Ovarian suppression induced with Buserelin or danazol in the management of endometriosis: a randomized, comparative study. Lupron depot (leuprolide acetate for depot suspension) in the treatment of endometriosis: a randomized, placebo-controlled, double-blind study. Lupron Study Group. Clinical experience treating endometriosis with nafarelin. [Medical treatment of endometriosis: comparative study of leuprolide acetate and danazol]. Pain of endometriosis: effects of nafarelin and danazol therapy. A comparative treatment trial of endometriosis using the gonadotrophin-releasing hormone agonist, nafarelin, and the synthetic steroid, danazol. An open randomized comparative study of the effect of goserelin depot and danazol in the treatment of endometriosis. Zoladex Endometriosis Study Team. A randomized, comparative trial of triptorelin depot (D-Trp6-LHRH) and danazol in the treatment of endometriosis. Nafarelin versus danazol in the treatment of endometriosis. Buserelin versus danazol in the treatment of endometriosis-associated infertility. Serum-soluble CD23 in patients with endometriosis and the effect of treatment with danazol and leuprolide acetate depot injection. A randomized, parallel, comparative study of the efficacy and safety of nafarelin versus danazol in the treatment of endometriosis in Taiwan. Depot leuprolide versus danazol in treatment of women with symptomatic endometriosis. I. Efficacy results. Administration of nasal nafarelin as compared with oral danazol for endometriosis. A multicenter double-blind comparative clinical trial. Buserelin acetate in the treatment of pelvic pain associated with minimal and mild endometriosis: a controlled study. Reversible pituitary ovarian suppression induced by an LHRH agonist in the treatment of endometriosis--comparison of two dose regimens. Clinical study on finding optimal dose of a potent LHRH agonist (buserelin) for the treatment of endometriosis--multicenter trial in Japan. The levonorgestrel-releasing intrauterine system and endometriosis staging. Nafarelin: a new medical therapy for endometriosis. A randomized comparative study of the effect of leuprorelin acetate depot and danazol in the treatment of endometriosis. 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. Nafarelin in the management of endometriosis: quality of life assessment. A randomized, prospective comparison of endocrine changes induced with intranasal leuprolide or danazol for treatment of endometriosis. Nafarelin vs. leuprolide acetate depot for endometriosis. Changes in bone mineral density and vasomotor symptoms. Nafarelin Study Group. [Influence of GnRH analogue on the intensification of endometriosis symptoms and infertility treatment]. A double-blind randomized study of the treatment of endometriosis with nafarelin or nafarelin plus norethisterone. Effects of the levonorgestrel-releasing intrauterine system on cardiovascular risk markers in patients with endometriosis: a comparative study with the GnRH analogue. Zoladex (goserelin acetate implant) in the treatment of endometriosis: a randomized comparison with danazol. The Zoladex Endometriosis Study Group. Effects of triptorelin versus placebo on the symptoms of endometriosis.
