Polygenic risk score phenome-wide association study reveals an association between endometriosis and testosterone

BMC Medicine, Journal Year: 2023, Volume and Issue: 21(1)

Published: Dec. 5, 2023

Abstract Background Endometriosis affects 1 in 9 women, yet it is poorly understood with long diagnostic delays, invasive diagnoses, and poor treatment outcomes. Characterised by the presence of endometrial-like tissue outside uterus, its main symptoms are pain infertility. often co-occurs other conditions, which may provide insights into origins endometriosis. Methods Here a polygenic risk score phenome-wide association study endometriosis was conducted UK Biobank to investigate pleiotropic effects genetic liability The relationship between for health blood urine biomarkers reproductive factors were investigated separately females, males females without an diagnosis. further using correlation Mendelian randomisation approaches identify causal relationships. Results Multiple associated each group, indicating many comorbidities not dependent on physical manifestation Differences traits highlighted importance sex-specific pathways overlap traits. Notably, lower testosterone levels identified. Follow-up analysis utilising suggested be both clear cell ovarian cancer. Conclusions This highlights diversity irrespective diagnosis A key finding identification effect randomisation.

Language: Английский

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Prenatal Origins of Endometriosis Pathology and Pain: Reviewing the Evidence of a Role for Low Testosterone

Journal of Pain Research, Journal Year: 2023, Volume and Issue: Volume 16, P. 307 - 316

Published: Feb. 1, 2023

Endometriosis is a polygenic, estrogen-dependent, inflammatory disorder of uncertain aetiology associated with pain, infertility and reduced quality life. While the positive association between endometriosis estrogen established, suite recent studies has demonstrated an inverse presence lesions levels testosterone both prenatally postnatally. The following narrative review provides new insights into roles in aetiology, diagnosis, management symptoms, especially pain. A relatively short anogenital distance (AGD) indicative lower during fetal development. shorter AGD recently been correlated higher risk developing adult life, known correlates including earlier onset reproductive cycling, ovarian follicle number, postnatal testosterone, premature insufficiency. During are positively key comorbidities endometriosis, days per month pelvic pain increased sensitivity. Biochemically, pro-inflammatory IL-1β β-endorphin. In rodents, prenatal administration to females reduces their sensitivity adulthood. emerging convergent links low provide evidence centrally mediated effect beginning early development, persisting through notable effects on They generate novel conceptual framework for understanding, studying treating this disorder, whereby by combination high endometrial tissue systemic testosterone.

Language: Английский

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Letrozole induced a polycystic ovary syndrome model in zebrafish by interfering with the hypothalamic-pituitary-gonadal axis

Environmental Pollution, Journal Year: 2024, Volume and Issue: 347, P. 123723 - 123723

Published: March 5, 2024

Language: Английский

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Shorter Anogenital Distance in Women with Ovarian Endometriomas and Adenomyosis, but Not Uterine Leiomyomas

Biomedicines, Journal Year: 2023, Volume and Issue: 11(10), P. 2618 - 2618

Published: Sept. 23, 2023

We investigated whether anogenital distance (AGD) is associated with adenomyosis, endometriosis and uterine leiomyomas (UL, also called fibroids). recruited 81 women UL, 105 ovarian endometrioma (OE), 116 28 both adenomyosis 100 control subjects other acquired gynecological conditions but not endometriosis, or polycystic syndrome. Measurements from the anterior clitoral surface to center of anus (AGDAC), tip clitoris (AGDACt), posterior fourchette (AGDAF) were made in all subjects. Multiple regression was performed estimate association between AGDs presence OE, UL while controlling for possible confounding factors. found that, compared controls, OE had significantly shorter AGDAF, AGDAC. However, amount variance that could be explained by disease status rather moderate, suggesting factors than status, bodyweight height responsible AGD. Thus, prenatal exposure reduced levels androgen may increase risk developing adenomyosis. contribute pathogenesis

Language: Английский

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Variation among human populations in endometriosis and PCOS A test of the inverse comorbidity model

Evolution Medicine and Public Health, Journal Year: 2021, Volume and Issue: 9(1), P. 295 - 310

Published: Jan. 1, 2021

Evidence linking endometriosis to low prenatal testosterone, and evidence that risk of polycystic ovary syndrome (PCOS) is associated with high have motivated the hypothesis PCOS exhibit inverse comorbidity. The comorbidity predicts populations exhibiting higher prevalence one disorder should show lower other. To test this prediction, data were compiled from literature on PCOS, levels serum testosterone in women during pregnancy digit ratios as indicators relation variation inferred or observed population ancestries. Published studies indicate rates are highest Asian populations, intermediate European lowest African (i.e. ancestry); by contrast, being women, Europeans individuals populations. Women also (which may increase risk, decrease daughters), (as indicated ratios), than women. These results subject caveats involving ascertainment biases, socioeconomic, cultural historical effects diagnoses, quality, uncertainties regarding genetic environmental bases differences causes symptoms endometriosis. Despite such reservations, findings provide convergent, preliminary support for model, they motivate further tests its predictions.

Language: Английский

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