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Fertility and Sterility Jul 2024Uterine fibroids (UFs) are the most common female benign pelvic tumors, affecting >60% of patients aged 30-44 years. Uterine fibroids are asymptomatic in a large... (Review)
Review
Uterine fibroids (UFs) are the most common female benign pelvic tumors, affecting >60% of patients aged 30-44 years. Uterine fibroids are asymptomatic in a large percentage of cases and may be identified incidentally using a transvaginal ultrasound or a magnetic resonance imaging scan. However, in approximately 30% of cases, UFs affect the quality of life and women's health, with abnormal uterine bleeding and heavy menstrual bleeding being the most common complaints, along with iron deficiency (ID) and ID anemia. Medical treatments used for UFs-related abnormal uterine bleeding include symptomatic agents, such as nonsteroidal antiinflammatory drugs and tranexamic acid, and hormonal therapies, including combined oral contraceptives, gonadotropin-releasing hormone agonists or antagonists, levonorgestrel intrauterine systems, selective progesterone receptor modulators, and aromatase inhibitors. Nevertheless, few drugs are approved specifically for UF treatment, and most of them manage the symptoms. Surgical options include fertility-sparing treatments, such as myomectomy, or nonconservative options, such as hysterectomy, especially in perimenopausal women who are not responding to any treatment. Radiologic interventions are also available: uterine artery embolization, high-intensity focused ultrasound or magnetic resonance-guided focused ultrasound, and radiofrequency ablation. Furthermore, the management of ID and ID anemia, as a consequence of acute and chronic bleeding, should be taken into account with the use of iron replacement therapy both during medical treatment and before and after a surgical procedure. In the case of symptomatic UFs, the location, size, multiple UFs, or coexistent adenomyosis should guide the choice with a shared decision-making process, considering long- and short-term treatment goals expected by the patient, including pregnancy desire or wish to preserve the uterus independently of reproductive goals.
Topics: Humans; Female; Leiomyoma; Uterine Neoplasms; Uterine Hemorrhage; Treatment Outcome; Uterine Myomectomy; Uterine Artery Embolization; Adult
PubMed: 38723935
DOI: 10.1016/j.fertnstert.2024.04.041 -
EBioMedicine Jun 2024Circadian rhythms regulate cellular physiology and could influence the efficacy of endocrine therapy (ET) in breast cancer (BC). We prospectively tested this hypothesis... (Randomized Controlled Trial)
Randomized Controlled Trial
Association between endocrine adjuvant therapy intake timing and disease-free survival in patients with high-risk early breast cancer: results of a sub-study of the UCBG- UNIRAD trial.
BACKGROUND
Circadian rhythms regulate cellular physiology and could influence the efficacy of endocrine therapy (ET) in breast cancer (BC). We prospectively tested this hypothesis within the UNIRAD adjuvant phase III trial (NCT01805271).
METHODS
1278 patients with high-risk hormonal receptor positive (HR+)/HER2 negative (HER2-) primary BC were randomly assigned to adjuvant ET with placebo or everolimus. Patients prospectively reported in a diary the daily timing of ET intake among four 6-h slots (06:00-11:59 (morning), 12:00-17:59 (afternoon), 18:00-23:59 (evening), or 24:00-05:59 (nighttime). The association between ET timing and disease-free survival (DFS) was a prespecified secondary endpoint of the trial and the results of this observational study are reported here.
FINDINGS
ET timing was recorded by 855 patients (67.2%). Patients declaring morning (n = 465, 54.4%) or afternoon (n = 45, 5.4%) ET intake were older than those declaring evening (n = 339, 39.6%) or nighttime (n = 5, 0.6%) intake. With a median follow-up of 46.7 months, 118 patients had a local (n = 30) or metastasis relapse (n = 84), and 41 patients died. ET intake timing was not associated with DFS in the whole population (HR = 0.77, 95% CI [0.53-1.12]). The association between ET intake timing and DFS according to the stratification factors revealed interactions with ET agent (tamoxifen versus Aromatase inhibitors (AI) with an increased DFS in the group of evening/nighttime versus morning/afternoon tamoxifen intake (HR = 0.43, 95% CI [0.22-0.85]), while no association was found for AI intake (HR = 1.07, 95% CI [0.68-1.69]). The interaction between ET intake timing and ET agent remained in multivariable analysis (HR = 0.38 [0.16-0.91]).
