Prevention of NSAID-induced gastric ulcer with misoprostol: multicentre, double-blind, placebo-controlled trial. A randomized, prospective comparison of endocrine changes induced with intranasal leuprolide or danazol for treatment of endometriosis. Placebo-controlled comparison of danazol and high-dose medroxyprogesterone acetate in the treatment of endometriosis after conservative surgery. Effect of ranitidine on gastroduodenal mucosal damage induced by nonsteroidal antiinflammatory drugs. Placebo-controlled comparison of danazol and high-dose medroxyprogesterone acetate in the treatment of endometriosis. Control of IUD-induced bleeding by three non-steroidal anti-inflammatory drugs. A randomized, parallel, comparative study of the efficacy and safety of nafarelin versus danazol in the treatment of endometriosis in Taiwan. Danazol and medroxyprogesterone acetate inefficacious in the treatment of infertility in endometriosis. A study of co-treatment of nonsteroidal anti-inflammatory drugs (NSAIDs) with misoprostol for cervical priming before suction termination of first trimester pregnancy. A randomized prospective trial comparing the levonorgestrel-releasing intrauterine system with thermal balloon ablation for the treatment of heavy menstrual bleeding. Duodenal and gastric ulcer prevention with misoprostol in arthritis patients taking NSAIDs. Misoprostol Study Group. Dysmenorrhea in women with intrauterine contraceptive device. Treatment with a prostaglandin synthetase inhibitor, naproxen. Randomized trial of 2 hormonal and 2 prostaglandin-inhibiting agents in women with a complaint of menorrhagia.
A double-blind, placebo-controlled study was carried out to see whether the synthetic E prostaglandin, misoprostol, would prevent gastric ulcer induced by non-steroidal anti-inflammatory drugs (NSAIDs). 420 patients with osteoarthritis and NSAID-associated abdominal pain were studied; they were receiving ibuprofen, piroxicam, or naproxen. Endoscopy was done at entry and after 1, 2, and 3 months of continuous treatment with 100 micrograms or 200 micrograms misoprostol or placebo, given four times daily with meals and at bedtime, concurrently with the NSAID. Abdominal pain was rated independently by patients and physicians. A treatment failure was defined as development of a gastric ulcer. Gastric ulcers (0.3 cm in diameter or greater) occurred less frequently (p less than 0.001) in both misoprostol treatment groups (5.6% 100 micrograms and 1.4% 200 micrograms) than in the placebo group (21.7%). The significant difference in ulcer formation between the placebo and the misoprostol treatment groups remained when comparisons were restricted to ulcers greater than 0.5 cm in diameter (12.3% placebo, 4.2% 100 micrograms misoprostol, and 0.7% 200 micrograms misoprostol). Mild to moderate, self-limiting diarrhoea was the most frequently reported adverse effect attributed to misoprostol. These results provide the first clear indication that NSAID-induced ulcers are preventable. 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 evaluate the clinical value of postoperative hormone therapy in endometriosis, 60 patients with advanced disease were randomized to receive in a double-blind study danazol (200 mg, 3 times daily), medroxyprogesterone acetate (MPA) (100 mg daily) or placebo post-operatively for 6 months. Treatment efficacy was evaluated clinically and at laparoscopy 6 months after medication. In relation to placebo, danazol and high-dose MPA treatments, which did not differ from each other in efficacy, significantly alleviated pelvic pain. In addition, the peritoneal endometriosis lesions found at 6-months laparoscopy were significantly smaller in the MPA and danazol groups than in the placebo group. Breakthrough bleeding, weight gain and acne complicated danazol treatment but only breakthrough bleeding complicated MPA treatment. These data suggest that postoperative treatment of advanced endometriosis with high-dose MPA or danazol is clinically beneficial. The effect of ranitidine in preventing mucosal damage caused by nonsteroidal antiinflammatory drugs (NSAIDs) was evaluated for eight weeks in a prospective study of 144 patients requiring NSAIDs. Patients with normal endoscopic findings were randomly assigned to receive either ranitidine 150 mg twice daily or placebo for eight weeks, along with either ibuprofen, indomethacin, naproxen, sulindac, or piroxicam. Duodenal damage was significantly less in the ranitidine group compared with the placebo group by weeks 4 and 8 (P less than or equal to 0.01). Duodenal ulcers did not develop in any patients on ranitidine (0/57) compared with 4/49 patients (8%) on placebo (P = 0.02). No significant difference was found between treatment groups with respect to gastric damage; 6/60 (10%) in the ranitidine group compared with 6/50 (12%) in the placebo group developed gastric ulcers. These findings suggest that acid suppression is of greater importance for mucosal protection in the duodenum than in the stomach, where other defense mechanisms may be operative. While ranitidine is an effective prophylaxis for NSAID-induced damage in the duodenum, further studies are needed to define specific risk groups and