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Discover Oncology Jun 2024The global BOLERO-2 trial established the efficacy and safety of combination everolimus (EVE) and exemestane (EXE) in the treatment of estrogen receptor positive...
BACKGROUND
The global BOLERO-2 trial established the efficacy and safety of combination everolimus (EVE) and exemestane (EXE) in the treatment of estrogen receptor positive (ER +), HER2-, advanced breast cancer (ABC). BOLERO-5 investigated this combination in a Chinese population (NCT03312738).
METHODS
BOLERO-5 is a randomized, double-blind, multicenter, placebo controlled, phase II trial comparing EVE (10 mg/day) or placebo (PBO) in combination with EXE (25 mg/day). The primary endpoint was progression-free survival (PFS) per investigator assessment. Secondary endpoints included PFS per blinded independent review committee (BIRC), overall survival (OS), overall response rate (ORR), clinical benefit rate (CBR), pharmacokinetics, and safety.
RESULTS
A total of 159 patients were randomized to EVE + EXE (n = 80) or PBO + EXE (n = 79). By investigator assessment, treatment with EVE + EXE prolonged median PFS by 5.4 months (HR 0.52; 90% CI 0.38, 0.71), from 2.0 months (PBO + EXE; 90% CI 1.9, 3.6) to 7.4 months (EVE + EXE; 90% CI 5.5, 9.0). Similar results were observed following assessment by BIRC, with median PFS prolonged by 4.3 months. Treatment with EVE + EXE was also associated with improvements in ORR and CBR. No new safety signals were identified in BOLERO-5, with the incidence of adverse events in Chinese patients consistent with the safety profile of both drugs.
CONCLUSION
The efficacy and safety results of BOLERO-5 validate the findings from BOLERO-2, and further support the use of EVE + EXE in Chinese post-menopausal women with ER + , HER2- ABC. NCT03312738, registered 18 October 2017.
PubMed: 38904918
DOI: 10.1007/s12672-024-01027-8 -
MedRxiv : the Preprint Server For... May 2024Mosaic loss of chromosome Y (mLOY) in leukocytes of men reflects genomic instability from aging, smoking, and environmental exposures. A similar mosaic loss of...
BACKGROUND
Mosaic loss of chromosome Y (mLOY) in leukocytes of men reflects genomic instability from aging, smoking, and environmental exposures. A similar mosaic loss of chromosome X (mLOX) occurs among women. However, the associations between mLOY, mLOX, and risk of incident heart diseases are unclear.
METHODS
We estimated associations between mLOY, mLOX, and risk of incident heart diseases requiring hospitalization, including atrial fibrillation, myocardial infarction, ischemic heart disease, cardiomyopathy, and heart failure. We analyzed 190,613 men and 224,853 women with genotyping data from the UK Biobank. Among these participants, we analyzed 37,037 men with mLOY and 13,978 women with mLOX detected using Mosaic Chromosomal Alterations caller. Multivariable Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of each incident heart disease in relation to mLOY in men and mLOX in women. Additionally, Mendelian randomization (MR) was conducted to estimate causal associations.
RESULTS
Among men, detectable mLOY was associated with elevated risk of atrial fibrillation (HR=1.06, 95%CI:1.03-1.11). The associations were apparent in both never-smokers (HR=1.07, 95%:1.01-1.14) and ever-smokers (HR=1.05, 95%CI:1.01-1.11) as well as men > and ≤60 years of age. MR analyses supported causal associations between mLOY and atrial fibrillation (HR=1.15, 95%CI:1.13-1.18). Among post-menopausal women, we found a suggestive inverse association between detectable mLOX and atrial fibrillation risk (HR=0.90, 95%CI:0.83-0.98). However, associations with mLOY and mLOX were not found for other heart diseases.
CONCLUSIONS
Our findings suggest that mLOY and mLOX reflect sex-specific biological processes or exposure profiles related to incident atrial fibrillation requiring hospitalization.
PubMed: 38903105
DOI: 10.1101/2024.05.29.24308171 -
Scientific Reports Jun 202417β-estradiol, the most biologically active estrogen, exerts wide-ranging effects in brain through its action on estrogen receptors (ERs), influencing higher-order...
