RESUMO
Perimenopause significantly impacts women's health globally, often managed with hormone replacement therapy (HRT) despite the associated risks. This study explores a novel alternative exosome therapy, aimed at stimulating estrogen production in ovarian tissues, thus offering a potential non-hormonal treatment for perimenopausal symptoms. Employing ex vivo methodologies, ovarian cortex specimens from perimenopausal women were treated with exosomes derived from human umbilical cord mesenchymal stem cells and cultured under specific conditions (patent number: PCT/US2022/073467). The exosomes were produced under cyclic guanosine monophosphate (cGMP) conditions, ensuring high safety standards. Estrogen levels were quantified using enzyme-linked immunosorbent assay (ELISA), and gene expression changes in estrogen and follicle-stimulating hormone (FSH) receptors were assessed via quantitative polymerase chain reaction (PCR). Immunohistochemistry (IHC) was utilized to evaluate cellular proliferation and apoptotic markers. The results indicated a significant increase in estrogen levels and estrogen receptor-alpha (Erα) expression in treated tissues compared to controls. Additionally, a decrease in apoptotic markers and an increase in cellular proliferation markers were observed. These findings suggest that exosome therapy can effectively enhance estrogen production and modulate receptor sensitivity in perimenopausal ovarian tissues. This approach could serve as a safer alternative to HRT, aligning with the body's natural regulatory mechanisms and potentially offering a more effective treatment option for managing perimenopausal symptoms.
Assuntos
Estrogênios , Exossomos , Perimenopausa , Humanos , Exossomos/metabolismo , Feminino , Perimenopausa/metabolismo , Estrogênios/metabolismo , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/citologia , Proliferação de Células , Receptor alfa de Estrogênio/metabolismo , Receptor alfa de Estrogênio/genética , Pessoa de Meia-Idade , Apoptose , Receptores do FSH/metabolismo , Receptores do FSH/genética , Ovário/metabolismoRESUMO
Polycystic ovary syndrome (PCOS) is known as the most common endocrine disorder in women. Previously, we suggested that human mesenchymal stem cells (MSCs) can reverse the PCOS condition by secreting factors. Here, we evaluated the therapeutic capability of MSC-derived extracellular vesicles (EVs), also known as exosomes, in both in vitro and in vivo PCOS models. Exosomes were used to treat androgen-producing H293R cells and injected in a mouse model through intraovarian and intravenous injection into a letrozole (LTZ)-induced PCOS mouse model. We assessed the effects of the exosomes on androgen-producing cells or the PCOS mouse model by analyzing steroidogenic gene expression (quantitative real-time polymerase chain reaction (qRT-PCR)), body weight change, serum hormone levels, and fertility by pup delivery. Our data show the therapeutic effect of MSC-derived EVs for reversing PCOS conditions, including fertility issues. Interestingly, intravenous injection was more effective for serum glucose regulation, and an intraovarian injection was more effective for ovary restoration. Our study suggests that MSC-derived exosomes can be promising biopharmaceutics for treating PCOS conditions as a novel therapeutic option. Despite the fact that we need more validation in human patients, we may evaluate this novel treatment option for PCOS with the following clinical trials.
Assuntos
Vesículas Extracelulares , Células-Tronco Mesenquimais , Síndrome do Ovário Policístico , Animais , Camundongos , Humanos , Feminino , Síndrome do Ovário Policístico/metabolismo , Androgênios/metabolismo , Vesículas Extracelulares/metabolismo , Células-Tronco Mesenquimais/metabolismoRESUMO
Currently, there is no viable option for fertility preservation in prepubertal boys. Experimentally, controlled vitrification of testicular tissue has been evaluated and found to cause potential structural damage to the spermatogonial stem cell (SSC) niche during cryopreservation. In this report, we leveraged the regenerative effect of human umbilical cord-derived Mesenchymal stem cell exosomes (h-UCMSC-Exo) to protect against testicular damage from the cytotoxic effects of polychemotherapy (CTX). A chemotherapy-induced testicular dysfunctional model was established by CTX treatment with cyclophosphamide and Busulfan in vitro (human Sertoli cells) and in prepubescent mice. We assessed the effects of the exosomes by analyzing cell proliferation assays, molecular analysis, immunohistochemistry, body weight change, serum hormone levels, and fertility rate. Our data indicates the protective effect of h-UCMSC-Exo by preserving the SSC niche and preventing testicular damage in mice. Interestingly, mice that received multiple injections of h-UCMSC-Exo showed significantly higher fertility rates and serum testosterone levels (p < 0.01). Our study demonstrates that h-UCMSC-Exo can potentially be a novel fertility protection approach in prepubertal boys triaged for chemotherapy treatment.
