Endometriosis is an estrogen-dependent gynecological disorder, defined as the growth of endometrial stromal cells and glands at extrauterine sites. Endometriotic lesions are more frequently located into the abdominal cavity, although they can also be implanted in distant places. Among its etiological factors, the presence of immune dysregulation occupies a prominent place, pointing out the beneficial and harmful outcomes of macrophages in the pathogenesis of this disease. Macrophages are tissue-resident cells that connect innate and adaptive immunity, playing a key role in maintaining local homeostasis in healthy conditions and being critical in the development and sustainment of many inflammatory diseases. Macrophages accumulate in the peritoneal cavity of women with endometriosis, but their ability to clear migrated endometrial fragments seems to be inefficient. Hence, the characteristics of the peritoneal immune system in endometriosis must be further studied to facilitate the search for new diagnostic and therapeutic tools. In this review, we summarize recent relevant advances obtained in both mouse, as the main animal model used to study endometriosis, and human, focusing on peritoneal macrophages obtained from endometriotic patients and healthy donors, under the perspective of its future clinical translation to the role that these cells play on this pathology.

BACKGROUND: Endometriosis is a gynaecological hormone-dependent disorder that is defined by histological lesions generated by the growth of endometrial-like tissue out of the uterus cavity, most commonly engrafted within the peritoneal cavity, although these lesions can also be located in distant organs. Endometriosis affects ~10% of women of reproductive age, frequently producing severe and, sometimes, incapacitating symptoms, including chronic pelvic pain, dysmenorrhea and dyspareunia, among others. Furthermore, endometriosis causes infertility in ~30% of affected women. Despite intense research on the mechanisms involved in the initial development and later progression of endometriosis, many questions remain unanswered and its aetiology remains unknown. Recent studies have demonstrated the critical role played by the relationship between the microbiome and mucosal immunology in preventing sexually transmitted diseases (HIV), infertility and several gynaecologic diseases.OBJECTIVE AND RATIONALE: In this review, we sought to respond to the main research question related to the aetiology of endometriosis. We provide a model pointing out several risk factors that could explain the development of endometriosis. The hypothesis arises from bringing together current findings from large distinct areas, linking high prenatal exposure to environmental endocrine-disrupting chemicals with a short anogenital distance, female genital tract contamination with the faecal microbiota and the active role of genital subclinical microbial infections in the development and clinical progression of endometriosis.SEARCH METHODS: We performed a search of the scientific literature published until 2019 in the PubMed database. The search strategy included the following keywords in various combinations: endometriosis, anogenital distance, chemical pollutants, endocrine-disrupting chemicals, prenatal exposure to endocrine-disrupting chemicals, the microbiome of the female reproductive tract, microbiota and genital tract, bacterial vaginosis, endometritis, oestrogens and microbiota and microbiota–immune system interactions.OUTCOMES: On searching the corresponding bibliography, we found frequent associations between environmental endocrine-disrupting chemicals and endometriosis risk. Likewise, recent evidence and hypotheses have suggested the active role of genital subclinical microbial infections in the development and clinical progression of endometriosis. Hence, we can envisage a direct relationship between higher prenatal exposure to oestrogens or estrogenic endocrine-disrupting compounds (phthalates, bisphenols, organochlorine pesticides and others) and a shorter anogenital distance, which could favour frequent postnatal episodes of faecal microbiota contamination of the vulva and vagina, producing cervicovaginal microbiota dysbiosis. This relationship would disrupt local antimicrobial defences, subverting the homeostasis state and inducing a subclinical inflammatory response that could evolve into a sustained immune dysregulation, closing the vicious cycle responsible for the development of endometriosis.WIDER IMPLICATIONS: Determining the aetiology of endometriosis is a challenging issue. Posing a new hypothesis on this subject provides the initial tool necessary to design future experimental, clinical and epidemiological research that could allow for a better understanding of the origin of this disease. Furthermore, advances in the understanding of its aetiology would allow the identification of new therapeutics and preventive actions.

Sevilla IÑ, et al. J Gynecol Oncol. 2018 Aug;30:e63. https://doi.org/10.3802/jgo.2019.30.e63

Endometriosis is a chronic inflammatory disorder characterized by the abnormal growth of endometrial-like tissue outside the uterine cavity, affecting 10–15% of women of reproductive age. Pain is the most common symptom. Treatment options include surgery, which has limited effectiveness and high recurrence rates, and pharmacotherapy. Hormonal therapies, commonly used for symptom management, can have side effects and contraceptive outcomes, contributing to the infertility associated with endometriosis, with pain and lesions often reappearing after treatment cessation. Among its etiological factors, immunological and inflammatory dysregulation plays a significant role, representing an interesting target for developing new therapeutic strategies. This review critically analyzes recent studies to provide an updated synthesis of ongoing research into potential new pharmacotherapies focusing on lesion progression, pain relief, and improving quality of life. Immunotherapy, natural anti-inflammatory and antioxidant compounds and drug repurposing show promise in addressing the limitations of current treatments by targeting immunological factors, potentially offering non-invasive solutions for managing pain and infertility in endometriosis. Promising results have been obtained from in vitro and animal model studies, but clinical trials are still limited. More effort is needed to translate these findings into clinical practice to effectively reduce disease progression, alleviate pain symptoms and preserve the reproductive capacity, improving patients’ overall wellbeing.

Introduction The prevalence of menopausal women with confirmed vulvovaginal atrophy (VVA) oscillates between 67–98%. Aim To assess the prevalence of postmenopausal women with VVA confirmed by gynecologic clinical assessment among all women attending menopause centers in Spain, as well as to describe the impact of VVA on quality of life and sexual functioning. Methods Women aged 45–75 years old with the last menstrual period >12 months before were included in a cross-sectional study. Main Outcome Measures Women with ≥1 VVA symptoms filled out a number of questionnaires, including EuroQoL, Day-to-Day Impact of Vaginal Aging, Female Sexual Function Index, and Female Sexual Distress Scale-revised. A gynecologic examination was performed to confirm diagnosis. Results 1,177 evaluable patients were included. VVA was confirmed in 87.3% of the patients. Almost 80% of women who acknowledged being sexually active (n = 717) presented pain during intercourse. As compared with patients without confirmed VVA (n = 66), patients with confirmed VVA (n = 1,028) were significantly older (P < .0001), had lower rates of sexual activity (P < .05), and used more VVA treatments (P < .05). Severe vaginal atrophy and severe vulvar atrophy were more prevalent in VVA-confirmed women (P < .0001, in both cases). No differences regarding the confirmation of VVA were observed for EuroQoL and Day-to-Day Impact of Vaginal Aging quality-of-life questionnaires. Sexual function measured through the Female Sexual Function Index score was significantly reduced in sexually-active patients with confirmed VVA (P < .05). Conclusion VVA signs and symptoms are highly prevalent in Spanish postmenopausal women. Confirmation of VVA diagnosis was associated with impaired sexual function. The early recognition of VVA symptoms should be actively promoted in medical practice, instead of waiting until signs appear to exclude other reasons for VVA and to manage treatment effectively.