Management of recurrent implantation failure by gonadotropin-releasing hormone agonist and aromatase inhibitor suppression, in women without evidence of endometriosis.
Endometriosis implants are characterized by unbalanced local oestrogen metabolism leading to hyperoestrogenism and aromatase up-regulation is one of main mechanism involved.
As an attractive approach for the treatment of endometriosis-associated pelvic pain, IVRs delivering a combination of the aromatase inhibitor anastrozole (ATZ) and the progestin levonorgestrel (LNG) have been developed.
A total of 420 women with colorectal endometriosis treated with combined oral contraceptives, progestins, gonadotropin releasing-hormone (GnRH) agonists and aromatase inhibitors have been described in eight case series, two retrospective cohort studies and four case reports.
Two key pathways have been implicated: while there is contradictory data on the participation of the aromatase enzyme (encoded by <i>CYP19A1</i>), there is increasing evidence that the steroid sulphatase pathway plays a role in both the aetiology and pathology of endometriosis.
The emergence of intracrinology, associated with disordered expression of key enzymes such as aromatase, in the aetiology of common women's health disorders such as endometriosis and endometrial cancer has prompted renewed interest in the development of drugs targeting these pathways, opening up new opportunities for targeted therapies and precision medicine.
In short, coumarin core can be tailored with specific ring and polar moiety substitutions to block either the sulphatase pathway or the aromatase pathway for treating breast cancer and endometriosis.
Aromatase inhibitors are a promising therapeutic option that may be helpful for the management of endometriosis-associated pain in combination therapy with progestins.
Aromatase inhibitors are a promising therapeutic option that may be helpful for the management of endometriosis-associated pain in combination therapy with progestins.
A more complete understanding of the mechanisms that modulate aromatase and its activity is required to develop novel estrogen-targeted therapies for endometriosis.
Aromatase inhibitors act by decreasing extra-ovarian estrogen production and by blocking the feed-forward stimulation loop between inflammation and aromatase within endometriosis lesions.
These epigenetic changes along with differential binding of ERβ (as a transcription factor) in CYP19A1 promoters may impair follicular steroidogenesis, leading to poor Oocyte and embryo condition in endometriosis patients.
In conclusion, DNG exerts comprehensive inhibition of abnormal estrogen production through inhibition of aromatase and HSD17β1, contributing to a therapeutic effect of DNG on endometriosis.
This finding may be helpful in understanding infertility associated with endometriosis and reduced P450 aromatase activity in endometriotic granulosa cells.
The findings of our study on histone acetylation, endometriosis and the CYP19 gene provide insight which may aid in the research of histone acetylation and suggest that the CYP19 gene may be a novel therapeutic target and method for the treatment of endometriosis.