Markers of Local and Systemic Estrogen Metabolism in Endometriosis

Othman, Essam R.; Khashbah, Maha Y.; Abdelaal, Ibrahim I.; ElMelegy, Tarek T; Fetih, Ahmed N.; Houwen, Lisette E. Van der; Lambalk, Cornelis B.; Mijatovic, Velja

doi:10.1007/s43032-020-00383-4

Cited by 14 publications

(6 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In fact, 2OH-3MeO-E 1 was higher in cases compared to controls, supporting a potential EM origin. Consistent with our observation, a previous study evaluated a subset of estrogen metabolites in preoperative urine samples of 62 EM cases and 52 controls and found increased levels of the 2OH-3MeO-E 1 precursor 2OH-E 1 (51). Our findings that the 2OH pathway is significantly more elevated in ovarian EM cases is also consistent with a study that used proton nuclear magnetic resonance (H-NMR) spectroscopy to investigate potential non-invasive metabolomic markers in 31 infertile women with stage II and III EM cases and 15 healthy or control women (52).…”

Section: Discussionsupporting

confidence: 91%

Circulating estradiol and its biologically active metabolites in endometriosis and in relation to pain symptoms

et al. 2023

View full text Add to dashboard Cite

ObjectivesEndometriosis (EM) is an estrogen-dominant inflammatory disease linked to infertility that affects women of reproductive age. EM lesions respond to hormonal signals that regulate uterine tissue growth and trigger inflammation and pain. The objective of this study was to evaluate whether estradiol (E2) and its biologically active metabolites are differentially associated with EM given their estrogenic and non-estrogenic actions including proliferative and inflammatory properties.DesignWe performed a retrospective study of 209 EM cases and 115 women without EM.MethodsPain-related outcomes were assessed using surveys with validated scales. Preoperative serum levels of estradiol (E2) and estrone (E1), their 2-, 4- and 16- hydroxylated (OH) and methylated (MeO) derivatives (n=16) were measured by mass spectrometry. We evaluated the associations between estrogen levels and EM anatomic sites, surgical stage, risk of EM, and symptoms reported by women. Spearman correlations established the relationships between circulating steroids.ResultsOf the sixteen estrogens profiled, eleven were detected above quantification limits in most individuals. Steroids were positively correlated, except 2-hydroxy 3MeO-E1 (2OH-3MeO-E1). Higher 2OH-3MeO-E1 was linked to an increased risk of EM (Odd ratio (OR)=1.91 (95%CI 1.09-3.34); P=0.025). Ovarian EM cases displayed enhanced 2-hydroxylation with higher 2MeO-E1 and 2OH-E1 levels (P< 0.009). Abdominal, pelvic and back pain symptoms were also linked to higher 2OH-3MeO-E1 levels (OR=1.86; 95%CI 1.06-3.27; P=0.032).ConclusionsThe 2-hydroxylation pathway emerges as an unfavorable feature of EM, and is associated with ovarian EM and pain related outcomes.

show abstract

Section: Discussionsupporting

confidence: 91%

Circulating estradiol and its biologically active metabolites in endometriosis and in relation to pain symptoms

et al. 2023

View full text Add to dashboard Cite

show abstract

“…Thus, 16-keto-17β-estradiol and 2-hydroxyestradiol of the 2-OH pathway were the most affected by the presence of endometriosis depending on the usage of hormonal suppression therapy and surgical interventions. To date, the only two published studies investigating the role of estrogen metabolites in endometriosis concluded that 2-hydroxyestradiol and 2-methoxyestradiol reduced endometriotic cell growth via estrogen receptor independent mechanisms [ 39 ]; and endometriosis metabolizes estrogen preferentially to the biologically active of 2-hydroxyestradiol, and genotoxic 4-hydroxyestradiol and 4-hydroxyestrone metabolites [ 40 ]. Various reports have also indicated that prolonged exposure of target tissues or cells to excessive estrogens is an important etiological factor for the induction of estrogen-associated cancers in experimental animals [ 41 ], and in humans [ 42 – 44 ].…”

Section: Discussionmentioning

confidence: 99%

Association of microbial dynamics with urinary estrogens and estrogen metabolites in patients with endometriosis

