Nonsurgical options for menorrhagia
What the data reveal about common therapies, and why you don’t need to “prove” menorrhagia before treating it
IN THIS ARTICLE
Complaints of menorrhagia but normal findings
Lindsey, a 22-year-old gravida 0, complains about periods that interfere with her life. Although she describes her flow as heavy, she says her periods start every 28 to 30 days, last for 5 days, and do not soak tampons or pads. Nonetheless, she finds them difficult and often misses work because of them. She reports no intermenstrual bleeding, medical problems, prior surgery, pregnancy, or smoking. She is sexually active with a single partner using condoms for birth control. Her physical exam is unremarkable, and her hematocrit is 38%.
Should she be treated for menorrhagia?
Although Lindsey appears to be normal, her periods clearly have a negative impact on her life. In the past, her normal findings might have persuaded her physician to forego treatment, but there is good reason to focus on subjective complaints rather than withholding treatment for “unproven” menorrhagia.
Lindsey is an ideal candidate for medical management because her symptoms are subjective and involve quality of life without much medical risk. She can be started on nonsteroidal anti-inflammatory drugs (NSAIDs) and an oral contraceptive (OC). A suggested regimen: ibuprofen 600 to 800 mg every 6 hours, starting at the beginning of her period, and a progesterone-dominant combined OC.
This article surveys the medical treatments most appropriate for menorrhagia:
- antifibrinolytics, and
- the highly effective progestin-releasing intrauterine system (see “How medical therapies stack up”).
Danazol reduces menorrhagia, but severe androgenic side effects limit its use.
The treatments described here are for ovulatory women with a normal uterus, although some may also be effective in women with structural lesions. (Many women reporting menorrhagia have lesions, especially polyps and fibroids. However, in 1 series of hysterectomy for menorrhagia, 50% of patients had no pathology.1)
Women with anovulatory bleeding (ie, dysfunctional uterine bleeding) are best managed with OCs or progestins.
No formal studies have explored these therapies in combination, but it may be reasonable to use more than 1, such as OCs and NSAIDs at the same time.
How medical therapies stack up
DECREASE IN MEAN MENSTRUAL BLOOD LOSS (%)*
PERCENT OF WOMEN BENEFITING FROM TREATMENT*
RANKING DECISION ANALYSIS†
Naproxen 500 mg every 12 hours starting at onset of period
Simple Inexpensive Also relieves dysmenorrhea
Gastritis Peptic ulcer disease
Norethindrone 5 mg 3 times daily on cycle days 5–26
Requires frequent pill-taking Side effects
Medroxy-progesterone acetate 10 mg on cycle days 16–25
100–200 mg daily
Listed only for completeness
Androgenic side effects; poorly tolerated; need for contraception at this dose
Combined oral contraceptives
Ethinyl estradiol 30 μg and desogestrel 15 mg
Simple Inexpensive Provides contraception
Requires daily pill-taking Poorly tolerated by subgroup of women
Risk factors for thromboembolism, myocardial infarction
Tranexamic acid 1 g 4 times daily on cycle days 1–5
Not available in United States Nausea Leg cramps Diarrhea
Risk factors for thromboembolism
Progestin-releasing intrauterine system
20 μg levonorgestrel per day (released by device)
Effective Simple Provides contraception
More expensive Some cases of breakthrough bleeding
High risk for sexually transmitted disease
* Estimates taken from New Zealand Guidelines Group10 note 5.
† Decision analysis from New Zealand Guidelines Group10 note 7.
If she says it’s heavy bleeding, it is
Heavy menstrual bleeding, or menorrhagia, usually is defined:
- subjectively, as heavy menstrual bleeding occurring over several cycles and disturbing to the patient, or
- objectively, as menstrual blood loss of more than 80 mL.
Most research uses the objective definition, while most patient referrals are based on subjective symptoms. Although the objective definition may be more precise, it is difficult to use in clinical practice, as it relies on patient self-perception, pad counts, pictograms, and measures of anemia, with varying degrees of accuracy. Besides, there is ample reason to believe that subjective findings warrant treatment as much as objective ones do.
Typical menstrual blood loss is 30 to 40 mL per cycle, with 90% of women experiencing blood loss of less than 80 mL. Many more women meet the subjective definition of menorrhagia than the objective one: 31% describe their bleeding as “heavy.”2
The roughly 20% of women who do not meet the objective definition but perceive themselves as having heavy menstrual bleeding usually have real symptoms and experience substantial morbidity.
Objective and subjective groups overlap significantly. Warner et al3 noted comparable increases in mood changes, pain with periods, difficulties in containment, and impact on daily life regardless of whether women lost 50 to 79 mL or 80 to 119 mL of menstrual blood. Differences were noted only between extremes: women whose blood loss was less than 50 mL and women with blood losses of 120 mL or more.
Higham and Shaw4 noted that 49% of outpatients who complained of heavy periods had normal blood loss (<80 mL), and 27.7% of women who reported normal periods had blood loss exceeding 80 mL.
Nor does sanitary product use reflect blood loss or its impact. Warner et al5 showed that women with 30 to 40 mL of blood loss used anywhere from less than 21 to more than 45 products per cycle.