17β-estradiol, the most biologically active estrogen, exerts wide-ranging effects in brain through its action on estrogen receptors (ERs), influencing higher-order cognitive function and neurobiological aging. However, our knowledge of ER expression and regulation by neuroendocrine aging in the living human brain is limited. This in vivo brain F-fluoroestradiol (F-FES) Positron Emission Tomography (PET) study of healthy midlife women reveals progressively higher ER density over the menopause transition in estrogen-regulated networks. Effects were independent of age, plasma estradiol and sex hormone binding globulin, and were highly consistent, correctly classifying all women as being postmenopausal or premenopausal. Higher ER density in target regions was associated with poorer memory performance for both postmenopausal and perimenopausal groups, and predicted presence of self-reported mood and cognitive symptoms after menopause. These findings provide novel insights on brain ER density modulation by female neuroendocrine aging, with clinical implications for women's health.
Topics: Humans; Female; Middle Aged; Cognition; Brain; Aging; Receptors, Estrogen; Positron-Emission Tomography; Adult; Estradiol; Neurosecretory Systems; Menopause
PubMed: 38902275
DOI: 10.1038/s41598-024-62820-7 -
Journal of Neuroinflammation Jun 2024A significant decrease in estrogen levels puts menopausal women at high risk for major depression, which remains difficult to cure despite its relatively clear etiology.... (Review)
Review
A significant decrease in estrogen levels puts menopausal women at high risk for major depression, which remains difficult to cure despite its relatively clear etiology. With the discovery of abnormally elevated inflammation in menopausal depressed women, immune imbalance has become a novel focus in the study of menopausal depression. In this paper, we examined the characteristics and possible mechanisms of immune imbalance caused by decreased estrogen levels during menopause and found that estrogen deficiency disrupted immune homeostasis, especially the levels of inflammatory cytokines through the ERα/ERβ/GPER-associated NLRP3/NF-κB signaling pathways. We also analyzed the destruction of the blood-brain barrier, dysfunction of neurotransmitters, blockade of BDNF synthesis, and attenuation of neuroplasticity caused by inflammatory cytokine activity, and investigated estrogen-immuno-neuromodulation disorders in menopausal depression. Current research suggests that drugs targeting inflammatory cytokines and NLRP3/NF-κB signaling molecules are promising for restoring homeostasis of the estrogen-immuno-neuromodulation system and may play a positive role in the intervention and treatment of menopausal depression.
Topics: Humans; Female; Menopause; Estrogens; Animals; Depression; NLR Family, Pyrin Domain-Containing 3 Protein; Signal Transduction; Cytokines
PubMed: 38898454
DOI: 10.1186/s12974-024-03152-1 -
Scientific Reports Jun 2024We compared the efficacy of 4 mg drospirenone (DRSP) progestin-only pills (POPs) versus combined oral contraceptive pills (COCs) containing 0.02 mg of ethinyl... (Randomized Controlled Trial)
Randomized Controlled Trial
We compared the efficacy of 4 mg drospirenone (DRSP) progestin-only pills (POPs) versus combined oral contraceptive pills (COCs) containing 0.02 mg of ethinyl estradiol (EE) and 0.075 mg of gestodene (GS) in ovulation inhibition and inducing unfavorable cervical mucus changes using a delayed-starting approach. This randomized controlled trial involved 36 participants aged 18-45 years. The major outcomes included ovulation inhibition assessed using the Hoogland and Skouby score, and cervical mucus permeability, assessed using the modified World Health Organization score. The results demonstrated ovulation inhibition rates of 77.8% for the EE/GS group and 88.9% for the DRSP group. The risk ratio and absolute risk reduction were 0.50 (95% confidence interval [CI]: 0.10, 2.40) and - 0.11 (95% CI: - 0.35, 0.13), respectively, satisfying the 20% non-inferiority margin threshold. The median time to achieve unfavorable cervical mucus changes was comparable between the DRSP (3 days, interquartile range [IQR]: 6 days) and EE/GS (3.5 days, IQR: 4 days) groups. However, the DRSP group had a higher incidence of unscheduled vaginal bleeding (55.56% vs. 11.11%; p = 0.005). DRSP-only pills, initiated on days 7-9 of the menstrual cycle, were non-inferior to EE/GS pills in ovulation inhibition. However, they exhibited delayed unfavorable cervical mucus changes compared to the standard two-day backup recommendation.Clinical trial registration: Thai Clinical Trials Registry (TCTR20220819001) https://www.thaiclinicaltrials.org/show/TCTR20220819001 .
Topics: Humans; Female; Adult; Ethinyl Estradiol; Androstenes; Young Adult; Adolescent; Contraceptives, Oral, Combined; Ovulation Inhibition; Single-Blind Method; Middle Aged; Norpregnenes; Ovulation; Cervix Mucus
PubMed: 38898193
DOI: 10.1038/s41598-024-64753-7 -
Cell Reports. Medicine Jun 2024Menopause experiences and care vary widely because of biological, sociodemographic, and sociocultural factors. Treatments for troublesome symptoms are not uniformly...