The effectiveness of Buserelin (Hoechst-Roussel Pharmaceuticals, Inc., Somerville, NJ) (0.2 mg subcutaneously [SC] or 1.2 mg intranasally [IN] per day) and danazol (800 mg per day) in inducing ovarian suppression for the management of endometriosis was compared in a prospective randomized study. During 6 months of treatment, peripheral follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol concentrations were suppressed to a similar degree in both groups. Symptomatic improvement and laparoscopically assessed regression of endometriotic lesions also were comparable. After treatment, 8 of 18 infertile women treated with Buserelin and 5 of 8 treated with danazol conceived. General and hypoestrogenic side effects were similar in both groups, while androgenic and anabolic were more frequent with danazol. High density lipoprotein (HDL)-cholesterol increased in the Buserelin and decreased in the danazol group. The study indicates that at the dose tested, buserelin and danazol induce a similar degree of ovarian suppression resulting in a comparable clinical improvement and regression of endometriotic lesions. The safety and efficacy of leuprolide acetate (LA) for depot suspension (Lupron depot; TAP Pharmaceuticals, North Chicago, IL), 3.75 mg versus placebo, in the treatment of pain associated with endometriosis was assessed in a randomized, double-blind, multicenter study involving 52 patients. Dysmenorrhea, pelvic pain, and pelvic tenderness all responded significantly to LA treatment in comparison with placebo. Menses were suppressed in all of the LA patients. Estradiol decreased significantly to menopausal levels in the LA group. There were small to moderate changes in a variety of laboratory parameters, but these were not clinically significant. The most common adverse event was vasodilatation, occurring significantly more frequently in the LA group. Lupron depot was shown to be safe and effective in inducing a hormonal and menstrual suppression in patients with endometriosis, resulting in alleviation of pain symptoms. The preliminary results from an ongoing multicenter trial further support the efficacy and excellent tolerability of nafarelin in the management of endometriosis. Hypo-oestrogenaemia following surgical oophorectomy leads to a regression of the ectopic endometrial tissue. A medical and transitory oophorectomy can be obtained using leuprolide ac., an analogue of LH-RH. In this study we compare the results of therapy with danazol or leuprolide in the treatment of endometriosis. Fifty patients affected by endometriosis were selected laparoscopically and recorded under the classification of American Fertility Society. 20-40 year old women who were admitted had not received any therapy for endometriosis within the previous 12 months. They were allocated at random to open treatment with intramuscular injection of leuprolide (3.75 mg/monthly) or oral danazol. The dose regimen used for this last drug was 600 mg/daily in the majority of patients. 47 women completed a six months therapy, and 42 underwent to a second laparoscopy to evaluate the effects of the treatment. Both danazol and leuprolide were associated to a decreasing of clinical symptoms and to adverse effects that we described in this paper. To compare the efficacy of nafarelin acetate with danazol in the treatment of dysmenorrhea, dyspareunia, and pelvic pain associated with endometriosis.
                Prospective, randomized 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 randomly 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.
                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]
                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 randomized and double-blind trial was carried out comparing intranasal nafarelin acetate (400 micrograms daily) and oral danazol (600 mg daily), given over 6 months, in the treatment of 49 patients with laparoscopically proven endometriosis. Both drugs produced a highly significant and similar reduction (of 60 to 70%) in objective American Fertility Society scoring, even in severe disease. No effect was seen on adhesions. Both drugs suppressed oestradiol levels to a similar extent, although nafarelin caused a substantial rise in the first 2 weeks after the initiation of therapy. Nafarelin suppressed LH substantially and FSH, testosterone and prolactin to a small degree, whereas FSH and LH increased slightly during danazol. Pregnancies occurred in 12 of 22 infertile women in the 12 months following nafarelin, and in 6 of 14 in the danazol group. Side-effects were reported at a similar rate with both drugs, but the pattern was different. Hot flushes were the predominant side effect with nafarelin, although oestradiol levels were not suppressed to the extent expected. Small amounts of spotting or light bleeding were experienced with both drugs, but these tended to decrease with time with nafarelin and increase with danazol. To compare the efficacy and safety of goserelin depot and danazol for endometriosis.
                Open, randomized comparative trial.
                Multicenter European academic clinical institutions.
                A total of 307 patients with laparoscopically diagnosed endometriosis were randomized to goserelin (n = 204) or danazol (n = 103); 249 patients underwent second look laparoscopy (175 received goserelin and 74 danazol) and were analyzed for efficacy.
                A 3.6-mg depot of goserelin monthly subcutaneously or oral danazol 200 mg three times a day administered for 24 weeks.
                Efficacy assessments were based on changes in visible deposits at laparoscopy before and after treatment and subjective symptom scores at 4-week intervals during treatment and 8-week intervals after treatment for up to 24 weeks. Safety was assessed by adverse event reporting and clinical laboratory measures.
