Development Of Fibroids Research Articles

Immunohistochemical Expression of the SERPINA3 Protein in Uterine Fibroids.

SERPINA3 (α-1-antichymotrypsin, AACT, ACT) is produced by the liver and released into plasma in an anti-inflammatory response and plays a role as a modulator of extracellular matrix (ECM) by inhibiting serine proteases. Numerous studies proved an increased level of SERPINA3 in many types of cancer, which could be linked to SERPINA3's anti-apoptotic function. In the context of progressive ECM fibrosis during the development of uterine fibroids, which are one of the most common hypertrophic changes within the uterus, it is interesting to describe the level of SERPINA3 protein in this type of lesion and the surrounding tissues. We used immunohistochemical staining of the SERPINA3 protein and compared the intensity of the signal between the myoma tissue and the surrounding normal tissue. We showed a surprising reduction in the amount of the SERPINA3 protein within uterine fibroids compared to surrounding tissues. This observation sheds new light on the role of this protein in the formation of proliferative changes and suggests that understanding the mechanism of its action may become the basis for the development of new diagnostic and therapeutic tools.

Factors associated with uterine fibroids in women of reproductive age: A cross-sectional study

Background. Uterine fibroids is a benign monoclonal tumor originating from the smooth muscle layer of the uterus. Non-modifiable risk factors for the development of uterine fibroids, such as age, ethnicity, age at menarche, etc, have been studied quite extensively, while the role of many controllable factors remains debatable.The aim of the study. To identify the main modifiable factors associated with uterine fibroids in women of reproductive age living in the Baikal region, including certain ethnic groups.Materials and methods. We carried out a multicenter cross-sectional study in 2016–2019 in institutions of Irkutsk and Bokhan (Irkutsk region) and Ulan-Ude (Republic of Buryatia). The subjects of the study were women to have annual workplace medical examination. The study included 1,347 participants of reproductive age (34.33 ± 6.37 years) who met the inclusion criteria. Among all women included in the study, there were 867 (64.37 %) Caucasians, 361 (26.80 %) Asians, and 119 (8.83%) women of mixed (Caucasian-Asian), ethnicity. The research methods included a questionnaire, general clinical and gynecological examination, and pelvic ultrasound examination.Results. According to our study, the main non-modifiable factors associated with the presence of uterine fibroids were: Asian ethnicity; age at menarche 12–13 years; age of the study participant 40–44 years; menopausal symptoms; adenomyosis. The “controllable” factors included: city residency; body mass index over 40 kg/m2; history of abortions and miscarriages; metabolic syndrome; using combined oral contraceptives; lack of sexual activity; smoking; presence of anumber of occupational hazards.Conclusion. Our study identified the main controllable factors associated with the presence of uterine fibroids in a multiethnic population of women of reproductive age.

A Case of a Prolapsing Cervical Myoma Managed with Robot-assisted Total Laparoscopic Hysterectomy

The development of cervical fibroids is rare, but they are often symptomatic and can be associated with complications such as bleeding, pain, constipation, and prolapse. Necrosed, prolapsing fibroids can lead to massive acute hemorrhage. Treatment is, therefore, typically necessary, but surgical management is frequently technically difficult given distorted anatomy. We present several images of a prolapsing cervical fibroid treated by hysterectomy in a 53-year-old patient.

HMGA2 overexpression induces plasticity in myometrial cells and a transcriptomic profile more similar to that of uterine fibroids