Assuntos
Exossomos , Células-Tronco Mesenquimais , Masculino , Humanos , Animais , Camundongos , Quimioterapia Combinada , Fertilidade , EspermatogôniasRESUMO
Uterine fibroids (UFs) are the most common prevalent benign tumor among women of reproductive age, disproportionately affecting women of color. This paper introduces an innovative management strategy for UFs, emphasizing the curbing of disease prevention and progression. Traditionally, medical intervention is deferred until advanced stages, necessitating invasive surgeries such as hysterectomy or myomectomy, leading to high recurrence rates and increased healthcare costs. The strategy, outlined in this review, emphasizes UF disease management and is named LIFE UP awareness-standing for Lifestyle Interventions, Food Modifications, and Environmental Practices for UF Prevention. These cost-effective, safe, and accessible measures hold the potential to prevent UFs, improve overall reproductive health, reduce the need for invasive procedures, and generate substantial cost savings for both individuals and healthcare systems. This review underscores the importance of a proactive UF management method, paving the way for future research and policy initiatives in this domain.
Assuntos
Leiomioma , Miomectomia Uterina , Neoplasias Uterinas , Feminino , Humanos , Neoplasias Uterinas/prevenção & controle , Neoplasias Uterinas/patologia , Leiomioma/prevenção & controle , Leiomioma/patologia , Estilo de Vida , Poder PsicológicoRESUMO
BACKGROUND: Uterine leiomyomas (often referred to as fibroids or myomas) are common benign, hormone-dependent tumors that grow in the uterus and occur in approximately 25% of reproductive age women, depending on selected population. Treatment recommendation is typically based on fibroid size, location, the patient's age, reproductive plans, and obstetrical history. Despite the range of treatment options available for uterine fibroids and their symptoms, including hysterectomy, myomectomy, endometrial ablation, endometrial uterine artery embolization, and magnetic resonance-guided focused-ultrasound surgery, myomectomy remains the gold standard treatment for patients who desire fertility-preserving surgery for their uterine fibroids. Myomectomy, while a prevalent surgical option for the removal of fibroids, carries known risks such as fibroid recurrence, symptom recurrence, and the subsequent need for reintervention. Despite ongoing research and advances in medical treatments for fibroids, there currently are no universally recommended therapeutic interventions proven to effectively delay the recurrence of fibroids or the return of symptoms following this procedure. This situation underscores a significant area of unmet medical need and highlights the importance of continued investigation into preventive strategies and long-term management options for patients undergoing fibroid removal with uterine preservation. We designed a study to assess the efficacy of the new FDA-approved GnRH antagonist, Myfembree in delaying the return of fibroids and their associated symptoms. METHODS: A randomized, prospective, open-label clinical trial. The participants (n = 136) will be randomly distributed into two groups. The Control Group (Standard of care) will receive treatment with standard of care (SoC) after surgical myomectomy and the treatment group will receive Relugolix combination therapy (Myfembree®) after surgical myomectomy. The study protocol was approved by the University of Chicago's Institutional Review Board (IRB#22-0282), ensuring that all participants would provide written informed consent before their inclusion. DISCUSSION: In this project, we propose the use of daily dosed Relugolix combination therapy (Relugolix with estradiol and norethindrone acetate), which is approved for uterine fibroids treatment, has the potential to delay the recurrence of fibroid symptoms, prolong the improved quality of life and delay need for re-intervention after uterine sparing surgery. TRIAL REGISTRATION: The study protocol was approved by the Institutional Review Board of the University of Chicago on 9/16/2022 and was registered at ClinicalTrials.gov with number NCT05538689 on Sep 7, 2022. All subjects will provide informed consent to participate.