                There were similar proportions of symptomatic (73%) and asymptomatic (but infertile) (27%) and comparable distribution of different severity of endometriosis randomized to each treatment. Significantly fewer patients randomized to goserelin (6.4%) withdrew during treatment compared with 20.4% randomized to danazol (P less than 0.05). There were significantly reduced visible deposits of endometriosis found post-treatment (P less than 0.0001) within each group but no differences between the treatments. The mean total subjective symptoms scores remained significantly less than entry at 24 weeks post-treatment (P less than 0.05). Hypoestrogenic side effects were more common in those receiving goserelin, particularly hot flushes, but anabolic/androgenic side effects of weight gain and muscle cramps were more common in those receiving danazol.
                The monthly administered 3.6-mg depot preparation of goserelin was highly effective at inducing resolution of endometriotic implants and relieving the symptoms of endometriosis with prevention of their return during 24 weeks follow-up in the majority of patients. However, results were not significantly different from those achieved with danazol 600 mg/d. To compare treatment efficacy and safety parameters a total of 55 premenopausal women with histologically proven endometriosis (stage II-IV) were randomized to receive the LHRH-analogue depot triptorelin (n = 30) or the steroid danazol (n = 25) for a total of 24 weeks. Immediately after cessation of the endocrine therapy a second-look operation was performed. Four as well as 24 weeks after the end of treatment patients were seen for re-evaluation of clinical symptoms and safety parameters. Estradiol suppression was significantly more pronounced with triptorelin, while the free androgenic index rose with danazol. Both substances were equally effective in reducing endometriotic implants (58% and 51%, respectively). Dysmenorrhea was absent at the end of medical therapy in both treatment groups. Dyspareunia and pelvic pain decreased at least by 50%. Red blood count, thrombocytes, liver enzymes and the atherogenic index rose with danazol, while the urinary calcium/creatinine ratio showed a marked elevation with triptorelin. Adverse effects were mainly due to the hypoestrogenism of the LHRH analogue and the androgenic/anabolic properties of the steroid. Triptorelin and danazol are equally effective in treating endometriosis. Therefore, choice of treatment should be based on the patient's medical history and the pharmacological profile of each substance. 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. A total of 62 infertile women with a laparoscopic diagnosis of endometriosis were allocated randomly to two treatment groups, one of which (32 patients) received oral danazol 600 micrograms/day and the other (30 patients) received intranasal buserelin 1200 micrograms/day for 6 months. Suppression of serum levels of estradiol was greater with the gonadotropin-releasing hormone agonist treatment. Pain symptoms improved markedly during treatment in both groups. At the end of treatment a repeat laparoscopy was performed only in the patients who agreed to it (12 in the buserelin group and 13 in the danazol group), and it did not reveal significant differences in the effects of the two treatments on the endometriotic implants. All of the patients were followed up for at least 12 months, during which pregnancy was attempted. At 18 months the cumulative pregnancy rate was 48% in the patients treated with buserelin and 43% in those treated with danazol. Pain recurrence was observed in about half of the patients in each group 1 year after treatment suspension. The side effects were more frequent and more severe in the danazol-treated patients, whereas those given buserelin generally reported only symptoms of hypoestrogenism. The results of this study suggests that buserelin is at least as effective as danazol in the treatment of endometriosis when the outcome is considered in terms of restored fertility, and its side effects are less severe. Activated B cells have recently been shown to produce soluble CD23 from their membranes. The serum-soluble CD23 concentration in 21 patients with pelvic pain diagnosed as having endometriosis and confirmed by histology, and in 18 patients without pelvic pain, who had a normal pelvis during laparoscopic sterilization, was studied by chemiluminescent enzyme-linked immunosorbent assay. The endometriosis patients were randomized to 3 months of either danazol or leuprolide acetate injection. Serum was taken before and after 3 months of therapy. The serum-soluble CD23 concentration was significantly elevated in patients with endometriosis when compared with the controls (P < 0.0001). There was no correlation between soluble CD23 concentrations and the severity of endometriosis (r = 0.48, P > 0.05). The serum concentration of soluble CD23 decreased significantly on treatment with danazol but not leuprolide acetate (P < 0.05). We conclude that the elevation of soluble CD23 in patients with endometriosis suggests that there is activation of B cells, which respond to danazol but not leuprolide acetate injection. The purpose of this study was to evaluate the efficacy and safety of nafarelin, a gonadotropin-releasing hormone (GnRH) analogue, versus danazol in the treatment of women with endometriosis in Taiwan.