ObjectiveTo study the possible role for HMGA2 overexpression in differentiated myometrial cells and its potential to induce a stem cell-like or dedifferentiating phenotype and drive fibroid development. DesignMyometrial cells were immortalized and transduced with an HMGA2 lentivirus to produce HMGA2hi cells. In vitro stem cell assays were conducted and RNA from HMGA2hi and control cells and fibroid-free myometrial (MyoN) and HMGA2 fibroid (HMGA2F) tissues were submitted for RNA-sequencing. SettingUniversity research laboratory SubjectsWomen undergoing hysterectomy for symptomatic uterine fibroids or other gynecological conditions. InterventionNot applicable. Main Outcome MeasuresIn-vitro stem-like properties from myometrium cell lines. RNA-sequencing and collagen production of HMGA2 overexpressing primary leiomyoma tissue and cell lines. ResultsHMGA2hi cells have enhanced self-renewal capacity, decreased proliferation, and have a greater ability to differentiate into other mesenchymal cell types. HMGA2hi cells exhibit a stem cell-like signature and share transcriptomic similarities with HMGA2F. Moreover, dysregulated extracellular matrix pathways are observed in both HMGA2hi cells and HMGA2F. ConclusionOur findings suggest that HMGA2 overexpression drives myometrial cells to dedifferentiate into a more plastic phenotype and provides evidence for an alternative mechanism for fibroid etiology, suggesting that fibroids may not only arise from a mutated stem cell but also from a mutated differentiated myometrial cell.

Hypoxia in uterine fibroids: role in pathobiology and therapeutic opportunities.

Uterine fibroids are the most common tumors in females affecting up to 70% of women world-wide, yet targeted therapeutic options are limited. Oxidative stress has recently surfaced as a key driver of fibroid pathogenesis and provides insights into hypoxia-induced cell transformation, extracellular matrix pathophysiology, hypoxic cell signaling cascades, and uterine biology. Hypoxia drives fibroid tumorigenesis through (1) promoting myometrial stem cell proliferation, (2) causing DNA damage propelling transformation of stem cells to tumor initiating cells, and (3) driving excess extracellular matrix (ECM) production. Common fibroid-associated DNA mutations include MED12 mutations, HMGA2 overexpression, and Fumarate hydratase loss of function. Evidence suggests an interaction between hypoxia signaling and these mutations. Fibroid development and growth are promoted by hypoxia-triggered cell signaling via various pathways including HIF-1, TGFβ, and Wnt/β-catenin. Fibroid-associated hypoxia persists due to antioxidant imbalance, ECM accumulation, and growth beyond adequate vascular supply. Current clinically available fibroid treatments do not take advantage of hypoxia-targeting therapies. Growing pre-clinical and clinical studies identify ROS inhibitors, anti-HIF-1 agents, Wnt/β-catenin inhibition, and TGFβ cascade inhibitors as agents that may reduce fibroid development and growth through targeting hypoxia.

Combined oral contraceptive utilization and uterine fibroid incidence: A prospective study in a cohort of African-American women.

Published associations between combined oral contraceptive use and uterine fibroid development have lacked prospective imaging with ultrasound to distinguish between incident and prevalent fibroids. The Study of Environment, Lifestyle, and Fibroids prospectively followed fibroid-free, African-American women (the group with the highest disease burden in the U.S.) to identify incident cases. We examined associations between combined oral contraceptive use and the 40-month cumulative risk of fibroids. History of hormonal contraceptive use was collected via telephone interview at enrollment. Fibroid identification was performed using transvaginal ultrasonography at enrollment, and at 20 and 40-months of follow-up. Inverse probability weights for exposures and censoring were used to construct weighted risk ratios (wRR) and weighted risk different (wRD) estimators which control for differences in fibroid risk factors between exposure groups. In addition, unweighted fully adjusted log-binomial regression models (aRR) were run for comparison. Of the 1,308 participants in the analysis sample, 70% had used combined oral contraceptives and 17% developed fibroids by 40 months. We observed an inverse association between ever use of combined oral contraceptives and cumulative fibroid incidence (wRR: 0.78; 95% Confidence Interval (CI): 0.60, 1.00; wRD: -0.05, 95% CI: -0.11, 0; aRR: 0.76, 95% CI: 0.60, 0.98). Fibroid incidence was greater in participants who started using combined oral contraceptives after age 17 years than among younger initiators, though the restriction to ever-users made this estimate less precise (wRR: 1.25; 95% CI: 0.89, 1.76; wRD: 0.04, 95% CI: -0.02, 0.10). No consistent patterns of fibroid incidence were seen among ever-users for duration of, or years since, last combined oral contraceptives use.

