Dienogest and the Risk of Endometriosis Recurrence Following Surgery: A Systematic Review and Meta-analysis

Zakhari, Andrew; Edwards, David R.; Ryu, Michelle; Matelski, John; Bougie, Olga; Murji, Ally

doi:10.1016/j.jmig.2020.05.007

Cited by 43 publications

(26 citation statements)

References 31 publications

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“…The main differences between EC-ESCs and normal ESCs are enhanced migration and invasion, overgrowth, and enhanced epithelial-mesenchymal transition [ 38 ]. Endometriosis has a high recurrence rate, even with the complete surgical removal of lesions [ 39 ]. Additionally, the mechanism of recurrence remains unknown.…”

Section: Discussionmentioning

confidence: 99%

Long non-coding RNA DHRS4 antisense RNA 1 inhibits ectopic endometrial cell proliferation, migration, and invasion in endometriosis by regulating microRNA-139-5p expression

Cui

Zhou²,

Lin

2022

Bioengineered

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Endometriosis is an estrogen-dependent chronic gynecological syndrome. Recent studies have shown that long non-coding RNAs participate in the pathogenesis and development of endometriosis. This study aimed to explore the mechanisms of DHRS4 antisense RNA 1 (DHRS4-AS1) in endometriosis. Dual-luciferase reporter assays were conducted to determine the relationship between DHRS4-AS1, microRNA (miR)-139-5p, and arrestin domain-containing 3 (ARRDC3). Furthermore, the expression of DHRS4-AS1 and miR-139-5p in ectopic endometrial stromal cells (EC-ESCs) and endometriosis tissues was examined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Additionally, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT), flow cytometry, and Transwell assays were performed to evaluate the proliferation, apoptosis, and migration and invasion of EC-ESCs, respectively. Western blotting and RT-qPCR were further utilized to determine cleaved-Caspase 3, Caspase 3, and matrix metalloproteinase 9 (MMP-9) expression levels. Compared with the EN group, DHRS4-AS1 levels were lower and miR-139-5p levels were higher in EC-ESCs and tissues obtained from patients with endometriosis. Functional assays validated that DHRS4-AS1 targets miR-139-5p, with ARRDC3 being a downstream target of miR-139-5p. Rescue experiments demonstrated that DHRS4-AS1 inhibited EC-ESC proliferation, migration, and invasion, but promoted apoptosis, by targeting miR-139-5p in endometriosis. cleaved-Caspase3 expression level and the cleaved-Caspase 3/Caspase 3 ratio increased, while the expression levels of MMP-9 decreased, after transfection with DHRS4-AS1 overexpression plasmids; however, the effects induced by DHRS4-AS1 overexpression could be partially reversed by co-transfection with the miR-139-5p mimic. The current study demonstrates that the DHRS4-AS1/miR-139-5p/ARRDC3 axis participates in the regulation of EC-ESC function.

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Section: Discussionmentioning

confidence: 99%

Long non-coding RNA DHRS4 antisense RNA 1 inhibits ectopic endometrial cell proliferation, migration, and invasion in endometriosis by regulating microRNA-139-5p expression

Cui

Zhou²,

Lin

2022

Bioengineered

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“…A retrospective study of 362 women of reproductive age who underwent laparoscopic surgery for endometrioma showed that postoperative GnRH-a combined with cyclic oral contraceptives signi cantly reduced the ve-year postoperative recurrence rate of endometrioma compared with GnRH-a alone [9]. Another meta-analysis revealed that patients who received dienogest after conservative surgery for endometriosis had a signi cantly lower risk of postoperative disease recurrence than those who were expectantly managed [31]. However, the results of the present study did not show that oral contraceptives alone or combined with GnRH-a could reduce the postoperative recurrence rate of endometrioma.…”

