title: Subcutaneous injection of depot medroxyprogesterone acetate compared with leuprolide acetate in the treatment of endometriosis-associated pain. Continuous versus cyclic use of oral contraceptives after surgery for symptomatic endometriosis: a prospective cohort study. The efficacy of drugs in the management of endometriosis. Role of the vaginally administered aromatase inhibitor anastrozole in women with rectovaginal endometriosis: a pilot study. Comparison of contraceptive ring and patch for the treatment of symptomatic endometriosis. Long-term oral contraceptive pills and postoperative pain management after laparoscopic excision of ovarian endometrioma: a randomized controlled trial. Updating the clinical experience in endometriosis – the European perspective Dienogest is as effective as leuprolide acetate in treating the painful symptoms of endometriosis: a 24-week, randomized, multicentre, open-label trial. Use of a levonorgestrel-releasing intrauterine device in the treatment of rectovaginal endometriosis. Letrozole and norethisterone acetate in rectovaginal endometriosis. Randomized controlled trial of depot leuprolide in patients with chronic pelvic pain and clinically suspected endometriosis. Pelvic Pain Study Group. A gonadotrophin‐releasing hormone agonist compared with expectant management after conservative surgery for symptomatic endometriosis Elagolix Treatment for Endometriosis-Associated Pain 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. Zoladex (Goserelin Acetate Implant) in the Treatment of Endometriosis: A Randomized Comparison With Danazol Effects of laparoscopic ovarian endometriosis cystectomy combined with postoperative GnRH-a therapy on ovarian reserve, pregnancy, and outcome recurrence. Long-term cyclic and continuous oral contraceptive therapy and endometrioma recurrence: a randomized controlled trial. Treatment of symptomatic rectovaginal endometriosis with an estrogen-progestogen combination versus low-dose norethindrone acetate. Danazol in the treatment of endometriosis: analysis of 100 cases with a 4-year follow-up. Efficacy of vaginal danazol treatment in women with recurrent deeply infiltrating endometriosis. 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. Nafarelin for endometriosis: a large-scale, danazol-controlled trial of efficacy and safety, with 1-year follow-up. The Nafarelin European Endometriosis Trial Group (NEET). Add-back therapy in the treatment of endometriosis-associated pain. A comparative study of the acceptability and effect of goserelin and nafarelin on endometriosis Efficacy and safety of nafarelin in the treatment of endometriosis. Goserelin acetate (Zoladex) with or without hormone replacement therapy for the treatment of endometriosis. Subcutaneous depot medroxyprogesterone acetate versus leuprolide acetate in the treatment of endometriosis-associated pain. Elagolix, an Oral GnRH Antagonist, Versus Subcutaneous Depot Medroxyprogesterone Acetate for the Treatment of Endometriosis Low-dose oral contraceptive pill for dysmenorrhea associated with endometriosis: a placebo-controlled, double-blind, randomized trial. Long-term use of dienogest for the treatment of endometriosis. Efficacy of medroxyprogesterone treatment in infertile women with endometriosis: a prospective, randomized, placebo-controlled study. Prospective randomized double-blind trial of 3 versus 6 months of nafarelin therapy for endometriosis associated pelvic pain. Progestins for symptomatic endometriosis: a critical analysis of the evidence. Depot leuprolide versus danazol in treatment of women with symptomatic endometriosis. I. Efficacy results. Combined surgical and hormone therapy for endometriosis is the most effective treatment: prospective, randomized, controlled trial. Administration of nasal Buserelin as compared with subcutaneous Buserelin implant for endometriosis. Dienogest is as effective as intranasal buserelin acetate for the relief of pain symptoms associated with endometriosis--a randomized, double-blind, multicenter, controlled trial. Treatment of endometriosis with leuprorelin acetate depot: a German multicentre study. Pain of endometriosis: effects of nafarelin and danazol therapy. Nafarelin versus danazol in the treatment of endometriosis. Nafarelin vs. leuprolide acetate depot for endometriosis. Changes in bone mineral density and vasomotor symptoms. Nafarelin Study Group. Administration of nasal nafarelin as compared with oral danazol for endometriosis. A multicenter double-blind comparative clinical trial. Elagolix, an Oral GnRH Antagonist for Endometriosis-Associated Pain: A Randomized Controlled Study Surgical versus medical treatment for endometriosis-associated severe deep dyspareunia: I. Effect on pain during intercourse and patient satisfaction. Low-dose add-back therapy during postoperative GnRH agonist treatment.
abstract: OBJECTIVE To compare the efficacy and safety of SC depot medroxyprogesterone acetate ( DMPA-SC 104 ) with that of leuprolide acetate in treatment of endometriosis . DESIGN Phase 3 , multicenter , r and omized , evaluator-blinded , comparator-controlled trial . SETTING Clinical trial sites in Canada and United States . PATIENT(S ) Two hundred seventy-four women with surgically diagnosed endometriosis . INTERVENTION(S ) Intramuscular injections of DMPA-SC ( 104 mg ) or leuprolide acetate ( 11.25 mg ) , given every 3 months for 6 months , with 12 months of posttreatment follow-up . MAIN OUTCOME MEASURE(S ) Reduction in five endometriosis symptoms or signs ( dysmenorrhea , dyspareunia , pelvic pain , pelvic tenderness , pelvic in duration ) ; change in bone mineral density ( BMD ) , hypoestrogenic symptoms , bleeding , and weight . RESULT ( S ) The depot medroxyprogesterone acetate given SC was statistically equivalent to leuprolide in reducing four of five endometriosis symptoms or signs at the end of treatment ( month 6 ) and in reducing all five symptoms after 12 months ' follow-up ( month 18 ) . Patients in the  DMPA-SC 104  group showed significantly less BMD loss than did leuprolide  patients at month 6 , with scores returning to baseline at 12 months ' follow-up . No statistically significant differences in median weight changes were observed between groups . Compared with leuprolide , DMPA-SC 104 was associated with fewer hypoestrogenic symptoms but more irregular bleeding . CONCLUSION ( S ) Efficacy of DMPA-SC 104 was equivalent to that of leuprolide for reducing endometriosis-associated pain , with less impact on