Add-back therapy in the treatment of endometriosis-associated pain. Quantification of endometriosis-associated pain and quality of life during the stimulatory phase of gonadotropin-releasing hormone agonist therapy: a double-blind, randomized, placebo-controlled trial. Detailed analysis of a randomized, multicenter, comparative trial of dienogest versus leuprolide acetate in endometriosis. Use of nafarelin versus placebo after reductive laparoscopic surgery for endometriosis. Hormonal suppression treatment or dietary therapy versus placebo in the control of painful symptoms after conservative surgery for endometriosis stage III-IV. A randomized comparative trial. Low-dose danazol after combined surgical and medical therapy reduces the incidence of pelvic pain in women with moderate and severe endometriosis. Low-dose oral contraceptive pill for dysmenorrhea associated with endometriosis: a placebo-controlled, double-blind, randomized trial. [Effectiveness and safety of laparoscopic presacral neurectomy in treating endometriosis-associated pain]. Human issues and medical economics of endometriosis. Three- vs. six-month GnRH-agonist therapy. Persistence of dysmenorrhea and nonmenstrual pain after optimal endometriosis surgery may indicate adenomyosis. Placebo-controlled study on serum concentrations of CA-125 before and after treatment of endometriosis with danazol or high-dose medroxyprogesterone acetate alone or after surgery. A gonadotrophin‐releasing hormone agonist compared with expectant management after conservative surgery for symptomatic endometriosis Randomized trial of leuprolide versus continuous oral contraceptives in the treatment of endometriosis-associated pelvic pain. The treatment with a COX-2 specific inhibitor is effective in the management of pain related to endometriosis. Delayed Oral Estradiol Combined with Leuprolide Increases Endometriosis-Related Pain Randomized clinical trial of a levonorgestrel-releasing intrauterine system and a depot GnRH analogue for the treatment of chronic pelvic pain in women with endometriosis. Continuous low‐dose oral contraceptive in the treatment of colorectal endometriosis evaluated by rectal endoscopic ultrasonography Prospective randomized double-blind trial of 3 versus 6 months of nafarelin therapy for endometriosis associated pelvic pain. Return of Chronic Pelvic Pain From Endometriosis After Raloxifene Treatment: A Randomized Controlled Trial Correlation between endometriosis and pelvic pain. Combined surgical and hormone therapy for endometriosis is the most effective treatment: prospective, randomized, controlled trial. Endometriosis is associated with central sensitization: a psychophysical controlled study. Factors associated with age of onset and type of menopause in a cohort of UK women. Very low dose danazol for relief of endometriosis-associated pelvic pain: a pilot study. Antioxidant supplementation reduces endometriosis-related pelvic pain in humans. Maintenance therapy with dienogest following gonadotropin-releasing hormone agonist treatment for endometriosis-associated pelvic pain. Migraine in women with chronic pelvic pain with and without endometriosis. Cyproterone acetate versus a continuous monophasic oral contraceptive in the treatment of recurrent pelvic pain after conservative surgery for symptomatic endometriosis. Depot medroxyprogesterone acetate versus an oral contraceptive combined with very-low-dose danazol for long-term treatment of pelvic pain associated with endometriosis. Prolonged gonadotropin-releasing hormone agonist treatment of symptomatic endometriosis: the role of cyclic sodium etidronate and low-dose norethindrone "add-back" therapy. Randomized controlled trial of depot leuprolide in patients with chronic pelvic pain and clinically suspected endometriosis. Pelvic Pain Study Group. Letrozole and norethisterone acetate in colorectal endometriosis. Depot leuprolide versus danazol in treatment of women with symptomatic endometriosis. I. Efficacy results. Efficacy of isotopic 13CO2 laser laparoscopic evaporation in the treatment of infertile patients with minimal and mild endometriosis: a life table cumulative pregnancy rates study. Use of a progestogen only preparation containing desogestrel in the treatment of recurrent pelvic pain after conservative surgery for endometriosis. Danazol in the treatment of endometriosis: analysis of 100 cases with a 4-year follow-up. Effectiveness of the association micronized N-Palmitoylethanolamine (PEA)-transpolydatin in the treatment of chronic pelvic pain related to endometriosis after laparoscopic assessment: a pilot study. Anti-TNF-α treatment for deep endometriosis-associated pain: a randomized placebo-controlled trial Elagolix Treatment for Endometriosis-Associated Pain Long-Term Follow-Up of a Controlled Trial of Laser Laparoscopy for Pelvic Pain Effectiveness of presacral neurectomy in women with severe dysmenorrhea caused by endometriosis who were treated with laparoscopic conservative surgery: a 1-year prospective randomized double-blind controlled trial. Surgical versus medical treatment for endometriosis-associated severe deep dyspareunia: I. Effect on pain during intercourse and patient satisfaction. Efficacy of vaginal danazol treatment in women with recurrent deeply infiltrating endometriosis. Treatment of symptomatic rectovaginal endometriosis with an estrogen-progestogen combination versus low-dose norethindrone acetate. Postsurgical medical treatment of advanced endometriosis: results of a randomized clinical trial. Pain of endometriosis: effects of nafarelin and danazol therapy.
OBJECTIVE To determine the efficacy of GnRH analogue plus add-back therapy compared with GnRH analogue alone and estroprogestin in patients with relapse of endometriosis-associated pain . DESIGN R and omized , controlled study . SETTING University hospital . PATIENT(S ) One hundred thirty-three women with relapse of endometriosis-related pain after previous endometriosis surgery . INTERVENTION(S ) Forty-six women were treated with GnRH analogue plus add-back therapy , 44 women were given GnRH analogue alone , and 43 women received estroprogestin , for 12 months . MAIN OUTCOME MEASURE(S ) Pain evaluation by a visual analogue scale , quality of life in treated patients according to the SF-36 question naire , and occurrence of adverse effects , including bone mass density loss , at pretreatment , after 6 months of treatment , at the end of treatment ( 12 months ) , and 6 months after discontinuation of treatment . RESULT ( S ) Patients treated either with GnRH analogue alone or GnRH analogue plus add-back therapy showed a higher reduction of pelvic pain , dysmenorrhea , and dyspareunia than patients treated with oral contraceptive , whereas patients treated with add-back therapy showed a better quality of life , as assessed with the SF-36 question naire , and adverse effects rate than the other two groups . CONCLUSION ( S ) Add-back therapy allows the treatment of women with relapse of endometriosis-associated pain for a longer period , with reduced bone mineral density loss , good control of pain symptoms , and better patient quality of life compared with GnRH analogue alone or oral contraceptive OBJECTIVE The purpose of this study was a quantification of changes in endometriosis-associated  pain and quality of life during the stimulatory phase of gonadotropin-releasing hormone agonist therapy . STUDY DESIGN One hundred twenty women with significant endometriosis-associated pain participated in a 1-month double-blind , r and omized , placebo-controlled trial . Pain was measured at baseline and at 2 and 4 weeks with  visual analog scales  and the Endometriosis Symptom Severity score . Quality of life was measured with the SF-36 instrument . Group means and SEMs were calculated . Paired t tests were used after determination of data normality . RESULTS Compared with placebo-treated control subjects women treated with gonadotropin-releasing hormone agonist had a statistically ( P < . 0001 ) and clinical ly significant temporary increase in pain and a concomitant decrease in quality of life . CONCLUSION The stimulatory phase of gonadotropin-releasing hormone agonist therapy is associated with an increase in endometriosis-associated pain and a decrease in quality of life OBJECTIVE To analyze the secondary efficacy and safety outcomes from a recent trial comparing dienogest ( DNG ) with leuprolide acetate ( LA ) in women with endometriosis . METHODS A 24-week , open-label , r and omized , multicenter study of DNG versus LA  in women with endometriosis-related pain was assessed for outcomes such as responder rates ( using predefined thresholds of pain relief ) , changes in single symptoms/signs and sum scores from the Biberoglu and Behrman ( B&B ) scale , clinical laboratory parameters , and measures of quality of life . RESULTS Dienogest was non-inferior to LA for treatment response using all predefined thresholds of pain relief and provided equivalent improvements in B&B symptoms and signs . No clinical ly relevant changes in laboratory parameters were observed during DNG treatment , whereas estrogen levels decreased in the LA group . Compared with LA , DNG was associated with pronounced improvements in specific quality -of-life measures . CONCLUSION The analyses provide supportive evidence that the efficacy of DNG is equivalent to that of LA for treating endometriosis symptoms , with