to assess the potential usefulness of more complete acid suppression in preventing gastric mucosal damage. A prospective, double-blind, placebo-controlled study was designed to evaluate the clinical efficacy and tolerance of danazol and high-dose medroxyprogesterone acetate (MPA) in the treatment of mild-moderate endometriosis. After laparoscopical confirmation of endometriosis, 59 patients were randomized to receive danazol (200 mg 3 times daily), MPA (100 mg daily) or placebo for 6 months. Clinical examinations were done before and 1, 3, 6 and 12 months after the beginning of the study, and a 2nd laparoscopy 6 months after termination of the medication. Eighteen patients in the danazol group, 16 in the MPA group and 17 in the placebo group completed the trial. Total or partial resolution of peritoneal implants was observed in 60% of the patients receiving danazol and in 63% of the patients receiving MPA. In the placebo group, resolution was observed in 18%, while the size of the implants was estimated to be increased in 23% of the patients. In relation to placebo, danazol and MPA significantly alleviated endometriosis-associated pelvic pain, lower back pain and defecation pain, but they did not differ from each other in these actions. The appearance of acne, muscle cramps, edema, weight gain and spotting bleeding complicated MPA treatment. The present results indicate that because of good efficacy and tolerance, high-dose MPA is a useful alternative in the hormonal treatment of endometriosis. Administration of nonsteroidal anti-inflammatory drugs (NSAIDs) reduced excessive IUD-induced bleeding. The effect of 3 different oral NSAIDs, namely indomethacin, Alclofenac, and flufenamic acid, on menstrual blood loss (MBL) and pain among women fitted with copper IUDs was studied and compared with a placebo on a randomized single blind basis. Each drug was given to 6 subjects (18 cases) over 2 consescutive cycles and was either preceded or followed by placebo for 2 more cycles. 1/2 of the cases on each drug started placebo medication in the 1st 2 months while the other 1/2 started by the drug. The oral treatment was begun on the 1st day of menstrual bleeding or spotting. Estimation of the daily MBL was done by the alkaline hematin method with mechanical extraction of sanitary pads. The 3 drugs tested in this study induced a significant reduction in MBL: maximum reduction by flufenamic acid medication, less with Alclofenac, and least with indomethacin medication. However, these reductions were not statistically different, and marked improvement in IUD-induced pain was observed under the effect of the 3 drugs. 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. Danazol (200 mg three times a day) and medroxyprogesterone acetate (MPA, 100 mg a day) were compared with placebo in the treatment of infertility of patients with endometriosis. Twenty-seven patients had medical therapy alone for 6 months, and 22 patients received it after conservative surgery. The clinical characteristics of the patients in the danazol group (n = 18), the MPA group (n = 17), and the placebo group (n = 14) were comparable to each other. The follow-up time was 30 months. The cumulative pregnancy rates, 33% in the danazol group (n = 6), 42% in the MPA group (n = 7), and 46% in the placebo group (n = 6), did not differ significantly from each other. The time to pregnancy after the start of therapy was 17.7 +/- 8.4 (standard deviation [SD]) months in the danazol group, 18.0 +/- 9.0 months in the MPA group and 10.0 +/- 5.8 months in the placebo group with no significant difference between the groups. The abortion rate was 26%, and there was no significant difference among the groups. Cox multivariant analysis did reveal ovarian endometriosis a prognostically significant negative indicator as regards fecundation in endometriosis (P less than 0.05). In summary, correction of infertility alone does not appear to be an indication for the use of danazol or MPA in the treatment of endometriosis, and ovarian endometriotic lesions but not peritoneal ones do make a worse prognosis as regards fecundation in endometriosis. This double-blind randomized control study was conducted to evaluate whether a nonsteroidal anti-inflammatory drug (NSAID) could act as an effective pain control method during first trimester suction abortion, and whether co-treatment of NSAID with misoprostol will decrease the efficacy of the cervical ripening effect of misoprostol. Subjects were randomized to receive misoprostol alone or misoprostol together with diclofenac sodium. Both groups of subjects suffered from similar incidence of preoperative side effects. Co-treatment of NSAID with misoprostol did not attenuate the cervical ripening efficacy of misoprostol. There was no significant pain reduction in the group treated with NSAID, except that a marginal benefit was found in the subgroup of multiparous women. About two thirds of the subjects in both treatment groups found that this was a satisfactory pain relief method during the procedure. Use of the levonorgestrel-releasing intrauterine system (LNG-IUS) was compared with thermal balloon ablation (TBA) for the treatment of heavy menstrual bleeding (HMB).