BMD and fewer hypoestrogenic side effects but more bleeding OBJECTIVE To evaluate the efficacy of continuous oral contraceptive ( OC ) use versus the usual cyclic fashion in the recurrence of endometriosis-related symptoms after surgery . DESIGN Prospect i ve cohort trial involving patients in two tertiary care units . SETTING Academic institution in collaboration with a private hospital . PATIENT(S ) 356 patients underwent surgical treatment by laparoscopy for symptomatic endometriosis . INTERVENTION(S ) After surgical treatment for endometriosis , patients offered 6-month course of cyclic OC ( including a 7-day pill-free period ) or continuous OC . MAIN OUTCOME MEASURE(S ) Recurrence rate of endometriosis-related symptoms and endometriomas after fertility-sparing surgery . RESULT ( S ) Out of 356 patients , 167 were placed on the usual cyclic OC course  and 85 on  continuous OC for a minimum of 6 months . The continuous OC group experienced a statistically significant reduction in recurrence rates for endometrioma , dysmenorrhea , and non-menstrual pelvic pain as compared with the cyclic OC group . There was no reduction in the recurrence of dyspareunia between the two groups . CONCLUSION ( S ) After surgical treatment of endometriosis , the use of both cyclic and continuous OC improves pain symptoms when compared with preoperative scores . Continuous OC appears to be associated with a reduced recurrence rate for dysmenorrhea , non-menstrual pelvic pain , and endometrioma but not for dyspareunia as compared with cyclic OC STUDY OBJECTIVE To establish the crude effects of danazol and gonadotropin-releasing hormone ( GnRH ) analogs in the management of endometriosis .  DESIGN Prospect i ve case-control study . SETTING Unit of the Pathophysiology of Reproduction outpatient department . PATIENTS Two groups of 110 women each with endometriosis ( American Fertility Society score 1 - 3 ) who received danazol and GnRH analogs , and a control group who did not receive any drugs . INTERVENTIONS Women in the treatment groups received danazol 200 mg every 8 hours for 6 months , or a different GnRH agonist at st and ard dosages for 6 months . Laparoscopy was performed twice , at the time of diagnosis and just before the end of treatment ( or no therapy for controls ) . Surgical treatment of the implants was performed at the second laparoscopy . MEASUREMENTS AND MAIN RESULTS Sample s of both eutopic and ectopic endometrium were collected during both laparoscopies . Both danazol and GnRH agonists were useful in reducing the AFS scores to inactive endometriotic implants , and there were no significant differences between the effects ( p < 0.001 ) . Fibrosis was found after 6 months of observation in the implants in one control woman ( 0.9 % ) , in 20 patients ( 18.2 % ) treated with danazol ( p < 0.001 vs controls ) , and in 4 patients ( 3.6 % ) treated with GnRH agonists ( NS vs controls ) . A correlation between a clinical diagnosis of AFS score zero and histologic features of fibrosis in the ectopic specimens after therapies was observed in 28 % of women , with poor agreement ( k = 0.07 ) . CONCLUSIONS Fibrosis , which represent the absence of endometrial cells within the specimens of endometriotic lesions or eutopic endometrium , did not appear in eutopic endometria but it was found in some endometriotic implants . Danazol and GnRH agonists reduced the clinical AFS scores of endometriosis , but their histologic effects in completely and permanently eliminating endometriotic implants were unacceptable In the present nonr and omized pilot study we determined the role of the vaginally administered aromatase inhibitor anastrozole ( 0.25 mg anastrozole/d for 6 months ) in the treatment of women with histologically proven rectovaginal endometriosis . In a series of 10 patients , dysmenorrhea , physical and social functioning , but not chronic pelvic pain and dyspareunia , improved during therapy OBJECTIVE To evaluate the efficacy and tolerability of a contraceptive vaginal ring and transdermal patch in the treatment of  endometriosis-associated pain .  DESIGN Patient preference cohort study . SETTING Academic center . PATIENT(S ) Two-hundred and seven women with recurrent moderate or severe pelvic pain after conservative surgery for symptomatic endometriosis . INTERVENTION(S ) Continuous , 12-month treatment with a vaginal ring supplying 15 mcg of ethinyl E and 120 mcg of etonogestrel per day or a transdermal system delivering 20 mcg of ethinyl E and 150 mcg norelgestromin per day . MAIN OUTCOME MEASURE(S ) Satisfaction with treatment . RESULT ( S ) One-hundred and twenty-three women preferred the ring , and 84 preferred the patch . Forty-four ring users ( 36 % ) and 51 patch users ( 61 % ) withdrew . Thirty-six of 79 subjects ( 46 % ) in the ring group and 14 of 33 ( 42 % ) in the patch group shifted from continuous to cyclic use because of irregular bleeding . Pain symptoms were reduced by both treatments , with the ring being more effective than the patch in patients with rectovaginal lesions . According to an intention-to-treat analysis , 88 of 123 ring users ( 72 % ) and 40 of 84 patch users ( 48 % ) were satisfied with the treatment received . CONCLUSION ( S ) Patients who preferred the ring were significantly more likely to be satisfied and to comply with treatment than those who chose the patch . Both systems were associated with poor bleeding control when used continuously OBJECTIVE To evaluate postoperative long-term cyclic and continuous administration of combined oral contraceptive ( OC ) pills in preventing endometriosis-related pain recurrence . DESIGN Prospect i ve , r and omized , controlled trial . SETTING Tertiary care university hospital . PATIENT(S ) Three hundred eleven women who underwent laparoscopic excision for symptomatic ovarian endometrioma . INTERVENTION(S ) Patients were r and omly divided into three groups : nonuser group receiving no therapy , and cyclic user group and continuous user group receiving low-dose , monophasic OC pills for 24 months in either cyclic or continuous administration . MAIN OUTCOME MEASURE(S ) Presence and intensity of dysmenorrhea , dyspareunia , and chronic pelvic pain were assessed by a 10-point visual analogue scale ( VAS ) at 6 , 12 , 18 , and 24 months postoperatively . RESULT ( S ) A significant reduction in recurrence rate and VAS scores for dysmenorrhea was evident in the continuous users versus the other groups at 6 months , and in cyclic users versus nonusers