Comparison between mefenamic acid and danazol in the treatment of established menorrhagia

Forty women with established menorrhagia were treated with either mefenamic acid (500 mg thrice daily for 3-5 days in two cycles) or danazol (100 mg twice daily for 60 days) in an open parallel group randomized study. Mefenamic acid reduced mean menstrual blood loss from 160 ml to 127 ml (20%, P less than 0.01). Danazol reduced mean menstrual loss from 163 ml to 65 ml (60%, P less than 0.001). The percentage reduction in menstrual blood loss was significantly greater in the danazol group than in the mefenamic acid group, but the adverse side-effects occurred significantly more often in the danazol group (75%) than in the mefenamic acid group (30%, P less than 0.005). Overall, approximately half the women in each group were prepared to continue with the treatment they received to reduce their menstrual bleeding.     

Long-term treatment of menorrhagia with mefenamic acid

Thirty-six women with menorrhagia were treated with mefenamic acid during all menstrual periods for more than 1 year. These women had experienced objective and subjective benefit--menstrual blood loss was reduced and other menstrual symptoms improved during a preliminary 4-cycle double-blind placebo-controlled trial with mefenamic acid (placebo cycles: 65.6 +/- 5.3 ml; mefenamic acid cycles: 45.3 +/- 5.1 ml, mean +/- SEM). This reduction in menstrual blood loss was maintained at 6 to 9 months (49.2 +/- 9.9 ml) and at 12 to 15 months (42.8 +/- 4.8 ml) after the trial. These reductions were significant at the 6- to 9-month (paired t test = 2.18; P less than .05) and the 12- to 15-month interval (paired t test =- 4.40; P less than .001). Significant sustained reductions in blood loss were seen in the women with menorrhagia due to ovulatory dysfunctional bleeding and in those who had undergone tubal sterilization. Significant reductions were also seen in dysmenorrhea, headache, nausea, diarrhea, depression, number of sanitary towels used, and number of mefenamic acid capsules taken. A significant increase in serum ferritin was found between admission and completion of the follow-up trial in 11 women (P less than .01).     

Endocrine consequences of danazol treatment in menorrhagia

In order to study the endocrine side-effects of danazol, 15 patients with severe, benign menorrhagias, were individually treated with this drug to stop bleeding. LH, FSH, testosterone, free testosterone, DES-S, androstenedione, prolactin, estradiol and cortisol serum concentrations were measured before and after the 3 month treatment period. Danazol was found to be effective in reducing the amount of bleeding in patients with benign, severe menorrhagias; however, the weight gain of patients was significant during the 3 month period. LH and estradiol concentrations decreased; testosterone, free testosterone and dehydroepiandrosterone sulfate increased; prolactin, FSH, androstenedione and cortisol serum concentrations did not change, and SHBG disappeared from the serum, during the treatment period. We are of the opinion that danazol is an effective drug in menorrhagias with side-effects. In our view the hyperandrogenicity is the most important side-effect of this substance, which might be the result of some metabolites, but which might be the effect of a peripheral action of the drug as well.     

Effects of mefenamic acid on menstrual hemostasis in essential menorrhagia.

Prostaglandin synthesis inhibitors decrease menstrual blood loss by 30% to 50% in patients with essential menorrhagia. To obtain insight into their mechanism of action, we measured menstrual blood loss in menorrhagic women, who were receiving mefenamic acid (500 mg, three times daily) (n = 6) or placebo (n = 5) in a double-blind way. In addition we studied the morphology of early menstrual hemostasis. The subjects' uteri were extirpated in the first 24 hours of menstruation, and light and electron microscopy were used to perform morphologic and morphometric studies. In the group treated with mefenamic acid mean menstrual blood loss was decreased by 40%. In uteri of the women treated with mefenamic acid hemostatic plugs were further transformed, and fewer vessels without a plug were observed than in uteri of the group receiving placebo. These data suggest that mefenamic acid may act through an improvement of platelet aggregation and degranulation and through increased vasoconstriction.     