specific quality -of-life benefits and a favorable safety profile OBJECTIVE To evaluate the efficacy of the GnRH agonist ( GnRH-a ) nafarelin compared with placebo administered for 6 months after reductive laparoscopic surgery for symptomatic endometriosis . DESIGN R and omized , prospect i ve , placebo-controlled , multicenter clinical trial . SETTING Thirteen clinics including private practice and university centers . PATIENT(S ) One hundred nine women aged 18 - 47 with laparoscopically proven endometriosis and pelvic pain who had undergone reductive laparoscopic surgery for endometriosis . INTERVENTION(S ) Patients were r and omized to receive either the GnRH-a nafarelin ( 200 micrograms twice daily ) or placebo for 6 months . MAIN OUTCOME MEASURE(S ) Time to initiation of alternative treatment ( the length of time from beginning study medication to receiving alternative therapy or to deeming that the study drug was ineffective ) and patient-reported and physician-assessed pelvic pain scores . RESULT ( S ) The median time to initiation of alternative treatment was > 24 months in the nafarelin group versus 11.7 months in the placebo group . Fifteen ( 31 % ) of 49 nafarelin-treated patients required alternative therapy , compared with 25 ( 57 % ) of 44 placebo-treated patients . The patients ' pelvic pain scores dropped significantly in the nafarelin and placebo groups after 6 months of treatment . Physician summary ratings showed significant improvement in the nafarelin group and no significant changes in the placebo group after 6 months of treatment . CONCLUSION ( S ) Compared with placebo , nafarelin administered after reductive laparoscopic surgery for endometriosis significantly delays the return of endometriosis symptoms requiring further treatment OBJECTIVE To evaluate the effectiveness for the outcomes of endometriosis-related pain and quality of life of conservative surgery plus placebo compared with conservative surgery plus hormonal suppression treatment or dietary therapy . DESIGN R and omized comparative trial . SETTING University hospital . PATIENT(S ) Two hundred twenty-two consecutive women who underwent conservative pelvic surgery for symptomatic endometriosis stage III-IV ( r-AFS ) . INTERVENTION(S ) Six months of placebo ( n = 110 ) versus GnRH-a ( tryptorelin or leuprorelin , 3.75 mg every 28 days ) ( n = 39 ) or continuous estroprogestin ( ethynilestradiol , 0.03 mg plus gestoden , 0.75 mg ) ( n = 38 ) versus dietary therapy ( vitamins , minerals salts , lactic ferments , fish oil ) ( n = 35 ) . MAIN OUTCOME MEASURE(S ) Painful symptoms ( visual analogue scale score ) and quality -of-life endometriosis-related symptoms ( SF-36 score ) at 12 months ' follow-up . RESULT ( S ) Patients treated with postoperative hormonal suppression therapy showed less visual analogue scale scores for dysmenorrhoea than patients of the other groups . Hormonal suppression therapy and dietary supplementation were equally effective in reducing nonmenstrual pelvic pain . Surgery plus placebo showed significative decrease in dyspareunia scores . Postoperative medical and dietary therapy allowed a better quality of life than placebo . CONCLUSION ( S ) Postoperative hormonal suppression treatment or dietary therapy are more effective than surgery plus placebo to obtain relief of pain associated with endometriosis stage III-IV and improvement of quality of life The most effective therapy for endometriosis is a matter for debate . The aim of the present r and omized study was to evaluate the efficacy of low doses of danazol on recurrence of pelvic pain in patients with moderate or severe endometriosis , who had undergone laparoscopic surgery and 6 months of gonadotrophin-releasing hormone analogue ( GnRHa ) therapy .  After surgery , 28 patients with moderate or severe endometriosis underwent therapy for 6 months with GnRHa i. m. every 4 weeks . They were then r and omized into two groups : group A ( 14 subjects ) was treated with 100 mg/day danazol for 6 months ; group B ( 14 subjects , control )  did not receive any type of therapy . After 12 months of treatment , group A had a significantly ( P < 0.01 ) lower pain score than group B. There was no significant difference between the groups in oestrogen concentrations , bone mineral density or side-effects . The results suggest that low-dose danazol therapy reduces recurrence of pelvic pain in patients with moderate or severe endometriosis , treated surgically , and has few or no metabolic side-effects OBJECTIVE To evaluate the efficacy of a low-dose oral contraceptive pill ( OCP ) for patients with dysmenorrhea associated with endometriosis . DESIGN A double-blind , r and omized , placebo-controlled trial . SETTING S Clinical trial sites in Japan . PATIENT(S ) One hundred patients with dysmenorrhea associated with endometriosis . Most enrolled patients had radiologic evidence of endometriosis rather than surgical diagnosis . INTERVENTION(S ) Patients were r and omly assigned to receive either monophasic OCP ( ethinylestradiol plus norethisterone ) or placebo . Participants used their usual pain medications as needed during the trial . MAIN OUTCOME MEASURE(S ) After four cyclic treatments , we used a zero- to three-point verbal rating scale and a visual analogue scale to measure the severity of disability because of dysmenorrhea in daily life , and the patients ' use of analgesics . RESULT ( S ) Total dysmenorrhea scores assessed by the verbal rating scale were significantly decreased at the end of treatment in both groups . From the first cycle through the end of treatment , dysmenorrhea in the OCP group was significantly milder than in the placebo group . Nonmenstrual pelvic pain was present at baseline in 24.5 % ( 12 of 49 ) of the OCP group and 34.0 % ( 16 of 47 ) of the placebo group . The volume of endometrioma ( larger than 3 cm in diameter ) was significantly decreased in the OCP group , but not in the placebo group . No serious adverse events related to using OCPs occurred . CONCLUSION ( S ) The present study clearly demonstrated for the first time that OCPs could be used to effectively and safely treat pain associated with endometriosis OBJECTIVE To explore the effectiveness and safety of laparoscopic presacral neurectomy ( LPN ) in treating endometriosis-associated pain . METHODS Totally 64 patients with endometriosis were divided into two groups using prospect i ve non-r and om method . Patients in the control group received only the conventional laparoscopic resection of endometriosis lesions , while patients in the LPN group underwent LPN in addition to the resection of endometriosis lesions . The pre-operative pain scores , intra-operative staging results , surgical duration , intra-surgical blood loss , post-operative pain relief were compared between these two groups . RESULTS These two groups showed no significant differences in terms of age , body weight , pre-operative pain score , surgery staging , surgical duration , and intra-operative blood loss ( all P > 0.05 ) . All patients were followed up for 6 to 18 months ( median : 12.8 months ) . The post-operative pain relief rate was 89.28 % ( 25/ 28 ) in LPN group and 61.29 % ( 19/31 ) in the control group ( P = 0.030 ) . CONCLUSION LPN can effectively and safely in treating endometriosis and its associated pain OBJECTIVE To project the efficacy and economic consequence of short-term intranasal gonadotropin-releasing hormone agonist ( GnRH-a ) for diagnosis of and therapy for endometriosis . STUDY DESIGN Multicenter , placebo-controlled clinical trials of GnRH-a comparing three vs. six months of treatment , three months of retreatment and three months of postoperative treatment for the symptoms and signs of laparoscopically diagnosed endometriosis . RESULTS The reduction in symptoms and signs of endometriosis was similar at the end of three months to the relief at six months . Retreatment was as effective as initial treatment , and the return of symptoms after laparoscopic surgery plus postoperative treatment for three months was delayed by approximately 18 months as compared to surgery alone . The projected charges for the surgical approaches ( laparoscopy or minilaparoscopy ) to diagnosis and therapy were 50 - 60 % greater than those for the medical approach . CONCLUSION GnRH-a administration for three months could be a cost-effective approach to the presumptive diagnosis and treatment of endometriosis among women with chronic pelvic pain OBJECTIVE To evaluate whether persistence of pelvic pain after excision of endometriosis was associated with adenomyosis as defined by a thickened uterine junctional zone ( JZ ) on magnetic resonance ( MR ) imaging . DESIGN Prospect i ve clinical trial . SETTING Government research hospital . PATIENT(S ) Fifty-three women with chronic pelvic pain . INTERVENTION(S ) Preoperative MR imaging to measure uterine JZ thickness , surgical excision , and pathologic diagnosis of endometriosis . Those with biopsy-proven endometriosis were r and omized to raloxifene or placebo .  