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.
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
( 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 .