Innovative Oral Treatments of Uterine Leiomyoma

Uterine fibroids (leiomyoma), the benign tumors of the uterine wall, are very common cause of morbidity in reproductive age women usually in the form of excessive vaginal bleeding, chronic pelvic pain, miscarriage and infertility. These tumors are the leading indication for hysterectomy in the United States. Uterine fibroids are about 4 times higher in blacks compared to whites and constitute a major health disparity challenge. The estimated cost of uterine fibroids is up to $34.4 billion annually. Additionally, women who suffer from this disease and desire to maintain their future fertility have very limited treatment choices. Currently, there is no effective long-term medicinal treatment for uterine fibroids. While surgery has traditionally been the gold standard for the treatment of uterine fibroids, there is growing interest towards orally administered medications for the management of leiomyoma-related symptoms. In this paper, we will discuss these promising innovative oral medical treatments in detail

Laparoscopic management of a large torted ovarian cyst in an adolescent virgin: a case report

We report a case of a torted mature cystic teratoma in a 23-year-old, sexually inactive, virgin female which necessitated immediate laparoscopy. The patient and her family stressed that the integrity of the hymen must be maintained at any cost, for cultural reasons. We opted out of our routine intravaginal preparation for laparoscopic surgery to honor the patient’s request to maintain the integrity of the hymen. Left salpingo-oophorectomy was accomplished, and the specimen was removed using a large nephrectomy endobag. Here, we describe techniques that are useful for this procedure, including the use of gauze attached to ovum forceps to manipulate the uterus through the rectum, and a review of the literature

Gut and genital tract microbiomes: Dysbiosis and link to gynecological disorders

Every year, millions of women are affected by genital tract disorders, such as bacterial vaginosis (BV), endometrial cancer, polycystic ovary syndrome (PCOS), endometriosis, and uterine fibroids (UFs). These disorders pose a significant economic burden on healthcare systems and have serious implications for health and fertility outcomes. This review explores the relationships between gut, vaginal, and uterine dysbiosis and the pathogenesis of various diseases of the female genital tract. In recent years, reproductive health clinicians and scientists have focused on the microbiome to investigate its role in the pathogenesis and prevention of such diseases. Recent studies of the gut, vaginal, and uterine microbiomes have identified patterns in bacterial composition and changes across individuals’ lives associated with specific healthy and diseased states, particularly regarding the effects of the estrogen–gut microbiome axis on estrogen-driven disorders (such as endometrial cancer, endometriosis, and UFs) and disorders associated with estrogen deficiency (such as PCOS). Furthermore, this review discusses the contribution of vitamin D deficiency to gut dysbiosis and altered estrogen metabolism as well as how these changes play key roles in the pathogenesis of UFs. More research on the microbiome influences on reproductive health and fertility is vital

Vitamin D and Female Reproduction

Vitamin D deficiency has an impact on the reproduction of more than 40% of reproductive age women globally. Fibroids are more common among African-American females owing to their decreased milk consumption and reduced absorption of ultraviolet rays, supporting the relation between vitamin D deficiency and fibroid development. Vitamin D has an inhibitory effect on leiomyoma cells by suppression of proliferation cell nuclear antigen (PCNA), BCL-2, BCL-w, CDK1, and catechol-O-methyltransferase (COMT) protein levels. A growing evidence support the relationship between vitamin D deficiency and endometriosis through overexpression of vitamin D recseptor (VDR) and α-hydroxylase enzyme, however, it is still unclear if the endometriosis patients could benefit from vitamin D supplementation. Effect of vitamin D supplementation on the metabolic outcomes of polycystic ovary (PCO) has been studied and reveled that it is negatively correlated with fasting glucose, fasting insulin, triglycerides, C-reactive protein, free androgen index, and Dehydroepiandrosterone (DHEAS) and positively associated with quantitative insulin sensitivity check index (QUICKI), high density lipoprotein cholesterol (HDL-C), and sexual hormone binding globulin (SHBG), whereas its impact on the ovarian function is still unclear. Vitamin D deficiency may worse the obstetrical outcomes, including preeclampsia, gestational diabetes, low birth weight, increased cesarean section rate, neonatal asthma, seizures, and preterm labor. The relationship between serum levels of 25-hydroxy-vitamin D (25(OH) D) and pregnancy rates in ART is still debatable, with the need to conduct more clinical trials toward it. The in vitro antiproliferative and prodifferentiative effect of vitamin D might find a role in control of hyperplastic overactive bladder. Several studies support that vitamin D deficiency constitutes a risk factor for development of many types of cancer such as breast, ovarian, and colorectal