Section: Discussionmentioning

confidence: 99%

Risk Factors for Postoperative Recurrence of Ovarian Endometrioma in Young Women

Xing¹,

Song²,

Zhao³

et al. 2021

Preprint

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Background: Ovarian endometroma seriously affects women's health, and is susceptible to recurrence after surgery. However, only a few studies have been conducted to asses the risk factors for postoperative recurrence of ovarian endometrioma in young women, and no risk factors associated with recurrence have been found. The purpose of this study is to analyse the risk factors for postoperative recurrence of ovarian endometrioma in young women. Materials and Methods: We retrospectively analysed 196 young women who underwent ovarian endometrioma resection in Peking Union Medical College Hospital and Shengjing Hospital from January 2008 to January 2018 and were followed-up for at least 3 years postoperatively. The patients were divided into a recurrence group or a non-recurrence group. Their preoperative histories, laboratory indexes, intraoperative manifestations, and follow-up symptoms were analysed. Results: The cumulative recurrence rate of ovarian endometrioma in young women 3 and 5 years after surgery was 8.0%, and 20.3%, respectively. Univariate analysis showed significant differences in cancer antigen-125 levels (hazard ratio [HR]: 3.207, 95% confidence interval [CI]: 1.126–9.135, P = 0.029), the revised American Fertility Society (rAFS) disease stage (HR: 4.588, 95%CI: 1.422–14.805, P =0.011), postoperative pregnancy (HR: 0.28, 95%CI: 0.109–0.723, P = 0.008), and postoperative dysmenorrhoea (HR: 2.465, 95%CI :1.320–4.604, P = 0.005) between the two groups. Cox multivariate proportional risk analysis showed that rAFS disease stage (HR:3.783, 95%CI: 1.162–12.311, P=0.027) and postoperative dysmenorrhoea (HR: 2.291, 95%CI :1.222–4.296, P = 0.01) were risk factors for postoperative recurrence of ovarian endometrioma, whereas postoperative pregnancy (HR: 0.361, 95%CI: 0.138–0.944, P=0.038) was a protective factor for postoperative recurrence. There was no significant correlation between recurrence of ovarian endometrioma and age at surgery, age at the time of menarche, body mass index, duration of dysmenorrhoea, degree of dysmenorrhoea, genital malformation, surgical approach, maximum diameter of the cyst, and postoperative medication. Conclusion: rAFS disease stage and postoperative dysmenorrhoea are risk factors for the recurrence of ovarian endometrioma during long-term follow-up, whereas postoperative pregnancy is a protective factor.

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“…Long-term (60-month) treatment effectively reduced endometriosis-associated pain and avoided pain recurrence post-surgery without sever adverse effects [ 202 , 203 ], especially on bone mineral density (BMD)[ 189 ]. Therefore, its use as first-line therapy for long-term management of debilitating and chronic endometriosis-associated pain represents an interesting option.…”

Section: Endocrine Background Of Hormonal Treatments For Endometriosismentioning

confidence: 99%

Hormonal treatments for endometriosis: The endocrine background

Vannuccini

Clemenza

Rossi

et al. 2021

Rev Endocr Metab Disord

133

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Endometriosis is a benign uterine disorder characterized by menstrual pain and infertility, deeply affecting women’s health. It is a chronic disease and requires a long term management. Hormonal drugs are currently the most used for the medical treatment and are based on the endocrine pathogenetic aspects. Estrogen-dependency and progesterone-resistance are the key events which cause the ectopic implantation of endometrial cells, decreasing apoptosis and increasing oxidative stress, inflammation and neuroangiogenesis. Endometriotic cells express AMH, TGF-related growth factors (inhibin, activin, follistatin) CRH and stress related peptides. Endocrine and inflammatory changes explain pain and infertility, and the systemic comorbidities described in these patients, such as autoimmune (thyroiditis, arthritis, allergies), inflammatory (gastrointestinal/urinary diseases) and mental health disorders.The hormonal treatment of endometriosis aims to block of menstruation through an inhibition of hypothalamus-pituitary-ovary axis or by causing a pseudodecidualization with consequent amenorrhea, impairing the progression of endometriotic implants. GnRH agonists and antagonists are effective on endometriosis by acting on pituitary-ovarian function. Progestins are mostly used for long term treatments (dienogest, NETA, MPA) and act on multiple sites of action. Combined oral contraceptives are also used for reducing endometriosis symptoms by inhibiting ovarian function. Clinical trials are currently going on selective progesterone receptor modulators, selective estrogen receptor modulators and aromatase inhibitors. Nowadays, all these hormonal drugs are considered the first-line treatment for women with endometriosis to improve their symptoms, to postpone surgery or to prevent post-surgical disease recurrence. This review aims to provide a comprehensive state-of-the-art on the current and future hormonal treatments for endometriosis, exploring the endocrine background of the disease.

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Dienogest and the Risk of Endometriosis Recurrence Following Surgery: A Systematic Review and Meta-analysis

Cited by 43 publications

References 31 publications

Long non-coding RNA DHRS4 antisense RNA 1 inhibits ectopic endometrial cell proliferation, migration, and invasion in endometriosis by regulating microRNA-139-5p expression

Long non-coding RNA DHRS4 antisense RNA 1 inhibits ectopic endometrial cell proliferation, migration, and invasion in endometriosis by regulating microRNA-139-5p expression

Risk Factors for Postoperative Recurrence of Ovarian Endometrioma in Young Women

Hormonal treatments for endometriosis: The endocrine background

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