Control of menorrhagia by the cyclo-oxygenase inhibitors naproxen sodium and mefenamic acid

Thirty-five patients with menorrhagia were treated in a double-blind crossover study with naproxen sodium and mefenamic acid after measurement of their blood loss during control menstrual cycles. Treatment with these compounds reduced the excessive bleeding by an average of 46 and 47% respectively. Drugs in the prostaglandin synthetase inhibitor group are considered to have an important place in the treatment of menorrhagia.     

Comparison of fennel and mefenamic acid for the treatment of primary dysmenorrhea.

OBJECTIVES: To compare the effect of Foeniculum vulgare variety dulce (Sweet Fennel) vs. mefenamic acid for the treatment of primary dysmenorrhea. METHODS: A cohort of seventy women, 15-24 years old from a local university and high-school, who complained of dysmenorrhea were enrolled in this study. Ten cases were excluded due to evidence of secondary dysmenorrhea. The remaining 60 patients were graded mild, moderate and severe on the basis of a verbal multidimensional scoring system. Thirty patients with mild dysmenorrhea were also excluded from the study. Each of the 30 cases with moderate to severe dysmenorrhea was evaluated for three cycles. In the first cycle no medication was given (control cycle), in the second cycle the cases were treated by mefenamic acid (250 mg q6h orally) and in the third cycle, essence of Fennel's fruit with 2% concentration (25 drops q4h orally), was prescribed at the beginning of the cycle. These cycles were compared day by day for the effect, potency, time of initiation of action and also complications associated with each treatment modality, by using a self-scoring system. Intensity of pain was reported by using a 10-point linear analog technique. Statistical analyses were performed by the independent sample t-test, paired t-test and repeated measurement analysis method. RESULTS: In the study group the mean age of menarche was 12.5+/-1.3 years, the mean duration of menstruation was 6.6+/-1.4 days with the mean cycle days of 27+/-3. The findings observed during menses were as follows: headache in 26.7%, nausea in 63.3%, vomiting in 23.3%, diarrhea in 33.3%, fatigue in 93.3% and leaving the daily tasks undone was reported in 86.9% of the cases. Both of the drugs effectively relieved menstrual pain as compared with the control cycles (P<0.001). The mean duration of initiation of action was 67.5+/-46.06 min for mefenamic acid and 75+/-48.9 min for fennel. The difference was not statistically significant (P=0.57). Mefenamic acid had a more potent effect than fennel on the second and third menstrual days (P<0.05), however, the difference on the other days was not significant. No complication was reported in mefenamic acid treated cycles, but five cases (16.6%) withdrew from the study due to fennel's odor and one case (3.11%) reported a mild increase in the amount of her menstrual flow. CONCLUSIONS: The essence of fennel can be used as a safe and effective herbal drug for primary dysmenorrhea, however, it may have a lower potency than mefenamic acid in the dosages used for this study.     

Studies in menorrhagia: (a) mefenamic acid, (b) endometrial prostaglandin concentrations

Twenty-two women with unexplained heavy menstrual blood loss (average loss for two cycles of >80 ml) were treated with the prostaglandin synthetase inhibitor menfenamic acid during two consecutive menstruations. There was a significant reduction in menstrual blood loss on mefenamic acid therapy, the median loss being 137 ml before treatment and 76 ml while on treatment. Reduction in menstrual loss was achieved in 20 of the 22 patients but varied from a 2% to 78% reduction. The greater the menstrual loss before treatment, the more it was reduced on mefenamic acid therapy. Endometrial concentrations of prostaglandins E2 and F2 alpha in the follicular phase of the cycle were similar whether or not patients had menorrhagia. In the luteal phase, however, 6 of 14 patients with menorrhagia had higher endometrial prostaglandin E2 and F2 alpha concentrations than all 13 controls.     