Visual analog scale ( VAS ) was used to rate dysmenorrhea and nonmenstrual pain severity before surgery and 3 months later . MAIN OUTCOME MEASURE(S ) Comparison of JZ thickness and pain severity before and 3 months after surgery in women with endometriosis controlling for medical treatment . RESULT ( S ) Forty of the 53 patients had biopsy-proven endometriosis , and 6 of these 40 women with endometriosis had a thickened JZ . Overall , dysmenorrhea at 3 months was positively correlated with preoperative JZ thickness ( r = 0.47 , P=.01 ) . Dysmenorrhea pain severity showed no significant decrease in those patients whose JZ measured > or=11 mm compared with those with JZ < 8 mm ( P<.0001 ; VAS decreased 4.3 + /- 0.6 ) , or > or=8 and < 11 mm ( P<.02 ; VAS decreased 4.8 + /- 1.3 ) . Nonmenstrual pain severity was correlated with JZ thickness ( r = 0.51 , P=.004 ) at 3 months with a significant decrease in nonmenstrual pain only in women with a JZ < 8 mm ( VAS decreased 4.0 + /- 0.7 , P<.0001 ) . The association between dysmenorrhea and nonmenstrual pain reduction and thinner JZ remained after controlling for medical treatment . CONCLUSION ( S ) Following surgical excision of endometriosis , chronic pelvic pain was significantly more likely to persist with JZ thickness > 11 mm on preoperative MR imaging . This suggests that myometrial JZ abnormalities or adenomyosis may contribute to chronic pelvic pain in women with endometriosis Serum concentrations of CA-125 were determined in association with 6-month medical ( n = 48 ) or surgical and medical therapy ( n = 40 ) of endometriosis . The concentration of CA-125 was significantly higher in stages III + IV ( 66.6 + /- 22.0 [ st and ard deviation ] U/ml ) than in stage I ( 20.9 + /- 2.3 U/ml ) or II ( 28.4 + /- 2.8 U/ml ) ; in stage II , the concentration was higher than in stage I. Surgical elimination of endometriosis significantly decreased the level of CA-125 , as did danazol , but not medroxyprogesterone acetate ( MPA ) , although these drugs were equal in clinical efficacy . The CA-125 changes during hormonal treatment did not correlate with the clinical response . Postoperatively , CA-125 responses to danazol , MPA , or placebo did not differ significantly from each other . During the 6-month follow-up after medication , the CA-125 concentrations tended to increase , especially in danazol-treated women . The determination of CA-125 is useful in estimating the extent of the disease , but it is less valuable in monitoring the treatment effect . The ability of danazol to suppress CA-125 expression emphasizes the specific properties of this drug Objective To ascertain whether the frequency of pelvic pain recurrence is reduced and time to symptoms recurrence is prolonged in women with symptomatic endometriosis undergoing conservative surgery and post‐operative hormonal therapy  compared with women treated with  surgery  only . Pregnancy rates and time to conception in women wanting children were also evaluated OBJECTIVE To compare the efficacy of leuprolide and continuous oral contraceptives in the treatment of endometriosis-associated pain . DESIGN Prospect i ve , r and omized , double-blind controlled trial . SETTING Academic medical centers in Rochester , New York , and Boston , Massachusetts . PATIENT(S ) Forty-seven women with endometriosis-associated pelvic pain . INTERVENTION(S ) Forty-eight weeks of either depot leuprolide , 11.25 mg IM every 12 weeks with hormonal add-back using norethindrone acetate 5 mg orally , daily ; or a generic monophasic oral contraceptive ( 1 mg norethindrone + 35 mg ethinyl estradiol ) given daily . MAIN OUTCOME MEASURE(S ) Biberoglu and Behrman ( B&B ) pain scores , numerical rating scores ( NRS ) , Beck Depression Inventory ( BDI ) , and Index of Sexual Satisfaction ( ISS ) . RESULT ( S ) Based on enrollment of 47 women r and omized to continuous oral contraceptives and to leuprolide , there were statistically significant declines in B&B , NRS , and BDI scores from baseline in both groups . There were no significant differences , however , in the extent of reduction in these measures between the groups . CONCLUSION ( S ) Leuprolide and continuous oral contraceptives appear to be equally effective in the treatment of endometriosis-associated pelvic pain OBJECTIVE To evaluate the efficacy and safety of a cyclooxygenase (COX)-2 specific inhibitors versus placebo in the treatment of endometriosis-associated pelvic pain . STUDY DESIGN A group of women ( n = 28 ) with pelvic pain after conservative surgery for symptomatic endometriosis ( Stage I and II ) were enrolled at the Department of Pediatric , Obstetrics and Reproductive Medicine of University of Siena . A treatment with a COX-2 specific inhibitors ( rofecoxib , 25 mg per day ) ( n = 16 ) or placebo ( n = 12 ) was given for 6 months . Pelvic pain quantification with a clinical evaluation , including Visual Analogue Scale ( VAS ) for pain , was performed before and up to 6 months after treatment . RESULTS A significant improvement of both pelvic pain and dyspareunia was observed after a 6 months persisting since the end of the treatment ( P < 0.0001 ) . The efficacy of rofecoxib was higher than placebo and no recurrence occurred , while in the placebo-treatment a 16 % ( 2/12 ) occurred . No significant side effects have been found with the use of rofecoxib . CONCLUSIONS The use of COX-2 specific inhibitors was effective , safe and low cost therapy in the management of pelvic pain associated to endometriosis and might be also proposed in early stage of endometriosis Objectives : To determine if low-dose estrogen replacement can be added to GnRH agonist therapy after three months to reduce hypoestrogenic symptoms while allowing continued relief of pain in patients with endometriosis . Material s and Methods : Thirteen women with endometriosis and pain were treated with six months of leuprolide acetate in a prospect i ve , r and omized double-blind placebo controlled study . After three months of therapy , six subjects initiated oral estradiol 1 mg daily , and seven received an identical placebo . Results : Dysmenorrhea improved in both groups , and dyspareunia significantly improved in the GnRH agonist plus placebo group . The mean pain scores of the oral estrogen group tended to be higher than the placebo group , and hot flushes tended to be less severe with estrogen treatment . However , differences observed between the study and placebo groups did not reach statistical significance . Conclusion : In a prospect i ve , r and omized study , low-dose estrogen replacement increases endometriosis-related pain during GnRH agonist therapy . The study was terminated after the first 13 subjects due to the concerning trend toward recurrent symptoms in women who received oral estradiol during GnRH agonist therapy for endometriosis-related pain . With the trend toward increasing pain with estrogen add-back therapy , a larger study would not seem to be justifiable BACKGROUND The objective of this multicentre r and omized , controlled clinical trial was to compare the efficacy of a levonorgestrel-releasing intrauterine system ( LNG-IUS ) and a depot-GnRH-analogue in the control of endometriosis-related pain over a period of six months . METHODS Eighty-two women , 18 to 40 years of age ( mean 30 years ) , with endometriosis , dysmenorrhoea and /or CPP , were r and omized using a computer-generated system of sealed envelopes into either LNG-IUS ( n = 39 ) or GnRH analogue ( n = 43 ) treatment groups at three university centres . Daily scores of endometriosis-associated CPP were evaluated using the Visual Analogue Scale ( VAS ) , daily bleeding score was calculated from bleeding calendars , and improvement in quality of life was evaluated using the Psychological General Well-Being Index Question naire ( PGWBI ) . The pain score diary was based on the VAS in which women recorded the occurrence and intensity of pain on a daily basis . A monthly score was calculated from the result of the sum of the daily scores divided by the number of days in each observation period . RESULTS CPP decreased significantly from the first month throughout the six months of therapy with both forms of treatment and there was no difference between the groups ( P > 0.999 ) . In both treatment groups , women with stage III and IV endometriosis showed a more rapid improvement in the VAS pain score than women with stage I and II of the disease ( P < 0.002 ) . LNG-IUS users had a higher bleeding score than GnRH-analogue users at all time points of observation with 34 % and 71 % of patients in the LNG-IUS and GnRH-analogue groups , respectively , reporting no bleeding during the first treatment month , and 70 % and 98 % reporting no bleeding during the sixth month . No difference was observed between groups with reference to improvement in quality of life . CONCLUSIONS Both , the LNG-IUS and the GnRH-analogue were effective in the treatment of CPP-associated endometriosis , although no differences were observed between the two treatments . Among the additional advantages of the LNG-IUS is the fact that it does not provoke hypoestrogenism and that it requires only one medical intervention for its introduction every 5 years . This device could therefore become the treatment of choice for CPP-associated endometriosis in women who do not wish to conceive Objective . Limited attention has been focused on the medical treatment of bowel endometriosis . This study evaluates the efficacy of administration of a continuous low‐dose oral contraceptive in treating pain and other symptoms associated with colorectal endometriotic nodules , as evaluated by rectal endoscopic ultrasonography . Design . Prospect i ve observational study . Setting . Academic Department of San Raffaele Scientific Institute , Obstetrics and Gynecology Unit . Population . Symptomatic women of reproductive age ( n=26 ) with colorectal nodules infiltrating at least the bowel muscularis propria and without a stenosis > 50 % . In 31 % of the patients , endoscopic ultrasonography permitted diagnosis of nodules located more than 10 cm from the anal rim . Methods . Patients received a continuous low‐dose oral contraceptive containing 15 μg ethinylestradiol and 60 μg gestodene for 12 months . Subjective symptoms were prospect ively evaluated , and nodule volumes were monitored using endoscopic ultrasonography . Main outcome measures . Nodule measurements were performed at baseline and after 12 months of treatment . Symptoms at the start and after 12 months were evaluated . Results . A significant improvement in the intensity of all the considered symptoms ( dysmenorrhea , non‐menstrual pelvic pain , deep dyspareunia and painful defecation ) was seen when evaluated by a visual analog scale . A reduction in terms of both diameter ( mean reduction 26 % ) and volume of the nodules ( mean reduction 62 % ) was observed after a 12 month period . Conclusions . A continuous low‐dose oral contraceptive therapy may reduce bowel endometriosis‐associated symptoms . In addition , this therapy induces a significant volumetric reduction of colorectal plaques when evaluated by endoscopic ultrasonography OBJECTIVES To determine the effectiveness of a 3-month course of nafarelin and , furthermore , to determine the long-term efficacy in patients treated for 3 and 6 months with nafarelin for symptoms associated with endometriosis . DESIGN Double-blind , prospect i ve , multicenter , clinical trial . SETTING Fifteen reproductive endocrine clinics throughout the United States . PATIENTS One hundred seventy-nine women with pelvic pain and endometriosis . INTERVENTIONS Patients were assigned r and omly to 3 months nafarelin followed by 3 months of placebo ( n = 91 ) or to 6 months nafarelin ( n = 88 ) in a prospect i ve , r and omized , double-blind multicenter trial . Patients were followed for 12 months after cessation of therapy . MAIN OUTCOME MEASURES Patient-reported pain scores and physician-reported physical exam findings . RESULTS Pain scores dropped significantly by the end of treatment in both groups . Symptoms recurred in both groups , and pain scores gradually increased during the follow-up period but always remained below baseline in both groups . No significant difference in efficacy was noted between the groups . A total of 26 % of patients in each group underwent retreatment for recurrent symptoms . CONCLUSIONS A 3-month course of nafarelin provided effective symptom relief for endometriosis . One year follow-up demonstrated continued pain relief but with gradual return of symptoms OBJECTIVE : To evaluate whether 6 months of raloxifene was effective in treatment of  chronic pelvic pain in women with endometriosis . METHODS : Women with chronic pelvic pain and no endometriosis treatment for 6 months underwent laparoscopy for excision of all lesions . Those with biopsy-proven endometriosis were r and omly allocated to raloxifene ( 180 mg ) or placebo daily . A second laparoscopy was performed at 2 years , or earlier , if pain returned . Return of pain was defined as 2 months of pain equal to or more severe than that at study entry . Menstrual cycles and adverse events were recorded . The log rank test was used to compare the time to return of pain by drug group . Analyses were done as intent-to-treat . RESULTS : A total of 127 of 158 women underwent surgery . Of these , 93 had biopsy-confirmed endometriosis and were r and omly assigned to study treatment . Menstrual cycle length , pelvic pain severity , quality of life , bone mineral density , and adverse events did not differ between treatment groups . The Data Safety Monitoring Committee terminated the study early when the raloxifene group experienced pain ( P=.03 ) and had second surgery ( P=.016 ) significantly sooner than the placebo group . Interestingly , biopsy-proven endometriosis was not associated with return of pain ( P=.6 ) . CONCLUSION : Raloxifene significantly shortened the time to return of chronic pelvic pain . Because recurrence of endometriosis lesions did not correlate with return of pain , other factors are implicated in pelvic pain . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www.cliicaltrials.gov , NCT00001848 LEVEL OF EVIDENCE : STUDY OBJECTIVE To evaluate the relationship between prevalence and severity of  chronic pelvic pain ( CPP ) and stage , site , and type of endometriosis . DESIGN Prospect i ve , observational study ( Canadian Task Force classification II-2 ) . SETTING University Hospital . PATIENTS Of 90 consecutive women with biopsy-proved endometriosis , laparoscopy was performed in 69 for pelvic pain and in 21 for infertility or clinical and ultrasonographic suspicion of ovarian endometriosis . INTERVENTION Preoperatively , using a 10-point visual analog scale , the severity of dysmenorrhea , CPP , and deep dyspareunia was assessed . During laparoscopy all visible endometriotic lesions were recorded and treated . MEASUREMENTS AND MAIN RESULTS Ten women ( 11.1 % ) had no pain ; 72 had dysmenorrhea ( mild in 13 , moderate in 37 , severe in 22 ) ; 55 had CPP ( mild in 11 , moderate in 25 , severe in 19 ) ; and 39 deep dyspareunia ( mild in 5 , moderate in 31 , severe in 3 ) . The severity of dysmenorrhea significantly correlated with the presence and extent of pelvic adhesions ( p = 0.004 ) ; the severity of CPP correlated with deep endometriosis on the uterosacral ligaments ( p = 0.0001 ) and extent of pelvic adhesions ( p = 0.02 ) ; and deep dyspareunia correlated with deep endometriosis on the uterosacral ligaments ( p = 0.04 ) . Total pain score significantly correlated with deep endometriosis on the uterosacral ligaments ( p = 0.0001 ) , peritoneal adhesions ( p = 0.01 ) , and extent of adnexal adhesions ( p = 0.01 ) . No significant correlation was found among revised American Fertility Society stage of endometriosis ; presence and size of ovarian endometriomas ; extent , type , and site of peritoneal lesions ; and pain scores . By logistic regression analysis , the presence and intensity of total pain could be predicted simultaneously by the presence of deep endometriosis ( p = 0.0001 ) and presence and extent of adnexal adhesions without cystic endometriosis ( p = 0.01 ) , and by the presence of ovarian endometrioma with periovarian adhesions ( p = 0.03 ) . Chronic pelvic pain was predicted by both deep endometriosis ( p = 0.0001 ) and ovarian endometriomas with adnexal adhesions ( p = 0.03 ) . Deep dyspareunia was predicted simultaneously by deep endometriosis ( p = 0.01 ) and an ovarian endometrioma with periovarian adhesions ( p = 0 . 008 ) . Conclusion . Deep endometriosis , pelvic adhesions , and ovarian cystic endometriosis were independent predictors of pelvic pain . These data strongly suggest that it is not the size of ovarian cystic endometriosis but the association with adhesions that causes pelvic pain STUDY OBJECTIVE To evaluate 3 therapy strategies : hormone therapy , surgery , and combined treatment . DESIGN Prospect i ve , r and omized , controlled study ( Canadian Task Force classification I ) . SETTING University-based teaching hospital . PATIENTS Four hundred fifty patients with genital endometriosis , aged 18 to 44 years , before first laparoscopy . INTERVENTIONS Patients were r and omly assigned to 1 of 3 treatment groups : hormone therapy , surgery , or combined treatment . Patients were reevaluated at second-look laparoscopy , at 2 to 2 months after 3-month hormone therapy in groups 1 and 3 and at 5 to 6 months in group 2 ( surgical treatment alone ) . Outcome data were focussed on the endometriosis stage , recurrence of symptoms , and pregnancy rate . MEASUREMENTS AND MAIN RESULTS All treatment options , independent of the initial Endoscopic Endometriosis Classification stage , achieved an overall cure rate of ≥50 % . A cure rate of 60 % was achieved with the combined treatment , 55 % with exclusively hormone therapy , and 50 % with exclusively surgical treatment . Recurrence of symptoms was lowest in patients who received combined treatment . Significant benefit was achieved for dysmenorrhea and dyspareunia . An overall pregnancy rate of 55 % to 65 % was achieved , with no significant difference between the therapeutic options . CONCLUSION In the quest to find the most effective treatment of genital endometriosis , this clinical r and omized study shows the lowest incidence of recurrence with combined surgical and medical treatment and improved pregnancy rate in any medically treated patients with or without surgery . The highest cure rate ( Endoscopic Endometriosis Classification stage 0 ) for endometriosis was also achieved in the combined treatment group Endometriosis is a pain syndrome representing a major cause of pelvic pain in women of reproductive age . The aim of this study was to test the hypothesis that persistent nociceptive input from endometriotic tissues leads to central sensitization manifested by somatic hyperalgesia and increased referred pain areas to experimental saline-induced muscle pain in patients with endometriosis , compared to healthy control subjects . Ten women with laparoscopically confirmed endometriosis and 10 healthy , age-matched women participated in the study .  