Mediator Kinase Disruption in MED12-Mutant Uterine Fibroids From Hispanic Women of South Texas

Context: Mutations in the gene encoding Mediator complex subunit MED12 are dominant drivers of uterine fibroids (UFs) in women of diverse racial and ethnic origins. Previously, we showed that UF-linked mutations in MED12 disrupt its ability to activate cyclin C-CDK8/19 in Mediator. However, validation of Mediator kinase disruption in the clinically relevant setting of MED12-mutant UFs is currently lacking. Objective: The objective of this study was twofold. First, to extend the ethnic distribution profile of MED12 mutations by establishing their frequency in UFs from Hispanic women of South Texas. Second, to examine the impact of MED12 mutations on Mediator kinase activity in patient-derived UFs. Methods: We screened 219 UFs from 76 women, including 170 tumors from 57 Hispanic patients, for MED12 exon 2 mutations, and further examined CDK8/19 activity in Mediator complexes immunoprecipitated from MED12 mutation-negative and MED12 mutation-positive UFs. Results: MED12 exon 2 mutations in UFs from Hispanic women are somatic in nature, predominantly monoallelic, and occur at high frequency (54.1%). We identified a minimal cyclin C-CDK8 activation domain on MED12 spanning amino acids 15 through 80 that includes all recorded UF-linked mutations in MED12, suggesting that disruption of Mediator kinase activity is a principal biochemical defect arising from these pathogenic alterations. Analysis of Mediator complexes recovered from patient UFs confirmed this, revealing that Mediator kinase activity is selectively impaired in MED12-mutant UFs. Conclusions: MED12 mutations are important drivers of UF formation in Hispanic women of South Texas. MED12 mutations disrupt Mediator kinase activity, implicating altered CDK8/19 function in UF pathogenesis.Peer reviewe

Bone Marrow Transplantation Restores Follicular Maturation and Steroid Hormones Production in a Mouse Model for Primary Ovarian Failure

Recent studies suggest that bone marrow stem cells (BMSCs) are promising grafts to treat a variety of diseases, including reproductive dysfunction. Primary ovarian failure is characterized by amenorrhea and infertility in a normal karyotype female, with an elevated serum level of follicle-stimulating hormone (FSH) and a decrease level of estrogen caused by a mutation in FSH receptor (FSHR) gene. Currently, there is no effective treatment for this condition. The phenotype of FSHR (−/−) mouse, FORKO (follitropin receptor knockout), is a suitable model to study ovarian failure in humans. Female FORKO mice have elevated FSH, decreased estrogen levels, are sterile because of the absence of folliculogenesis, and display thin uteri and small nonfunctional ovaries. In this study, we determined the effects of BMSC transplantation on reproductive physiology in this animal model. Twenty four hours post BMSC transplantation, treated animals showed detectable estroidogeneic changes in daily vaginal smear. Significant increase in total body weight and reproductive organs was observed in treated animals. Hemotoxylin and eosin (H&E) evaluation of the ovaries demonstrated significant increase in both the maturation and the total number of the follicles in treated animals. The FSH dropped to 40–50% and estrogen increased 4–5.5 times in the serum of treated animals compared to controls. The FSHR mRNA was detected in the ovaries of treated animals. Our results show that intravenously injected BMSCs were able to reach the ovaries of FORKO mice, differentiate and express FHSR gene, make FSHR responsive to FSH, resume estrogen hormone production, and restore folliculogenesis