at 18 months postoperatively . No significant differences in recurrence rate and VAS scores for dyspareunia and chronic pelvic pain were demonstrated among the groups . The increase of VAS scores from 6 - 24 months during the study period for dysmenorrhea , dyspareunia , and chronic pelvic pain was significantly higher in nonusers than in the other groups . CONCLUSION ( S ) Long-term postoperative use of OC pills can reduce the frequency and the severity of recurrent endometriosis-related dysmenorrhea In a large , double‐blind , multicentre study , 269 patients with confirmed endometriosis were r and omly allocated to receive either danazol ( 200 mg twice daily ; n= 137 ) or gestrinone ( 2.5 mg twice weekly ; n= 132 ) for 6 months . The two groups were comparable in terms of the staging of endometriosis by the American Fertility Society ( 1979 ) score . After the sixth month of treatment , repeat laparoscopy was performed . Clinical assessment , haematological and biochemical investigations were carried out during the 6 months of treatment and for a further 12 months ' follow‐up and are compared between the two groups . A total of 15 patients from the gestrinone group , including four patients with hirsutism , and 17 patients from the danazol group , including six patients with headache , withdrew because of adverse symptoms . An additional 22 patients , including 10 from the gestrinone group and 12 from the danazol group withdrew because of lack of efficacy , pregnancy , elevated hepatic function tests or for reasons unrelated to the trial . Total American Fertility Society scoring showed an improvement of 73.3 % in 101 patients receiving gestrinone and 72.7 % in 99 patients receiving danazol . The results showed a significant reduction in the severity of dysmenorrhoea by the third month in the danazol group and at 6 months in both groups . There was a significant ( P < 0.001 ) increase in weight observed in both groups during treatment . Overall , the tolerability  of danazol and gestrinone was good ; however , significantly more patients with gestrinone complained of hirsutism while significantly more with danazol complained of leg cramps . During the 12 months of follow‐up , mild , moderate or severe degrees of lower abdominal pain , dysmenorrhoea and deep dyspareunia all fluctuated , with no statistically significant increase in frequency in either group BACKGROUND Dienogest is a selective progestin that has been investigated in a clinical trial programme for the treatment of endometriosis . The current non-inferiority trial compared the efficacy and safety of dienogest against leuprolide acetate ( LA ) for treating the pain associated with endometriosis . METHODS Patients with confirmed endometriosis were r and omized to treatment with dienogest ( 2 mg/day , orally ) or LA ( 3.75 mg , depot i.m . injection , every 4 weeks ) for 24 weeks . The primary efficacy variable was absolute change in pelvic pain from baseline to end of treatment , assessed by visual analogue scale ( VAS ) . Safety variables included adverse event profile , laboratory parameters , bone mineral density ( BMD ) , bone markers and bleeding patterns . RESULTS A total of 252 women were r and omized to treatment with dienogest ( n = 124 ) or LA ( n = 128 ) ; 87.9 and 93.8 % of the respective groups completed the trial . Absolute reductions in VAS score from baseline to Week 24 were 47.5 mm with dienogest and 46.0 mm with LA , demonstrating the equivalence of dienogest relative to LA .  Hypoestrogenic effects ( e.g. hot flushes ) were reported less frequently in the dienogest group . As expected , bleeding episodes were suppressed less with dienogest than with LA . Changes in mean lumbar BMD between screening and final visit were + 0.25 % with dienogest and -4.04 % with LA subgroups ( P = 0.0003 ) . Markers of bone resorption increased with LA but not dienogest . CONCLUSIONS Dienogest 2 mg/day orally demonstrated equivalent efficacy to depot LA at st and ard dose in relieving the pain associated with endometriosis , although offering advantages in safety and tolerability OBJECTIVE To evaluate the effectiveness of a levonorgestrel-releasing IUD as therapy for endometriosis of the rectovaginal septum . DESIGN Prospect i ve therapeutic non-r and omized , self-controlled clinical trial analyzing changes in pain symptoms and size of lesions induced by the levonorgestrel-releasing IUD over 12 months . SETTING Tertiary referral center for treatment of deep endometriosis . PATIENT(S ) Eleven symptomatic patients with rectovaginal endometriosis . INTERVENTION(S ) A levonorgestrel-releasing IUD was inserted and maintained for 12 months . MAIN OUTCOME MEASURE(S ) Severity of dysmenorrhea , pelvic pain , and deep dyspareunia were assessed before insertion of the IUD and throughout treatment . The size of rectovaginal endometriotic lesions were evaluated by using transrectal and transvaginal ultrasonography . RESULT ( S ) Dysmenorrhea , pelvic pain , and deep dyspareunia greatly improved and the size of the endometriotic lesions was significantly reduced by treatment . CONCLUSION ( S ) Insertion of a levonorgestrel-releasing IUD alleviates pain and reduces the size of lesions in patients with endometriosis of the rectovaginal septum This open-label prospect i ve study evaluated the efficacy of letrozole ( 2.5 mg/day ) combined with norethisterone acetate ( 2.5 mg/day ) in the treatment of  pain symptoms related to the presence of rectovaginal endometriosis . The treatment significantly and quickly decreased the intensity of symptoms , but pain recurred at 3-month follow-up ; five women underwent surgery during the follow-up , and histologic examination of rectovaginal nodules revealed the presence of active endometriotic lesions 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 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 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 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 Objective : To compare the efficacy , endocrine effects , and safety of Zoladex ( goserelin acetate ) and danazol in the treatment of premenopausal women with endometriosis in a multicenter , r and omized , open study . Methods : Three hundred fifteen patients with stages I-IV endometriosis ( revised American Fertility Society [ AFS ] classification ) were treated with Zoladex , 3.6 mg every 28 days by subcutaneous injection , or danazol , 400 mg orally twice daily for 24 weeks . Efficacy was assessed by determination of pelvic signs and symptoms scores and revised AFS endometriosis scores . Endocrine effects were determined by measurements of hormone levels . Safety was evaluated by physical examination , laboratory indices , occurrence of adverse events , and bone mineral density changes . Results : Both treatments significantly ( P < .0001 ) reduced mean subjective signs and symptoms scores both during and after therapy . The mean percent reduction in the revised AFS endometriosis score after 24 weeks of treatment was 53 % for Zoladex and 33 % for danazol , and reduction in the endometrial implants score was 56 % for Zoladex and 46 % for danazol .  