Comparison between the levonorgestrel intrauterine system (LNG-IUS) and thermal balloon ablation in the treatment of menorrhagia

OBJECTIVES: To compare the effectiveness of endometrial thermal ablation and the levonorgestrel intrauterine system (LNG-IUS) in the management of menorrhagia. STUDY DESIGN: Fifty women attending a gynaecology clinic at a District General Hospital in south-west England were randomised to either surgical treatment using thermal ablation (Thermochoice, Gynecare) or medical treatment using a LNG-IUS (Mirena, Schering Healthcare). A pictorial menstrual chart was completed pre-insertion/operatively and again at 6 months post-insertion/operatively. Non-parametric tests (Mann-Whitney) were used for statistical analysis. RESULTS: Follow-up analysis was possible in 23 women in the Thermochoice group and 21 women in the Mirena group. The menstrual scores were slightly higher in the Thermochoice group (median 101) than the Mirena group (median 75) (P=0.025) pre-insertion/operatively but this difference was lost post-insertion/operatively (P=0.689) with median menstrual scores of 27 for the Thermochoice group and 19 for the Mirena group, respectively. CONCLUSION: Both Thermochoice endometrial ablation and a Mirena LNG-IUS are equally effective in the management of menorrhagia. The choice of treatment should be tailored to the woman's needs and preferences.     

A double-blind randomised study comparing danazol and medroxyprogesterone acetate in the management of 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.     

An objective evaluation of flurbiprofen and tranexamic acid in the treatment of idiopathic menorrhagia

The effect of flurbiprofen (100 mg x 2 for 5 days) was compared with tranexamic acid (1.5 g x 3 for 3 days, 1 g x 2 days 4 and 5) in the treatment of 15 women with idiopathic menorrhagia. The mean blood loss during two medication-free periods was 295 +/- 52 ml. A significant (p less than 0.01) reduction in menstrual blood loss was recorded during treatment with both flurbiprofen and tranexamic acid. The menstrual blood loss was significantly (p less than 0.01) lower during treatment with tranexamic acid (155 +/- 33 ml) than with flurbiprofen (223 +/- 44 ml). Various side effects were recorded by 7 of 15 women during treatment with tranexamic acid and by 4 women of 15 during treatment with flurbiprofen. Many women with menorrhagia suffer simultaneously from dysmenorrhea. Thus although tranexamic acid was generally more effective in reducing menstrual blood loss, flurbiprofen provides an important therapeutic alternative to antifibrinolytic agents, especially in patients with concomitant dysmenorrhea.     

Gestrinone in the treatment of menorrhagia

The role of gestrinone, 2.5 mg twice weekly, in treating proven menorrhagia (greater than 80 ml) was examined in 19 women. They were treated for five cycles (2 placebo, 3 active), taking one capsule twice weekly. Placebo had no effect on menstrual blood loss (MBL). On gestrinone 10 women became amenorrhoeic, in five MBL was markedly reduced (5-74 ml) and four did not respond. In three of the non-responders submucous leiomyomas were found at subsequent hysterectomy. Follow-up periods showed a persistent reduction in MBL for nine women in the first post-treatment menstruation.     

Gestrinone in the treatment of menorrhagia

Summary. The role of gestrinone, 2.5 mg twice weekly, in treating proven menorrhagia (>80 ml) was examined in 19 women. They were treated for five cycles (2 placebo, 3 active), taking one capsule twice weekly. Placebo had no effect on menstrual blood loss (MBL). On gestrinone 10 women became amenorrhoeic, in five MBL was markedly reduced (5–74 ml) and four did not respond. In three of the non-responders submucous leiomyomas were found at subsequent hysterectomy. Follow-up periods showed a persistent reduction in MBL for nine women in the first post-treatment menstruation.     

Comparison of the pharmacology of nafarelin and danazol

The pharmacologic profiles of danazol and nafarelin differ considerably from each other. Danazol interacts with multiple classes of proteins, whereas the gonadotropin-releasing hormone agonist nafarelin interacts only with the pituitary gonadotropin-releasing hormone receptor. Differences in the molecular, endocrine, and clinical pharmacologic properties of these agents may provide clues to their varying effects in the management of women with endometriosis.