INTERPRETATION
Tamoxifen intake in the evening/nighttime could be recommended in patients with high-risk HR+/HER2- BC while awaiting for results from further ET timing studies.
FUNDING
UNIRAD was Supported by a grant from the French Ministry of Health PHRC 2012 and received funding from La Ligue contre le Cancer, Cancer Research-UK, Myriad Genetics, and Novartis.
Topics: Humans; Breast Neoplasms; Female; Middle Aged; Aged; Adult; Chemotherapy, Adjuvant; Antineoplastic Agents, Hormonal; Disease-Free Survival; Neoplasm Staging; Tamoxifen; Treatment Outcome; Circadian Rhythm; Antineoplastic Combined Chemotherapy Protocols
PubMed: 38718683
DOI: 10.1016/j.ebiom.2024.105141 -
Annals of Pediatric Endocrinology &... Apr 2024Gynecomastia (GM) is a common and continuously evolving condition that commonly occurs during adolescence. It is the source of significant embarrassment and...
Gynecomastia (GM) is a common and continuously evolving condition that commonly occurs during adolescence. It is the source of significant embarrassment and psychological stress in adolescent males. GM is characterized by enlargement of the male breast due to the proliferation of glandular ducts and stromal components. The main cause of GM during adolescence is physiological or pubertal GM, which is primarily attributed to an imbalance between estrogen and androgen activity. Physiological GM is typically transient and resolves within several months, although it may take several years to resolve. GM may also be caused by other pathological conditions and could be indicative of an endocrine disease. It is crucial to understand the pathogenesis of GM to distinguish it from normal developmental variants due to pathological causes. The aim of this review is to highlight the significance of GM during adolescence in terms of potential etiologies, clinical and laboratory diagnoses, and current management.
PubMed: 38712491
DOI: 10.6065/apem.2346142.071 -
Australian Journal of General Practice May 2024Oestrogen deprivation is the mainstay of treatment for women with hormone receptor-positive breast cancer, but unfortunately it causes multiple side effects that can... (Review)
Review
BACKGROUND
Oestrogen deprivation is the mainstay of treatment for women with hormone receptor-positive breast cancer, but unfortunately it causes multiple side effects that can significantly impair quality of life. Genitourinary symptoms are very common and although these symptoms can be effectively managed with vaginal oestrogens, concerns about their safety in women with breast cancer limits their use.
OBJECTIVE
The aim of this review is to provide a summary of the data on the safety of vaginal oestrogens in women with breast cancer to help general practitioners advise their patients in this situation.
DISCUSSION
Although there are no large randomised prospective studies to assess safety, the current evidence suggests reassurance can be provided to the majority of women with a history of breast cancer considering vaginal oestrogens. Consultation with the oncology team is advised for women taking aromatase inhibitors, where the safety of vaginal oestrogens is less certain.
Topics: Humans; Female; Breast Neoplasms; Estrogens; Administration, Intravaginal; Female Urogenital Diseases; Quality of Life
PubMed: 38697062
DOI: 10.31128/AJGP-02-23-6709 -
Acta Obstetricia Et Gynecologica... Jul 2024
Expression of concern: Randomized comparison of superovulation with letrozole vs. clomiphene citrate in an IUI program for women with recently surgically treated minimal to mild endometriosis.
Topics: Humans; Female; Letrozole; Endometriosis; Clomiphene; Nitriles; Fertility Agents, Female; Triazoles; Superovulation; Insemination, Artificial; Aromatase Inhibitors; Randomized Controlled Trials as Topic; Infertility, Female; Adult
PubMed: 38693815
DOI: 10.1111/aogs.14872 -
Cardio-oncology (London, England) May 2024Breast cancer is estimated to comprise about 290,560 new cases in 2022. Aromatase inhibitors (AIs) are recommended as adjuvant treatment for estrogen-receptor positive...
BACKGROUND
Breast cancer is estimated to comprise about 290,560 new cases in 2022. Aromatase inhibitors (AIs) are recommended as adjuvant treatment for estrogen-receptor positive (ER+) breast carcinoma in postmenopausal women, which includes approximately two-thirds of all women with breast cancer. AIs inhibit the peripheral conversion of androgens to estrogen by deactivation of the aromatase enzyme, leading to a reduction in serum estrogen level in postmenopausal women with ER+ breast carcinoma. Estrogen is known for its cardiovascular (CV) protective properties through a variety of mechanisms including vasodilation of blood vessels and inhibition of vascular injury resulting in the prevention of atherosclerosis. In clinical trials and prospective cohorts, the long-term use of AIs can increase the risk for hypertension and hyperlipidemia. Studies demonstrate mixed results as to the impact of AIs on actual CV events and overall survival.