Serum estradiol levels decreased to the postmenopausal range in the Zoladex group and to the early follicular phase range in the danazol group . Hypoestrogenic effects occurred more frequently with Zoladex , whereas and rogenic side effects were more common with danazol . There was a higher percentage of withdrawals due to adverse events with danazol than with Zoladex .  Mean bone mineral density decreased from baseline by 5.4 % in the Zoladex group and increased by 1.0 % in the danazol group at the end of treatment . Conclusion : Zoladex is as well tolerated and as effective as danazol in the treatment of premenopausal women with endometriosis OBJECTIVE The aim of this study was to investigate the impacts of laparoscopic ovarian endometriosis cystectomy combined with postoperative GnRH-a therapy on ovarian reserve , pregnancy outcome and recurrence . MATERIAL S AND METHODS This was a prospect i ve control study . The experimental group : 63 patients with combinations of laparoscopic bilateral ovarian endometrial cystectomies and gonadotropin-releasing hormone agonist ( GnRH-a ) treatment for three months . CONTROL GROUP 62 patients with laparoscopic bilateral ovarian endometrial cystectomies .  Benchmarks : the changes of follicle stimulating hormone ( FSH ) and FSH/luteinizing hormone ( LH ) , etradiol ( E2 ) in preoperative and postoperative three months or menstrual two to three days , menstrual two to three days after surgery , natural pregnancy , and cyst recurrence in 18th month during postoperative follow-up . RESULTS In experimental group after six months , the percentage of returned FSH accounted for 95.3 % of normal range , in the control group it was 82.2 % , and the difference was significant ( p < 0.05 ) . The natural pregnancy rate of preoperative infertility patients ( 57.1 % ) was higher than the control ( 36.8 % ) ( p < 0.05 ) . The recurrence rate of preoperative infertility patients ( 12.7 % ) was lower than the control ( 27.4 % ) ( p < 0.05 ) . CONCLUSION After bilateral laparoscopic ovarian endometrial cystectomy , an implement of GnRH-a therapy can improve the postoperative pregnancy rate , which changes with clinical stage and patient age , reduces ovarian recurrence , and its influence on ovarian reserve is lesser OBJECTIVE To evaluate long-term cyclic and continuous administration of oral contraceptive pills ( OCP ) in preventing ovarian endometrioma  recurrence after laparoscopic cystectomy . DESIGN Prospect i ve , r and omized , controlled trial . SETTING Tertiary care University Hospital . PATIENT(S ) Two hundred thirty-nine women who underwent laparoscopic excision of ovarian endometriomas . INTERVENTION(S ) Patients were divided r and omly into three groups : nonusers receiving no therapy and cyclic and continuous users receiving low-dose , monophasic OCP for 24 months in cyclic or continuous administration , respectively . MAIN OUTCOME MEASURE(S ) Endometrioma recurrence , size of recurrent endometrioma , and growth rate during at least 2 years follow-up evaluated by transvaginal ultrasonography . RESULT ( S ) The crude recurrence rate within 24 months was significantly lower in cyclic ( 14.7 % ) and continuous users ( 8.2 % ) compared with nonusers ( 29 % ) . The recurrence-free survival was significantly lower in nonusers compared with cyclic and continuous users . The mean recurrent endometrioma diameter at first observation was significantly lower in cyclic ( 2.17 + /- 0.45 cm ) and continuous users ( 1.71 + /- 0.19 cm ) compared with nonusers ( 2.73 + /- 0.56 cm ) . The mean diameter increase every 6 months of follow-up was significantly reduced in cyclic users ( 0.31 + /- 0.18 cm ) and continuous users ( 0.25 + /- 0.09 cm ) versus nonusers ( 0.48 + /- 0.3 cm ) . No significant differences between cyclic users and continuous users in terms of endometrioma recurrence were demonstrated . CONCLUSION ( S ) Long-term cyclic and continuous postoperative use of OCP can effectively reduce and delay endometrioma recurrence 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 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 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 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 compare the efficacy and safety of nafarelin and danazol for endometriosis . DESIGN R and omized , double-blind , double-dummy . SETTING Multiple European institutions . PATIENTS In total , 307 patients with laparoscopically diagnosed endometriosis received nafarelin ( n = 206 ) or danazol ( n = 101 ) ; 263 ( 171 nafarelin , 92 danazol ) were analyzed for efficacy . INTERVENTIONS Intranasal nafarelin 200 micrograms two times a day or oral danazol 200 mg three times a day were administered for 6 months . MAIN OUTCOME MEASURES Efficacy assessment s were based on preadmission and end-of-treatment laparoscopic scores and subjective symptom scores at admission , end of treatment , 1 , 3 , 6 , and 12 months after treatment . Safety was evaluated by adverse events and clinical laboratory tests . RESULTS In each group , endometriosis growth and symptoms significantly improved during treatment ( P less than 0.001 ) . After treatment , symptoms returned in each group , but severity was less than at admission at all time points ( P less than or equal to 0.016 ) . Mean body weight increased in the danazol-treated group ( P less than 0.001 ) , serum glutamic oxaloacetic transaminase increased in both groups ( P less than 0.001 for both ) but significantly more in danazol users ( P less than 0.002 ) , and more nafarelin recipients had hot flushes ( P less than 0.001 ) . CONCLUSIONS Nafarelin and danazol were equally effective in reducing endometriosis growth and symptoms during treatment and in preventing the return of symptoms during 12-month follow-up 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 The effects of