Association of polymorphic variants of cytokines genes, endothelial growth factor and matrix metalloproteinases with the development of uterine fibroids among russian women

One of the factors in the development of uterine fibroids is a genetic predisposition to its occurrence in some women, but the real molecular genetic mechanisms of this phenomenon remain unknown. Aim of the study was the distribution analysis of gene polymorphism of cytokines TNFα, IL-1β, IL-4, IL-6, IL-10, factors of angiogenesis (vascular endothelial growth factor, VEGF) and remodeling of extracellular matrix (metalloproteinases MMP2, MMP3, MMP9), which are associated with their levels. Material and methods. Genotyping was performed by real-time PCR using commercial test systems SYBR GreenI (Litech, Russia) and TaqMan (Syntol, Russia) in accordance with the instructions of the developer. Cytokine content in blood serum was determined by flow cytometry using microspheres coated with monoclonal antibodies to cytokines (Bio-Plex ProTM Human Cytokine 27-plex Assay), according to the instructions for Bio-Plex 200 (Bio-Rad Laboratories, USA).To evaluate the results obtained, in addition to the generally accepted methods of statistical processing for case – control studies, computational methods of bioinformatics were used for comparative analysis of the diagnostic value of various combined genetic traits. Results. It was shown that the maximum odds ratio value of uterine fibroids development are combined genetic traits that include representatives of all four regulatory factors: cytokines with pro-inflammatory activity, cytokines with anti-inflammatory activity, vascular endothelial growth factors and metalloproteinases (p = 0.002). Conclusions. The presented data reveal the real mechanisms of manifestation of the genetic predisposition of individual women to the uterine fibroids development, associated with the presence of polymorphism of certain genes in their genome, which provide features of the structure of cytokine networks with the predominance of certain activities in the regulation of tissue processes in the uterus. In addition to purely scientific interest, these results indicate the real possibility of their clinical application in the form of prognostic criteria with a certain level of prognostic significance.

Hypertension, Cardiovascular Risk Factors, and Uterine Fibroid Diagnosis in Midlife

Fibroids are benign neoplasms associated with severe gynecologic morbidity. There are no strategies to prevent fibroid development. To examine associations of hypertension, antihypertensive treatment, anthropometry, and blood biomarkers with incidence of reported fibroid diagnosis in midlife. The Study of Women's Health Across the Nation is a prospective, multisite cohort study in the US. Participants were followed-up from enrollment (1996-1997) through 13 semiannual visits (1998-2013). Participants had a menstrual period in the last 3 months, were not pregnant or lactating, were aged 42 to 52 years, were not using hormones, and had a uterus and at least 1 ovary. Participants with prior fibroid diagnoses were excluded. Data analysis was performed from November 2022 to February 2024. Blood pressure, anthropometry, biomarkers (cholesterol, triglycerides, and C-reactive protein), and self-reported antihypertensive treatment at baseline and follow-up visits were measured. Hypertension status (new-onset, preexisting, or never [reference]) and hypertension treatment (untreated, treated, or no hypertension [reference]) were categorized. Participants reported fibroid diagnosis at each visit. Discrete-time survival models estimated hazard ratios (HRs) and 95% CIs for associations of time-varying hypertension status, antihypertensive treatment, anthropometry, and biomarkers with incident reported fibroid diagnoses. Among 2570 participants without a history of diagnosed fibroids (median [IQR] age at screening, 45 [43-48] years; 1079 [42.1%] college educated), 526 (20%) reported a new fibroid diagnosis during follow-up. Risk varied by category of hypertension treatment: compared with those with no hypertension, participants with untreated hypertension had a 19% greater risk of newly diagnosed fibroids (HR, 1.19; 95% CI, 0.91-1.57), whereas those with treated hypertension had a 20% lower risk (HR, 0.80; 95% CI, 0.56-1.15). Among eligible participants with hypertension, those taking antihypertensive treatment had a 37% lower risk of newly diagnosed fibroids (HR, 0.63; 95% CI, 0.38-1.05). Risk also varied by hypertension status: compared with never-hypertensive participants, participants with new-onset hypertension had 45% greater risk of newly diagnosed fibroids (HR, 1.45; 95% CI, 0.96-2.20). Anthropometric factors and blood biomarkers were not associated with fibroid risk. Participants with untreated and new-onset hypertension had increased risk of newly diagnosed fibroids, whereas those taking antihypertensive treatment had lower risk, suggesting that blood pressure control may provide new strategies for fibroid prevention.