Hypertonic saline ( 0.5 mL , 5.8 % ) was injected intramuscularly , in r and om succession , into 1 site of menstrual pain referral ( the multifidus muscle at the low back ) and into 1 non-pain control site ( first dorsal interosseous muscle [ FDI ] of the h and ) . The post-saline pain intensity and pain areas at the FDI were significantly greater in patients with endometriosis than in control subjects ( P < .05 ) but were not different between the groups for the back . An absence of enhancement of post-saline pain responses at the back in the endometriosis group suggests that saline-induced pain at the back appears to activate segmental inhibitory systems in patients with endometriosis . Manifestation of central sensitization in women with endometriosis is demonstrated by increased muscle nociceptor input in the form of increased post-saline pain intensity , pain areas at the FDI , and hypersensitivity to pressure stimulation . These findings provide new insights into the complex pain mechanisms associated with endometriosis OBJECTIVE We sought to describe the pattern of  age at menopause  and factors associated with type of menopause . STUDY DESIGN This was a prospect i ve cohort study of 5113 postmenopausal health survey respondents in the Royal College of General Practitioners ' Oral Contraception Study .  Logistic regression was used to evaluate associations between sociodemographics , lifestyle , and medical history and menopause type . RESULTS Median age at natural menopause ( n = 3650 ) was 49.0 years ( interquartile range , 45.0 - 51.0 ) , and at surgical menopause ( n = 1463 ) was 42.4 years ( 38.0 - 46.4 ) . Early natural menopause was associated with smoking , ever-use of oral contraception , sterilization , and history of endometriosis ( all increased odds ratios ) and ever-use of hormone replacement therapy ( decreased ) . Surgical menopause was associated with manual social class , sterilization , and having a history of endometriosis , menorrhagia , or painful menstruation ( all increased ) , and ever-use of hormone replacement therapy ( decreased ) . CONCLUSION Age at natural menopause was younger in this cohort than in other studies . More associations were found for surgical menopause than early natural menopause OBJECTIVES To evaluate the efficacy and safety of very low dose danazol in improving pelvic pain in women with endometriosis , the benefit of preceding the treatment by a short course of a GnRH agonist , symptoms recurrence after drug withdrawal , and variations in menstrual pattern . DESIGN Open-label , r and omized study . SETTING University hospital endometriosis center . PATIENTS Forty-two women with moderate or severe pelvic pain and laparoscopically diagnosed endometriosis . INTERVENTIONS Treatment with oral danazol , 50 mg/d , for 9 months ( group I , n = 21 ) or leuprolide depot for 3 months followed by oral danazol , 50 mg/d , for 6 months ( group II , n = 21 ) , and a 6-month follow-up . MAIN OUTCOME MEASURES Variations in severity of symptoms during treatment and at the end of follow-up as shown by a linear analog scale and a verbal rating scale ; menstrual blood loss as assessed by a pictorial chart . RESULTS Four patients withdrew from the study , one in each group at the fifth month of treatment ( for persistent pain ) and one in each group during follow-up ( they requested additional therapy ) ; one woman in group I was lost to follow-up . Significant improvements were obtained in dysmenorrhea , deep dyspareunia , and nonmenstrual pain in both treatment schedules without differences between the groups . Also menstrual blood loss was significantly reduced in both groups . A temporary fall in high and rise in low density lipoprotein cholesterol was observed in the study population . At the end of follow-up symptoms recurred without significant differences in median pain scores with respect to baseline . CONCLUSION Very low dose danazol may be an alternative for temporary relief of endometriosis-associated pain . Ovulation is not always inhibited and barrier contraception is needed . Side effects occur but are rarely severe . Further data are required to evaluate the influence of long-term administration on the lipid profile We previously suggested that women with endometriosis have increased oxidative stress in the peritoneal cavity . To assess whether antioxidant supplementation would ameliorate endometriosis-associated symptoms , we performed a r and omized , placebo-controlled trial of antioxidant vitamins ( vitamins E and C ) in women with pelvic pain and endometriosis . Fifty-nine women , ages 19 to 41 years , with pelvic pain and history of endometriosis or infertility were recruited for this study . Patients were r and omly assigned to 2 groups : vitamin E ( 1200 IU ) and vitamin C ( 1000 mg ) combination or placebo daily for 8 weeks before surgery . Pain scales were administered at baseline and biweekly . Inflammatory markers were measured in the peritoneal fluid obtained from both groups of patients at the end of therapy . Our results indicated that after treatment with antioxidants , chronic pain ( " everyday pain " ) improved in 43 % of patients in the antioxidant treatment group ( P = 0.0055 ) compared with the placebo group . In the same group , dysmenorrhea ( " pain associated with menstruation " ) and dyspareunia ( " pain with sex " ) decreased in 37 % and 24 % patients , respectively . In the placebo group , dysmenorrhea-associated pain decreased in 4 patients and no change was seen in chronic pain or dyspareunia . There was a significant decrease in peritoneal fluid inflammatory markers , regulated upon activation , normal T-cell expressed and secreted ( P ≤ 0.002 ) , interleukin-6 ( P ≤ 0.056 ) , and monocyte chemotactic protein-1 ( P ≤ 0.016 ) after antioxidant therapy compared with patients not taking antioxidants . The results of this clinical trial show that administration of antioxidants reduces chronic pelvic pain in women with endometriosis and inflammatory markers in the peritoneal fluid OBJECTIVE To examine whether long-term administration of dienogest following gonadotropin-releasing hormone agonist ( GnRH-a ) therapy would prolong the relief of pelvic pain while reducing the amount of irregular uterine bleeding . STUDY DESIGN This was a prospect i ve , non-r and omized clinical trial . Among the patients suffering from chronic pelvic pain associated with recurrent endometriosis , Group G ( n=38 ) received GnRH-a for 4 - 6 months and then dienogest ( 1 mg/day ) for 12 months . The dose of dienogest was increased to 1.5 or 2 mg/day when a patient had uncontrollable uterine bleeding { n=15 (39%)}. Group D ( n=33 ) received only dienogest ( 2 mg/day ) for 12 months . Pelvic pain was assessed using a visual analog scale ( VAS ) . Uterine bleeding was semi-quantified using a pictorial blood loss assessment chart ( PBAC ) . RESULTS In Group G , GnRH-a significantly reduced the VAS score for pelvic pain , and alleviation was maintained during the 12-month therapy with dienogest . There was no significant difference in pain reduction between Group G and Group D. The PBAC score during the first 6 months on dienogest was significantly smaller in Group G than in Group D. CONCLUSION Treatment with a GnRH-a followed by long-term dienogest therapy maintains the relief of endometriosis-associated pelvic pain achieved with GnRH-a therapy for at least 12 months . This regimen reduces the amount of irregular uterine bleeding that often occurs during the early phase of dienogest therapy OBJECTIVE To examine the prevalence of migraine in women with chronic pelvic pain with and without endometriosis . DESIGN Prospect i ve study of headache , pelvic pain , and quality of life before laparoscopic surgery for pelvic pain . Endometriosis was diagnosed pathologically . Headaches were classified as migraine or non-migraine using International Headache Society criteria . SETTING Clinical research hospital . PATIENT(S ) 108 women in a clinical trial for chronic pelvic pain ( NCT00001848 ) . INTERVENTION(S ) Laparoscopy to diagnose endometriosis , assessment by neurologist to assess headaches . MAIN OUTCOME MEASURE(S ) Prevalence of migraine and other headaches in women with chronic pelvic pain with or without endometriosis . Headache frequency , severity and relationship to pelvic pain and endometriosis . RESULT ( S ) Lifetime prevalence of definite or possible migraine was 67 % of women with chronic pelvic pain . An additional 8 % met criteria for possible migraine . Migraine was no more likely in women with endometriosis than those without . Women with the most severe headaches had a lower quality of life compared with those with pelvic pain alone . CONCLUSION ( S ) Migraine headache is common in women with chronic pelvic pain , regardless of endometriosis , and contributes to disability in those with both conditions . The strong association suggests a common pathophysiology OBJECTIVE To evaluate the efficacy and safety of cyproterone acetate versus an oral contraceptive in the treatment of endometriosis-associated recurrent pelvic pain . DESIGN R and omized controlled trial . SETTING Academic center . PATIENT(S ) Ninety women with recurrent moderate or severe pelvic pain after conservative surgery for symptomatic endometriosis . INTERVENTION(S ) Six months of continuous treatment with oral cyproterone acetate , 12.5 mg/d , or an oral contraceptive containing