goserelin and nafarelin were compared in a prospect i ve , r and omized , open , parallel study of 6 months ' treatment of 252 women with symptomatic , laparoscopically proven endometriosis . Twenty-eight departments of obstetrics and gynecology in Sweden , Norway , Denmark and Finl and were included . Evaluations were made every 3 months for quantification of pain , bleeding and adverse events and convenience of treatment , and at 3 months after the end of treatment , when a control laparoscopy was performed for evaluation of changes in endometriotic lesion size , color and location . Thirty-nine patients withdrew and 113 women given goserelin and 100 women given nafarelin completed the study . There were no statistically significant differences between the groups , either in adverse events or in bleeding . There were no correlations between location , lesion size or type of lesion , and symptom score in either group , or between treatments with regard to change in endometriosis score . In both groups , the percentage of red and black lesions was reduced while the proportion of white lesions increased . The pain score was significantly reduced in both groups . Local irritation in the nasal mucosa was reported in both groups , mostly in the nafarelin-treated group . The goserelin-treated group also reported local symptoms at the injection site . We conclude that there is no statistically significant difference in treatment results or side-effects between goserelin and nafarelin when used for the treatment of endometriosis The efficacy and safety of the gonadotropin-releasing hormone agonist nafarelin for treatment of endometriosis were compared with those of danazol in two large-scale , double-blind trials . Assessment s of severity of symptoms , laparoscopic scores before and after therapy , and pregnancy rates showed that nafarelin , 400 and 800 micrograms administered intranasally , was as efficacious as oral danazol , 600 and 800 mg . The adverse effects seen with nafarelin , mainly hot flashes , were related to its mode of action , namely hypoestrogenemia induced by reversible inhibition of ovarian hormone production . Hypoestrogenemia was associated with a decrease of bone density in the lumbar vertebrae , but these changes were partially or completely reversible after treatment was discontinued . No significant changes in bone mass occurred in the distal radius . Danazol was associated with and rogenic and metabolic adverse effects , including weight gain , negative effects on the lipid profile , and elevated liver enzyme levels .  Nafarelin was found to be as effective as danazol for the management of endometriosis , with a different and more favorable safety profile OBJECTIVE To determine whether hormone replacement therapy ( HRT ) plus goserelin ( Zoladex ) is as effective as goserelin alone for the relief of pelvic symptoms of endometriosis and to determine whether it reduces both the loss of bone mineral density ( BMD ) and the physiologic side effects associated with goserelin therapy . DESIGN Prospect i ve , placebo-controlled study , open label for goserelin therapy and double-blind for HRT . SETTING Forty-two teaching or community hospitals . PATIENT(S ) Premenopausal women with symptomatic endometriosis . RESULT ( S ) Statistically significant mean decreases from baseline in the total pelvic symptom score and total subjective score were observed by week 24 for all three groups . There were no statistically significant treatment differences for change in total symptom score . Some degree of BMD loss occurred in the three groups ; however , the percentage loss was consistently greater in the HRT0 group than in the HRT1 or HRT2 groups . When analyzed separately , no overall age effect on BMD change was seen in women > 30 years of age versus women < or = 30 years . The HRT1 and HRT2 groups had fewer occurrences of hot flushes and vaginal dryness than did the HRT0 group . CONCLUSION ( S ) Goserelin plus HRT is as effective as goserelin alone in relieving pelvic symptoms of endometriosis and attenuates both the loss of BMD and the physiologic side effects of hot flushes and vaginal dryness associated with goserelin therapy BACKGROUND A clinical study compared efficacy and safety of depot medroxyprogesterone acetate ( DMPA ) with leuprolide for  endometriosis-associated pain .  METHODS This multicentre , 18 month , evaluator-blinded , comparator-controlled trial r and omized 300 women with laparoscopically diagnosed endometriosis to 6 month treatment with subcutaneous injection of  104 mg/0.65 ml DMPA ( DMPA-SC 104 ) every 3 months or leuprolide ( 3.75 mg monthly or 11.25 mg every 3 months ) , with 12 months post-treatment follow-up . Endpoints included patient response to treatment in five signs/symptoms ( dysmenorrhoea , dyspareunia , pelvic pain , pelvic tenderness , in duration ) and changes in bone mineral density ( BMD ) and productivity at 6 and 18 months . RESULTS DMPA-SC 104 and leuprolide produced equivalent ( P < 0.02 ) reductions in at least four pain categories and significant ( P < 0.001 ) improvements in composite score at months 6 and 18 . At month 6 , reductions in total hip and lumbar spine BMD were significantly less ( P < 0.001 ) with DMPA-SC 104 versus leuprolide .  BMD returned to pre-treatment levels 12 months post-treatment in the DMPA-SC 104 but not the leuprolide group . Total productivity also significantly ( P < or = 0.05 ) improved in both groups at 6 and 18 months . CONCLUSIONS DMPA-SC 104 reduces endometriosis-associated pain as effectively as leuprolide and improves productivity with significantly less BMD decline This r and omized double-blind study , with 24-week treatment and 24-week posttreatment periods , evaluated the effects of elagolix ( 150 mg every day , 75 mg twice a day ) versus subcutaneous depot medroxyprogesterone acetate ( DMPA-SC ) on bone mineral density ( BMD ) , in women with endometriosis-associated pain ( n = 252 ) . All treatments induced minimal mean changes from baseline in BMD at week 24 ( elagolix 150 mg : −0.11%/−0.47 % , elagolix 75 mg : −1.29%/−1.2 % , and DMPA-SC : 0.99%/−1.29 % in the spine and total hip , respectively ) , with similar or less changes at week 48 ( posttreatment ) . Elagolix was associated with improvements in endometriosis-associated pain , assessed with composite pelvic signs and symptoms score ( CPSSS ) and visual analogue scale , including statistical noninferiority to DMPA-SC in dysmenorrhea and nonmenstrual pelvic pain