Quality-of-life impact is enormous
Menorrhagia is thought to occur in 9% to 14% of healthy women.6 It is a frequent cause of anemia, but its quality-of-life implications go far beyond that. Women in the United Kingdom with heavy menstrual bleeding reported that it had a substantial negative impact on their sex life, social life, and domestic responsibilities.7
In the National Health Interview Survey, US women with self-reported heavy bleeding were 45% more likely to use health services than other women,8 and 38% less likely to be working, with an estimated $1,692 in lost annual wages.9
Who to treat
Given the difficulty of achieving an objective diagnosis, and the negative effect on quality of life in patients with subjective symptoms alone, offering treatment to any woman complaining of heavy bleeding makes sense. Unfortunately, all randomized trials to date have involved only women with objectively determined blood loss. Nevertheless, the findings of randomized trials are probably generalizable to women with subjective complaints.
How success is measured is important in any treatment. Most studies rely on objective measurements of changes in blood loss. However, the impact on quality of life may not be related to measured blood loss. Thus, we have only limited data on the subjective effect of treatment.
This article summarizes evidence of decreasing blood loss and improved quality of life. For more extensive reviews, see the Cochrane database.
In addition, the New Zealand Guidelines Group10 developed a superb summary that uses decision analysis to balance cost, efficacy, and quality-of-life. The same group authored both the Cochrane reviews and the New Zealand guidelines, so the overlap is substantial.
Although these guidelines are 7 years old, little new data has been published in the intervening years for most regimens. When newer data are available, they are summarized here.
Imaging studies. In general, women with an enlarged uterus, history of polyps or fibroids, or other history or findings suggestive of structural lesions should be evaluated with ultrasound, sonohysterogram, or hysterosalpingogram. Hysteroscopy can be used when there is reason to suspect submucosal myomas or polyps.
Endometrial biopsy may be indicated in older patients with intermenstrual bleeding or risk factors for endometrial carcinoma such as diabetes, obesity, or hypertension.
Confirm ovulatory status to rule out anovulatory bleeding, which usually is well managed with progestins or OCs.
Consider bleeding disorders in adolescents with severe menorrhagia, for whom the American College of Obstetricians and Gynecologists11 recommends screening for von Willebrand’s disease. A recent meta-analysis12 found no evidence to support routine screening in adult women.
Two studies have demonstrated higher risks of bleeding disorders in women reporting heavy bleeding.13,14 However, neither suggest routine measurement of the prothrombin or partial thromboplastin times. A CBC is helpful, and can be used to monitor therapy in women with anemia.
A poor response to initial therapy may warrant studies for structural lesions, endometrial sampling, and more extensive hematologic evaluation, if these assessments have not already been done.
When observation may be helpful
Many women have been coping with their menorrhagia for some time prior to seeking care. If the bleeding is not causing anemia, its main impact is on quality of life. Although observation has not been formally studied, many women have—intentionally or not—selected no treatment.
Observation is an option for women who merely want reassurance and are willing to live with heavy periods, provided they have no signs of becoming seriously iron-deficient. Observation can continue as long as they desire, but these patients should be followed with serial measurements of hemoglobin or hematocrit. Iron supplementation should be encouraged.
Why some women with normal flow report menorrhagia
In a study of 226 women between the ages of 35 and 49 who complained of menorrhagia, Hurskainen and colleagues24 found normal menstrual flow (ie, <60 mL) in 29%. When they explored whether other factors might be linked to the perception of heavy menstrual flow in these women, they detected an increased incidence of psychosocial problems.
For example, these women were more likely to be unemployed and to have had more pain than women with more blood loss. In addition, on univariate analysis, they had higher levels of anxiety and were more likely to have a history of nongynecologic surgery and physician appointments for reasons other than menorrhagia.
These women appear to differ from women with objectively measured menorrhagia, but it is unclear if they have different personality types that render them less tolerant of bleeding or if their bleeding exacerbates underlying conditions.
NSAIDs are cheap and effective
These drugs are inexpensive, well tolerated, and moderately effective. A Cochrane review15 of 9 randomized trials concluded they were significantly better than placebo at reducing blood loss, but less effective than antifibrinolytics or danazol. No differences were noted in comparison with progestins, the progestin-releasing intrauterine system, or OCs—but these studies were underpowered. The New Zealand Guidelines Group10 found a 20% to 50% decrease in mean menstrual blood loss with NSAIDs.
No real differences between NSAIDs. The oldest and most frequently studied drug is mefenamic acid, but investigators have also considered newer, more commonly used drugs, such as ibuprofen and naproxen, finding no differences.
The drugs in the COX-2 inhibitor class are far more expensive, have not been studied for this use, and were recently linked to an increased risk of cardiovascular complications. Thus, their routine use for menorrhagia should be avoided.
The few trials of NSAIDs that showed no effect involved lower doses, suggesting that maximal doses are important. These drugs usually are initiated at prescription strength at the onset of menses and continued past the usual time of heavy bleeding.
Gastrointestinal side effects limit use of NSAIDs, which should not be given to women with peptic ulcer disease or gastritis. Because these drugs are used episodically, some women who cannot use them chronically can tolerate their use for menorrhagia.
Effect extends to dysmenorrhea. NSAIDs are ideally suited to relieve pain in patients with severe dysmenorrhea.
Women tend to perceive NSAIDs as being less effective than other methods.15
Progestins are effective—but not as they are usually prescribed
Menorrhagia can be managed with a progestin, but not in the way these agents are all too frequently administered: in the luteal phase as medroxyprogesterone (10 mg) for 10 days immediately preceding the expected menses. Although we lack placebo-controlled trials,16 4 trials have compared blood loss during this regimen with blood loss during cycles prior to its use in the same patient, showing no improvement.10 One of these trials showed a 20% increase over baseline with this progestin regimen. In addition, the New Zealand Guidelines Group noted a 4% increase in estimated menstrual blood loss.