ethinyl estradiol , 0.02 mg , and desogestrel , 0.15 mg . MAIN OUTCOME MEASURE(S ) Degree of satisfaction with therapy . RESULT ( S ) Six patients in the cyproterone acetate arm and nine in the oral contraceptive arm withdrew because of side effects ( n = 9 ) , treatment inefficacy ( n = 4 ) , or loss to follow-up ( n = 2 ) . At 6 months , dysmenorrhea , deep dyspareunia , and nonmenstrual pelvic pain scores were substantially reduced , and significant improvements were observed in health-related quality -of-life , psychiatric profile , and sexual satisfaction ; no major between-group differences were seen . Subjective and metabolic side effects were limited . According to an intention-to-treat analysis , 33 of 45 ( 73 % ) of patients in the cyproterone acetate group and 30 of 45 ( 67 % ) in the oral contraceptive group were satisfied with the treatment received . CONCLUSIONS Both cyproterone acetate and a continuous monophasic oral contraceptive were effective , safe , and inexpensive therapy for recurrent pain after conservative surgery for endometriosis OBJECTIVE Our purpose was to evaluate the efficacy and safety of depot medroxyprogesterone acetate versus an oral contraceptive combined with very-low-dose danazol in the long-term treatment of pelvic pain in women with endometriosis . STUDY DESIGN Eighty patients with endometriosis and moderate or severe pelvic pain were r and omized to treatment for 1 year with intramuscular depot medroxyprogesterone acetate 150 mg every 3 months or a cyclic monophasic oral contraceptive ( ethinyl estradiol 0.02 mg , desogestrel 0.15 mg ) combined with oral danazol 50 mg a day for 21 days of each 28-day cycle . The women were asked to grade the degree of their satisfaction at the end of therapy . Variations in severity of symptoms during treatment were determined by a 10 cm visual analog and a 0- to 3-point verbal rating scale . RESULTS Twenty nine of 40 subjects ( 72.5 % ) in the depot medroxyprogesterone acetate group were satisfied after 1 year of therapy compared with 23 of 40 ( 57.5 % ) in the oral contraceptive plus danazol group ( chi 2(1 ) = 1.37 , p = 0.24 , odds ratio 1.95 , 95 % confidence interval 0.76 to 4.97 ) . A significant decrease was observed in all symptom scores in both study groups . At 1-year assessment dysmenorrhea was significantly greater in women allocated to oral contraceptive plus danazol . CONCLUSION Depot medroxyprogesterone acetate seems to be an effective , safe , and convenient low-cost treatment for pelvic pain associated with endometriosis . However , women should be carefully counseled regarding menstrual changes and the potential prolonged delay in the return of ovulation OBJECTIVE To examine the safety and efficacy of combining cyclic sodium etidronate and low-dose norethindrone with a long-acting GnRH agonist ( GnRH-a ) for prolonged therapy of symptomatic endometriosis . DESIGN Prospect i ve r and omized open label study . SETTING Tertiary care university-affiliated reproductive medicine program . PATIENTS Nineteen regularly cycling women with laparoscopically diagnosed symptomatic endometriosis and 18 regularly cycling untreated controls without endometriosis . INTERVENTIONS All patients received a depot preparation of the GnRH-a leuprolide acetate IM monthly for 48 weeks . Group I patients ( n = 10 ) received supplemental sodium etidronate cycled with calcium carbonate as well as 2.5 mg norethindrone daily . Group II patients ( n = 9 ) received only supplemental 10 mg norethindrone daily . Group III volunteers ( n = 18 ) were untreated and followed for bone density changes . MAIN OUTCOME MEASURES Disease extent at follow-up laparoscopy ; pain , vasomotor , and vaginal symptom scores ; bone mineral density ( serial dual-energy roentgenogram absorptiometry scans ) ; serum estrogens , lipids , and glucose and insulin response to glucose challenge . RESULTS Painful symptoms and extent of endometriosis were reduced in both treatment groups . Despite maintenance of a chronically hypoestrogenic state for 48 weeks , no changes in bone density over time or in comparison to group III untreated controls were noted . Similarly , no evidence of significant vasomotor symptoms were reported in either treatment group . However , adverse changes over time in circulating low-density lipoprotein ( LDL ) cholesterol and apolipoprotein A1 levels as well as the ratio of high-density lipoprotein to LDL were noted only in group II . CONCLUSIONS The combination of cyclic sodium etidronate and low-dose norethindrone with a long-acting GnRH-a served to safely prolong medical therapy of symptomatic endometriosis . Clinical efficacy was preserved while prophylaxis against significant hypoestrogenic side effects was achieved OBJECTIVE To evaluate and compare the safety and efficacy of leuprolide versus placebo in managing chronic pelvic pain in women with clinical ly suspected endometriosis . METHODS Women 18 - 45 years of age with moderate to severe pelvic pain of at least 6 months ' duration underwent extensive , noninvasive diagnostic testing and laboratory evaluation , including pelvic ultrasound , complete blood count , determination of erythrocyte sedimentation rate , and endocervical cultures . Those with clinical ly suspected endometriosis were r and omized to double-blind treatment for 3 months with depot leuprolide ( 3.75 mg/mo ) or placebo . The accuracy of the clinical diagnosis of endometriosis was evaluated by posttreatment laparoscopy . RESULTS Of 100 women r and omized , 95 completed the study : 49 in the leuprolide group and 46 in the placebo group . Women in the leuprolide group had clinical ly and statistically significant ( P < or = .001 ) mean improvements from baseline after 12 weeks of therapy in all pain measures . These mean improvements were significantly greater ( P < or = .001 ) than those in the placebo group . At 12 weeks , mean decreases in physician-rated scores for dysmenorrhea , pelvic pain , and pelvic tenderness were 1.7 , 1.0 , and 0.8 points greater , respectively , in the leuprolide group than in the placebo group ( on a four-point scale ) . Thirty-eight ( 78 % ) of 49 and 40 ( 87 % ) of 46 patients in the leuprolide and placebo groups , respectively , had laparoscopically confirmed endometriosis after 12 weeks of treatment . No women withdrew from the study because of adverse events . CONCLUSION Depot leuprolide was effective and safe for treating patients with chronic pelvic pain and clinical ly suspected endometriosis , confirming the potential of its empiric use in these patients 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 prospect i ve 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 OBJECTIVE We aim ed to assess the efficacy of depot leuprolide versus danazol in the treatment of endometriosis . STUDY DESIGN A double-blind r and omized trial of 270 patients from 22 centers compared the pretreatment and posttreatment laparoscopic extent of endometriosis . Pretreatment and posttreatment endometriosis symptoms and signs were assessed with st and ardized methods . RESULTS When compared with danazol , leuprolide depot caused a more rapid and profound suppression of estradiol .  Leuprolide depot and danazol were similarly efficacious in decreasing the extent of endometriosis , as well as the pain and tenderness associated with endometriosis . CONCLUSION Depot leuprolide is an effective alternative to danazol in decreasing the extent of endometriosis and endometriosis-related pain STUDY OBJECTIVE To assess the efficacy of 13CO2 laser laparoscopy in treating infertile women with minimal to mild endometriosis according the American Fertility Society classification in terms of pregnancy rates . DESIGN Prospect i ve study . SETTING Medical school-affiliated hospital . PATIENTS One hundred seventy-six women whose infertility was associated with minimal or mild endometriosis diagnosed by laparoscopy . INTERVENTIONS The patients were treated with one of four methods : 49 underwent operative laparoscopy with newly developed 13CO2 laser vaporization and /or resection ; 45 were treated by operative laparoscopy with simple monopolar electrocoagulation ; 43 who had undergone only diagnostic laparoscopy did not receive any treatment ; and 39 received danazol 800 mg/day for 3 months after diagnostic laparoscopy . MEASUREMENTS AND MAIN RESULTS Estimated cumulative pregnancy rates using life table analyses were indicators of treatment of success and compared among the treatments . A subgroup of 111 patients considered to have endometriosis as the only major infertility factor were also evaluated and compared among treatment options . Pregnancy rates in the CO2 laser laparoscopy group were significantly higher than in the other three groups and in endometriosis-only subset . CONCLUSIONS Advanced laparoscopic surgery with the CO2 laser can be more efficient than other modalities in treating infertile women with minimal to mild endometriosis in terms of pregnancy rates . It appears that in experienced h and s , laser laparoscopy has more favorable results than the other treatments OBJECTIVE To assess the effect of a new progestin progestogen only pill ( desogestrel ) versus an oral contraceptive in the treatment of recurrent endometriosis . STUDY DESIGN A r and omized prospect i ve clinical study . A group of women with endometriosis ( n=40 ) who showed recurrent dysmenorrhea and /or pelvic pain after conservative