Assessment of quality of life, psychological aspects, and sexual function of women with endometriosis according to pain and infertility: a cross sectional study.

PURPOSE: To evaluate the quality of life, sexual function, anxiety, and depression of women with endometriosis according to pain symptoms and infertility. METHODS: This cross-sectional multicenter study included 229 women with endometriosis followed up at a tertiary hospital in Campinas, a tertiary hospital in São Paulo, and a reproductive medicine clinic in Campinas from 2018 to 2021. The women were divided into four groups according to the presence of pain symptoms and infertility. The Endometriosis Health Profile Questionnaire, Female Sexual Function Index, Beck Depression Inventory, and Beck Anxiety Index were applied to assess quality of life, sexual function, depression, and anxiety of women with endometriosis. RESULTS: The women were grouped as follows: group 1 (45 women without infertility and without pain), group 2 (73 women without infertility and with pain), group 3 (49 women with infertility and without pain), and group 4 (62 women with infertility and pain). Of the women with infertility, the majority had primary infertility. Most women had deep endometriosis (p = 0.608). Women with pain had higher anxiety and depression scores and worse quality of life than women without pain (p < 0.001). Regarding sexual function, all the groups were at risk for sexual dysfunction (p = 0.671). The group of women with pain and infertility have worse anxiety scores (25.31 ± 15.96) and depression (18.81 ± 11.16) than the other groups. CONCLUSION: Pain symptoms worsen anxiety, depression, and quality of life of women with endometriosis and when associated with infertility, greater impairment of psychological aspects may occur.

Pilot study of treatment of patients with deep infiltrative endometriosis with methotrexate carried in lipid nanoparticles.

OBJECTIVE: Previously, lipid nanoparticles (LDE) injected in women with endometriosis were shown to concentrate in the lesions. Here, the safety and feasibility of LDE carrying methotrexate (MTX) to treat deep infiltrating endometriosis was tested. DESIGN: Prospective pilot study. SETTING: Perola Byington Hospital Reference for Women's Health. SUBJECTS: Eleven volunteers (aged 30-47 years, BMI 26.15 ± 6.50 kg/m2) with endometriosis with visual analog scale pelvic pain scores (VAS) > 7 and rectosigmoid lesions were enrolled in the study. INTERVENTION: Three patients were treated with LDE-MTX at single intravenous 25 mg/m2 dose of MTX and eight patients with two 25 mg/m2 doses with 1-week interval. MAIN OUTCOME MEASURES: Clinical complaints, blood count, and biochemistry were analyzed before treatment and on days 90, 120, and 180 after LDE-MTX administration. Endometriotic lesions were evaluated by pelvic and transvaginal ultrasound (TVUS) before treatment and on days 30 and 180 after LDE-MTX administration. RESULTS: No clinical complaints related with LDE-MTX treatment were reported by the patients, and no hematologic, renal, or hepatic toxicities were observed in the laboratorial exams. FSH, LH, TSH, free T4, anti-Müllerian hormone, and prolactin levels were also within normal ranges during the observation period. Scores for deep dyspareunia (p < 0.001), chronic pelvic pain (p = 0.008), and dyschezia (p = 0.025) were improved over the 180-day observation period. There was a non-significant trend for reduction of VAS scores for dysmenorrhea. Bowel lesions by TVUS were unchanged. No clear differences between the two dose levels in therapeutic responses were observed. CONCLUSION: Results support the safety and feasibility of using LDE-MTX in women with deep infiltrating endometriosis as a novel and promising therapy for the disease. More prolonged treatment schemes should be tested in future placebo-controlled studies aiming to establish the usefulness of this novel nanomedicine approach.

Asymptomatic postmenopausal women: what are the risk factors for endometrial malignancies? A multicentric retrospective study.

OBJECTIVE: To evaluate the prevalence and risk factors for endometrial malignancies in asymptomatic postmenopausal women. METHODS: Multicentric retrospective analytical study in two Brazilian Reference Centers. All women without postmenopausal bleeding who were submitted to hysteroscopy with biopsy were included (1665). Excluded women without anatomopathological results (625) and whose medical records were incomplete (37). The variables analyzed were age; parity; body mass index; duration of menopausal status; systemic arterial hypertension; diabetes mellitus; use of hormone replacement therapy; use of tamoxifen; duration of use of tamoxifen; endometrial thickness and biopsy results. RESULTS: The frequency of endometrial malignancies in asymptomatic postmenopausal women was 2.39%. Endometrial thickness ≥8 mm increased the chance of endometrial malignancies, even more, with an endometrial thickness ≥12.55 mm the chance of endometrial malignancies increased by 4.68 times (p < .001 and 95% CI: 1.99-11.03). CONCLUSION: The prevalence of endometrial malignancies was low and the only risk factor for endometrial malignancies in asymptomatic postmenopausal women was endometrial thickness.

mRNA levels of low-density lipoprotein receptors are overexpressed in the foci of deep bowel endometriosis.

