Abstract
This systematic review aims to assess the efficacy of aromatase inhibitors (AIs) in treating pain symptoms caused by endometriosis. A comprehensive literature search was conducted to identify all the published studies evaluating the efficacy of type II nonsteroidal aromatase inhibitors (anastrozole and letrozole) in treating endometriosis-related pain symptoms. The MEDLINE, EMBASE, PubMed, and SCOPUS databases and the Cochrane System Reviews were searched up to October 2010. This review comprises of the results of 10 publications fitting the inclusion criteria; these studies included a total of 251 women. Five studies were prospective non-comparative, four were randomized controlled trials (RCTs) and one was a prospective patient preference trial. Seven studies examined the efficacy of AIs in improving endometriosis-related pain symptoms, whilst three RCTs investigated the use of AIs as post-operative therapy in preventing the recurrence of pain symptoms after surgery for endometriosis. All the observational studies demonstrated that AIs combined with either progestogens or oral contraceptive pill reduce the severity of pain symptoms and improve quality of life. One patient preference study demonstrated that letrozole combined with norethisterone acetate is more effective in reducing pain and deep dyspareunia than norethisterone acetate alone. However, letrozole causes a higher incidence of adverse effects and does not improve patients' satisfaction or influence recurrence of symptoms after discontinuation of treatment. A RCT showed that combining letrozole with norethisterone acetate causes a lower incidence of adverse effects and lower discontinuation rate than combining letrozole with triptorelin. Two RCTs demonstrated that, after surgical treatment of endometriosis, the administration of AIs combined with gonadotropin releasing hormone analogue for 6 months reduces the risk of endometriosis recurrence when compared with gonadotropin releasing hormone analogue alone. In conclusion, AIs effectively reduce the severity of endometriosis-related pain symptoms. Since endometriosis is a chronic disease, future investigations should clarify whether the long-term administration of AIs is superior to currently available endocrine therapies in terms of improvement of pain, adverse effects and patient satisfaction.
Highlights
Endometriosis is a chronic estrogen dependent gynaecological condition characterized by the presence of ectopic glands and stroma outside the uterine cavity
Of the 28 studies found, 4 were excluded because they were only published in the abstracts or proceedings of scientific meetings [20,21,22,23], 12 were excluded because they were case reports or included less than 10 patients [24,25,26,27,28,29,30,31,32,33,34,35], 1 study was excluded because of duplicate publication [36] and 1 study was excluded because the instruments used to describe the changes in pain symptoms during treatment were not clearly defined [37]
Three studies investigated the use of aromatase inhibitors (AIs) as postoperative therapy in preventing the recurrence of pain after surgical treatment of endometriosis [39,45,46]; seven studies examined the effect of AIs in improving endometriosis-related pain symptoms
Summary
Endometriosis is a chronic estrogen dependent gynaecological condition characterized by the presence of ectopic glands and stroma outside the uterine cavity. Since the late 1990s, several independent studies based either on polymerase chain reaction or immunohistochemistry have demonstrated that aromatase P450 is over-expressed in both eutopic and ectopic endometrium of patients with endometriosis, while this enzyme is not detectable in eutopic endometrium obtained from healthy women and in endometriosis free peritoneal tissue [6,7,8,9,10,11,12,13]. It was demonstrated that endometriotic lesions could create a hyperestrogenic environment increasing the reduction of estrone into 17-b estradiol and decreasing the oxidation of 17-b estradiol into estrone [14] In agreement with these observations, Colette et al found that aromatase P450 is undetectable by immunohistochemistry in the glandular and stromal compartments of ectopic endometrial tissue [16]. The authors suggested that what was believed to be aromatase protein was mainly endogenous biotic labeling or iron deposits [15]
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