TRANSLATIONAL BASIC SCIENCE & CLINICAL RESEARCH NEWS
The staff of The Reproductive Times here offers brief referenced notifications on interesting translational basic science & clinical research news with broad relevance to reproductive medicine and biology. Some of these news items may become subjects of more detailed reporting in The Reproductive Times on later occasions. The purpose of these relatively short notifications is to give readers the opportunity to get immediately more detailed information by looking up the listed references.
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December 13, 2024.
What’s new in endometriosis?
The Microbiome and endometriosis: It is a complex and heterogenous condition affecting at least 10% of women during reproductive years, and yet so little is known about endometriosis. One principal reason for the still widespread ignorance about endometriosis is, likely, the fact that – to this day – we cannot be certain who has the disease because we cannot perform laparoscopies on everybody and – even that – would not solve the problem because so much of endometriosis is microscopic and can be missed even with laparoscopy.
This is why a recent report caught our attention that claimed that the possible solution may be a non-invasive stool test.1
Yes, it may be again the gut microbiome – stupid – as a recent study by U.S. based investigators from several universities suggests:2 It appears that women with endometriosis have a distinct stool metabolome for non-invasive diagnosis. Their bacteria-derived metabolites are associated with those in inflammatory bowel disease (IBD). Moreover, bacteria-derived 4-hydroxyindole levels are lower in stool from women with endometriosis, and 4-hydroxyindole appears to inhibit the onset and progression of endometriosis.
These are the first findings that suggest a distinct stool metabolite signature in women with endometriosis, which could serve as stool-based non-invasive diagnostics. Furthermore, the gut-microbiota-derived 4-hydroxyindole could be a therapeutic candidate for ameliorating endometriosis.
What is not mentioned in the paper is that the observation of similarities with the microbiome of IBD might also explain why endometriosis – like IBD – demonstrates so much concurrence with autoimmunity.
REFERENCES
1. Thomas A. Medscape Medical News . October 15, 2024. https://www.medscape.com/viewarticle/does-road-treating-endometriosis-start-gut-2024a1000itr?form=fpf
2. Talwar et al., Science Direct. 2024. https://doi.org/10.1016/j.medj.2024.09.006
3. Tulandi T, Vercellini P. Reprod Biomed Online 2024;49(3):104292
Endometriosis-associated pain: Many cases of endometriosis are associated with significant pain. Current treatments, however, are limited in their ability to relieve this pain and leave many patients with persisting and often agenizing pain. A recent Commentary article in Cell Reports Medicine very well reviewed this problem highlighting how recent work in the context of chronic pain has altered our understanding and how current treatment options have the potential of improving clinical care.1
The historic and current understanding of pain mechanisms in that endometriosis-associated pain (EAP) can involve nociceptive, neuropathic, and nociplastic mechanisms. Moreover, there is also increasing understanding of the importance in pelvic pain of viscero-visceral hyperalgesia between pelvic organs, the gut-brain axis, and the hypothalamic-pituitary-adrenal (HPA) axis. Furthermore, we now also understand that there is a bidirectional relationship between pain and psychological distress (such as anxiety and depression), fatigue, and sleep, which further complicates the picture and can contribute to the impact of EAP on quality of life.
It is also increasingly clear how important and common dyspareunia is for women with EAP, a symptom generally particularly poorly considered in preclinical models. Although there are preclinical endometriosis models where sensitivity to vaginal distension can be demonstrated, it remains to be seen whether this can be reversed with therapeutic strategies.
REFERENCE
1. Coxon et al., Cell Reports Med 2024; 5(10): 101769
Why is progress so slow in endometriosis? A recent unsigned editorial in The Lancet attempted to point out the roots of the slow progress in endometriosis research.1 Referring to a recent paper in Nature Genetics,2 the editorial noted the publication of a recent map of the endometrium across the menstrual cycle, suggesting a new understanding of processes that may be involved in the occurrence of endometriosis. The editorial, however, also notes that “basic science is a long way from reaching the clinic.”
The editorial puts the onus on governments and their funding processes, noting that at least some are “slowly waking up to the substantial health burden of endometriosis.”
In a short Commentary in Reproductive Medicine Online, Togas Tulandi and Paolo Verecellini reemphasized the increasingly accepted hypothesis that endometriosis is really a systemic disease,3 while investigators from Belgium in a Review article in the same journal reemphasize how frequently unexplained infertility diagnoses really represent a failure to diagnose endometriosis,4 a point made by the CHR’s Norbert Gleicher in 1994.5
REFERENCES
1. Editorial, Lancet 2024;404:1279
2. Marecková, et al. Nat Renet 20224; 56:1925-1937
3. Tulandi T, Vercellini P. Reprod Biomed Online 2024;49(3):104292
4. Van Gestel et al., Reprod Biomed Online 2024;49(3):103848
5. Gleicher N. Immunol Allerg Clin North Am. 1994;14(4):753-758
Is endometriosis associated with early menopause and cardiovascular disease? Yale University’s chair of OB/GYN, Hugh S. Taylor, MD, has been for some time one of the strongest proponents of endometriosis as a systemic disease. He now published with a colleague an Opinion paper in JCEM suggesting such an association.1 In it, the two authors noted that studies have demonstrated an association between endometriosis and earlier menopause onset. Recent studies also found a correlation between endometriosis and an increased risk of cardiovascular disease (CVD). The authors suggest that endometriosis, early menopause, and cardiovascular risks may be linked by primary or secondary mechanisms. In large cohort studies, relevant risk and confounding factors, such as oophorectomy, were considered to refine estimates of associations. The authors, however, criticized that none of the studies considered endometriotic cystectomy, a frequent treatment for endometriosis-associated pelvic pain and infertility, as a cofounding factor and endometriotic cystectomies, of course often can harm ovarian reserve and may even lead to early menopause.
REFERENCE
1. Younis JS, Taylor HS. J Clin Endocrinol Metab 2024; 109(100:e1946-e1949