Menopause experiences and care vary widely because of biological, sociodemographic, and sociocultural factors. Treatments for troublesome symptoms are not uniformly available or accessed. Intersectional factors may affect the experience and are poorly understood. Disparities across populations highlight the opportunity for a multifaceted equitable approach that includes patient-centered care, education, and policy change.
Topics: Humans; Menopause; Female; Socioeconomic Factors; Healthcare Disparities; Sociodemographic Factors
PubMed: 38897172
DOI: 10.1016/j.xcrm.2024.101616 -
Psychoneuroendocrinology Jun 2024Increased sensitivity to ovarian hormone changes is implicated in the etiology of reproductive mood disorders across the female lifespan, including menstrually-related...
Increased sensitivity to ovarian hormone changes is implicated in the etiology of reproductive mood disorders across the female lifespan, including menstrually-related mood disorders, perinatal mood disorders, and perimenopausal depression. Developing a method to accurately quantify sensitivity to endogenous hormone fluctuations may therefore facilitate the prediction and prevention of these mental health conditions. Here, we propose one such method applying a synchrony analysis to compute time-lagged cross-correlations between repeated assessments of endogenous hormone levels and self-reported affect. We apply this method to a dataset containing frequent repeated assessments of affective symptoms and the urinary metabolites of estradiol (E2) and progesterone (P4) in 94 perimenopausal females. These preliminary findings suggest that, with further refinement and validation, the proposed method holds promise as a diagnostic tool to be used in clinical practice and to advance research investigating the etiology of reproductive mood disorders.
PubMed: 38896987
DOI: 10.1016/j.psyneuen.2024.107095 -
Cancer Medicine Jun 2024The optimal adjuvant endocrine therapy (ET) in hormone receptor positive (HR+) and human epidermal growth factor receptor 2 positive (HER2+) premenopausal breast cancer...
BACKGROUND
The optimal adjuvant endocrine therapy (ET) in hormone receptor positive (HR+) and human epidermal growth factor receptor 2 positive (HER2+) premenopausal breast cancer (BC) remains unclear. Moreover, the benefit and clinical indications of ovarian suppression (OS) is poorly elucidated. We described real-world patterns surrounding choice of ET and clinicopathologic features which predicted treatment with OS in a contemporary cohort of premenopausal women with HR+/HER2+ BC.
METHODS
This retrospective analysis included premenopausal patients with nonmetastatic HR+/HER2+ BC from the CancerLinQ Discovery database from January 2010 to May 2020. Women were less than 50 years and received chemotherapy, anti-HER2 therapy, and ET. They were categorized into 1 of 4 groups based on type of ET prescribed at initiation: aromatase inhibitor (AI) + OS, OS, tamoxifen + OS, or tamoxifen. Multivariable logistic regression assessed associations between clinicopathologic features and OS use.
RESULTS
Out of 360,540 patients with BC, 937 were included. The majority (n = 818, 87%) were prescribed tamoxifen, whereas 4 (0.4%), 50 (5.3%), and 65 (6.9%) received OS, tamoxifen + OS and AI + OS, respectively. No clinicopathologic features predicted OS use apart from age; patients <35 years were more likely to receive OS compared with those ≥35 years (odds ratio 2.33, p < 0.001).
CONCLUSIONS
This is the first real-world study evaluating ET treatment patterns in HR+/HER2+ premenopausal BC. OS use was uncommon and the majority received tamoxifen as the preferred ET regardless of most clinicopathologic risk factors. Additional research is needed to optimize ET decisions in young women with this distinct BC subtype.
Topics: Humans; Female; Breast Neoplasms; Premenopause; Adult; Retrospective Studies; Receptor, ErbB-2; Chemotherapy, Adjuvant; Antineoplastic Agents, Hormonal; Tamoxifen; Aromatase Inhibitors; Middle Aged; Receptors, Estrogen; Receptors, Progesterone; Ovary
PubMed: 38895891
DOI: 10.1002/cam4.7317 -
International Journal of Women's Health 2024Additive human menopausal gonadotropin (HMG)/recombinant luteinizing hormone (r-LH) to follicle-stimulating hormone (FSH) can improve pregnancy outcomes in patients with...
Assisted Reproductive Technology Outcomes in Women with Normal Ovarian Response Receiving Recombinant Luteinizing Hormone/Human Menopausal Gonadotropin: An Observational Study.