components of the CPSSS . The most common adverse events ( AEs ) in elagolix groups were headache , nausea , and nasopharyngitis , whereas the most common AEs in the DMPA-SC group were headache , nausea , upper respiratory tract infection , and mood swings . This study showed that similar to DMPA-SC , elagolix treatment had minimal impact on BMD over a 24-week period and demonstrated similar efficacy on endometriosis-associated pain 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 AIM To investigate the safety and efficacy of 52 weeks of dienogest treatment in patients with endometriosis . METHODS One hundred and thirty-five patients with endometriosis received 2 mg of dienogest orally each day for 52 weeks . Adverse drug reactions and bone density were evaluated . Global improvement was assessed based on the changes in severity categories of five subjective symptoms during non-menstruation ( lower abdominal pain , lumbago , dyschezia , dyspareunia , and pain on vaginal examination ) and two objective findings ( in duration involving the pouch of Douglas and limited uterine mobility ) . RESULTS The most common adverse drug reactions included metrorrhagia ( 71.9 % ) , headaches ( 18.5 % ) , and constipation ( 10.4 % ) . No clinical ly significant changes were noted in the incidence or severity of reactions associated with the course of the treatment period ( 52 weeks ) . Changes from the baseline bone mineral density of the lumbar spine measured by dual-energy X-ray absorptiometry were -1.6 + /- 2.4 % and -1.7 + /- 2.2 % ( mean + /- st and ard deviation ) at 24 and 52 weeks , respectively , which were statistically significant decreases ; however , there was no cumulative decrease . The proportions of patients assessed as marked or moderate improvement in terms of global improvement were 72.5 % ( 95/131 cases ) at 24 weeks and 90.6 % ( 106/117 cases ) at 52 weeks . CONCLUSION The long-term effect of dienogest on bone mineral density was slight , whereas the efficacy increased cumulatively OBJECTIVE To determine the efficacy of medroxyprogesterone acetate ( MPA ) , 50 mg/d for 3 months , in treating endometriosis , with a follow-up of 6 months . DESIGN Prospect i ve , r and omized , double-blind , placebo-controlled trial . SETTING Academic infertility unit in a teaching hospital . PATIENT(S ) One hundred infertile women found to have endometriosis at laparoscopy , with 50 recruited to each treatment arm . INTERVENTION(S ) Laparoscopy within 3 months of finishing therapy . MAIN OUTCOME MEASURE(S ) Initial and second-look laparoscopy for revised American Fertility Society stages and scores , pregnancies achieved , effects on well-being via symptomatic improvement , and side effects . RESULT ( S ) Whether initially high or low , both MPA and placebo therapy achieved similar statistically significant reductions in stages and scores at second-look laparoscopy .  MPA was rated more effective in improving overall well-being . Side effects were minimal in both groups ( 10 % MPA ; 2 % placebo ) . Six pregnancies occurred without other endometriosis therapy being instituted in the placebo group ( 3 during therapy ) , and one with MPA ( 0 during therapy ) . CONCLUSION ( S ) Both MPA and placebo appear equally and significantly effective in treating endometriosis over a 3-month period , as judged by comparative laparoscopy . Therefore , not only must the use of MPA at 50 mg/d over 3 months be question ed , but the performance of placebo also suggests the need to review whether therapy should be instituted at all as well as the present concept that endometriosis is frequently a spontaneously progressive phenomenon 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 obtain estimates of the effects of progestin treatment for pelvic pain associated with endometriosis . DATA IDENTIFICATION Information from studies published in the English- language literature between 1966 and 1996 was pooled . Articles were identified through h and and computerized search es using MEDLINE . STUDY SELECTION A total of 27 trials that were published in peer- review ed journals were identified , and 13 of these were excluded from the analysis because of method ologic limitations . Nine of the remaining 14 studies were noncomparative ( 8 prospect i ve and 1 retrospective ) , 1 was quasi-r and omized , and 4 were true r and omized controlled trials . DATA EXTRACTION AND SYNTHESIS The sample size was generally limited ; the mean number of patients included was 26 in the noncomparative trials and 29 in the r and omized controlled trials . The mean duration of treatment was 6 months . A total of 355 women had pain at entry . Considering all noncomparative studies , the pooled frequency of nonresponders at the end of treatment was 9 % ( 18/203 ; 95 % confidence interval [ CI ] , 5.3 % to 13.6 % ) . The common odds ratio from the four r and omized controlled trials comparing progestins with danazol or a GnRH agonist was 1.1 ( 95 % CI , 0.4 to 3.1 ) , suggesting equivalence in treatment effect . In the only double-blind , placebo-controlled trial , the frequency of nonresponders was not significantly different in the two arms . Only four studies assessed pain after drug withdrawal . The pooled frequency of pelvic pain at the end of follow-up was 50 % ( 35/70 ; 95 % CI , 37.8 % to 62.2 % ) . The overall crude conception rate after therapy among women who desired pregnancy was 44 % ( 86/194 ; 95 % CI , 37.2 % to 51.6 % ) . Side effects of limited clinical relevance were observed frequently . CONCLUSION ( S ) The available data suggest that the efficacy of progestins for temporary relief of  endometriosis-associated pelvic pain  is good and comparable to that of other , less safe treatments 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 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 One hundred infertile patients with laparoscopically confirmed ovarian endometriosis were treated with either intranasal ( IN ) Buserelin ( Hoechst , AG , Frankfurt am Main , West Germany ) ( 300 micrograms three times a day ) or subcutaneous ( SC ) Buserelin implant ( 6.6 mg Buserelin ) . Serum estradiol was suppressed in the menopausal range in both groups , but the inhibition of the pituitary ovarian axis appeared more profound and consistent in the SC group than in the IN group . Laparoscopic findings proved that the SC Buserelin emerged superior to the IN Buserelin . Indeed , the score of endometriotic lesions and the ovarian cyst diameter were more