surgery , and did not desire a pregnancy . Continuous treatment for 6 months with desogestrel ( 75 microg/d ) ( n=20 ) versus a combined oral contraceptive ( ethinyl estradiol 20 microg plus desogestrel 150 microg ) ( n=20 ) was performed . RESULTS A significant improvement of both pelvic pain and dysmenorrhea was observed following each type of treatment ( P<0.001 ) . The use of desogestrel progestogen only pill was associated with a breakthrough bleeding in 20 % patients , while a significant body weight increase was observed in 15 % after oral contraceptive . CONCLUSIONS Both desogestrel and an oral estro-progestinic were effective , safe and low cost therapy of pain symptoms after endoscopic surgery for endometriosis , the former showing an impact on breakthrough bleeding , the later an incidence on body weight increase A prospect i ve study to evaluate the efficacy of danazol in the treatment of endometriosis was initiated in 1976 . One hundred patients with endometriosis , as demonstrated by laparoscopy , were entered into the study . The mean length of patient follow-up was 49 months . All patients were treated with 800 mg of danazol per day . The mean duration of danazol therapy was 17.3 weeks . Eighty-nine percent of the patients reported symptomatic improvement , and 94 % were improved , as demonstrated by repeat laparoscopy or laparatomy . After completing a course of danazol therapy , 57 % of the patients underwent conservative laparotomy for fertility enhancement , pain control , or ovarian masses . Two patients underwent total abdominal hysterectomy-bilateral salpingo-oophorectomy for advanced disease poorly responsive to danazol therapy . In those patients desiring fertility ( 56 ) , there were 38 pregnancies in 26 women , for an overall fertility rate of 46 % . The overall recurrence rate was 33 % , as determined by symptoms and physical findings . Significant side effects from danazol were reported by 85 % of the patients . The major side effects were weight gain , edema , decrease in breast size , oily skin , hirsutism , and deepening of the voice . Only one patient discontinued danazol therapy due to side effects . Clinical tissues concerning the use of danazol with or without surgery and the miscarriage rate following danazol therapy are discussed OBJECTIVE Aim of our study was to evaluate the effectiveness of the association between N-Palmitoylethanolamine and transpolydatin in the management of  chronic pelvic pain related to EMS . STUDY DESIGN This was a r and omized , double-blind , parallel-group , placebo-controlled clinical trial involving 61 subjects , su bmi tted to a first line laparoscopic conservative surgery , who were r and omized into 3 groups receiving : group A ( n=21 ) the association N-Palmitoylethanolamine-transpolydatin 400 mg + 40 mg twice a day for 3 months ; group B ( n=20 ) the placebo for 3 months ; group C ( n=20 ) a single course of Celecoxib 200 mg twice a day for 7 consecutive days . Assessment s of the severity of pelvic endometriosis ( pelvic pain , dysmenorrhoea and dyspareunia ) were recorded before and after treatment on a question naire and a 10-point VAS . Differences between groups were verified with Kruskal-Wallis ANOVA for non-parametric multiple comparisons . RESULTS A marked decrease in dysmenorrhoea , dyspareunia and pelvic pain was observed in all groups , and the association between N-Palmitoylethanolamine and transpolydatin result ed to be more effective than placebo ( P<.001 ) . Additionally , the treatment with Celecoxib result ed in a decrease in pelvic pain more effective either than the association N-Palmitoylethanolamine and transpolydatin or placebo . CONCLUSION These preliminary results show that the association between micronized N-Palmitoylethanolamine and transpolydatin is effective in the management of pelvic pain related to endometriosis after laparoscopy . Additionally , this association seems to be safe , shows an optimal control of pain and can be used in patients who are unable to receive other therapies BACKGROUND Endometriosis is associated with an inflammatory response . Hence infliximab , an anti-TNF-α monoclonal antibody , might relieve pain . METHODS A r and omized placebo-controlled trial was design ed with 21 women with severe pain and a rectovaginal nodule of at least 1 cm . After 1 month of observation , three infusions of infliximab ( 5 mg/kg ) or placebo were given . Surgery was performed 3 months later and follow-up continued for 6 months . The primary end-point was pain ( dysmenorrhea , deep dyspareunia and non-menstrual pain ) rated at each visit by the clinician and on a daily basis by the patient who in addition scored pain by visual analog pain scale and analgesia intake . Secondary end-points included the volume of the endometriotic nodule , pelvic tenderness and the visual appearance of endometriotic lesions at laparoscopy . RESULTS Pain severity decreased during the treatment by 30 % in both the placebo ( P < 0.001 ) and infliximab groups ( P < 0.001 ) . However , no effect of infliximab was observed for any of the outcome measures . After surgery , pain scores decreased in both groups to less than 20 % of the initial value . CONCLUSIONS Infliximab appears not to affect pain associated with deep endometriosis . Treatment is associated with an important placebo effect . After surgery , pain decreases to less than 20 % . Trials registration number Clinical Trials.gov : NCT00604864 This Phase 2 study evaluated the safety and efficacy of elagolix for treating  endometriosis-associated pain . A total of 155 women with laparoscopically confirmed endometriosis were r and omized to placebo , elagolix 150 mg , or elagolix 250 mg once daily for 12 weeks . Placebo patients were rer and omized to elagolix and elagolix patients continued their dosing assignment for 12 additional weeks ; the primary efficacy measure was changed from baseline in the monthly mean numerical rating scale for pain at week 12 . Monthly mean ( st and ard error of the mean ) reductions were greater with elagolix versus placebo ( −1.19 ± 0.18 , −1.25 ± 0.18 , and −0.88 ± 0.18 for elagolix 150 mg , 250 mg , and placebo , respectively ) ; differences were not statistically significant . Monthly mean dysmenorrhea and nonmenstrual pelvic pain scores were reduced with elagolix , with significant differences for dysmenorrhea at weeks 8 and 12 versus placebo ( P < .05 ) . Minimal bone mineral density changes were observed with elagolix treatment . In women with endometriosis-associated pain  , elagolix demonstrated an acceptable efficacy and safety profile in this Phase 2 study Background and Objectives : The purpose of this study was to assess the long-term efficacy of laparoscopic laser surgery in the treatment of  painful pelvic endometriosis .  Methods : We conducted a long-term follow-up of 56 patients who had participated in a r and omized , double-blind controlled study at a tertiary referral center for the laparoscopic treatment of endometriosis . The patients had pelvic pain , minimal-to-moderate endometriosis , and underwent laser laparoscopy .  We asked patients whether they had now achieved satisfactory symptom relief or whether they had received any further medical intervention for their endometriosis . The main outcome measure was continued symptom relief after treatment and subsequent medical history . Results : Of the original 56 patients , we were able to contact 38 ( 67.9 % ) . The mean ( range ) time since operation was 73 months . Painful symptoms had recurred in 28/38 ( 73.7 % ) patients at some point since their operation . The median ( range ) time for recurrence was 19.7 ( 5 - 60 ) months . At the time of follow-up , satisfactory symptom relief was reported in 21/38 ( 55.3 % ) patients . The remaining 17/38 ( 44.7 % ) patients continued to experience painful symptoms , and eight eventually had a hysterectomy . Conclusions : This study suggests that operative laparoscopy can have long-term benefits for the majority of women with pelvic pain due to endometriosis , but because of the small numbers , this study lacks the power to demonstrate this conclusively OBJECTIVE The purpose of this study was to assess the effectiveness of presacral neurectomy in women with severe dysmenorrhea caused by endometriosis that was treated with conservative surgical intervention . STUDY DESIGN One hundred forty-one sexually active women of fertile age with chronic severe dysmenorrhea caused by endometriosis were treated with conservative laparoscopic surgery . Patients were assigned r and omly to not receive ( group A ) or receive ( group B ) presacral neurectomy . At 6 and 12 months after the surgical procedures , the cure rate was evaluated in each patient . The frequency and severity of dysmenorrhea , dyspareunia , and chronic pelvic pain were also evaluated at the same time intervals . RESULTS The cure rate was significantly higher in group B compared with group A at a follow-up examination at 6 months ( 87.3 % vs 60.3 % ) and 12 months ( 85.7 % vs 57.1 % ) . At follow-up visits , the frequency and severity of dysmenorrhea , dyspareunia , and chronic pelvic pain were significantly lower in both groups compared with baseline values ; in particular , significantly lower values were observed in group B versus group A for the severity . CONCLUSION Presacral neurectomy improves the cure rate in women who are treated with conservative laparoscopic surgery for severe dysmenorrhea caused by endometriosis STUDY QUESTION Does surgical or medical treatment for endometriosis-associated severe deep dyspareunia achieve better results in terms of patients ' satisfaction ( main study outcome ) , variation of coital pain and frequency of intercourse ? SUMMARY ANSWER Surgery and progestin therapy were equally effective in the treatment of deep dyspareunia in women with rectovaginal endometriosis , whereas medical therapy performed significantly better than excisional treatment in those without deeply infiltrating lesions . WHAT IS KNOWN AND WHAT THIS PAPER ADDS Conservative surgery and hormonal therapies have been used independently for endometriosis-associated deep dyspareunia with inconsistent results . This study reports a direct comparison between the two treatment options in women with severe pain during intercourse . DESIGN Patient preference , parallel cohort study with a 12-month follow-up . The effect of conservative surgery at laparoscopy was compared with treatment with a low-dose of norethisterone acetate per os ( 2.5 mg/day ) in women with persistent/recurrent severe deep dyspareunia after first-line surgery . PARTICIPANTS AND SETTING A total of 51 patients chose repeat surgery and 103 progestin treatment .  