Coexistence of Polycystic Ovary Syndrome and Endometriosis in Women with Infertility

Holoch, K.; Savaris, Ricardo Francalacci; Forstein, David A.; Miller, P. L.; Higdon, H. Lee; Likes, C.E.; Lessey, Bruce A.

doi:10.5301/je.5000181

Cited by 22 publications

(16 citation statements)

References 31 publications

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“…The synthetic androgen danazol is able to successfully shrink endometriotic lesions in women but is not commonly prescribed because of unwanted androgenic side effects (32). Women with PCOS are reported to have a high risk for endometriosis in some studies (33) and reports also suggest an elevated risk for endometrial cancer (34). But in our cohort of rhesus females that developed endometriosis, no one treatment group was significantly overrepresented (Supplemental Table 1).…”

Section: Discussionmentioning

confidence: 66%

Mild hyperandrogenemia in presence/absence of a high-fat, Western-style diet alters secretory phase endometrial transcriptome in nonhuman primates

et al. 2020

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Objective: To identify novel transcriptomic changes to eutopic endometrium by exposure to chronic mild hypernadrogenemia (testosterone [T]) with/without exposure to an obesogenic Western-style diet (WSD). Design: Two-by-two factorial arrangement of treatments. Setting: National primate research center. Animal(s): Rhesus macaque females were chronically exposed to T and/or consumed a WSD from menarche through adulthood. After 4.5 years of treatment, Tru-Cut endometrial biopsies were obtained at the midsecretory phase (n ¼ 6-4/group), and paired-end sequencing of RNA was performed. Several females in the T, WSD, and TþWSD cohorts developed endometriosis within 6 months of biopsy; a separate analysis was performed contrasting diagnosis of endometriosis stage 0-2 versus stages 3 and 4 (American Society for Reproductive Medicine revised criteria). Intervention(s): Chronic exposure to mild elevation of T ($five-fold elevation) and/or WSD from menarche until adulthood. Main Outcome Measure(s): Limma voom empirical Bayes pipeline was performed to detect differentially expressed RNAs (DEs) significantly impacted by treatments and endometriosis severity. Differentially expressed RNAs were then interrogated by Ingenuity Pathway Analyses and Protein Analysis through Evolutionary Relationships. Result(s): Total DEs included C versus T, 469; C versus WSD, 525; C versus TþWSD, 549; and T versus TþWSD, 1,505. The majority of DEs mapped to the ontology pathways: heterotrimeric G-protein signaling pathways Gi alpha and Gs alpha (C vs. T), WNT signaling (C vs. WSD and T vs. TþWSD), and Huntington disease (C vs. TþWSD). A total of 2,171 DEs from eutopic endometrium were altered by the presence of stage 3 and 4 endometriosis lesions. Conclusion(s):The present global transcriptomic analyses demonstrate that the greatest magnitude of changes occurred in contrasts of C and T versus TþWSD, adding to the evidence that these two insults have a synergistic effect on female physiology. These data also support the concept that prior alterations to the function of eutopic endometrium increase the risk for endometriosis. (Fertil Steril Sci Ò 2020;1:172-82. Ó2020 by American Society for Reproductive Medicine.

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Section: Discussionmentioning

confidence: 66%

Mild hyperandrogenemia in presence/absence of a high-fat, Western-style diet alters secretory phase endometrial transcriptome in nonhuman primates

et al. 2020

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“…These studies yielded rates of endometriosis that center around 19% (Barbosa et al, 2009 ; Rawson, 1991 ; Tissot et al, 2017 ). Holoch et al ( 2014 ) reported high rates of endometriosis in women with PCOS (>70%), but the PCOS group was subject to ascertainment bias because the women were examined for endometriosis only if they self‐reported pelvic pain and/or infertility. Taken together, these studies suggest that, among women without any clear symptoms of endometriosis (pain, heavy bleeding, infertility), the rate of this disorder as determined by laparoscopy is about one‐half to one‐third lower in women with PCOS than in women with no known reproductive issues.…”

Section: Resultsmentioning

confidence: 99%

Endometriosis and polycystic ovary syndrome are diametric disorders

Dinsdale

Crespi

2021

Evolutionary Applications

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Evolutionary and comparative approaches can yield novel insights into human adaptation and disease. Endometriosis and polycystic ovary syndrome (PCOS) each affect up to 10% of women and significantly reduce the health, fertility, and quality of life of those affected. PCOS and endometriosis have yet to be considered as related to one another, although both conditions involve alterations to prenatal testosterone levels and atypical functioning of the hypothalamic-pituitary-gonadal (HPG) axis. Here, we propose and evaluate the novel hypothesis that endometriosis and PCOS represent

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“…First, we observe (both in the learned posteriors and in the computed associations) that patients assigned to subtype A track symptoms related to several comorbidities already reported in the literature. Diagnosis of endometriosis has been linked to anxiety, depression, and other mood disorders 48,49 , migraines 50 , high blood pressure 51 , PCOS 52 , and chronic fatigue syndrome 6,53,54 . The significant associations found for phenotype A reflected a higher surgical burden, and a lack of adequate treatment of the disease.…”

Section: Discussionmentioning

confidence: 99%

Learning endometriosis phenotypes from patient-generated data

2020

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Endometriosis is a systemic and chronic condition in women of childbearing age, yet a highly enigmatic disease with unresolved questions: there are no known biomarkers, nor established clinical stages. We here investigate the use of patient-generated health data and data-driven phenotyping to characterize endometriosis patient subtypes, based on their reported signs and symptoms. We aim at unsupervised learning of endometriosis phenotypes using self-tracking data from personal smartphones. We leverage data from an observational research study of over 4000 women with endometriosis that track their condition over more than 2 years. We extend a classical mixed-membership model to accommodate the idiosyncrasies of the data at hand, i.e., the multimodality and uncertainty of the self-tracked variables. The proposed method, by jointly modeling a wide range of observations (i.e., participant symptoms, quality of life, treatments), identifies clinically relevant endometriosis subtypes. Experiments show that our method is robust to different hyperparameter choices and the biases of self-tracking data (e.g., the wide variations in tracking frequency among participants). With this work, we show the promise of unsupervised learning of endometriosis subtypes from self-tracked data, as learned phenotypes align well with what is already known about the disease, but also suggest new clinically actionable findings. More generally, we argue that a continued research effort on unsupervised phenotyping methods with patient-generated health data via new mobile and digital technologies will have significant impact on the study of enigmatic diseases in particular, and health in general.

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Coexistence of Polycystic Ovary Syndrome and Endometriosis in Women with Infertility

Cited by 22 publications

References 31 publications

Mild hyperandrogenemia in presence/absence of a high-fat, Western-style diet alters secretory phase endometrial transcriptome in nonhuman primates

Mild hyperandrogenemia in presence/absence of a high-fat, Western-style diet alters secretory phase endometrial transcriptome in nonhuman primates

Endometriosis and polycystic ovary syndrome are diametric disorders

Learning endometriosis phenotypes from patient-generated data

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