UTERINE FIBROIDS AND THE CORRELATION WITH BLACK WOMEN

Uterine fibroids are common benign tumors in the uterus of women of reproductive age and can cause symptoms such as heavy menstrual bleeding, pelvic pain and increased abdominal volume. Studies have shown a higher prevalence of uterine fibroids in black women compared to women of other ethnicities. Understanding the causes of this disparity is fundamental to developing more effective prevention and treatment strategies. Investigating the relationship between the incidence of uterine fibroids and black ethnicity, analyzing the genetic and social factors that may contribute to this correlation and proposing measures to reduce the incidence of uterine fibroids in black women are the aims of this study. This is a systematic literature review using an exploratory and narrative method, with qualitative and quantitative premises. The databases used were PubMed, Scielo, Scopus, Web of Science and the Virtual Health Library. The articles analyzed were selected by exclusion and inclusion criteria, which are set out here, using the health sciences descriptors “uterine fibroids”, “black women and uterine fibroids”, “genetic factors and uterine fibroids” and “environmental factors and uterine fibroids”, reaching a total of 617 articles searched and 9 used in this study. Genetic studies have suggested a genetic predisposition to the development of uterine fibroids in black women, with the identification of genetic variants associated with a higher risk. In addition, social factors such as limited access to quality healthcare, socioeconomic inequalities and exposure to psychosocial stressors may also play an important role. Lack of access to preventive healthcare and unequal access to effective treatments may contribute to a higher prevalence of uterine fibroids in black women. Measures to reduce this disparity include promoting equitable access to healthcare, reproductive health education and public policies that address the underlying causes of health inequalities. The correlation between uterine fibroids and black women highlights the need for integrated approaches that consider both genetic and social factors. Promoting equity in access to health care and implementing public policies aimed at women’s health are key to reducing the incidence of uterine fibroids and improving the quality of life of black women.

Uterine fibroids and longitudinal profiles of the vaginal microbiota in a cohort presenting for transvaginal ultrasound.

Bacterial vaginosis, characterized in part by low levels of vaginal Lactobacillus species, has been associated with pro-inflammatory cytokines which could fuel uterine fibroid development. However, prior work on the associations between uterine fibroids and vaginal bacteria is sparse. Most studies have focused on assessment of individual taxa in a single sample. To address research gaps, we sought to compare short, longitudinal profiles of the vaginal microbiota in uterine fibroid cases versus controls with assessment for hormonal contraceptives (HCs), a possible confounder associated with both protection from fibroid development and increases in Lactobacillus-dominated vaginal microbiota. This is a secondary analysis of 83 reproductive-age cisgender women who presented for transvaginal ultrasound (TVUS) and self-collected mid-vaginal swabs daily for 1-2 weeks before TVUS (Range: 5-16 days, n = 697 samples). Sonography reports detailed uterine fibroid characteristics (N = 21 cases). Vaginal microbiota was assessed by 16S rRNA gene amplicon sequencing and longitudinal microbiota profiles were categorized by hierarchical clustering. We compared longitudinal profiles of the vaginal microbiota among fibroid cases and controls with exact logistic regression. Common indications for TVUS included pelvic mass (34%) and pelvic pain (39%). Fibroid cases tended to be older and report Black race. Cases less often reported HCs versus controls (32% vs. 58%). A larger proportion of cases had low-Lactobacillus longitudinal profiles (48%) than controls (34%). In unadjusted analysis, L. iners-dominated and low-Lactobacillus profiles had higher odds of fibroid case status compared to other Lactobacillus-dominated profiles, however these results were not statistically significant. No association between vaginal microbiota and fibroids was observed after adjusting for race, HC and menstruation. Results were consistent when number of fibroids were considered. There was not a statistically significant association between longitudinal profiles of vaginal microbiota and uterine fibroids after adjustment for common confounders; however, the study was limited by small sample size.