reduced in the SC group than in the IN group . Moreover , the histologic study showed a lower incidence of active endometriosis and a lower mitotic index of ovarian endometrial epithelium in the SC group than in the IN group . In conclusion , the release of a gonadotropin-releasing hormone agonist by a biodegradable implant achieved better efficacy in reducing endometriotic lesions than the IN mode of administration OBJECTIVE To compare the efficacy and safety of dienogest ( DNG ) with intranasal buserelin acetate ( BA ) in patients with endometriosis . DESIGN Phase III , r and omized , double-blind , multicenter , controlled trial . SETTING Twenty-four study centers in Japan . PATIENT(S ) Two hundred seventy-one patients with endometriosis . INTERVENTION(S ) Dienogest ( 2 mg/day , orally ) or BA ( 900 microg/day , intranasally ) for 24 weeks . MAIN OUTCOME MEASURE(S ) The pre- to posttreatment changes in the scores of five subjective symptoms during nonmenstruation ( lower abdominal pain , lumbago , defecation pain , dyspareunia , and pain on internal examination ) and two objective findings ( in duration in the pouch of Douglas and limited uterine mobility ) . RESULT ( S ) Dienogest reduced the scores of all symptoms and findings at the end of treatment , and the mean changes in the scores of all symptoms and findings except in duration in the pouch of Douglas were comparable to those obtained with BA . Compared with BA , DNG was associated with irregular genital bleeding more frequently and with fewer hot flushes . The reduction in bone mineral density ( BMD ) during DNG treatment was significantly lower than that during BA treatment . CONCLUSION ( S ) DNG is as effective as intranasal BA in alleviating endometriosis , and causes less BMD loss During the past decade , the development of various gonadotrophin-releasing hormone ( Gn-RH ) agonists , which induce reversible hypo-oestrogenism has opened a new area in the medical management of endometriosis . In an open , multicentre phase III study , the efficacy , tolerance and safety of the Gn-RH agonist leuprorelin acetate were tested . The preliminary results of 104 women treated in seven German centres are presented . Pelvic endometriosis was diagnosed by laparoscopy and classified according to the American Fertility Society scoring system : 33 % of patients had minimal , 22 % mild , 28 % moderate and 8 % severe endometriosis and in 9 % no pathological results were obtained . The patients ' mean age was 30 + /- 6 years and 66 had infertility problems . Treatment was started within the first 3 days of the menstrual cycle and consisted of a subcutaneous injection of leuprorelin acetate 3.75 mg , repeated once monthly over 24 weeks . A follow-up period of 12 months after the last injection has been completed in 70 patients , including a second laparoscopy . At all visits , symptoms were evaluated , physical examinations performed , and blood sample s collected for haematological screening , serum chemistry determinations and measurement of the gonadotrophins oestradiol and progesterone and leuprorelin acetate . The median score at laparoscopy fell from 12 before operation to 8 after operation and 2 after treatment with leuprorelin acetate . Of the total number of patients , 89 % had improvements in their endometriosis , 8 % a deterioration and 3 % no change . Patients reported improvement in the following : dysmenorrhoea 93 % , dyspareunia 62 % and pelvic pain 70 % . However , all women complained of at least one of the following symptoms : hot flushes 86 % , sleep disturbance 62 % , sweating 61 % , headache 41 % , nausea 32 % and depression 20 % . Fifty-five percent of patients reported additional side effects such as vaginal dryness , fatigue and lower abdominal pain . After the third injection , amenorrhoea persisted in 94 % of the women . Four weeks after the first leuprorelin acetate injection median concentrations of oestradiol fell from 45 pg/ml to 11 pg/ml , follicle-stimulating hormone from 7 U/L to 3 U/L and luteinising hormone from 5 U/L to 1 U/L and remained almost unchanged over the observation period . During the 6 months ' treatment , laboratory parameters showed no significant deviations from normal ; only total cholesterol , high-density lipoprotein cholesterol and alkaline phosphatase increased . Treatment results were judged as good and satisfactory in 82 % and 11 % of cases , respectively . On the basis of this study , it can be concluded that leuprorelin acetate treatment is safe , well tolerated and effective in the medical management of endometriosis and endometriosis-related complaints 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 A double-blind , double-dummy , 6-month multicenter study comparing the effects of nafarelin and danazol in the treatment of endometriosis was completed recently by investigators from 13 institutions in seven European countries . The 194 patients ( aged 18 to 45 years ) selected for the study were divided into two groups . One group received nafarelin , 200 micrograms twice daily , and placebo capsules identical to danazol , twice daily . The other group received danazol capsules , 200 mg twice daily , and a placebo nasal spray identical to nafarelin , twice daily . A comparison of decreases in both groups of American Fertility Society endometriosis scores and in severity scores developed by the investigators indicates that nafarelin and danazol are equally effective in the treatment of endometriosis OBJECTIVE To compare intranasal nafarelin and intramuscular leuprolide acetate ( LA ) depot in the management of  endometriosis .  STUDY DESIGN A multicenter , prospect i ve , r and omized , double-placebo , double-blind study was conducted on subjects who had symptoms and signs of endometriosis and bone mineral density ( BMD ) within the age-appropriate normal range . For 6 months , 99 subjects received nafarelin , 200 micrograms twice daily , and placebo injections once monthly ; 93 subjects received LA depot injections , 3.75 mg once monthly , and placebo nasal spray , twice daily . Subjects were followed throughout treatment and for six months after treatment . The main outcome measures were changes in endometriosis symptoms and signs , BMD measurements , subject-reported and objective ly measured hot flushes and circulating estradiol concentrations . RESULTS Nafarelin was as effective as LA depot in alleviating symptoms and signs of endometriosis .  