Randomized trial of 2 hormonal and 2 prostaglandin-inhibiting agents in women with a complaint of menorrhagia. Randomised comparative trial of the levonorgestrel intrauterine system and norethisterone for treatment of idiopathic menorrhagia. A double-blind randomised study comparing danazol and medroxyprogesterone acetate in the management of menorrhagia. Prospective, randomised study with three HRT regimens in postmenopausal women with an intact uterus. Comparison between antifibrinolytic and antiprostaglandin treatment in the reduction of increased menstrual blood loss in women with intrauterine contraceptive devices. Reduction by naproxen of excessive menstrual bleeding in women using intrauterine devices.
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. To compare the efficacy and acceptability of the levonorgestrel intrauterine system and norethisterone for the treatment of idiopathic menorrhagia.
                A randomised comparative parallel group study.
                Gynaecology outpatient clinic in a teaching hospital.
                Forty-four women with heavy regular periods and a measured menstrual blood loss exceeding 80 ml.
                Twenty-two women had a levonorgestrel intrauterine system inserted within the first seven days of menses, and 22 women received norethisterone (5 mg three times daily) from day 5 to day 26 of the cycle for three cycles.
                The main outcome measure was the change in objectively assessed menstrual blood loss after three months of treatment.
                When menstrual blood loss at three months was expressed as a percentage of the control, the levonorgestrel intrauterine system reduced menstrual blood loss by 94% (median reduction 103 ml; range 70 to 733 ml), and oral norethisterone by 87% (median reduction 95 ml; range 56 to 212 ml). After three cycles of treatment 76% of the women in the levonorgestrel intrauterine system group wished to continue with the treatment, compared with only 22% of the norethisterone group.
                Both the levonorgestrel intrauterine system and oral norethisterone in this regimen provided an effective treatment for menorrhagia in terms of reducing menstrual blood loss to within normal limits. The levonorgestrel intrauterine system was associated with higher rates of satisfaction and continuation with treatment, and thus offers an effective alternative to currently available medical and surgical treatments for menorrhagia. A randomised study was undertaken comparing danazol 200 mg daily and medroxyprogesterone acetate 10 mg daily from days 16 to 25 in the management of menorrhagia. Twenty-three women were recruited to the study over a 12-month period. Eighteen subjects were suitable for analysis. Three months' therapy was given and patients were observed for a 3-month period following discontinuation of therapy. Menstrual blood loss was estimated during initial patient assessment and then during each of the 6 months of the study. In the danazol group mean blood loss at all treatment phase months was significantly decreased from baseline. In contrast, blood loss was not reduced significantly in any study month when compared with baseline in the medroxyprogesterone acetate group. During the post-treatment phase the mean blood loss in the danazol group increased to above normal levels but remained significantly lower than baseline, and there was a significant reduction in menstrual blood loss in the medroxyprogesterone acetate group. To compare compliance, symptom control, bleeding patterns, lipid and biochemical changes in postmenopausal women treated with three regimens of HRT.
                In a prospective, randomised, group comparative study, with 165 patients, the effects on the aforementioned parameters, as well as treatment compliance and side effects were studied with oral tibolone 2.5 mg per day, with cyclic combined regimen of transdermal oestrogen and progestogen (transdermal patch of 17beta-oestradiol 50 microg/day during 14 days and transdermal patch of 17beta-oestradiol 50 microg/day plus 0.25 mg/day NETA during the following 14 days), and with intermittent progesterone regimen (transdermal 17beta-oestradiol 50 microg/day and oral micronised natural progesterone 200 mg twice a week). Statistical analysis was carried out using the Fisher-test, analysis of the variance (ANOVA) and the Bouferoni test.
                Ten women dropped out of the tibolone group, 11 dropped out of the intermittent dosing group and 21 dropped out of the cyclid combined group. Irregular bleeding occurred at more rates in the cyclid combined group. Similar reductions in climacteric symptoms were found in the three groups. No differences were observed with respect to biochemical analysis.
                Efficacy and safety of the three treatment regimens being comparable, but the patients in our study preferred those that did not produce bleeding episodes. The effects of a fibrinolysis inhibitor (tranexamic acid, TA) and prostaglandin synthesis inhibitor (diclofenac sodium, DS) were compared in the reduction of excessive menstrual blood loss in 19 women with an intrauterine contraceptive device (IUCD). These women (mean blood loss before treatment to 135.1 +/- 18.9 SE ml, range 70-294 ml) were treated in random order with TA (1.5 g three times daily for 5 days starting on the first day of menstruation for two periods), and with DS (50 mg three times on the first day followed by 25 mg three times daily for 4 days, for two periods), or with placebo (one period) in a double-blind trial. The placebo treatment did not change menstrual blood loss (128.3 +/- 15.6 ml). The TA treatment decreased blood loss to 59.4 +/- 7.7 ml (P less than 0.001) and the DS treatment to 102.1 +/- 13.6 ml (P less than 0.01). Neither treatment abolished pelvic discomfort during menstruation or shortened its duration. Various side-effects were noted by 12 women during 19 TA treatments and by five women during six DS treatments. Thus, while TA is generally far more effective, DS gave pronounced decreases in menstrual bleeding in some women and had less frequent side-effects. Thirty-four patients using intrauterine contraceptive devices and experiencing excessive menstrual bleeding (more than 80 ml average loss for 2 cycles) were treated with the prostaglandin synthetase inhibitor naproxen. The trial was conducted according to a double-blind placebo-controlled crossover design. Each patient received 2 of 3 treatments: naproxen in high dose (1250 mg/day for 5 days), naproxen in low dose (500-mg loading dose, than 750 mg/day for 5 days), or placebo. Each treatment was taken during 2 consecutive menstruations. When all data were pooled, statistically significant reduction in menstrual bleeding was found with both high- and low-dose naproxen treatment compared with placebo therapy (P < .002). Low- and high-dose naproxen reduced menstrual blood loss by 22% and 32%, respectively, whereas the change with placebo was minimal. Although the dose had no significant effect on mean menstrual loss, the number of treatment cycles in which menstrual blood loss was reduced by 50% as compared with pretreatment cycles strongly suggested a dose response. In almost 60% of naproxen-treated cycles, mean menstrual blood loss was less than 80 ml, whereas during placebo-treated cycles the distribution of menstrual loss was similar to that of control cycles.
Progestogens administered from day 15 or 19 to day 26 of the cycle offer no advantage over other medical therapies such as danazol, tranexamic acid, non-steroidal anti-inflammatory drugs (NSAIDs) and the IUS in the treatment of menorrhagia in women with ovulatory cycles. Progestogen therapy for 21 days of the cycle results in a significant reduction in menstrual blood loss, although women found the treatment less acceptable than intrauterine levonorgestrel. This regimen of progestogen may have a role in the short-term treatment of menorrhagia.