Body Mass Index and Uterine Fibroid Development: A Prospective Study.

Fibroids are hormonally dependent uterine tumors. The literature on adiposity and fibroid prevalence is inconsistent. Previous work usually combined all those with body mass indexes (BMIs) ≥30kg/m2 into a single category and relied on clinically diagnosed fibroids which misclassifies the many women with undiagnosed fibroids. We used a prospective cohort design with periodic ultrasound screening to investigate associations between repeated measures of BMI and fibroid incidence and growth assessed at each follow-up ultrasound. The Study of Environment, Lifestyle & Fibroids (SELF) followed 1,693 Black/African American women, ages 23-35 from Detroit, Michigan with ultrasound every 20 months for 5 years. Measured height and repeated weight measures were used to calculate BMI. Fibroid incidence was modeled using Cox models among those who were fibroid-free at the enrollment ultrasound. Fibroid growth was estimated for individual fibroids matched across visits as the difference in log-volume between visits and was modeled using linear mixed models. All models used time-varying BMI and adjusted for time-varying covariates. Compared to BMI <25kg/m2 those with BMI 30-<35kg/m2 had increased fibroid incidence (adjusted hazard ratio (aHR) 1.37, (95% Confidence Interval (CI): 0.96-1.94)), those with BMI ≥40kg/m2 had reduced incidence (aHR 0.61, (95% CI: 0.41-0.90)). Fibroid growth had mostly small magnitude associations with BMI. BMI has a non-linear association with fibroid incidence that could be driven by effects of BMI on inflammation and reproductive hormones. More detailed measures of visceral and subcutaneous adiposity and their effects on hormones, DNA damage, and cell death are needed.

Influence of nutrition on the course of uterine fibroids

Currently, there is a negative trend in the increase in the incidence of uterine fibroids, often diagnosed at a later date, requiring more invasive laparotomic myomectomy, up to hysterectomy. It was also revealed that the patients had an aggravated premorbid background in the form of obesity and related diseases.The purpose of the study. To study domestic and foreign studies. To identify the features of the course of uterine fibroids in patients with hypersthenic and normosthenic body types.Materials and methods. Anonymous and voluntary questionnaire survey with an in-depth collection of food history, interviews of 260 patients and analysis of their case histories with uterine fibroids who underwent laparoscopic and laparotomic myomectomy were carried out, dividing them into 2 groups according to BMI.Results. In both groups, there was the following distribution according to the presence of pregnancies: 0 – 4 % and 5 %, 1 – 86 % and 84 %, 2 – 10 % and 11 % for groups I and II, respectively (p = 0.041 criterion). 25 % in group I and 31 % in group II had a history of surgery – caesarean section. The presence of inflammatory diseases of the pelvic organs in both groups was 89.3 % and 91.6 %, respectively. Also noted was a high consumption of beef and pork by 10 and 23 %, potatoes by 8 % and 13 %, white cabbage by 12 % and 11 %, bakery products by 21 % and 26 %. Low consumption of seafood and fish products by 35 % and 56 %, dairy products by 44 % and 47 %, absolutely low content of olive oil in the daily diet. The above data are presented for groups I and II, respectively. (criterion p = 0.029-0.054).Сonclusions. Obesity plays a role as a risk factor for the development of uterine fibroids, acting either through hormonal or inflammatory mechanisms. Obesity can contribute to the development of insulin resistance and hyperinsulinemia, which can directly or indirectly influence the development of fibroids by promoting the proliferation of myometrial smooth muscle cells and increasing circulating levels of ovarian hormones.

