Desogestrel-only contraceptive pill versus sequential contraceptive vaginal ring in the treatment of rectovaginal endometriosis infiltrating the rectum: a prospective open-label comparative study.

OBJECTIVE: To compare the efficacy of two hormonal therapies in treating symptoms caused by bowel endometriosis. DESIGN: Patient preference study. SETTING: University hospital. POPULATION: A total of 143 women with rectovaginal endometriosis infiltrating the rectum. METHODS: This study was performed between January 2008 and June 2011. Patients were treated with a desogestrel-only contraceptive pill or with the sequential combined contraceptive vaginal ring for 12 months. MAIN OUTCOME MEASURES: The primary endpoint of the study was the rate of satisfied patients at 12-month follow up. The changes in symptoms and in the volume of the nodules were secondary endpoints. RESULTS: At 12-month follow up, the rate of satisfied patients was higher in the group treated with the desogestrel-only contraceptive pill than in the group treated with the sequential combined contraceptive vaginal ring (p = 0.004). When only changes in gastrointestinal symptoms were considered, 50% of patients treated with the desogestrel-only contraceptive pill and 31.3% of those treated with the sequential combined contraceptive vaginal ring were satisfied (p = 0.037). The reduction in the volume of the nodules, the percentages of patients who discontinued the therapy after the completion of the study and of those who decided to undergo surgery were similar between the two groups. CONCLUSIONS: Both hormonal therapies are efficacious in treating symptoms caused by rectovaginal endometriosis infiltrating the rectum. Patient satisfaction is higher with the desogestrel-only pill than with a vaginal ring.

Use of aromatase inhibitors to treat endometriosis-related pain symptoms: a systematic review.

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.

Letrozole and norethisterone acetate versus letrozole and triptorelin in the treatment of endometriosis related pain symptoms: a randomized controlled trial.

BACKGROUND: When aromatase inhibitors are used to treat premenopausal women with endometriosis, additional drugs should be used to effectively down-regulate gonadal estrogen biosynthesis. This randomized prospective open-label study compared the efficacy in treating pain symptoms and the tolerability of letrozole combined with either norethisterone acetate or triptorelin. METHODS: Women with pain symptoms caused by rectovaginal endometriosis were treated with letrozole (2.5 mg/day) and were randomized to also receive either oral norethisterone acetate (2.5 mg/day; group N) or intramuscular injection of triptorelin (11.25 mg every 3 months; group T). The scheduled length of treatment was 6 months. A visual analogue scale and a multidimensional categorical rating scale were used to assess the severity of pain symptoms. The volume of the endometriotic nodules was estimated by ultrasonography using virtual organ computer-aided analysis. Adverse effects of treatment were recorded. RESULTS: A total of 35 women were randomized between the two treatment protocols. Significantly more patients in group N rated their treatment as satisfactory or very satisfactory (64.7%) as compared to group T (22.2%; p=0.028). The intensity of both non-menstrual pelvic pain and deep dyspareunia significantly decreased during treatment in both study groups, though no statistically meaningful difference between the two groups was apparent. Reduction in the volume of endometriotic nodules was significantly greater in group T than in group N. Interruption of treatment due to adverse effects significantly differed between the groups, with 8 women in group T (44.4%) and 1 woman in group N (5.9%) interrupting treatment (p=0.018). Similarly, 14 women included in group T (77.8%) and 6 women included in group N (35.3%) experienced adverse effects of treatment (p=0.018). During treatment, mineral bone density significantly decreased in group T but not in group N. CONCLUSIONS: Aromatase inhibitors reduce the intensity of endometriosis-related pain symptoms. Combining letrozole with oral norethisterone acetate was associated with a lower incidence of adverse effects and a lower discontinuation rate than combining letrozole with triptorelin.

Bowel endometriosis: Recent insights and unsolved problems.

Bowel endometriosis affects between 3.8% and 37% of women with endometriosis. The evaluation of symptoms and clinical examination are inadequate for an accurate diagnosis of intestinal endometriosis. Transvaginal ultrasonography is the first line investigation in patients with suspected bowel endometriosis and allows accurate determination of the presence of the disease. Radiological techniques (such as magnetic resonance imaging and multidetector computerized tomography enteroclysis) are useful for estimating the extent of bowel endometriosis. Hormonal therapies (progestins, gonadotropin releasing hormone analogues and aromatase inhibitors) significantly improve pain and intestinal symptoms in patients with bowel stenosis less than 60% and who do not wish to conceive. However, hormonal therapies may not prevent the progression of bowel endometriosis and, therefore, patients receiving long-term treatment should be periodically monitored. Surgical excision of bowel endometriosis should be offered to symptomatic patients with bowel stenosis greater than 60%. Intestinal endometriotic nodules may be excised by nodulectomy or segmental resection. Both surgical procedures improve pain, intestinal symptoms and fertility. Nodulectomy may be associated with a lower rate of complications.

Letrozole and norethisterone acetate in colorectal endometriosis.

OBJECTIVE: Up to now limited attention has been given to the medical treatment of bowel endometriosis. This study evaluates the efficacy of aromatase inhibitors and norethisterone acetate in treating pain and gastrointestinal symptoms caused by bowel endometriosis. STUDY DESIGN: This prospective pilot study included six women with colorectal endometriosis; all women had intestinal nodules infiltrating at least the muscularis propria of the bowel and did not have a stenosis of the bowel lumen >60%; the patients suffered from pain and intestinal symptoms. The study subjects received letrozole (2.5 mg/day) and norethisterone acetate (2.5 mg/day) continuously for 6 months. The presence and intensity of symptoms were evaluated before starting the treatment, and after 3 and 6 months of treatment. RESULTS: The double-drug regimen improved pain, non-menstrual pelvic pain, deep dyspareunia, dyschezia, symptoms mimicking diarrhoea-predominant irritable bowel syndrome, intestinal cramping, abdominal bloating and passage of mucus in the stools, and 67% of the patients declared that the treatment improved their gastrointestinal symptoms. CONCLUSIONS: The administration of letrozole and norethisterone acetate reduces pain and gastrointestinal symptoms of women with colorectal endometriosis, particularly when patients suffer from symptoms mimicking diarrhoea-predominant irritable bowel syndrome.

Pharmacological treatment of endometriosis: experience with aromatase inhibitors.

Current treatment of endometriosis is mainly based on surgery and ovarian suppressive agents. In the last 10 years, it has been demonstrated that aromatase P450, a key enzyme for estrogen biosynthesis, may have a pathogenic role in endometriosis because it is aberrantly expressed in endometriotic implants and in eutopic endometrium of women with endometriosis. Therefore, inhibition of aromatase activity may represent a new therapeutic option for endometriosis. Case reports and observational studies have shown that pain symptoms caused by endometriosis quickly improve after administration of aromatase inhibitors. Limited data are available on the long-term course of pain symptoms after completion of treatment with aromatase inhibitors; however, some recent studies suggest that symptoms may recur at short-term follow-up. A range of results are reported on the effects of aromatase inhibitors on endometriotic lesions, with some authors describing improvements and other authors reporting persistence of pelvic lesions at second-look laparoscopy after treatment. No severe adverse effect has been reported during treatment with aromatase inhibitors both in pre- and postmenopausal women. On the basis of the available data, administration of aromatase inhibitors should now be offered only to the small number of women who have severe pain despite previous surgical and hormonal therapies. Further research in the form of randomized controlled trials will be required before recommending the routine use of these agents.