A gonadotropin-releasing hormone agonist versus a low-dose oral contraceptive for pelvic pain associated with endometriosis. Treating dysmenorrhea with anti-inflammatory agents: a double-blind trial with naproxen sodium. Dysmenorrhea in women with intrauterine contraceptive device. Treatment with a prostaglandin synthetase inhibitor, naproxen. [Menstrual prostaglandin and dysmenorrhea: modulation by non-steroidal antiinflammatory drugs]. The efficacy and safety of aceclofenac versus placebo and naproxen in women with primary dysmenorrhoea. Diclofenac potassium attenuates dysmenorrhea and restores exercise performance in women with primary dysmenorrhea. Comparison of GnRH antagonist with long GnRH agonist protocol after OCP pretreatment in PCOs patients. 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. Updating the clinical experience in endometriosis--the European perspective.
To evaluate the efficacy of goserelin versus a low-dose cyclic oral contraceptive (OC) in improving pelvic pain in women with endometriosis and to compare recurrence of symptoms during follow-up.
                Open-label, randomized trial.
                University hospital endometriosis center.
                Fifty-seven women with moderate or severe pelvic pain and laparoscopically diagnosed endometriosis.
                Six-month treatment with goserelin depot (n = 29) or a low-dose cyclic OC (n = 28) followed by 6-month follow-up.
                Variation in severity of symptoms during treatment and at the end of follow-up as shown by a linear analog scale and a verbal rating scale.
                At 6 months of treatment, a significant reduction in deep dyspareunia was observed in both groups, with goserelin superior to the OC at linear analog scale assessment. Nonmenstrual pain was diminished on both scales without differences between treatments. Women taking the OC experienced a significant reduction in dysmenorrhea. At the end of follow-up, symptoms reappeared without differences in severity between the groups.
                Low-dose cyclic OCs may be a valuable alternative for the treatment of dysmenorrhea and nonmenstrual pain associated with endometriosis. Symptoms recurred in most subjects 6 months after drug withdrawal. Thirty-two dysmenorrheic patients participated in a double-blind trial of naproxen sodium for three consecutive menstrual cycles. The women were divided into two groups: 15 women were given naproxen sodium (the sodium salt of d-2-(6-methoxy-2-naphthyl) propionic acid) and 17 women received placebo tablets. The women were prescribed two tablets (550 mg) at the first sign of menstrual pain and one tablet (275 mg) thereafter every six hours, as required. There were no significant differences between the two groups in physical characteristics, obstetric and gynecologic histories, including the character of dysmenorrhea and pretreatment pain intensity scores (p = 0.7). Following intake of the drug or placebo, the participants rated the relief provided by the medication with a six-point scoring system. When the scores for pain relief were tallied for the three treatment cycles, the naproxen sodium group averaged 13.7 +/- 0.65 standard error, while the placebo group averaged 8.8 +/- 0.95 standard error out of a possible maximum relief score of 18. The difference between the two groups was statistically significant at p = 0.0004. Few patients reported side effects. 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. The analgesic efficacy and tolerance of lysine clonixinate (LC) as well as LC-induced changes in menstrual prostaglandin levels were studied according to a prospective double-blind randomized crossover design, controlled with ibuprofen (I) and placebo (P). Treatment consisted in 4 consecutive phases: in the first phase, patients refrained from taking medication and during the remaining three phases, they received double-blind fixed doses of 1 tablet of lysine clonixinate 125 mg, I 400 mg or P, q.6 h. at random, three days before onset of menses and during 8 days thereafter. Controls were carried out at each menstrual cycle, assessing pain according to a scale from 0 to 4, onset of premenstrual and intramenstrual symptoms, relief of pain and occurrence of side-effects. During menstruation, patients recorded their assessments of pain in a diary and collected the whole menstrual bleeding during the first three days. The intensity of menstrual pain remained unchanged in controls upon admission (3.16) and during the phase with no treatment (3.04), but was significantly reduced with P (2.4), LC (1.79) and I (1.54). Significantly lower pain intensities compared with placebo were seen with active treatment phases. Forty-two percent of patients treated with P reported premenstrual pain which was significantly reduced to 17% with LC and to 12.5% with I. Active treatment phases revealed 21% of asymptomatic patients during premenstrual and menstrual periods and 71% (LC) and 75% (I) of cases with partial relief of pain. Patients' diaries showed significant pain reductions with LC and I, during the 1st and 2nd days compared with P; such differences were gradually reduced to nil by the 4th day. Levels of menstrual PGs changed according to pain intensity reductions from baseline (P: 29%, (NS); LC: 58% and I: 61%; both were statistically significant, p < 0.01). To determine the analgesic efficacy and safety of a single oral dose of aceclofenac 100 mg and compare that with placebo and naproxen 500 mg in women with primary dysmenorrhoea.