                Fifty-nine women with laparoscopically and pathologically confirmed endometriosis were randomized to receive nafarelin or danazol for 180 days. Efficacy was assessed from mean changes in laparoscopy score (LS) and total symptom severity score (TSSS). Adverse events (AEs) and laboratory parameters, including hematology, hepatic function, blood pressure, and lipid levels, were monitored for safety evaluations.
                All demographic and baseline factors, except body weight, were comparable between the 2 treatment groups. Both nafarelin and danazol satisfactorily resolved pelvic tenderness, induration, pelvic pain, dysmenorrhea and dyspareunia. No significant differences were noted in efficacy endpoints between nafarelin and danazol regarding LS and TSSS at 90 and 180 days of treatment. No significant difference was observed between the 2 groups regarding the overall incidence of AEs, except for laboratory-related AEs. However, nafarelin tended to have less impact than danazol on aspartate transaminase and alanine transaminase, and nafarelin was better tolerated than danazol regarding changes in lipid profiles. Both treatments had little or no effect on hematologic parameters.
                Nafarelin and danazol demonstrated similar clinical efficacy, but nafarelin was associated with fewer laboratory changes and a stable lipid profile, relative to danazol. Moreover, intranasally administered nafarelin is noninvasive, and may be a more comfortable and safer alternative to slow-release injectable GnRH agonists. Based on this study, we suggest that nafarelin, like other GnRH analogues, may be a treatment of choice for Taiwanese women with endometriosis. However, direct comparative studies of nafarelin with slow-release injectable GnRH agonists are now required. We aimed to assess the efficacy of depot leuprolide versus danazol in the treatment of endometriosis.
                A double-blind randomized 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 standardized methods.
                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.
                Depot leuprolide is an effective alternative to danazol in decreasing the extent of endometriosis and endometriosis-related pain. 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 randomly 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. To evaluate the changes of pain symptoms induced by buserelin acetate, a gonadotropin-releasing hormone agonist, in a group of patients with endometriosis.
                Thirty-five infertile patients with one or more of the following symptoms (dysmenorrhea, pelvic pain, deep dyspareunia, and endometriosis stage I or II) were allocated randomly to treatment with buserelin acetate 1,200 micrograms/d IN for 6 months (n = 19) or expectant management (n = 16). Pain symptoms were recorded by the women themselves using a questionnaire that included two scales for pain evaluation: one analogue and one multidimensional. The treated and untreated patients were followed for a minimum of 18 and 12 months from the time of randomization, respectively.
                Buserelin acetate markedly reduced dysmenorrhea, pelvic pain, and dyspareunia during the treatment and also for the 12 subsequent months. During follow-up of the expectant management group, dysmenorrhea resolved in 19% (3/16) of the cases, and pelvic pain did not recur after diagnostic laparoscopy in one of the three women affected nor did deep dyspareunia in two of the five who reported the symptom before laparoscopy.