STUDY QUESTION: Is mRNA expression of LDL receptors altered in deep bowel endometriotic foci? SUMMARY ANSWER: mRNA expression of LDL receptors is up-regulated in deep bowel endometriotic foci of patients with endometriosis. WHAT IS KNOWN ALREADY: Several studies have demonstrated the overexpression of low-density lipoprotein receptors in various tumour cell lines and endometriosis has similar aspects to cancer, mainly concerning the pathogenesis of both diseases. This is the first study we know of to investigate lipoprotein receptors expression in deep endometriosis with bowel involvement. STUDY DESIGN, SIZE, DURATION: During 2014-2015, an exploratory case-control study was conducted with 39 patients, including 20 women with a histological diagnosis of deep endometriosis compromising the bowel and 19 women without endometriosis who underwent laparoscopic tubal ligation. PARTICIPANTS/MATERIALS, SETTING, METHODS: Peripheral blood samples were collected on the day of surgery for lipid profile analysis, and samples of endometrial tissue and of bowel endometriotic lesions were also collected. The tissue samples were sent for histopathological analysis and for LDL-R and LRP-1 gene expression screening using quantitative real-time PCR. MAIN RESULTS AND THE ROLE OF CHANCE: Patients with deep endometriosis had lower LDL-cholesterol than patients without the disease (119 ± 23 versus 156 ± 35; P = 0.001). Gene expression analysis of LDL receptors revealed that LDL-R was more highly expressed in endometriotic lesions when compared to the endometrium of the same patient but not more than in the endometrium of women without endometriosis (0.027 ± 0.022 versus 0.012 ± 0.009 versus 0.019 ± 0.01, respectively; P < 0.001). LRP-1 was more highly expressed in endometriotic lesions, both when compared with the endometrium of the same patient and when compared with the endometrium of patients without the disease (0.307 ± 0.207 versus 0.089 ± 0.076 and versus 0.126 ± 0.072, respectively; P < 0.001). The study also showed that LDL-R gene expression in the endometrium of women with endometriosis was higher during the secretory phase of the menstrual cycle (P = 0.001). LRP-1 gene expression was increased during the secretory phase in the endometrium of women without the disease (P = 0.008). LIMITATIONS, REASONS FOR CAUTION: In the endometriotic lesions, the presence of fibrosis is substantial, restricting access to the stromal and glandular components of the lesion. Despite that, we found that LDL receptor mRNA was overexpressed. Future studies may perform laser microdissection to isolate the area of interest in the target tissue, excluding fibrosis contamination. WIDER IMPLICATIONS OF THE FINDINGS: This study supports the feasibility of LDL-R targeted therapy in the treatment of deep endometriosis. STUDY FUNDING/COMPETING INTERESTS: This study was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP #2011/17245-0). The authors have no conflicts of interest to declare.

Could statins constitute a novel treatment for endometriosis? Systematic review of the literature.

Endometriosis, defined as the presence of endometrial glands and/or stroma outside the uterine cavity, is an estrogen-dependent disease that affects about 10% of reproductive age women. Theories to explain the etiology of endometriosis abound. These include the alteration of epithelial cells on peritoneal surface, metaplasia of embryonic remnants of the mullerian ducts, immune system abnormalities, and the dissemination of endometrial cells through the circulation or lymphatic system, as well as retrograde menstruation, the hypothesis currently favored for the development of endometriosis. Angiogenesis, the development of new capillaries from pre-existing blood vessels, has been proposed as a key mechanism in the pathogenesis of endometriosis. Again from an etiological perspective, the formation of endometriotic implants requires ectopic fixation and proliferation of endometrial stroma and glands. The process of invasive insertion of endometriotic tissues involves the degradation of the extracellular matrix, and altered expression of matrix metalloproteinases (MMPs) in the eutopic and ectopic endometrium. Considering the antiproliferative, antiangiogenic, antioxidant, anti-inflammatory properties and matrix metalloproteinase activity inhibition of statins and the original studies addressing the possible mechanisms of action in endometriosis, the aim of this systematic review was to synthesize the research conducted to date in order to propose statins as possible and effective tools for controlling this disease.

Laparoscopy as the most effective tool for management of postmenopausal complex adnexal masses when expectancy is not advisable.

Postmenopausal women with adnexal masses suspicious for malignancy must undergo surgery for histopathologic confirmation. The low positive predictive value for malignancy of the currently available preoperative examinations results in 5 to 220 surgeries performed for each case of pelvic malignancy detected, depending on the evaluation method and patient selection. Although extensively reviewed as an effective tool for the investigation and treatment of adnexal masses, laparoscopy is still underused for this purpose in postmenopausal women. Some reasons are uncertainty about the incidental diagnosis of a malignant lesion during laparoscopy, concern about the effect of laparoscopy over the course of a pelvic malignant lesion, and inadequate referral of patients at high risk to specialized centers with oncologic gynecologists. Identification of patients at low risk might also be inadequate, causing them to undergo unnecessary laparotomy. Herein we demonstrate through a comprehensive literature review that laparoscopy is a highly effective tool for investigation and treatment of suspected adnexal masses in postmenopausal women, both in general medical settings without oncologic backup and in specialized centers. The indications for laparoscopy in this context can be further expanded without oncologic harm if patients at low and high risk are appropriately selected for surgery at general and specialized settings, respectively.