Assuntos
Leiomioma , Padrão de Cuidado , Miomectomia Uterina , Neoplasias Uterinas , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Leiomioma/cirurgia , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Miomectomia Uterina/métodos , Neoplasias Uterinas/cirurgiaRESUMO
INTRODUCTION: Uterine fibroids, the most common nonmalignant tumors affecting the female genital tract, are a significant medical challenge. This article focuses on the most recent studies that attempted to identify novel non-hormonal therapeutic targets and strategies in UF therapy. AREAS COVERED: This review covers the analysis of the pharmacological and biological mechanisms of the action of natural substances and the role of the microbiome in reference to UFs. This study aimed to determine the potential role of these compounds in UF prevention and therapy. EXPERT OPINION: While there are numerous approaches for treating UFs, available drug therapies for disease control have not been optimized yet. This review highlights the biological potential of vitamin D, EGCG and other natural compounds, as well as the microbiome, as promising alternatives in UF management and prevention. Although these substances have been quite well analyzed in this area, we still recommend conducting further studies, particularly randomized ones, in the field of therapy with these compounds or probiotics. Alternatively, as the quality of data continues to improve, we propose the consideration of their integration into clinical practice, in alignment with the patient's preferences and consent.
Assuntos
Leiomioma , Neoplasias Uterinas , Humanos , Leiomioma/tratamento farmacológico , Feminino , Animais , Neoplasias Uterinas/tratamento farmacológico , Terapia de Alvo Molecular , Microbiota/efeitos dos fármacos , Probióticos/farmacologia , Probióticos/administração & dosagem , Desenvolvimento de Medicamentos , Catequina/farmacologia , Catequina/análogos & derivados , Catequina/administração & dosagem , Vitamina D/farmacologiaRESUMO
Uterine fibroids significantly impact women's reproductive health, influencing fertility potential and pregnancy outcomes. Their growth, often facilitated by hormonal influences like estrogen and progesterone, can cause considerable disruptions in the uterus, leading to symptoms and complications that impact the quality of life and reproductive prospects of women.This article provides an exhaustive discussion of uterine fibroids, including pathophysiology, their impact on endometrial function, receptivity, fertility, and pregnancy outcomes, and the management of infertility in patients with uterine fibroids. It underlines the critical role of uterine fibroids in women's reproductive health, emphasizing the importance of effective diagnosis and treatment to promote fertility and improve pregnancy outcomes.
Assuntos
Leiomioma , Miomectomia Uterina , Neoplasias Uterinas , Gravidez , Humanos , Feminino , Neoplasias Uterinas/complicações , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/terapia , Qualidade de Vida , Leiomioma/complicações , Leiomioma/diagnóstico , Leiomioma/terapia , FertilidadeRESUMO
Uterine leiomyomas or uterine fibroids are the most common benign soft tissue tumor in reproductive-aged women. Fumarate hydratase deficient (FH-d) uterine fibroids are a rare subtype that is diagnosed only on pathologic evaluation. FH-d uterine fibroids may be the first indicator of hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome. Therefore, identifying and understanding the clinical implication and diagnosis of FH-d uterine fibroids is critical for early diagnosis of HLRCC. This case series investigates the uncommon yet significant condition of FH-d uterine fibroids. We examined the clinical manifestation, diagnostic imaging, and histopathological characteristics of FH-d uterine fibroids in five cases identified at our institution over the last ten years. All diagnoses were confirmed by pathologic evaluation after surgical treatment. Gynecologists and pathologists play a critical role in the early diagnosis of FH-d uterine fibroids and must recognize the relevant clinical and pathologic findings that raise suspicion about this diagnosis. The detection of these cases is largely dependent on the pathologist's ability to recognize unique histopathologic features. Once these characteristics are identified, it should prompt a referral to a gynecologist to consider conducting germline genetic testing. The management of FH-d uterine fibroids necessitates a multidisciplinary approach, including proper genetic screening and regular surveillance, especially for renal tumors.
RESUMO
Uterine fibroids are the most common benign neoplasm of the female reproductive tract in reproductive age women. Their prevalence is age dependent and can be detected in up to 80% of women by the age of 50 years. Patients affected by uterine fibroids may experience a significant physical, emotional, social, and financial toll as well as losses in their quality of life. Unfortunately, curative hysterectomy abolishes future pregnancy potential, while uterine-sparing surgical and radiologic alternatives are variously associated with reduced long-term reproductive function and/or high tumor recurrence rates. Recently, pharmacological treatment against uterine fibroids have been widely considered by patients to limit uterine fibroid-associated symptoms such as heavy menstrual bleeding. This hormonal therapy seemed effective through blocking the stimulatory effects of gonadal steroid hormones on uterine fibroid growth. However, they are contraindicated in women actively pursuing pregnancy and otherwise effective only during use, which is limited because of long-term safety and other concerns. Accordingly, there is an urgent unmet need for safe, durable, and fertility-compatible non-surgical treatment options for uterine fibroids. In this review article, we cover the current pharmacological treatments for uterine fibroids including their comparable efficacy and side effects as well as emerging safe natural compounds with promising anti-uterine fibroid effects.
