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International Women's Health Update

Management Options

Antifibrinolytics

Tranexamic acid (Cyklokapron) is a new medicine which has recently become available for the treatment of heavy periods. Tranexamic acid is an inhibitor of plasminogen activator. It therefore inhibits endometrial fibrinolysis. Tranexamic acid has been widely used in Scandinavia for the treatment of heavy periods. It has also been used, particularly in the northern hemisphere, to reduce blood loss associated with various forms of surgery, 1n dentistry to reduce bleeding in patients with angioeurotic oedema and in the care of some patients with leukaemia.

Tranexamic acid is excreted through the kidneys and therefore should be used with a caution in patients with known kidney disease. Similarly, in patients with a past history of thrombosis, tranexamic acid should be used with caution, although it is not believed to have a general thrombogenic effect in the doses prescribed in gynaecology.

A particular gynaecological advantage of tranexamic acid is that treatment can commence on the first day of menstrual bleeding or the menstrual period. A typical dose is 1 gm (2 x 500mg) four times a day. This treatment is usually given for four days.

The mean peak plasma level of tranexamic acid after 1 gm orally is 8 mg/L. Such concentrations are believed to have no effect upon platelet counts or coagulation factors. Studies have found that thrombo-embolism after tranexamic acid is no greater than occurs spontaneously.1 Similarly, previous Scandinavian concern of an increased risk of stroke on tranexamic acid has not been confirmed.

The risk of spontaneous stroke is equivalent to that on Tranexamic acid and is approximately 1 in 20,000 women per year. These risks are safer than those of a continuing pregnancy in Australia in 1997, which has a risk of death of about 1 in 14,000. Studies by Rybo (1991) and other authors have confirmed the effectiveness of tranexamic acid as a medical treatment for heavy periods due to dysfunctional uterine bleeding.

Several studies have shown that 1 gm of tranexamic acid, 4 times per day for 4 days, beginning with menstruation will decrease measured menstrual blood loss by 50-54% in women with heavy periods (Fig 3).

Figure 3.
Figure 3
Prediction of menstrual blood loss over 3 cycles comparing tranexamic acid with mefenamic acid.

 

Patients should be carefully selected and advised of these results and what they mean. For a patient losing 150 mL of blood each month associated with menorrhagia, courses of tranexamic acid will return her menstruation to a heavy but otherwise normal period. For many women this will be satisfactory. However, other patients will expect, and sometimes demand, that their menstrual bleeding completely cease in order for them to be satisfied with medical treatment. Such patients are probably not suitable for tranexamic acid.3

Progestogens

Oral progestogens are probably the most widely prescribed medicine for the treatment of heavy periods. They are certainly the most misused. Most cases of heavy periods due to dysfunctional bleeding are patients with ovulatory dysfunctional uterine bleeding. For these women, typically over 40 years, high quality ovulation does not occur every month but increasingly erratically. It is usually not possible to measure any progesterone hormone deficiency in such women and progestogens must be administered with care if they are to have any benefit in these patients.

The use of progestogens such as oral norethisterone, 5 mg, 3 times per day from days 19-26 of the cycle in such patients has been shown to increase menstrual blood loss, rather than decrease such bleeding. The secret of effective treatment of such patients with ovulatory dysfunctional uterine bleeding with oral progestogens, is to administer progestogens for at least 20 days of each cycle. For example, oral norethisterone, 5 mg, 3 times daily from cycle day 5-26, is necessary to demonstrate reduced menstrual bleeding.

Non-Steroidal Anti-Inflammatory Drugs (NSAIDS)

Mefenamic acid is probably the best known prostaglandin synthetase inhibitor used in gynaecology as medical treatment for heavy periods. A typical dose is 500 mg 8-hourly. It is usually recommended that mefenamic acid be commenced, if possible, about 4 days before the onset of menstrual bleeding and this cannot always easily be predicted. Nevertheless, inhibition of the synthesis of prostaglandins at this time is important in helping to reduce measured menstrual blood loss and relief from heavy periods3. Bonnar and Sheppard demonstrated that commencement of mefenamic acid for 5 days from day 1 of menstrual bleeding only resulted in a 20% decrease in blood loss, which was unacceptable to their patients (Fig 3). An advantage of mefenamic acid and other NSAIDS is that, particularly when taken pre-menstrually, they will also decrease dysmenorrhoea and appear to be well tolerated by most patients.

Other Medical Treatments

>Some studies have demonstrated moderate benefit of fixed dose oral contraceptive pills in the management of anovulatory dysfunctional uterine bleeding causing heavy periods. Daily progestogen, on each and every day of medication, seems important in this limited benefit as described above for oral progestogens. For individual patients, we have found this of benefit if the patient takes the active oral contraceptive pills, and omits the placebo tablets, for an uninterrupted interval of 2 or 3 months at a time. Danazol is primarily indicated in the medical management of pain from endometriosis. As danazol is a weak androgen, and there are androgen receptors upon the endometrium, it does have benefit in patients with dysfunctional uterine bleeding