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Context Regulatory T (Treg) cells and T-helper-17 (Th17) cells may be involved in endometriosis. Information on the pattern of change in the percentages of Treg and Th17 cells in the peripheral blood (PB) and peritoneal fluid (PF) of women with early and advanced endometriosis is unclear. Objective To investigate the pattern of change in the percentages of Treg and Th17 cells in the PB and PF of women with early and advanced endometriosis. Methods We recruited 31 women with laparoscopically and histologically confirmed, revised American Society of Reproductive Medicine stage I-II endometriosis, 39 women with stage III-IV endometriosis, and 36 control subjects without visible endometriosis. PB and PF samples were collected and T-cell subpopulations analyzed by flow cytometry using specific monoclonal antibodies recognizing CD4+, CD25+, FOXP3+, and IL-17A+ markers. PF concentrations of TGF-β and IL-17 were measured by ELISA. Results The percentages of CD25+FOXP3+ Treg cells within the CD4+ T-cell population were significantly higher in the PF of women with advanced endometriosis than in either early endometriosis or in control subjects (P < 0.05 for both). A persistently lower percentage of CD4+IL-17A+ Th17 cells was found in both PB and PF of women with early and advanced endometriosis. Compared with IL-17 levels, PF levels of TGF-β were significantly higher in women with endometriosis (P = 0.01). Conclusion Our findings reconfirmed the current speculation that endometriosis is related to alteration of Treg and Th17 cells in the pelvis causing survival and implantation of ectopic endometrial lesions.

Treg cell deficiency exaggerates local inflammation and angiogenesis and simultaneously facilitates the attachment and growth of endometrial implants. The findings provide an insight into dysregulated immune response for the pathogenesis and development.

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Endometriosis is an estrogen-dependent disease. Abnormally biosynthesized estrogens in endometriotic tissues induce the growth of the lesion and worsen endometriosis-associated pelvic pain. Dienogest (DNG), a selective progesterone receptor agonist, is widely used to treat endometriosis and efficiently relieves the symptoms. However, its pharmacological action remains unknown. In this study, we elucidated the effect of DNG on enzymes involved in local estrogen metabolism in endometriosis. Surgically obtained specimens of 23 ovarian endometriomas (OE) and their homologous endometrium (EE), ten OE treated with DNG (OE w/D), and 19 normal endometria without endometriosis (NE) were analyzed. Spheroid cultures of stromal cells (SCs) were treated with DNG and progesterone. The expression of aromatase, 17b-hydroxysteroid dehydrogenase 1 (HSD17b1), HSD17b2, HSD17b7, HSD17b12, steroid sulfatase (STS), and estrogen sulfotransferase (EST) was evaluated by real-time quantitative PCR. The activity and protein level of HSD17b1 were measured with an enzyme assay using radiolabeled estrogens and immunohistochemistry respectively. OESCs showed increased expression of aromatase, HSD17b1, STS, and EST, along with decreased HSD17b2 expression, when compared with stromal cells from normal endometria without endometriosis (NESCs) (P!0.01) or stromal cells from homologous endometrium (EESCs) (P!0.01). In OESCs, DNG inhibited HSD17b1 expression and enzyme activity at 10 K7 M (P!0.01). Results of immunohistochemical analysis displayed reduced HSD17b1 staining intensity in OE w/D (P!0.05). In conclusion, DNG exerts comprehensive inhibition of abnormal estrogen production through inhibition of aromatase and HSD17b1, contributing to a therapeutic effect of DNG on endometriosis.

DNG therapy early after recurrence of postsurgical endometrioma appears to be viable for reducing the risk of repeated surgery.

Background It has been well established that endometriosis is an estrogen‐dependent disease. Although the exact pathogenesis of the disease is still unclear, it is known to be characterized by estrogen‐dependent growth and maintenance of the ectopic endometrium and increased local estrogen production. Methods The authors reviewed studies on local estrogen production and estrogen activities mediated by estrogen receptors in endometriotic tissues. Main findings Aberrant expression of several enzymes in local endometriotic lesions contributed to the production and metabolism of estrogens. Aromatase was one of the key therapeutic targets for the regulation of local estrogen formation. Our findings suggest that PGC‐1a, a transcriptional coactivator‐modulating steroid hormone, regulates aromatase expression and activity. Estrogen activities mediated by different types of estrogen receptors abnormally elevated in local tissues could also be involved in the development of endometriosis. The authors demonstrated that the isoflavone aglycone, a partial agonist of the estrogen receptor, suppressed the formation of endometriotic lesions. Conclusions Local estrogen production and estrogen activity mediated by estrogen receptors are important potential therapeutic targets for endometriosis.

Endometriosis is a common gynecological disease that causes various clinical symptoms, such as chronic pelvic pain, dysmenorrhea and infertility, seriously affecting women's health and their quality of life. The symptoms and endometriotic lesions are relieved, in many cases, after menopause, when estrogen levels are lowered. Therefore, endometriosis is considered to be estrogen-dependent. Aromatase, the enzyme responsible for the last step of estrogen biosynthesis converting testosterone and androgen to estrogen, was previously reported to be more abundant in endometriotic tissues than in the normal endometrium, leading to an increased local estrogen concentration. Therefore, aromatase is considered a key therapeutic target for regulating local estrogen biosynthesis in endometriosis. A more complete understanding of the mechanisms that modulate aromatase and its activity is required to develop novel estrogen-targeted therapies for endometriosis. In this review article, we outline the current understanding of the pathological processes involved in estrogen production in endometriosis and propose novel strategies to treat this disorder.