Assuntos
Leiomioma , Neoplasias Uterinas , Gravidez , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Uterinas/tratamento farmacológico , Neoplasias Uterinas/cirurgia , Qualidade de Vida , Recidiva Local de Neoplasia , Leiomioma/tratamento farmacológico , HisterectomiaRESUMO
Introduction and importance: Molar pregnancy is the most common type of gestational trophoblastic disease. It manifests as vaginal bleeding, accompanied by high levels of ß-human chorionic gonadotropin (ß-HCG). This case aims to highlight the importance of considering gestational trophoblastic disease as a potential diagnosis and its serious complications. Case presentation: A 24-year-old female presented with vomiting, nausea, and no complaint of vaginal bleeding. Laboratory tests indicated hyperthyroidism as a complication requiring challenging preoperative prophylactic management. Initially, the patient underwent suction and curettage, but a total hysterectomy had to be performed later. The histological study concluded with the diagnosis of a complete hydatidiform mole. Post-surgery follow-up evaluations revealed high blood pressure values, and the patient was appointed for further cardiology assessment. Discussion and conclusion: Although uncommon, complications of a molar pregnancy include anaemia, severe cardiac distress, and hyperthyroidism. Trophoblastic Hyperthyroidism is a result of extremely high levels of ß-HCG levels due to molecular cross-reactivity. History, clinical examination, and ultrasound, in addition to measuring ß-HCG levels, could all help in diagnosing a molar pregnancy, but the definitive diagnosis is based on histopathology and a karyotype study. Management procedures include dilation, suction and curettage, and hysterectomy. The treatment depends on the patient's age, desire for future pregnancies, and risk of developing gestational trophoblastic neoplasia. A follow-up with serial ß-HCG measurement is recommended to monitor possible complications. Attaining and maintaining euthyroidism is a life-saving procedure before molar pregnancy surgery. Methimazole, Propranolol, Lugol's iodine, and hydrocortisone can all be used in the prophylactic management of the thyroid storm.
RESUMO
Uterine fibroids (UFs) are the most important benign neoplastic threat to women's health worldwide, with a prevalence of up to 80% in premenopausal women, and can cause heavy menstrual bleeding, pain, and infertility. Progesterone signaling plays a crucial role in the development and growth of UFs. Progesterone promotes the proliferation of UF cells by activating several signaling pathways genetically and epigenetically. In this review article, we reviewed the literature covering progesterone signaling in UF pathogenesis and further discussed the therapeutic potential of compounds that modulate progesterone signaling against UFs, including selective progesterone receptor modulator (SPRM) drugs and natural compounds. Further studies are needed to confirm the safety of SPRMs as well as their exact molecular mechanisms. The consumption of natural compounds as a potential anti-UFs treatment seems promising, since these compounds can be used on a long-term basis-especially for women pursuing concurrent pregnancy, unlike SPRMs. However, further clinical trials are needed to confirm their effectiveness.
Assuntos
Leiomioma , Neoplasias Uterinas , Gravidez , Feminino , Humanos , Progesterona/uso terapêutico , Neoplasias Uterinas/tratamento farmacológico , Neoplasias Uterinas/patologia , Receptores de Progesterona/metabolismo , Leiomioma/tratamento farmacológico , Leiomioma/patologia , EsteroidesRESUMO
Uterine torsion (UT) is one of the most uncommon obstetric complications. It usually occurs in the third trimester. The confirmed diagnosis relies on > 45° rotation at the utero-cervical junction around its longitudinal axis. The etiology is unknown in 20% of cases. It might be asymptomatic in some rare cases; however, symptoms usually manifest with acute abdominal pain, fetal bradycardia, vaginal bleeding or failure of labor progress. Laparotomy is used to establish the diagnosis and the management of UT. We report a 180° uterine dextrotorsion case of an obese 24-year-old pregnant female who presented with severe abdominal pain at the 35th gestational week, which was diagnosed and managed by an emergency laparotomy. UT is a rare though serious condition and must be doubted before a suspicious clinical image. Therefore, it is suggested to avoid consecutive pregnancies and the resultant uterine rupture.