Aromatase as a target for treating endometriosis

Abstract

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.

High Doses of D-Chiro-Inositol Alone Induce a PCO-Like Syndrome and Other Alterations in Mouse Ovaries

“…A band of similar size was detected after all treatments, but additional bands were detected, as follows: protein extracts from DCIns 250-treated mice contained a band of smaller size (approximately 52 kDa), those from letrozole-treated mice had a band of closely smaller size (approximately 54 kDa), and extracts from DCIns 500- and DCIns 1000-treated mice had a band of much smaller size (approximately 50 kDa). Induction of different aromatase isoforms by various treatments in mouse ovarian cells appears reasonable in light of the observation that the control of aromatase expression in humans involves a complex mechanism of different promoter and downstream exons [ 37 ]. Densitometric measurements of the amounts of aromatase bands relative to GAPDH, showed a reduction in DCIns 250-ovaries (0.16 ± 0.02 relative units, RU) (mean ± SD) from those of negative control-ovaries (0.34 ± 0.03 RU) ( p < 0.05); on the contrary, an increase was observed in letrozole-ovaries (0.56 ± 0.06 RU) ( p < 0.05).…”

Endometriosis and ovarian cancer - what they have in common?

“…Secondly, an increased expression of aromatase, which is involved in estrogen biosynthesis, was found in endometriotic lesions. It enables the local production of estradiol [9]. In addition, a decreased expression of 17bhydroxysteroid dehydrogenase-2 was also found in endometriotic lesions.…”

Pharmaceuticals targeting signaling pathways of endometriosis as potential new medical treatment: A review

“…For women with EM who prefer symptomatic medical therapy, such side effects should be limited and well‐tolerated. Medicines that regulate E 2 levels usually result in hypoestrogenism and are associated with side effects such as hot flushes and vaginal dryness, which are acceptable, but not preferable 57 . Other common adverse effects, such as osteoporosis and venous thromboembolism, should be avoided.…”