Fibroid uterus: A case study

Fibroid uterus, also known as Uterine leiomyoma, represents a common gynecological disorder affecting women, particularly those in their reproductive years. This paper presents a case study focusing on the clinical manifestation, diagnosis, management, and nursing care of a 43-year-old woman with fibroid uterus. Fibroids, benign neoplasms of the uterine wall, are classified based on their location within the uterus. Risk factors for fibroid development include early puberty, obesity, genetic predisposition, and oral contraceptive use. Diagnosis often involves ultrasound imaging, revealing characteristic features such as heterogeneous hypoechoic lesions. Management options range from medical to surgical interventions, with considerations for patient age, fertility preservation, and symptom severity. Surgical procedures like myomectomy and hysterectomy may be necessary, while non-surgical alternatives such as uterine artery embolism and myolysis offer alternatives. Nursing care focuses on pain management, nutritional support, infection prevention, and patient education. Early detection and appropriate management are essential to mitigate the risk of complications and preserve fertility in affected women.

FRI414 Association Between Uterine Leiomyoma Prevalence And Metabolic Syndrome In A Reproductive Aged Latina/Latinx Population

Abstract Disclosure: E.L. Ferrell: None. S. Schon: None. L. Jiang: None. F. Valbuena: None. E. Manuel: None. M. Castillo-Mackenzie: None. M. Carnethon: None. D.D. Baird: None. L. Neff: Employee; Self; Eli Lilly &amp; Company. Stock Owner; Self; Eli Lilly &amp; Company. E.E. Marsh: Consulting Fee; Self; Pfizer, Inc., Myovant Sciences. Objectives: Uterine leiomyomas, commonly known as fibroids, are benign tumors in the wall of the uterus that affect approximately 30% of females by the age of 35, and 70% of females by the age of 50. Greater fibroid prevalence has been observed in certain cohorts, with some studies reporting &amp;gt; 85% prevalence in African American women by the age of 50. Increasing evidence suggests that cardiometabolic risk factors contribute to uterine fibroid development. Few studies have assessed either the prevalence of fibroids or their relationship with Metabolic Syndrome (MetS) in the Latina/Latinx population. The objective of this study was to assess the relationship between MetS and fibroid prevalence in a large cohort of Latina/Latinx females. Materials &amp; Methods: This is a cross-sectional analysis of data collected as part of a prospective longitudinal cohort study. The Environment, Leiomyomas, Latinas, and Adiposity Study (ELLAS) follows 707 Latina women over a 4-year period. All participants in this study were between the ages of 21-50 at the time of enrollment. Demographic and baseline information was collected by trained bilingual study staff. Anthropometric measurements were performed, and fasting blood samples were collected. Participants underwent a baseline pelvic ultrasound to assess for the presence of fibroids. MetS diagnosis was based on the 2005 AHA/NHLBI criteria. The association between MetS and fibroids were assessed as categorical variables. Statistical associations were determined using chi-squared tests and logistic regression. Results: Of the 707 participants enrolled in ELLAS, 621 completed the first study visit, and data from the criteria used to diagnose MetS were available from 590 participants. Of those 590, 578 participants completed ultrasound evaluation for fibroids and were included in final analysis. The mean age was 37.4±6.95 years and the mean BMI was 30.1±6.76 kg/m2. A total of 143 participants met criteria for MetS (24.7%). Prevalence of MetS was positively correlated with age. The prevalence of fibroids in this Latina population was 10.7%. There was no statistically significant association between MetS and the presence of fibroids (p value &amp;gt;0.05). Conclusion: Among a large cohort of Latinx females, MetS was not significantly associated with fibroids. The prevalence of fibroids in this population was lower than observed in other populations, suggesting a possible protective factor yet to be identified amongst Latinx females. Given the low prevalence, we were likely underpowered to detect an association. Further research is needed to determine the relationship between cardiovascular, metabolic, and reproductive outcomes in this understudied population. Presentation: Friday, June 16, 2023

Serum Calcium and Magnesium Levels in Women with Uterine Fibroids in Southwest Nigeria: a Cross-sectional Study.