METHODS
A single arm longitudinal study of 14 postmenopausal women with ER+ breast cancer prescribed adjuvant AIs at the University of Minnesota (UMN). Subjects with a history of known tobacco use, hypertension, hyperlipidemia, and diabetes were excluded to eliminate potential confounding factors. Participants underwent routine labs, blood pressure assessments, and vascular testing at baseline (prior to starting AIs) and at six months. Vascular assessment was performed using the EndoPAT 2000 and HDI/PulseWave CR-2000 Cardiovascular Profiling System and pulse contour analysis on two occasions as previously described. Vascular measurements were conducted by one trained vascular technician. Assessments were performed in triplicate, and the mean indices were used for analyses. All subjects were on an AI at the follow-up visit. The protocol was approved by the UMN Institutional Review Board and all participants were provided written informed consent. Baseline and follow-up characteristics were compared using Wilcoxon signed-rank tests. Analyses were performed using R version 3.6.1 (R Foundation for Statistical Computing, Vienna, Austria).
RESULTS
After six months of AI treatment, EndoPAT® ratio declined to a median 1.12 (Q1: 0.85, Q3: 1.86; p = 0.045; Figure 1) and median estradiol levels decreased to 2 pg/mL (Q1: 2, Q3: 3; p=0.052). There was no evidence of association between change in EndoPAT® and change in estradiol level (p = 0.91). There were no statistically significant changes in small or large arterial elasticity.
CONCLUSIONS
We hypothesize that long-term use of AI can lead to persistent endothelial dysfunction, and further investigation is necessary. In our study, patients were on AI for approximately 5-10 years. As a result, we do not have data on whether these changes, such as EndoPAT® ratio and the elasticity of small and large arterial, are reversible with discontinuation of AI. These findings set the stage for a larger study to more conclusively determine the association between AI exposure and cardiovascular outcomes. Further studies should evaluate for multivariate associations withmodifiable risk factors for CV disease.
PubMed: 38693561
DOI: 10.1186/s40959-024-00227-z -
BMJ Open Apr 2024Low vitamin D status is prevalent among women with polycystic ovary syndrome (PCOS). The objective of the study is to assess the effect of vitamin D supplementation on...
Effect of vitamin D in addition to letrozole on the ovulation rate of women with polycystic ovary syndrome: protocol of a multicentre randomised double-blind controlled trial.
INTRODUCTION
Low vitamin D status is prevalent among women with polycystic ovary syndrome (PCOS). The objective of the study is to assess the effect of vitamin D supplementation on (1) the ovulation rate to letrozole and (2) other reproductive, endocrine and metabolic outcomes after 1 year of supplementation in women with PCOS.
METHODS AND ANALYSIS
This is a multicentre, randomised, double-blind, controlled clinical trial. A total of 220 anovulatory women with PCOS diagnosed by the Rotterdam criteria will be recruited. They will be randomly assigned to either the (1) vitamin D supplementation group or (2) placebo group. Those in the vitamin D group will take oral Vitamin D3 50 000 IU/week for 4 weeks, followed by 50 000 IU once every 2 weeks for 52 weeks. Those who remain anovulatory after 6 months will be treated with a 6-month course of letrozole (2.5 mg to 7.5 mg for 5 days per cycle titrated according to response) for ovulation induction. The primary outcome is the ovulation rate. All statistical analyses will be performed using intention-to-treat and per protocol analyses.
ETHICS AND DISSEMINATION
Ethics approval was sought from the Institutional Review Board of the participating units. All participants will provide written informed consent before joining the study. The results of the study will be submitted to scientific conferences and peer-reviewed journals.
TRIAL REGISTRATION NUMBER
NCT04650880.
Topics: Adult; Female; Humans; Young Adult; Aromatase Inhibitors; Dietary Supplements; Double-Blind Method; Letrozole; Multicenter Studies as Topic; Ovulation; Ovulation Induction; Polycystic Ovary Syndrome; Randomized Controlled Trials as Topic; Vitamin D
PubMed: 38684265
DOI: 10.1136/bmjopen-2022-070801 -
Frontiers in Chemistry 2024Wall, a plant renowned for its ethno-medical properties, was investigated in this study for its antioxidant potential based on its wide therapeutic applications in...