                In this double-blind, prospective, multicentre, randomised, three-way, crossover study, women were randomly assigned to receive one of six treatment sequences, comprising single oral doses of aceclofenac 100 mg, naproxen 500 mg or placebo, when menstrual pain reached a predetermined level of severity. A single dose of the assigned study medication was taken on three menstrual periods; a different medication was taken on each treatment day. Analgesic efficacy was determined by self-reported analgesia scoring and participants' and investigators' global evaluation of treatment effectiveness. Measurements also included physical examination and adverse events.
                Total pain relief scores were not statistically significantly different for aceclofenac and naproxen, and both were statistically significantly more effective than placebo (p = 0.019 and 0.002, respectively). This finding was supported by secondary endpoints including sum of pain intensity differences (SPID/8), peak analgesia (peak pain intensity and peak pain relief), and participants' and investigators' overall evaluation of effectiveness. Both aceclofenac and naproxen were well tolerated.
                Aceclofenac (100 mg) and naproxen (500 mg) effectively treated the pain associated with primary dysmenorrhoea, and both were more effective than placebo at easing menstrual pain assessed by various pain relief criteria. We assessed the efficacy of diclofenac potassium, a nonsteroidal anti-inflammatory drug, in alleviating menstrual pain and restoring exercise performance to that measured in the late-follicular phase of the menstrual cycle. Twelve healthy young women with a history of primary dysmenorrhea completed, in a random order, laboratory exercise-testing sessions when they were in the late-follicular (no menstruation, no pain) phase of the menstrual cycle and when they were experiencing dysmenorrhea and receiving, in a double-blinded fashion, either 100 mg of diclofenac potassium or placebo. We assessed the women's leg strength (1-repetition maximum test), aerobic capacity (treadmill walking test), and ability to perform a functional test (task-specific test). Compared with placebo, diclofenac potassium significantly decreased dysmenorrhea on the day of administration (Visual Analog Scale, P < .001 at all times). When receiving placebo for menstrual pain, the women's performance in the tests was decreased significantly, compared with when they were receiving diclofenac potassium for menstrual pain (P < .05) and compared with when they were in the late-follicular phase of the menstrual cycle (P < .05 for treadmill test, P < .01 for task-specific test and 1-repetition maximum test). Administration of diclofenac potassium for menstrual pain restored exercise performance to a level not different from that achieved in the late-follicular phase of the cycle.
                In women with primary dysmenorrhea, menstrual pain, if untreated, decreases laboratory-assessed exercise performance. A recommended daily dose of a readily available nonsteroidal anti-inflammatory drug, diclofenac potassium, is effective in relieving menstrual pain and restoring physical performance to levels achieved when the women were in the late-follicular (no menstruation, no pain) phase of the menstrual cycle. To evaluate the efficacy of GnRH antagonist in comparison with the GnRH agonist protocol in OCP pretreated polycystic ovary syndrome (PCOs) patients undergoing their first ART cycle.
                Prospective randomized controlled trial. University-based tertiary fertility center. Ninety-five PCOs patients under 35 years of age, with primary infertility were randomized to an ovarian stimulation protocol consisting of either. GnRh antagonist (study group) or GnRH agonist (control group) after pretreatment with OCP. Coasting or GnRH agonist Trigger was used when estradiol level > or =3,000 pgr/ml in the control and study group, respectively. Both groups received 800 mg vaginal progesterone and 4 mg oral estradiol valerate for luteal phase support.
                There was no statistically significant difference in the age, body mass index, basal FSH, duration of infertility, the number of oocytes retrieved, the number of embryos transferred, Serum E2 levels on day of trigger, fertilization rate, chemical and clinical pregnancy rates between the two groups. None of the patients in the study group developed ovarian hyperstimulation syndrome (OHSS) compared with 22.2% of patients in the control group. Total duration of treatment and the number of HMG ampoules used were lower in the study group.
                Antagonist protocol and GnRH agonist trigger for ovulation whenever necessary has a similar cycle outcome to the GnRH-agonist protocol in OCP pretreated PCOs patients, with significantly reduced risk of OHSS. 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. In a large, double-blind, multicentre study, 269 patients with confirmed endometriosis were randomly 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.
There is limited evidence for pain improvement with the use of the OCP (both low and medium dose oestrogen) in women with dysmenorrhoea. There is no evidence of a difference between different OCP preparations.