Efficacy results from a phase 3, randomized, placebo-controlled trial testing two doses of Linzagolix in women with endometriosis-associated pain

A phase III randomized placebo-controlled trial tested two doses (75 and 200 mg) of Linzagolix (LGX), a novel oral selective estrogen antagonist, in women with moderate to severe endometriosis-associated pain (EAP). The study included 484 patients with efficacy endpoints of reduction in dysmenorrhea (DYS) and non-menstrual pelvic pain (NMPP). The responder rates for DYS at three months were 44% for the 75 mg dose and almost 73% for the 200 mg dose, and for NMPP, the 75 mg dose showed non-significant improvement from 30% responders to 38 % in 75 mg compared to the placebo, while the 200 mg + Add back therapy (ABT) dose showed a significant improvement in NMPP with 47% of responder rate. At six months, both doses of LGX showed significant improvement in DYS pain, Dyschezia, and NMPP than the placebo. Both doses of LGX showed a significant decrease in pain compared to the placebo at six months, and interference of pain with daily activity was also significantly reduced. In conclusion, both doses of LGX were well-tolerated, with minimal bone mineral density loss, and met the objectives of reducing DYS and NMPP.

Genital tract infection and pelvic surgery contribute to the development of endometriosis

Around 10% of women of reproductive age are estimated to have endometriosis (EM), but the actual prevalence remains unclear due to the invasive nature of the classical diagnostic methods. The bacterial contamination hypothesis suggests that the constant release of lipopolysaccharides (LPs) from Escherichia coli-contaminated menstrual blood leads to pelvic inflammation and the development of EM. Animal experiments were conducted in which mouse models infected with ureaplasma showed a higher incidence of EM, providing support for the bacterial contamination hypothesis. Clinical data analysis was also conducted to investigate the effects of tissue injury and pathogens on EM development. The study involved a large cohort of reproductive-age women, and it revealed that a history of genital tract infection (GTI) and surgical injury of the pelvic cavity increased the risk of EM development. Furthermore, women who experienced both genital tract infection (GTI) and pelvic surgery had a much higher incidence of EM than expected, indicating a synergistic effect between the two factors. To reduce the occurrence of EM, it is recommended to minimize tissue damage during pelvic surgery, promptly diagnose and treat GTIs, and consider testing high-risk groups with chronic inflammatory diseases.

The role of non-coding RNAs in endometriosis diagnosis: a systematic review and meta-analysis

Currently, diagnostic laparoscopy is the gold standard, but it is invasive and may not capture cases with mild or no symptoms. Non-coding RNAs (ncRNAs), which play a crucial role in gene regulation and biological processes, have been investigated as potential biomarkers for endometriosis. A systematic review and meta-analysis were conducted to test the diagnostic accuracy of ncRNAs in EM diagnosis. The results showed that several ncRNAs demonstrated good or moderate diagnostic efficiency, with 5 ncRNAs achieving excellent accuracy, highlighting AUC 1 for miR200c and miR-199a. When evaluating models with multiple non-coding RNAs, the diagnostic performance improved further. However, the analysis also revealed high heterogeneity among the studies, which could impact the reliability of the findings. To establish non-coding RNAs as valid biomarkers for endometriosis diagnosis, further research is needed. In conclusion, ncRNAs show promise as non-invasive biomarkers for endometriosis diagnosis. However, more robust evidence and advancements in personalized and precision medicine are necessary to fully utilize their potential and improve the management of endometriosis.

Gut microbiome in endometriosis: a cohort study on 1000 individuals

Another study focused on investigating the role of the gut microbiome in endometriosis. This cohort study involved 1,000 individuals, 166 of whom had endometriosis, and 164 were healthy controls. The findings showed two distinct enterotypes in the study population, but endometriosis was not associated with either cluster. The study identified 34 bacterial species that exhibited differential abundance between the two groups. Some species from the Ruminococcus sp were decreased in endometriosis, while bacteria from the Acetobacter sp and Fusobacterium sp were increased. Additionally, certain pathways were found to potentially be involved in endometriosis, including nitrogen metabolism and fatty acid biosynthesis. The study provided valuable insights into the association between the gut microbiome and endometriosis in a large cohort population.

The natural history of endometriosis in pregnancy: An ultrasound study of the morphological features of deep endometriosis (DE) and ovarian endometrioma 

A prospective observational cohort study was conducted to observe the morphological changes in endometrial lesions during pregnancy, particularly in size and decidualization frequency. Results showed that most women had deep disease alone or a combination of ovarian and deep disease. Ovarian endometriomas ranged from 11 to 82 mm, with a median size of 30 mm. Endometrial nodules were most commonly found in the posterior pelvic compartment, ranging from 3 to 32 mm. The study observed that endometrial cysts and nodules tended to regress in size during pregnancy. In some cases, there was evidence of growth in the first and second trimesters, followed by regression later in pregnancy and the postnatal period. Overall, the findings of this study support the hypothesis that pregnancy positively impacts the macroscopic appearance of endometrial lesions, indicating potential benefits for women with endometriosis during pregnancy.

Effects of Relugolix combination therapy in women with endometriosis-associated pain who received prior first-line hormonal treatment: spirit 1 and 2

The Spirit 1 and 2 trials were conducted as double-blind, placebo-controlled studies in multiple countries to evaluate the effectiveness of Relugolix combination therapy in women with EM. The trials included women aged 18 to 50 who had confirmed EM, moderate to severe DYS, and NMPP. After 24 weeks, the data showed that the Relugolix combination therapy group had a significantly higher proportion of DYS and NMPP responders than the placebo group. This improvement was observed in both the overall population and the subgroup that had received prior hormonal treatment. The timeline analysis indicated that significant improvements in DYS were observed after approximately eight weeks of treatment, and the reduction in pain was sustained over 24 weeks. Similar findings were seen for NMPP. Additionally, fewer patients in the treatment group required analgesia than in the placebo group. This difference was statistically significant for the overall population and the subgroup with prior hormonal treatment. In conclusion, Relugolix combination therapy effectively reduced DYS and NMPP in women with EM, including those who had received prior hormonal treatment. 

European Society of Human Reproduction and Embryology (ESHRE), 39th Annual Meeting, 25-28 June 2023, Copenhagen, Denmark