Wall, a plant renowned for its ethno-medical properties, was investigated in this study for its antioxidant potential based on its wide therapeutic applications in traditional healthcare systems. The study aimed to assess the antioxidant potential of the plant extract/fractions and to predict the active phytochemicals using computational techniques. Five fractions were obtained from the crude methanolic extract of and six concentrations (25, 50, 75, 100, 125, and 150 μg/mL) were prepared for each fraction. The antioxidant activity of these fractions was evaluated using the Tetraoxomolybdate (VI) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. docking studies and molecular dynamic simulations were conducted to further elucidate the molecular interactions underlying the antioxidant activity. The aqueous extract of exhibited significant antioxidant and free radical scavenging activity against DPPH. Additionally, the crude flavonoid extract demonstrated moderate activity with IC value of 57.863 μg/mL, indicating potent inhibition of cell growth. docking studies revealed a strong interaction between emetine and the aromatase protein, suggesting its potential as an antioxidant. The study findings highlight the antioxidant potential of extract, indicating its suitability as a source of natural antioxidants. These results suggest its potential application in pharmaceutical preparations aimed at harnessing antioxidant properties for therapeutic purposes.
PubMed: 38680459
DOI: 10.3389/fchem.2024.1379463 -
Biomolecules Apr 2024Amyotrophic lateral sclerosis (ALS) is a fatal motoneuron degenerative disease that is associated with demyelination. The () mouse exhibits motoneuron degeneration,...
Amyotrophic lateral sclerosis (ALS) is a fatal motoneuron degenerative disease that is associated with demyelination. The () mouse exhibits motoneuron degeneration, gliosis and myelin deterioration in the cervical spinal cord. Since male s display low testosterone (T) levels in the nervous system, we investigated if T modified myelin-relative parameters in s in the absence or presence of the aromatase inhibitor, anastrozole (A). We studied myelin by using luxol-fast-blue (LFB) staining, semithin sections, electron microscopy and myelin protein expression, density of IBA1 microglia and mRNA expression of inflammatory factors, and the glutamatergic parameters glutamine synthetase (GS) and the transporter GLT1. Controls and + T showed higher LFB, MBP and PLP staining, lower g-ratios and compact myelin than s and + T + A, and groups showing the rupture of myelin lamellae. s showed increased IBA1 cells and mRNA for CD11b and inflammatory factors (IL-18, TLR4, TNFαR and PYR) vs. controls or + T. IBA1 cells, and CD11b were not reduced in + T + A, but inflammatory factors' mRNA remained low. A reduction of GS cells and GLT-1 immunoreactivity was observed in s and + T + A vs. controls and + T. Clinically, + T but not + T + A showed enhanced muscle mass, grip strength and reduced paw abnormalities. Therefore, T effects involve myelin protection, a finding of potential clinical translation.
Topics: Animals; Mice; Myelin Sheath; Amyotrophic Lateral Sclerosis; Male; Disease Models, Animal; Testosterone; Spinal Cord; Excitatory Amino Acid Transporter 2; Microglia
PubMed: 38672445
DOI: 10.3390/biom14040428 -
Animals : An Open Access Journal From... Apr 2024The mechanism of sex determination and differentiation in animals remains a central focus of reproductive and developmental biology research, and the regulation of sex...
The mechanism of sex determination and differentiation in animals remains a central focus of reproductive and developmental biology research, and the regulation of sex differentiation in amphioxus remains poorly understood. Cytochrome P450 Family 19 Subfamily A member 1 () is a crucial sex differentiation gene that catalyzes the conversion of androgens into estrogens. In this study, we identified two aromatase-like genes in amphioxus: and . The is more primitive and may represent the ancestral form of in zebrafish and other vertebrates, while the is likely the result of gene duplication within amphioxus. To gain further insights into the expression level of these two , we examined their expression in different tissues and during different stages of gonad development. While the expression level of the two genes differs in tissues, both are highly expressed in the gonad primordium and are primarily localized to microsomal membrane systems. However, as development proceeds, their expression level decreases significantly. This study enhances our understanding of sex differentiation mechanisms in amphioxus and provides valuable insights into the formation and evolution of sex determination mechanisms in vertebrates.
PubMed: 38672288
DOI: 10.3390/ani14081140