopause Strategies: Finding Lasting Answers for Symptoms and Health trials was pooled. Baseline characteristics and FSFI-19 scores were compared across trials (F-test, homogeneity). FSFI-19 score associations with the FSDS-R were described. Receiver operating characteristic (ROC) curves were plotted to illustrate the choice of optimal FSFI-19 value to predict sexual distress. ROC curves were also estimated adjusting for trial number, clinical center, age, education, race, smoking, and BMI. Results: Nine hundred ninety eight women (79.2% postmenopausal), mean age 55.9 (SD 4.8) had complete FSFI-19, FSDS-R, and covariate data. Baseline mean FSFI-19 score among all participants and sexually active participants was 18.7 (SD 9.5) and 22.0 (SD 7.2), respectively. There was a consistent pattern across the trials of inverse association between poorer sexual function (FSFI-19) and greater sexual distress. Based on the ROC curve showing the likelihood of FSDS-R frequent or greater distress according to cut points of FSFI, the optimal cut point for FSD was FSFI-19 <21 for all participants. This cut point corresponded to sensitivity 87.2% (95% CI, 83.4-91.0), specificity 57.9% (95% CI, 54.3-61.6) and adjusted area under the ROC curve 78.8% (95% CI, 75.8-81.8). Conclusions: A new FSFI-19 cut point of ≥21 should be considered to describe normal sexual function in periand postmenopausal women as opposed to the standard cut point of >26.6. Video summary: http://links.lww.com/MENO/A915.