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STUDY QUESTION: What are the quantitative, qualitative, and temporal patterns of retrograde mentruation? SUMMARY ANSWER: The extreme quantitative and qualitative heterogeneity of the available studies prevents the definitive conclusion that retrograde menstruation is a universal and consistent phenomenon during the reproductive period. WHAT IS KNOWN ALREADY: Retrograde menstruation has been defined as a universal, physiological phenomenon that occurs similarly in about 90% of menstruators during the reproductive period. However, uncertainties still exist in terms of the event frequency, total amount, and cellular composition of retrograde menstruation and the differences between individuals with versus those without endometriosis. STUDY DESIGN SIZE DURATION: Two systematic reviews were performed, one for human studies, and one for non-human primate studies. We retrieved studies from the PubMed and Embase databases published between 1 January 1980 and 1 November 2023. Studies published in the English language were included and identified using a combination of MeSH terms. References from relevant publications were systematically screened and further articles were identified using PubMed's 'similar articles' and 'cited by' functions. PARTICIPANTS/MATERIALS SETTING METHODS: Results were reported in accordance with the PRISMA guidelines. Studies that did not report original data or provided a review of the field were excluded. Bias analysis was completed for each included human study by using the Newcastle-Ottawa scoring system. MAIN RESULTS AND THE ROLE OF CHANCE: Fifteen studies were finally included in the human systematic review, mostly with limited sample sizes. The macroscopic visualization of blood in PF during menses was reported with a frequency ranging from 9% to 100%. A prevalence of endometrial cells detected in peritoneal fluid ranging from 8% to 75% was reported in the various studies. Controversial findings were reported in relation to patients with endometriosis. Retrograde menstruation has been evaluated cross-sectionally on single occasions, and no information is available on the course of the phenomenon within an entire cycle and between subsequent cycles. Two studies were included in the non-human primate systematic review; one of them showed that retrograde menstruation was observed more frequently in baboons with naturally occurring endometriosis (83%) than in those with a normal pelvis (51%). LIMITATIONS REASONS FOR CAUTION: In humans, peritoneal fluid has often been collected at different cycle phases and not systematically during menstruation. The indication for laparoscopy was not always clear for all participants. A wide variety of methods were used to detect endometrial cells, including cytological staining, cell block analysis, immunocytochemistry, and various methods of cell culture. WIDER IMPLICATION OF THE FINDINGS: The idea that almost all women experience retrograde menstruation regularly and similarly during their reproductive life is currently unsubstantiated. It is an academic notion accepted uncritically. Development of endometriosis may derive from differences in the frequency or severity of the event. STUDY FUNDING/COMPETING INTERESTS: The review was partially funded by Italian Ministry of Health-Current Research IRCCS. P.Vi. serves as co-editor in Chief of Journal of Endometriosis and Uterine Disorders. E.S. serves as Editor in Chief of Human Reproduction Open and discloses research grants from Ferring, Ibsa, Gedeon Richter, and Theramex, and honoraria from Ibsa and Gedeon Richter. P.Ve. serves as Associate Editor for Human Reproduction Open; is a member of the Editorial Board of the Journal of Obstetrics and Gynaecology Canada, of the Italian Journal of Obstetrics and Gynaecology, and of the International Editorial Board of Acta Obstetricia et Gynecologica Scandinavica; has received royalties from Wolters Kluwer for chapters on endometriosis management in the clinical decision support resource UpToDate; and maintains both a public and private gynecological practice. All other authors declare they have no conflict of interest. REGISTRATION NUMBER: N/A.