Patient satisfaction was grade d according to a five-category scale . Variations in pain during intercourse were measured by means of a 100-mm visual analogue scale . MAIN RESULTS AND THE ROLE OF CHANCE In the surgery group , a marked and rapid short-term dyspareunia score reduction was observed , followed by partial recurrence of pain . The pain relief effect of the progestin was more gradual , but progressive throughout the study period . At a 12-month follow-up , the frequency of intercourse per month ( mean ± SD ) was 4.6 ± 1.8 in the surgery group and 5.3 ± 1.5 in the norethisterone acetate group ( P = 0.02 ) . A total of 22/51 ( 43 % ) women were satisfied in the surgery group compared with 61/103 ( 59 % ) in the progestin group [ adjusted odds ratios ( OR ) , 0.36 ; 95 % confidence interval ( CI ) , 0.16 - 0.82 ; P = 0.015 ] . Corresponding figures in women with and without rectovaginal endometriotic lesions were , respectively , 13/24 ( 54 % ) versus 18/35 ( 51 % ; adjusted OR , 0.77 ; 95 % CI , 0.22 - 2.67 ; P = 0.68 ) , and 9/27 ( 33 % ) versus 43/68 ( 63 % ; adjusted OR , 0.23 ; 95 % CI , 0.07 - 0.76 , P = 0.02 ) . BIAS , CONFOUNDING , AND OTHER REASONS FOR CAUTION : Treatments were not r and omly assigned , and distribution of participants as well as of dropouts between study arms was unbalanced . However , the possibility of choosing the treatment allowed assessment of the maximum potential effect size of the interventions . GENERALIZABILITY TO OTHER POPULATION S Caucasian patients able to choose their treatment . STUDY FUNDING /COMPETING INTEREST(S ) This study was supported by a research grant from the University of Milan School of Medicine ( PUR number 2009-ATE-0570 ) . None of the authors have a conflict of interest OBJECTIVE To describe a safe long-term medical treatment for deeply infiltrating endometriosis , a critical condition characterized by multiple painful symptoms and a high recurrence rate after surgical treatment . DESIGN Prospect i ve study . SETTING University of Siena . PATIENT(S ) Twenty-one women with deeply infiltrating endometriosis . INTERVENTION(S ) In a nonr and omized prospect i ve study a low dose of vaginal danazol ( 200 mg/d ) was self-administered for 12 months . After a previous laparoscopic surgery , these patients had reported recurrent severe dyspareunia , dysmenorrhea , and pelvic pain ( in five cases also painful defecation ) . MAIN OUTCOME MEASURE(S ) Before and every 3 months during the treatment a visual analogue pain scale was used . Transvaginal and transrectal ultrasound examinations were performed before and after 6 and 12 months of treatment . Adverse effects were registered , and serum concentration of cholesterol , triglycerides , aspartate aminotransferase , alanine aminotransferase , glycemia , protein S , protein C , antithrombin III , and homocysteine was evaluated before and after 12 months . RESULT ( S ) Dysmenorrhea , dyspareunia , and pelvic pain significantly decreased within 3 months and disappeared after 6 months of treatment , with a persistent effect during the 12 months of treatment . A relief of painful defecation was also shown . Ultrasound examination showed a reduction of the nodularity in the rectovaginal septum within 6 months . The medical treatment did not affect metabolic or thrombophilic parameters ; few local vaginal adverse effects were reported . CONCLUSION ( S ) Vaginal danazol result ed in effective medical treatment for the various painful symptoms in women with recurrent deeply infiltrating endometriosis , and because of the lack of significant adverse effects it may be proposed as an alternative to repeated surgery OBJECTIVE To evaluate the efficacy , safety , and tolerability of an estrogen-progestogen combination versus low-dose norethindrone acetate in the treatment of persistent pain after surgery for symptomatic rectovaginal endometriosis . DESIGN R and omized controlled trial . SETTING Academic center . PATIENT(S ) Ninety women with recurrent moderate or severe pelvic pain after unsuccessful conservative surgery for symptomatic rectovaginal endometriosis . INTERVENTION(S ) Twelve-month , continuous treatment with oral ethinyl E2 , 0.01 mg , plus cyproterone acetate , 3 mg/day , or norethindrone acetate , 2.5 mg/day . MAIN OUTCOME MEASURE(S ) Degree of satisfaction with therapy . RESULT ( S ) Seven women in the ethinyl E2 plus cyproterone acetate arm and five in the norethindrone acetate arm withdrew because of side effects ( n=5 ) , treatment inefficacy ( n=6 ) , or loss to follow-up ( n=1 ) . At 12 months , dysmenorrhea , deep dyspareunia , nonmenstrual pelvic pain , and dyschezia scores were substantially reduced without major between-group differences . Both regimens induced minor unfavorable variations in the serum lipid profile . According to an intention-to-treat analysis , 28 ( 62 % ) out of 45 patients in the ethinyl E2 plus cyproterone acetate group and 33 ( 73 % ) out of 45 in the norethindrone acetate group were satisfied with the treatment received . CONCLUSION ( S ) Low-dose norethindrone acetate could be considered an effective , tolerable , and inexpensive first-choice medical alternative to repeat surgery for treating symptomatic rectovaginal endometriotic lesions in patients who do not seek conception OBJECTIVE Our purpose was to investigate the efficacy of postsurgical treatment with nafarelin in women with advanced endometriosis . STUDY DESIGN Eligible for trial were women < or = 38 years old with unexplained infertility with or without chronic pelvic pain and stage III or IV endometriosis according to the American Fertility Society , revised , classification who underwent laparotomy as first surgical treatment for debulking or radical surgery of endometriotic lesions . Patients were assigned according to a r and omization list to nasal nafarelin , 400 micrograms/day ( 36 subjects ) or placebo nasal spray ( 39 subjects ) for 3 months . Pelvic pain was assessed before first surgery and at the 12-month follow-up visit in women with pelvic pain by means of a multidimensional score system and a 10-point linear pain scale . RESULTS No marked differences in pain scores emerged among women allocated to different treatments . The mean reduction of the multidimensional score was 3.6 and 4.0 , respectively , in women allocated to nafarelin and placebo and of the 10-point linear scale scores was 7.0 and 6.9 . These differences were not statistically significant . Within 1 year from r and omization , of the 36 women allocated to nafarelin and the 39 allocated to placebo , seven ( 19 % ) and seven ( 18 % ) , respectively , became pregnant . CONCLUSION This study suggests that medical treatment with nafarelin does not markedly improve pelvic pain and short-term reproductive prognosis in women with stages III and IV endometriosis OBJECTIVE To compare the efficacy of nafarelin acetate with danazol in the treatment of dysmenorrhea , dyspareunia , and pelvic pain associated with endometriosis . DESIGN Prospect i ve , r and omized double-blind controlled study . PATIENTS , SETTING , TREATMENTS : Two hundred thirteen patients aged 18 to 48 with laparoscopically confirmed pelvic endometriosis and dysmenorrhea , dyspareunia or pelvic pain were r and omly assigned to 6 months of treatment with either nafarelin acetate 800 micrograms per day or 400 micrograms per day , or danazol 800 micrograms per day . MAIN OUTCOME MEASURES The percentage of patients with dysmenorrhea , dyspareunia or pelvic pain before treatment who still had these symptoms after 6 months of treatment and 6 months following completion of treatment . RESULTS [ table : see text ] CONCLUSIONS Nafarelin acetate and danazol both provided significant relief of dysmenorrhea , dyspareunia , and pelvic pain during treatment and for 6 months following treatment in women with endometriosis
( S ) Few studies of medical therapies for endometriosis report outcomes that are relevant to patients , and many women gain only limited or intermittent benefit from treatment
OBJECTIVE To assess patient response rates to medical therapies used to treat endometriosis-associated pain .