Studies have suggested the potential roles of serum macronutrients such as calcium and magnesium in the development of uterine fibroids. The primary objective was to assess the association between serum magnesium and calcium levels and the prevalence of uterine fibroids in women of reproductive age. A cross-sectional study of 194 parity-matched women with or without a sonographic diagnosis of uterine fibroids enrolled at a university teaching hospital in Lagos, Southwest Nigeria. Participants' sociodemographic, ultrasound, and anthropometric information as well as the estimated serum levels of calcium and magnesium were collected for statistical analyses. This study found significant negative associations between low serum calcium levels and uterine fibroids (adjusted odds ratio = 0.06), uterine size, and the number of fibroid nodules. However, no significant association was observed between serum magnesium levels and uterine fibroids. This study found significant inverse associations between low serum calcium levels and uterine fibroids, uterine size, and the number of fibroid nodules.

TGFβ signaling links early life endocrine-disrupting chemicals exposure to suppression of nucleotide excision repair in rat myometrial stem cells

Environmental exposure to endocrine-disrupting chemicals (EDCs) is linked to the development of uterine fibroids (UFs) in women. UFs, non-cancerous tumors, are thought to originate from abnormal myometrial stem cells (MMSCs). Defective DNA repair capacity may contribute to the emergence of mutations that promote tumor growth. The multifunctional cytokine TGFβ1 is associated with UF progression and DNA damage repair pathways. To investigate the impact of EDC exposure on TGFβ1 and nucleotide excision repair (NER) pathways, we isolated MMSCs from 5-month-old Eker rats exposed neonatally to diethylstilbestrol (DES), an EDC, or to vehicle (VEH). EDC-MMSCs exhibited overactivated TGFβ1 signaling and reduced mRNA and protein levels of NER pathway components compared to VEH-MMSCs. EDC-MMSCs also demonstrated impaired NER capacity. Exposing VEH-MMSCs to TGFβ1 decreased NER capacity while inhibiting TGFβ signaling in EDC-MMSCs restored it. RNA-seq analysis and further validation revealed decreased expression of Uvrag, a tumor suppressor gene involved in DNA damage recognition, in VEH-MMSCs treated with TGFβ1, but increased expression in EDC-MMSCs after TGFβ signaling inhibition. Overall, we demonstrated that the overactivation of the TGFβ pathway links early life exposure to EDCs with impaired NER capacity, which would lead to increased genetic instability, arise of mutations, and fibroid tumorigenesis. We demonstrated that the overactivation of the TGFβ pathway links early life exposure to EDCs with impaired NER capacity, which would lead to increased fibroid incidence.

The Biological Effects of Vitamin D on the Development of Uterine Fibroids: A Literature Review

Uterine Fibroids (UFs), also known as uterineleiomyomas or myomas, are benign tumors derivedfrom smooth muscle tissue. Vitamin D deficiency is oneof the many factors involved in the development andgrowth of UFs. Many studies have shown that vitamin Dsupplementation decreases the size of fibroids despitea poorly understood pathogenesis. The activity ofvitamin D against UF cells has mainly been supportedby various in vitro and in vivo studies. For this review,we conducted in-depth research of published literatureon vitamin D's biological and pathophysiological effectson UFs. We searched on Google Scholar and PubMedusing common keywords and selected 23 studies fromthe search results. The literature chosen from the pastten years was read and analyzed thoroughly. However,because of the limited research on the effects of vitaminD on UFs and the different inclusion criteria, the clinicalefficacy of vitamin D on women with UFs remainsunclear. More extensive, well-organized studies on thespecific effects of vitamin D on the growth of UFs wouldprove efficacious in establishing treatments.

Association of genital talc and douche use in early adolescence or adulthood with uterine fibroids diagnoses

