Abnormal Menstrual Bleeding: New Definitions, New Strategies

Steven Fox

November 07, 2012

Editor's note: Heavy or prolonged menstrual bleeding is one of the most common symptoms in women presenting for medical evaluation.

In recent years, researchers have gained understanding about the causes of such symptoms and have devised improved strategies for intervening.

A presentation at the recent annual conference of the Nurse Practitioners in Women Health, held in Orlando, Florida, was delivered by Anita Nelson, MD, professor of Obstetrics and Gynecology at the David Geffen School of Medicine, at the University of California, Los Angeles.

In an email interview with Medscape Medical News, Dr. Nelson discussed the management of heavy or prolonged menstrual bleeding.

Medscape: What criteria and terminology are currently used to define abnormal menstrual bleeding, and have those changed in recent years?

Dr. Nelson: There have been substantial changes. Older terms to describe abnormal bleeding, which were imprecise, have been replaced by more specific terms.

Menstrual cycles are now more commonly described in 4 dimensions: frequency, duration, flow, and variability. The old term "menorrhagia" is now more accurately described as "prolonged or heavy" flow, or perhaps "prolonged and heavy" flow, depending upon the situation.

A newer classification system — the PALM-COEIN (polyp; adenomyosis; leiomyoma; malignancy and hyperplasia; coagulopathy; ovulatory dysfunction; endometrial; iatrogenic; and not yet classified) classification system for abnormal uterine bleeding — has been approved by the International Federation of Gynecology and Obstetrics and [supported by] the American College of Obstetrics and Gynecology (Int J Gynaecol Obstet. 2011;113:3-13).

Medscape: How common is heavy and/or prolonged menstrual bleeding?

Dr. Nelson: Studies show that 9% to 14% of women experience heavy blood loss, but 30% consider their bleeding to be excessive.

While anatomical abnormalities, such as carcinoma or large leiomyoma, may require surgical intervention, about 30% of hysterectomy specimens are reported to be normal on pathology.

Medscape: What are the main causes of abnormal bleeding, and which are the most common?

Dr. Nelson: The etiology of heavy bleeding is quite varied. Pregnancy complications must always be reported first, and then gynecological causes, such as anovulation, are investigated. Medications (like warfarin, anticonvulsants) and systemic diseases (such as thyroid dysfunction, renal failure, hepatic cirrhosis, and splenic dysfunction) can frequently figure into the etiology.

More recently, bleeding disorders have been identified as a cause of heavy menstrual bleeding. Classically, von Willebrand disease has been recognized as a cause presenting in adolescence. Now it is clear that platelet aggregation defects are a much more common cause of idiopathic excessive uterine bleeding, especially in older women. In cases such as these, collaboration between the woman's health provider and a hematologist is often needed.

Medscape: What are the primary steps in a work-up of patients who have abnormal menstrual bleeding?

Dr. Nelson: The work-up depends on the pattern of bleeding, the risk factors the woman has for endometrial disease, and her symptomology. A baseline complete blood count provides information about the urgency of intervention (based on the hemoglobin) and about the chronicity of the problem (based on mean corpuscular volume) and her platelet count. If history suggests other etiologies, chem7, thyroid-stimulating hormone, prothrombin time and partial thromboplastin time, and/or liver function tests may be appropriate.

If a bimanual exam suggests adenomyosis leiomyoma, a pelvic ultrasound may be helpful. Endometrial aspiration (with or without endocervical curettage) may be needed in women at increased risk for endometrial hyperplasia. Secondary tests, such as saline infusion sonography or hysteroscopy, may provide more detailed information about endometrial pathology (polyps, submucosal fibroid) if treatment-based first-level tests are not helpful.

Another important consideration is to test for coagulation defects, especially if there is repetitive prolonged/heavy bleeding and no other cause is identified.

Medscape: What is the best way to manage patients with excessive or prolonged bleeding?

Dr. Nelson: First, one must distinguish between acute and chronic bleeding. One of the newer treatments for acute bleeding is medroxyprogesterone acetate 20 mg orally 3 times a day for 7 days, then once daily for 21 days. That's been demonstrated to be as effective as the estrogen-containing options and has no medical contraindications (Obstet Gynecol. 2006;108:924-929).

For chronic heavy menstrual bleeding, 3 medical therapies have been approved by the US Food and Drug Administration (FDA).

One is the levonorgestrel intrauterine system (Mirena). It appears to be the most effective of all medical therapies — as effective as ablation — and has been shown to reduce blood loss by 90%.

Another approved therapy is estradiol valerate (or estradiol valerate/dienogest). It has been demonstrated to cut blood loss by more than 60%.

Still another is tranexamic acid, an antifibrinolytic agent. Two 650 mg tablets are taken orally 3 times daily for up to 5 days during menses. Studies indicate that it reduces blood loss by about 39%.

Medscape: What are some of the off-label medical therapies for chronic bleeding that have not been approved by the FDA?

Dr. Nelson: Some methods have been demonstrated to be effective in clinic trials (even Cochrane Reviews), but have not sought FDA approval. A first-line therapy is often nonsteroidal anti-inflammatory drugs, such as ibuprofen 800 mg orally 3 times a day during menses. This reduces blood loss by 20% to 30%.

Another off-label option is depot medroxyprogesterone acetate. When administered 150 mg intramuscularly every 11 to 13 weeks, it often results in amenorrhea.

Some clinicians use extended-cycle pills, contraceptive vaginal rings, cyclic combined hormonal methods, and progestin-only oral contraceptives.

Medscape: Are there interventions that are more suitable for short-term use?

Dr. Nelson: Yes. For the short term, gonadotropin-releasing hormone (GnRH) analogs have been used, again off-label, to suppress proliferation of endometrium. Danazol, a derivative of the synthetic steroid ethisterone (a modified testosterone), also known as 17-alpha-ethinyl testosterone, has been used with some success.

Each of these therapies can be very effective because they arrest ovarian steroidogenesis, but their side-effect profiles (osteoporosis for the GnRH agonist and irreversible androgenic side effects for danazol) limit their use as single-agent therapies to 4 to 6 months.

Dr. Nelson reports receiving grants/research from Bayer, Merck, Pfizer, and Teva; receiving honoraria and/or serving on speakers bureaus for Bayer, Ferring, Merck, and Teva; and serving as a consultant or on an advisory board for Agile, Bayer, Ferring, Merck, Teva, and Watson.