                Buserelin acetate induced a significant improvement of pain symptoms that persisted in approximately half of the patients even after withdrawal of the drug. However, symptoms associated with endometriosis showed a spontaneous remission in approximately one fifth of the untreated patients. Buserelin [D-Ser(TBU)6-des Gly NH2(10) LHRH ethylamide], an LHRH agonist, was administered intranasally at two dose levels, 200 micrograms t.d.s or 300 micrograms t.d.s., to 20 women with proven endometriosis, many with recurrent disease. Both dose schedules achieved significant suppression of circulating 17 beta-oestradiol levels often to within the postmenopausal range, the larger dose inducing significantly greater suppression (P less than 0.05). Serum FSH values were suppressed below baseline but serum LH remained at pretreatment levels or above, whilst on treatment. Complete resolution of endometriotic deposits was achieved in 68% of cases following 6 months treatment with dramatic and long-standing relief of symptoms with no apparent dose difference. In all other subjects there was significant reduction in the extent of endometriotic deposits and improvement in American Fertility Society classification of disease stage. The most commonly occurring side effect was hot flushes; their intensity and frequency related to the degree of suppression of serum oestradiol and the dose of Buserelin administered. nan This study aims to determine whether the levonorgestrel-releasing intrauterine system can influence American Society for Reproductive Medicine endometriosis staging scores, as assessed through second-look laparoscopies, and to compare the results with those obtained with a GnRH agonist. Both treatments reduced the extent of pelvic endometriotic lesions in patients with chronic pelvic pain. nan Administration of superactive agonistic analog of gonadotropin-releasing hormone (GnRH) has shown to induce a paradoxic and reversible suppression of gonadotropins, so that gonadal steroid concentrations are suppressed and hypoestrogenemia is induced. In order to compare the efficacy and safety of leuprorelin acetate depot (LA) and danazol in the treatment of endometriosis, we conducted this study.
                A total of forty-five patients with pelvic endometriosis of different severity at laparoscopy with biopsy of peritoneal implants (n = 33) and surgical procedure (enucleation of ovarian chocolate cysts, cystectomy, or fulguration, n = 12) were included in the study and followed during the 20 weeks of treatment. LA 3.75 mg was injected subcutaneously every 28 days, while the daily oral dose of danazol was 800 mg.
                Both treatments were associated with a lowering of severity score. There was a consistent decrease in women with stage IV disease in the LA group and an increase in patients with stage I disease in the danazol group, but no difference was found between both treatments. Hot flushing was the most common side effect reported in 97% of LA but occurred only in 13% of danazol-treated patients. In contrast, the androgenic, anabolic side effects of weight gain and myalgia were common in those receiving danazol. The CA-125 levels were significantly lower in both treatment groups compared with their pretreatment levels (p < 0.01). During the five months of the LA treatment, biochemical evaluation revealed no pathologic alternation. Only total protein albumin, alkaline phosphatase, total bilirubin, total cholesterol, high density lipoprotein-cholesterol, low density lipoprotein-cholesterol, uric acid and calcium increased significantly. Danazol was also associated with adverse metabolic effects and significantly increased low-density lipoprotein-cholesterol concentrations (p < 0.05). In the fourth week, serum estradiol (E2) levels decreased to nearly castrated levels (13.87 +/- 1.63 pg/ml) in all patients treated with LA, and remained at this level thereafter. On the contrary, a slight but significant increase of the serum E2 levels was noted during the danazol treatment. After five months of treatment with LA, no significant changes in bone density were observed at the femoral neck or the anteroposterior (AP) view of lumbar spine, but there was a significant loss in bone density at the lateral view of lumbar spine (-7.1%, p < 0.05).
                Both LA and danazol are effective in the treatment of endometriosis. The hypoestrogenic side effects of LA may be better tolerated than the androgenic, anabolic effects of danazol. However, the danazol treatment costs less than LA and has no significant side effect with osteoporosis. The objective of this multicentre randomized, 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.
                Eighty-two women, 18 to 40 years of age (mean 30 years), with endometriosis, dysmenorrhoea and/or CPP, were randomized 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 Questionnaire (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.
                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.