Genital talc and douching are practices that can involve exposure to chemical compounds linked to certain gynecologic cancers. However, it is unclear if they are associated with fibroid risk or age at fibroid diagnosis among women. This study aimed to evaluate the impact of early-adolescence genital talc use and douching on prevalence of fibroids diagnosed before the age of 35 and 50 years among Black/African American and non-Hispanic White women. Data were derived from the Sister Study (2003-2020), a prospective cohort of 50,884 US women aged 35 to 74 years at enrollment. Participants were asked if they ever had a fibroid diagnosis and at what age, and if they used genital talc and/or douched between the ages of 10 and 13 years or in the past 12 months. After applying predefined exclusion criteria, our analytical sample size was n=46,316 (Black, n=4310; non-Hispanic White, n=42,006). Multivariable logistic regression was used to compute adjusted odds ratios and 95% confidence intervals for having vs not having early-onset fibroids diagnosed before age 35 among women aged 35 to 74 years at enrollment, and fibroids diagnosed before age 50 among women aged 50 to 74 years at enrollment. We adjusted for early life factors (in utero diethylstilbestrol exposure, singleton or multiple birth, fed soy formula during infancy), childhood socioeconomic status, and relative weight and height compared with peers at age 10. We used multiple imputation (<10% missing in all analyses). Results were stratified by race/ethnicity given that Black women are more likely to develop fibroids at a younger age than non-Hispanic White women. Among Black/African American women, 29% had fibroids diagnosed before age 35. Both genital talc use at age 10 to 13 (adjusted odds ratio, 1.23; confidence interval, 1.06-1.41) and douching (adjusted odds ratio, 1.19; 95% confidence interval, 0.95-1.48) were associated with higher odds of having a fibroid diagnosed before age 35. Douching without talc use was not associated with increased odds, but combined use of genital talc and douche was associated with 52% increased odds of fibroids (confidence interval, 1.14-2.01). Among non-Hispanic White women, 9% reported fibroids diagnosed before age 35. Genital talc use (1.31; 1.20-1.44) but not douching (0.96; 0.77-1.20) at age of 10 to 13 years was associated with having a fibroid diagnosed before age 35. We observed similar patterns for non-Hispanic White women when we considered fibroids diagnosed before age 50, but neither practice was associated with fibroids diagnosed before age 50 in Black women. Genital talc use in early adolescence, alone and in combination with douching (but not douching alone), is associated with prevalence of fibroids diagnosed before age 35 among Black/African American women and before ages 35 and 50 among non-Hispanic White women. Early adolescence may be a window of susceptibility for fibroid development, suggesting that adolescent girls should be educated on abstention from or alternatives to talc use and douching.

Uterine Fibroids: Retrospective Study with Analysis of Different Risk Factors

Uterine fibroids are benign monoclonal neoplasms of the myometrium, representing the most common tumors in women worldwide. To date, no long-term or noninvasive treatment option exists for hormone-dependent uterine fibroids, due to the limited knowledge about the molecular mechanisms underlying the initiation and development of uterine fibroids.

Cost-effectiveness of Myomectomy versus Hysterectomy in Women with Uterine Fibroids

Increasing evidence suggests that hysterectomy to treat uterine fibroids (UFs), even with ovarian conservation (OC), is associated with a 33% increased risk of coronary artery disease (CAD). We sought to compare the cost-effectiveness of various treatment approaches for UFs to understand the trade-offs among development of CAD vs new fibroids. We developed a Markov model to include women with UFs who no longer desired pregnancy. The outcomes of interest were quality-adjusted life-years (QALYs) and total treatment costs. We conducted sensitivity analyses to test the effect of uncertain model inputs. Health system perspective. A hypothetical cohort of 10000 40-year-old women. Myomectomy, hysterectomy with OC, and hysterectomy without OC. Myomectomy was the best-value strategy, costing US$528217 and providing 19.38 QALYs. Neither hysterectomy with OC nor hysterectomy without OC was found to be cost-effective, assuming a willingness-to-pay threshold of $100000 per QALY gain as hysterectomy with OC provided more benefit than myomectomy at an average cost of $613144 to gain one additional QALY. The sensitivity analyses showed that if the risk of new symptomatic UFs that required treatment after myomectomy was more than 13%, annually (base case, 3.6%), or the quality of life after myomectomy was less than 0.815 (base case, 0.834), then myomectomy would no longer be cost-effective, under a willingness-to-pay amount of US$100000. Myomectomy is an optimal treatment of UFs compared with hysterectomy among women aged 40 years. The increased risk of CAD after hysterectomy and its associated costs and the effects on morbidity and quality of life made hysterectomy a costlier and less effective long-term strategy.