OBJECTIVE
Additive human menopausal gonadotropin (HMG)/recombinant luteinizing hormone (r-LH) to follicle-stimulating hormone (FSH) can improve pregnancy outcomes in patients with poor ovarian response during assisted reproductive procedures. However, their effects on patients with normal ovarian response during such procedures are unclear, which formed the aim of this study.
METHODS
This retrospective study enrolled 456 infertile women who underwent in vitro fertilization or intracytoplasmic sperm injection treatment. Group 1 received FSH; Group 2 received FSH+HMG/r-LH; Group 3 received FSH+HMG+r-LH.
RESULTS
The age and Body Mass Index were significantly greater in Group III. The endometrial thickness was greater in Groups II and III, suggesting better endometrial receptivity. Better pregnancy and birth outcomes were seen in Group 3. In sub-cohorts of women older than 32 years old or with overweight/obesity, pregnancy and birth outcomes were also much better in Group 3, albeit without statistical significance.
CONCLUSION
The addition of both HMG and r-LH to FSH may improve the chance of infertile women with normal ovarian responses to have more success in having live birth babies, specifically in those over 32 years of age or with overweight/obese patients who typically face challenges in conceiving and sustaining a pregnancy.
PubMed: 38895039
DOI: 10.2147/IJWH.S454410 -
Sensors (Basel, Switzerland) Jun 2024Osteopenia, caused by estrogen deficiency in postmenopausal women (PMW), lowers Bone Mineral Density (BMD) and increases bone fragility. It affects about half of older... (Randomized Controlled Trial)
Randomized Controlled Trial
Gamified Exercise with Kinect: Can Kinect-Based Virtual Reality Training Improve Physical Performance and Quality of Life in Postmenopausal Women with Osteopenia? A Randomized Controlled Trial.
BACKGROUND
Osteopenia, caused by estrogen deficiency in postmenopausal women (PMW), lowers Bone Mineral Density (BMD) and increases bone fragility. It affects about half of older women's social and physical health. PMW experience pain and disability, impacting their health-related Quality of Life (QoL) and function. This study aimed to determine the effects of Kinect-based Virtual Reality Training (VRT) on physical performance and QoL in PMW with osteopenia.
METHODOLOGY
The study was a prospective, two-arm, parallel-design, randomized controlled trial. Fifty-two participants were recruited in the trial, with 26 randomly assigned to each group. The experimental group received Kinect-based VRT thrice a week for 24 weeks, each lasting 45 min. Both groups were directed to participate in a 30-min walk outside every day. Physical performance was measured by the Time Up and Go Test (TUG), Functional Reach Test (FRT), Five Times Sit to Stand Test (FTSST), Modified Sit and Reach Test (MSRT), Dynamic Hand Grip Strength (DHGS), Non-Dynamic Hand Grip Strength (NDHGS), BORG Score and Dyspnea Index. Escala de Calidad de vida Osteoporosis (ECOS-16) questionnaire measured QoL. Both physical performance and QoL measures were assessed at baseline, after 12 weeks, and after 24 weeks. Data were analyzed on SPSS 25.
RESULTS
The mean age of the PMW participants was 58.00 ± 5.52 years. In within-group comparison, all outcome variables (TUG, FRT, FTSST, MSRT, DHGS, NDHGS, BORG Score, Dyspnea, and ECOS-16) showed significant improvements ( < 0.001) from baseline at both the 12th and 24th weeks and between baseline and the 24th week in the experimental group. In the control group, all outcome variables except FRT (12th week to 24th week) showed statistically significant improvements ( < 0.001) from baseline at both the 12th and 24th weeks and between baseline and the 24th week. In between-group comparison, the experimental group demonstrated more significant improvements in most outcome variables at all points than the control group ( < 0.001), indicating the positive additional effects of Kinect-based VRT.
CONCLUSION
The study concludes that physical performance and QoL measures were improved in both the experimental and control groups. However, in the group comparison, these variables showed better results in the experimental group. Thus, Kinect-based VRT is an alternative and feasible intervention to improve physical performance and QoL in PMW with osteopenia. This novel approach may be widely applicable in upcoming studies, considering the increasing interest in virtual reality-based therapy for rehabilitation.
Topics: Humans; Female; Quality of Life; Postmenopause; Bone Diseases, Metabolic; Middle Aged; Virtual Reality; Physical Functional Performance; Aged; Exercise Therapy; Prospective Studies; Exercise; Video Games; Hand Strength
PubMed: 38894367
DOI: 10.3390/s24113577