                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. Quality of life is important when comparing the relative advantages of nafarelin versus danazol for the treatment of endometriosis. Recent studies have investigated the potential differences between the safety profiles of nafarelin and danazol and the impact of these profiles on the patient's quality of life. Results show that although these drugs have similar efficacy, they are associated with very different safety profiles. Most notable are the androgenic effects such as weight gain associated with danazol. With nafarelin, hypoestrogenic side effects, such as hot flashes, are more common. More important, these differences in safety profiles may prove to be relevant to patient satisfaction and compliance with therapy. A prospective, randomized trial compared hormonal changes induced with intranasal leuprolide 1.6 mg/day to danazol 800 mg/day for treatment of endometriosis. Both regimens induced anovulation and ovarian suppression in all subjects. Mean estradiol (E2) and progesterone (P) levels were suppressed with both regimens, but were lower with leuprolide. There was no difference in cumulative follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels, although at times during treatment mean levels of these hormones were lower with leuprolide. Higher P levels in the danazol group, most likely of adrenal origin, indicated a suppressive effect on adrenal steroidogenesis. Symptomatic improvement was significant in both groups. Laparoscopy after treatment also demonstrated a decrease in endometriosis scores in both groups. At 12 months after treatment, cumulative pregnancy and live birth rates were similar in both groups. Leuprolide offers an attractive alternative to danazol for the medical treatment of endometriosis. To compare intranasal nafarelin and intramuscular leuprolide acetate (LA) depot in the management of endometriosis.
                A multicenter, prospective, randomized, 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 objectively measured hot flushes and circulating estradiol concentrations.
                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 objectively 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.
                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 objectively measured hot flushes. The aim of this study was to evaluate the influence of the treatment with oral doses of 50 mg GnRH analogue on the intensification of endometriosis symptoms and infertility amongst women with evident symptoms of endometriosis in comparison with placebo group. A group of 34 women at the age from 18 to 45 were introduced into the study. The inclusion criteria for investigated population contained: endometriosis symptoms, endometriosis diagnosed by laparoscopy, its surgical or pharmacological treatment, negative pregnancy test score and regular menses. The patients were divided into 2 groups: investigated group and control group. Women completed "Diary" every day in which they estimated main endometriosis symptoms: dysmenorrhea, dyspareunia, pelvic pain and vaginal bleeding (according to Pain Grading Scale). The intensification of dysmenorrhea and vaginal bleeding was reduced in the investigated group in comparison with control one. These differences were statistically significant. Although the extremity of dyspareunia was decreased in two groups, this correlation was statistically significant only in the investigated group. Pelvic pain evaluation showed that its level was lower in the investigated group (p > 0.05). It was found that 11 women (investigated group) and 5 women (control group) got pregnant after the period of 12-week treatment.
                GnRH analogues have an efficient influence on the reduction of endometriosis symptoms. GnRH analogues could be used in the management of infertility. The objective of this study was to compare the efficacy of nafarelin 200 micrograms (Group A), nafarelin 400 micrograms (Group B) and the combination of nafarelin 200 micrograms and norethisterone 1.2 mg (Group C) daily, in treating symptoms of endometriosis, American Fertility Society score and adverse events during 6 months of treatment. A prospective, randomized, double-blind parallel group study was performed in two centers and 49 women with endometriosis diagnosed laparoscopically were included. The patients were seen monthly for physical examination and records were taken for bleeding pattern, symptom score and adverse events. A control laparoscopy was performed at the end of 6 months of treatment. All patients were followed 6 months after treatment. At 3 and 6 months the pelvic examination total score had decreased significantly in all three groups. The total endometriosis score was significantly reduced in Groups B and C. After 2 months the total symptom score showed a significant decrease in Groups B and C. The frequency of hot flushes during the first month of treatment was lowest in Group C, but during the rest of treatment there were no differences between the groups. Best bleeding control was obtained in Group C. We conclude that nafarelin 200 micrograms daily has as good an effect on endometriosis symptoms as nafarelin 400 micrograms daily, and the addition of norethisterone 1.2 mg results in fewer hot flushes and better bleeding control. The study was conducted to evaluate the cardiovascular risk markers associated with endometriosis and the influence of the levonorgestrel intrauterine system (LNG-IUS) compared with the GnRH analogue (GnRHa) leuprolide acetate on these risk markers after 6 months of treatment.