                A prospective randomized trial comparing the LNG-IUS (n=30 women) and TBA (n=28 women).
                Hemoglobin levels increased (p<.001) and blood loss was reduced (p<.001) in both groups after 1 year of treatment. Menstrual bleeding was less in the LNG-IUS group compared to the TBA group at 6 and 12 months of treatment (p=.035 and p=.048, respectively). Intermenstrual bleeding was significantly less in the TBA group at 6 months compared to the LNG-IUS group (p=.044); however, there was no significant difference at 12 months (p=.129). No difference was found in psychological aspects between pre- and posttreatment variables in either of the groups (p=.537).
                Both the LNG-IUS and TBA appear to be effective in controlling HMB; however, posttreatment uterine bleeding patterns are different.
                Copyright (c) 2010 Elsevier Inc. All rights reserved. To determine the efficacy of misoprostol for the prevention of nonsteroidal anti-inflammatory drug (NSAID)-induced duodenal and gastric ulcers in arthritis patients receiving NSAID therapy.
                A randomized, double-blind, multicenter, placebo-controlled trial.
                Six hundred thirty-eight private, Veterans Affairs, health maintenance, and academic practices.
                Six hundred thirty-eight patients with chronic inflammatory or noninflammatory arthritis who were taking an NSAID but who did not have a gastric or duodenal ulcer on screening endoscopy received treatment with ibuprofen, piroxicam, naproxen, sulindac, tolmetin, indomethacin, or diclofenac daily for 3 months. Four hundred fifty-five (71%) patients completed the trial.
                Patients meeting the entry criteria were randomized to receive either misoprostol, 200 micrograms, or placebo, four times a day for 12 weeks.
                The endoscopy was repeated at 4, 8, and 12 weeks. The development of a duodenal or gastric ulcer (defined as a circumscribed mucosal defect > or = 0.5 cm in diameter and with perceptible depth) was regarded as prophylactic failure.
                By 12 weeks, a duodenal ulcer developed in 2 of 320 (0.6%; 95% CI, 0.2% to 3.9%) patients randomized to receive misoprostol, compared with 15 of 323 (4.6%; CI, 2.8% to 8%) patients receiving placebo (P = 0.002). A gastric ulcer developed in 6 of 320 (1.9%; (CI, 0.8% to 4.4%) patients, compared with in 25 of 323 (7.7%; CI, 5.1% to 11.4%), respectively.
                Misoprostol significantly lowers the frequency of both duodenal and gastric ulcer development in patients who require long-term therapy with NSAIDS. Twenty-one women with intrauterine contraceptive devices (IUCD) and severe dysmenorrhea were studied. All the women who participated in the study had primary dysmenorrhea of varying intensities. The insertion of IUCD increased the intensity of dysmenorrheic pain. The effect of naproxen (Naprosyn) on pain alleviation was studied in a double-blind cross-over trial using naproxen and placebo. The effect of naproxen was significantly better than that of placebo (P less than 0.01). No severe side effects occurred during the treatment. There was no difference in the duration and amount of the menstrual blood flow during naproxen treatment compared to placebo according to the women's own judgement. A series of 45 ovulatory women with a complaint of menorrhagia were randomized into 3 treatment groups, before receiving therapy with mefenamic acid in 2 cycles and 1 of 3 other agents in 2 cycles: naproxen (group 1; n = 14), a low dose monophasic combined oral contraceptive (group 2; n = 12) or low dose danazol (group 3; n = 12). Menstrual blood loss was measured in 2-4 control cycles and during therapy. Mefenamic acid reduced measured blood loss by 20%; 38%; and 39% in groups 1-3 respectively. Naproxen reduced blood loss by 12%; the oral contraceptive by 43%; and danazol by 49%. There was no statistically significant difference in blood loss reduction (mean of 2 cycles) between any of the treatments, although women on danazol experienced a dramatic and highly significant further reduction in blood loss after the first treatment cycle (p less than 0.003). These were all effective therapies in a majority of women, but some 'non-responders' were seen in each group. The 'non-responders' had a significantly lower pretreatment blood loss than responders. Several women in group 1 showed anomalous responses to prostaglandin inhibitors with consistent and substantial exacerbation of menorrhagia during therapy. A number of reasonable therapies exist for the medical treatment of menorrhagia, but because none is suitable for everyone management needs to be individualized for each patient.
NSAIDs reduce HMB when compared with placebo but are less effective than tranexamic acid, danazol or LNG IUS. However, adverse events are more severe with danazol therapy. In the limited number of small studies suitable for evaluation, no significant difference in efficacy was demonstrated between NSAIDs and other medical treatments such as oral luteal progestogen, ethamsylate, OCC or another type of intrauterine system, Progestasert.