LA depot recipients lost significantly more BMD , had more days with subjective hot flushes and more objective ly measured hot flushes than did nafarelin recipients . In the nafarelin group , estradiol levels were consistently higher than in the leuprolide depot group , with significant differences by month 3 of dosing . CONCLUSION Nafarelin and LA depot were equally effective despite higher estradiol levels in nafarelin recipients . Nafarelin-treated subjects lost less BMD , had fewer days with hot flushes and had fewer objective ly measured hot flushes Treatment with nafarelin , a gonadotropin-releasing hormone agonist , reversibly inhibits ovarian function and induces hypoestrogenemia . To determine the efficacy of such hormonal manipulation in the treatment of endometriosis , we r and omly assigned 213 patients with laparoscopically confirmed endometriosis to receive , for six months , either nafarelin by nasal spray ( 400 or 800 micrograms per day ) or oral danazol ( 800 mg per day ) . Placebo nasal spray and placebo tablets were used to double blind the study . Pretreatment and post-treatment laparoscopies were compared by means of the American Fertility Society 's scoring system . More than 80 percent of the patients in each treatment group had a reduction in the extent of disease as assessed by laparoscopy . The mean laparoscopic scores decreased from 21.9 to 12.6 with 800 micrograms of nafarelin , from 20.4 to 11.7 with 400 micrograms of nafarelin , and from 18.4 to 10.5 with danazol ( P = 0.0001 within each group ; there were no statistically significant differences between the groups ) . The percentage of women with severely painful symptoms of endometriosis decreased from about 40 percent to 5 to 10 percent , whereas the percentage with no or minimal discomfort rose from 25 to 70 percent . Of the 149 patients who tried to become pregnant , 58 ( 39 percent ) succeeded after the completion of treatment ; similar rates of pregnancy applied to the three treatment groups . Danazol use decreased high-density lipoprotein levels and increased low-density lipoprotein levels . These changes were not observed in nafarelin users , but a higher percentage of them reported hot flashes and decreased libido . We conclude that nafarelin is an effective agent for treating endometriosis and has few side effects other than hypoestrogenism Objective The aim of this study was to estimate the efficacy of elagolix , an oral gonadotropin-releasing hormone ( GnRH ) antagonist , for the treatment of endometriosis-associated pelvic pain . Methods This was a phase II , r and omized , placebo-controlled parallel group study conducted at 37 US centers , consisting of an 8-week double-blind period followed by a 16-week open-label period . Patients were 137 women aged 18 to 49 , with laparoscopically confirmed endometriosis and moderate to severe nonmenstrual pelvic pain and dysmenorrhea , who were administered elagolix 150 mg daily or placebo . The primary outcomes of the study were the daily assessment of dysmenorrhea , nonmenstrual pelvic pain and dyspareunia using a modified Biberoglu-Behrman scale . Results During the double-blind period , there were significantly greater mean reductions from baseline to week 8 in dysmenorrhea ( -1.13 ± 0.11 vs. −0.37 ± 0.11 , p<0.0001 ) , nonmenstrual pelvic pain ( -0.47 ± 0.07 vs. −0.19 ± 0.07 , p = 0.0066 ) , and dyspareunia scores ( -0.61 ± 0.10 vs. −0.23 ± 0.10 , p = 0.0070 ) in the elagolix group compared with placebo . Continued improvements were observed during the open-label treatment regardless of initial treatment allocation . Elagolix treatment was also associated with significant improvements in quality -of-life measures during the double-blind and open-label periods . The most common adverse events occurring with elagolix were nausea , headache and hot flush , each in 9.9 % of patients . Conclusion Elagolix effectively reduced endometriosis-associated pelvic pain over a 24-week period and was well-tolerated 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 Low-dose add-back therapy during postoperative GnRH agonist treatment could lower the risk of add-back-induced endometriosis recurrence and reduce treatment dropout compared with a regular dose . However , the effect of low-dose add-back therapy is still unknown . The aim of this study was to determine whether low-dose add-back therapy can also effectively relieve the hypoestrogenic side effects and simultaneously maintain a therapeutic response of GnRH agonist treatment . MATERIAL S AND METHODS This analysis was a prospect i ve cohort study . During postoperative GnRH agonist treatment , a total of 107 women were prescribed add-back therapy [ oral combination tablet ; estradiol valerate ( 1 mg ) and medroxyprogesterone acetate ( 2.5 mg ) ] ( Indivina ; Orion , Espoo , Finl and ) for 20 weeks . Patients in the low dose add-back therapy group were prescribed the tablet once a day , and patients in the regular dose group were given the tablet twice a day . Hypoestrogenic side effects , such as hot flashes and insomnia , were recorded . Patients were also question ed regarding their pelvic symptoms and pain to evaluate the possibility of endometriosis recurrence . Lumbar spine ( L2-L4 ) bone mineral density was measured using dual X-ray absorptiometry . The dropout rates in both groups were also evaluated . RESULTS The incidence of hypoestrogenic side effects was lower in the low dose group compared with the regular dose group , including hot flashes ( 19.2 % vs. 21.8 % , p = 0.741 ) and insomnia ( 15.4 % vs. 18.2 % , p = 0.699 ) , although there were no significant difference between the groups . In addition , a higher number of patients in the regular dose group dropped out of treatment compared to the low dose group ( 14.5 % and 9.6 % , respectively , p = 0.435 ) . The patients in both groups had a significant loss of mean bone mineral density during therapy ( p < 0.001 and p = 0.018 for the low dose and regular dose groups , respectively ) . CONCLUSION Low dose add-back therapy could effectively ameliorate hypoestrogenic side effects and simultaneously maintain the therapeutic response of GnRH agonist treatment . The treatment dropout was lower compared with a regular dose . Therefore , low dose add-back therapy can be considered a treatment choice during postoperative GnRH agonist treatment
target: ( 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
background: OBJECTIVE To assess patient response rates to medical therapies used to treat endometriosis-associated pain .