                This was a randomized, prospective, open clinical study, with 44 patients with laparoscopically and histologically confirmed endometriosis. Patients were randomized into two groups: the LNG-IUS group, composed of 22 patients who underwent LNG-IUS insertion, and the GnRHa group, composed of 22 patients who received a monthly GnRHa injection for 6 months. Body mass index; systolic and diastolic arterial blood pressure; heart rate; and laboratory cardiovascular risk markers such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), C-reactive protein (CRP), homocysteine (HMC), lipid profile, total leukocytes and vascular cell adhesion molecule (VCAM) were measured before and 6 months after treatment.
                After 6 months of treatment, a significant reduction in pain score occurred in both groups with no significant difference in improvement between the two medications evaluated. In the LNG-IUS group, from pretreatment to posttreatment period, there was a significant reduction in the levels (mean+/-SD) of VCAM (92.8+/-4.2 to 91.2+/-2.7 ng/mL, p=.04), CRP (0.38+/-0.30 to 0.28+/-0.21 mg/dL, p=.03), total cholesterol (247.0+/-85.0 to 180.0+/-31.0 mg/dL, p=.0002), triglycerides (118.0+/- 76.0 to 86.5+/-41.5 mg/dL, p=.003), low-density lipoprotein cholesterol (160.5+/-66.0 to 114.5+/-25.5 mg/dL, p=.0005) and high-density lipoprotein cholesterol (63.0+/-20.5 to 48.5+/-10.5 mg/dL, p=.002). The GnRHa group showed an increase in HMC levels (11.5+/-2.9 to 13.0+/-2.7 mumol/L, p=.04) and a reduction in IL-6 levels (4.3+/-3.9 to 2.3+/-0.8 pg/mL, p=.005), VCAM (94.0+/-3.8 to 92.0+/-1.6 ng/mL, p=.03) and total leukocytes (7330+/-2554 to 6350+/-1778, p=.01). In the GnRH group, the remaining variables, including lipid profile, did not show any statistical difference.
                This study shows that some cardiovascular risk markers are influenced by both GnRHa and the LNG-IUS, but the latter had a greater positive impact on the lipid profile, which could lead to a favorable effect during long-term treatment. 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, randomized, open study.
                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.
                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 androgenic 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.
                Zoladex is as well tolerated and as effective as danazol in the treatment of premenopausal women with endometriosis. To compare the effect of a GnRH-agonist, triptorelin, versus placebo on the symptoms of endometriosis.
                A prospective, randomized, double-blind study of 6 months of treatment followed by 12 months of follow-up.
                Departments of Obstetrics and Gynecology at two universities and one general hospital.
                Forty-nine women with symptoms of laparoscopically verified endometriosis.
                Triptorelin depot or placebo was given every 4 weeks. Clinical evaluation, including the Duration Intensity Behavior Scale and Visual Analogue Scale for pain, was performed before the injections and up to 12 months after treatment. A control laparoscopy was performed 4-6 weeks after the last injection.
                Quantitation of pain.
                Twenty-four patients had active treatment and 25 received placebo. Pain symptoms according to both scales were significantly more reduced after 2 months of triptorelin treatment compared to placebo. The extent of endometriotic lesions was reduced 50% during triptorelin treatment and increased 17% during placebo. The average area of endometriotic lesions was reduced 45% during triptorelin treatment but was unchanged during placebo. Side effects, mainly hot flushes, were experienced by 80% of the actively treated group but also by 33% of patients in the placebo group. Because of recurrent symptoms, only five patients could be observed for 12 months after completion of treatment.
                Triptorelin reduces endometriotic lesions and pain to a significantly higher degree than placebo.
GnRHas appear to be more effective at relieving pain associated with endometriosis than no treatment/placebo. There was no evidence of a difference in pain relief between GnRHas and danazol although more adverse events reported in the GnRHa groups. There was no evidence of a difference in pain relief between GnRHas and levonorgestrel and no studies compared GnRHas with analgesics.