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INTRODUCTION: Peritoneal infiltrating and fibrotic endometriosis, also known as deep endometriosis, is the most severe manifestation of the disease that can cause severe complications including bowel and ureteral stenosis. The natural history of these lesions and the possible effect of hormonal treatments on their progression are undefined. Therefore, we conducted a systematic review and meta-analysis to investigate whether and how frequently deep endometriosis progresses over time without or with ovarian suppression. This could inform management decisions in asymptomatic and mildly symptomatic patients. MATERIAL AND METHODS: For this pre-registered systematic review (CRD42023463518), the PubMed and Embase databases were screened, and studies published between 2000 and 2023 that serially evaluated the size of deep endometriotic lesions without or with hormonal treatment were selected. Data on the progression, stability, or regression of deep endometriotic lesions were recorded as absolute frequencies or mean volume variations. Estimates of the overall percentage of progression and corresponding 95% confidence intervals were calculated using a random-effect model. When studies reported lesion progression as pre- and post-treatment volume means, the delta of the two-volume means was calculated and analyzed using the inverse variance method. RESULTS: A total of 29 studies were identified, of which 19 studies with 285 untreated and 730 treated patients were ultimately selected for meta-analysis. The overall estimate of the percentage of lesion progression in untreated individuals was 21.4% (95% CI, 6.8-40.8%; I2 = 90.5%), whereas it was 12.4% during various hormonal treatments (95% CI, 9.0-16.1%; I2 = 0%). Based on the overall meta-analysis estimates, the odds ratio of progression in treated versus untreated patients was 0.52 (95% CI, 0.41-0.66). During hormonal suppression, the mean volume of deep endometriotic lesions decreased significantly by 0.87 cm3 (95% CI, 0.19-1.56 cm3; I2 = 0%), representing -28.5% of the baseline volume. CONCLUSIONS: Untreated deep endometriotic lesions progressed in about one in five patients. Medical therapy reduced but did not eliminate this risk. Given the organ function failure potentially caused by these lesions, the decision whether to use hormonal treatments in asymptomatic or mildly symptomatic women should always be shared, carefully weighing the potential benefits and harms of the two alternatives after extensive counseling.
ABSTRACT
The second-to-four digit ratio (2D:4D) has been proposed as a marker of prenatal hormonal exposure. It is suggested that prenatal exposure to androgens results in a shorter 2D:4D ratio, whereas a prenatal oestrogenic environment results in a longer one. In addition, previous research has shown an association between exposure to endocrine-disrupting chemicals and 2D:4D in animals and humans. On the endometriosis side, hypothetically, a longer 2D:4D ratio, reflecting a lower androgenic intrauterine milieu, could represent an indicator of the presence of the disease. In this light, we have designed a case-control study to compare 2D:4D measurements between women with and without endometriosis. Exclusion criteria included the presence of PCOS and previous trauma on the hand that could impact the measurement of the digit ratio. The 2D:4D ratio of the right hand was measured using a digital calliper. A total of 424 participants (endometriosis n = 212; controls n = 212) were recruited. The group of cases included 114 women with endometriomas and 98 patients with deep infiltrating endometriosis. The 2D:4D ratio was significantly higher in women with endometriosis compared to controls (p = 0.002). There is an association between a higher 2D:4D ratio and the presence of endometriosis. Our results support the hypothesis claiming potential influences of intrauterine hormonal and endocrine disruptors exposure on the onset of the disease.
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INTRODUCTION: Umbilical endometriosis (UE) is defined as the presence of endometrial-like tissue within the umbilicus and represents around 0.5-1% of all cases of endometriosis. UE is classified into primary or secondary UE. In this retrospective study, we aimed to assess symptoms, signs, recurrence rate of treated lesions, psychological wellbeing and health-related quality of life in women with UE. MATERIAL AND METHODS: We retrospectively reviewed all cases of women diagnosed with UE in the period 1990-2021 in our center. Post-operative recurrence of UE was considered as the reappearance of the umbilical endometriotic lesion, or as the recurrence of local symptoms in the absence of a well-defined anatomical recurrence of the umbilical lesion. Moreover, participants were invited to fill in standardized questionnaires on their health conditions. RESULTS: A total of 55 women with histologically proven UE were assessed in our center during the study period. At time of diagnosis, local catamenial pain and swelling were reported by 51% and 53.2% of women, respectively. A total of 46.8% of women reported catamenial umbilical bleeding. Concomitant non-umbilical endometriosis was identified in 66% of cases. As regards the treatment of UE, 83.6% of women underwent an en-bloc excision with histological confirmation of UE. During the follow-up period, 37 women (67.3%) agreed to undergo a re-evaluation. Recurrence of either umbilical symptoms, or umbilical nodule, was observed in 27% of patients, 11% of which did not receive post-operative hormonal therapy. Specifically, a recurrence of the umbilical endometriotic lesion was observed only in two women. Among the 37 women which we were able to contact for follow-up, 83.8% were satisfied with the treatment they had received. CONCLUSIONS: The high rate of patient satisfaction confirmed that surgical excision should be considered the gold standard treatment for umbilical endometriosis. Future studies should investigate the role of post-operative hormonal therapy, particularly in reducing the risk of symptom recurrence.