Cregger

Brown

et al. 2021

PLoS ONE

View full text Add to dashboard Cite

Endometriosis is an estrogen dependent gynecological disease associated with altered microbial phenotypes. The association among endogenous estrogen, estrogen metabolites, and microbial dynamics on disease pathogenesis has not been fully investigated. Here, we identified estrogen metabolites as well as microbial phenotypes in non-diseased patients (n = 9) and those with pathologically confirmed endometriosis (P-EOSIS, n = 20), on day of surgery (DOS) and ~1–3 weeks post-surgical intervention (PSI). Then, we examined the effects of surgical intervention with or without hormonal therapy (OCPs) on estrogen and microbial profiles of both study groups. For estrogen metabolism analysis, liquid chromatography/tandem mass spectrometry was used to quantify urinary estrogens. The microbiome data assessment was performed with Next generation sequencing to V4 region of 16S rRNA. Surgical intervention and hormonal therapy altered gastrointestinal (GI), urogenital (UG) microbiomes, urinary estrogen and estrogen metabolite levels in P-EOSIS. At DOS, 17β-estradiol was enhanced in P-EOSIS treated with OCPs. At PSI, 16-keto-17β-estradiol was increased in P-EOSIS not receiving OCPs while 2-hydroxyestradiol and 2-hydroxyestrone were decreased in P-EOSIS receiving OCPs. GI bacterial α-diversity was greater for controls and P-EOSIS that did not receive OCPs. P-EOSIS not utilizing OCPs exhibited a decrease in UG bacterial α-diversity and differences in dominant taxa, while P-EOSIS utilizing OCPs had an increase in UG bacterial α-diversity. P-EOSIS had a strong positive correlation between the GI/UG bacteria species and the concentrations of urinary estrogen and its metabolites. These results indicate an association between microbial dysbiosis and altered urinary estrogens in P-EOSIS, which may impact disease progression.

show abstract

“…A potential effect of the gut microbiome associated estrobolome—a collection of genes in the intestinal microbiome modulating the amount of resorption of estrogen passing from blood into the intestine - has been described. It was discussed that intestinal dysbiosis may lead to excess estrogens being reabsorbed, causing a hyper-estrogenic environment that will impact endometriosis ( 64 , 105 , 106 ). It has been shown that intestinal resident microbiota communities are influenced by hormonal changes, which behave cyclical.…”

Section: Introductionmentioning

confidence: 99%

Diet associations in endometriosis: a critical narrative assessment with special reference to gluten

Brouns,

Van Haaps,

Keszthelyi

et al. 2023

Front. Nutr.

Self Cite

View full text Add to dashboard Cite

Endometriosis is characterized by the presence of endometrium-like tissue outside the uterus. The etiology remains largely unknown. Despite adequate treatment, patients can still experience symptoms or side effects resulting in therapy incompliance and in self-management strategies such as dietary measures is increasing. A gluten free diet is thought to be contributory in reducing endometriosis-related pain, thereby optimizing quality of life. However, data is conflicting and currently provides no evidence for causality. This narrative review aims to put the effect of dietary self-management strategies on endometriosis in a balanced perspective, especially the effect of gluten and a gluten free diet. Several studies have found a strong overlap in symptoms, metabolic and immune responses associated with endometriosis and those associated with celiac disease, ulcerative colitis, Crohn’s disease, irritable bowel syndrome and non-celiac wheat sensitivity. However, it remains unclear whether these diseases and/or disorders are causal to an increased risk of endometriosis. Some studies have found a positive effect on the risk of endometriosis, endometriosis-related symptoms and quality of life (QoL) when women either avoided certain nutrients or foods, or applied a specific nutrient supplementation. This includes the avoidance of red meat and omega-3, an increasing intake of foods rich in anti-oxidants, micronutrients and dietary fibers (e.g., fruit, vegetables) and the appliance of a gluten free diet. However, data from the available studies were generally graded of low quality and it was noted that placebo and/or nocebo effects influenced the reported positive effects. In addition, such effects were no longer seen when adjusting for confounders such as overweight, when a translation was made from in vitro to in vivo, or when the nutrients were not supplemented as isolated sources but as part of a mixed daily diet. Finally, some studies showed that long-term adherence to a gluten free diet is often associated with an impaired diet quality and nutrient intake, leading to negative health outcomes and reduced QoL. Concluding, scientific evidence on the efficacy of dietary interventions on well-defined clinical endpoints of endometriosis is lacking and recommending a gluten free diet to women solely diagnosed with endometriosis should therefore not be advised.

show abstract

Markers of Local and Systemic Estrogen Metabolism in Endometriosis

Cited by 14 publications

References 58 publications

Circulating estradiol and its biologically active metabolites in endometriosis and in relation to pain symptoms

Circulating estradiol and its biologically active metabolites in endometriosis and in relation to pain symptoms

Association of microbial dynamics with urinary estrogens and estrogen metabolites in patients with endometriosis

Diet associations in endometriosis: a critical narrative assessment with special reference to gluten

Contact Info

Product

Resources

About