Strength of recommendations (A, B, C, D, I) and quality of evidence (High, Moderate, Low) are defined at the end of the "Major Recommendations" field.
Evaluation
History Taking & Diagnostics for Heavy Menstrual Bleeding (HMB)
Initially, a history should be taken from the woman, which should cover the nature of the bleeding (onset duration and quantity), related symptoms that might suggest structural or histological abnormality (pelvic pressure, change in urinary symptoms, dyspareunia), impact of quality of life and other factors that may determine treatment options (such as presence of medications, comorbidities or family history of bleeding disorders). (Brenner, 1996; Cameron 1989; Ely et al., 2006; Hurskainen et al., 2007; Munro et al., 2011; Munro, 2007; Sweet et al., 2012) (Grade A, Moderate Certainty)
Clinicians should take into account the range and natural variability in menstrual cycles and blood loss when diagnosing HMB (defined as a blood loss >80 mL per period), and discuss this variation with the woman. For instance, number of pads/tampons used, needing to change pads/tampons frequently (2 hr or less), period lasting more than 7 days, and bleeding associated with perceived or actual excessive blood loss. If the woman feels that she does not fall within the normal ranges or describes excessive menstrual bleeding then care options should be discussed. (Brenner, 1996; Cameron, 1989; Edmonds, 1989; Fraser, Warner, & Marantos, 2001; Garside, Britten, & Stein, 2008; Warner et al., "Menorrhagia II," 2004) (Grade A, Moderate Certainty)
If the history suggests HMB with structural or histological abnormality, with symptoms such as intermenstrual or post-coital bleeding, pelvic pain and/or pressure symptoms, a physical examination and/or other investigations (such as ultrasound) should be performed. (Ely et al., 2006; Hurskainen et al., 2007; Sweet et al., 2012) (Grade B, Moderate Certainty)
Measurement of Menstrual Blood Loss
Measuring menstrual blood loss either directly (alkaline hematin) or indirectly (pictorial blood loss assessment chart) is not recommended for HMB. Whether menstrual blood loss is a problem should be determined not by measuring but by the woman herself, and then evaluated by the health care provider. (Garside, Britten, & Stein, 2008; Warner et al., "Menorrhagia I," 2004; Warner et al., "Menorrhagia II," 2004) (Grade B, Moderate Certainty)
Physical Examination for HMB
A physical examination should be carried out (including pelvic and abdominal exam) before (Brenner, 1996; Cameron, 1989; Ely et al., 2006; Munro et al., 2011; Sweet et al., 2012) (Grade A, High Certainty):
- Long-acting reversible contraception is initiated
- Investigations for structural abnormalities are done
- Investigations for histological abnormalities are done
Women with fibroids that are palpable abdominally or who have intra-cavity fibroids and/or whose uterine length, as measured at ultrasound or sonohysterogram, is greater than 12 cm should be offered immediate referral to a specialist. (Ely et al., 2006; Hurskainen et al., 2007; Sweet et al., 2012) (Grade A, Moderate Certainty)
Laboratory Tests for HMB
A complete blood count should be carried out on all women with HMB. (Cameron, 1989; Ely et al., 2006; Munro, 2007; Sweet et al., 2012) (Grade A, High Certainty)
Testing for coagulation disorders (for example, von Willebrand disease) should be considered in women who have had HMB since menarche and have personal or family history suggesting a coagulation disorder such as bruising without known injury (or easy bruisability) or mucous membrane bleeding (e.g., epistaxis greater than 10 minutes duration; bleeding w/brushing teeth). (Edmonds, 1989; Ely et al., 2006; Munro et al., 2011; Sweet et al., 2012) (Grade B, Moderate Certainty)
A serum ferritin test should not routinely be carried out on women with HMB. (Ely et al., 2006; Sweet et al., 2012) (Grade B, Moderate Certainty)
Female hormone testing should not be carried out on women with HMB. (Cameron, 1989; Sweet et al., 2012) (Grade B, Moderate Certainty)
Thyroid testing should be carried out in all women presenting with HMB even if other signs and symptoms of thyroid disease are not present. (Cameron, 1989; Edmonds, 1989; Ely et al., 2006; Hurskainen et al., 2007; Munro, 2007; Sweet et al., 2012; Wilansky & Greisman, 1989) (Grade A, High Certainty)
Treatment for a thyroid-stimulating hormone (TSH) >3 should be considered in any woman presenting with HMB. (Wilansky & Greisman, 1989) (Grade B, Moderate Certainty)
A pregnancy test should be given for women who are sexually active presenting with HMB. (Cameron, 1989; Edmonds, 1989; Ely et al., 2006; Hurskainen et al., 2007; Munro, 2007; Sweet et al., 2012) (Grade B, High Certainty)
Pap smear should be up to date or perform Pap smear. (Ely et al., 2006; Sweet et al., 2012) (Grade A, Moderate Certainty)
Further Diagnostic Testing for HMB
If appropriate, a biopsy should be taken to exclude endometrial cancer or atypical hyperplasia. Indications for a biopsy include: persistent inter-menstrual bleeding, no definite cause of HMB identified, in women aged 35 and over, and treatment failure or ineffective treatment. (Ely et al., 2006; Munro et al. 2011; Sweet et al. 2012) (Grade B, Moderate Certainty)
Imaging should be undertaken in the following circumstances (Ely et al., 2006; Hurskainen et al., 2007; Sweet et al., 2012) (Grade B, Moderate Certainty):
- The uterus is palpable abdominally
- Vaginal examination reveals a pelvic mass of uncertain origin
- Pharmaceutical treatment fails
Ultrasound is the first-line diagnostic tool for identifying structural abnormalities. (Cameron, 1989; Ely et al., 2006; Munro et al., 2011) (Grade A, High Certainty)
Referral for hysteroscopy should be used as a diagnostic tool only when ultrasound results are inconclusive, for example, to determine the exact location of a fibroid or the exact nature of the abnormality. (Ely et al., 2006; Munro et al., 2011; Sweet et al., 2012) (Grade A, Moderate Certainty)
If imaging shows the presence of uterine fibroids then appropriate treatment should be planned based on size, number and location of the fibroids. (Ely et al., 2006; Sweet et al., 2012) (Grade A, High Certainty)
Also consider referral for endometrial biopsy in women between the ages of 18 and 35 who have risk factors for endometrial cancer: family or personal history of ovarian, breast, colon, or endometrial cancer; tamoxifen use; chronic anovulation; obesity; estrogen therapy; prior endometrial hyperplasia; diabetes. (Ely et al., 2006; Munro et al., 2011; Sweet et al., 2012) (Grade B, Moderate Certainty)
Saline infusion sonography (sonohysterography) should not be used as a first-line diagnostic tool. (Cameron, 1989; Ely et al., 2006; Sweet et al., 2012) (Grade A, Moderate Certainty)
Pharmacological Interventions
The following recommendations are based upon good clinical practice:
- Pharmacologic treatment should be considered for heavy menstrual bleeding after underlying etiologies have been ruled out.
- When selecting the appropriate treatment, patient preference and the need for contraception should be taken into account, as well as benefits and risk associated with each agent.
- Non-hormonal agents: if there is no improvement in HMB after three cycles the treatment should be stopped.
Hormonal Agents
- Intrauterine Levonorgestrel-Releasing Systems (Mirena) – first line therapy (Lethaby, Cooke, & Rees, 2010) (Grade A, High Certainty)
- Indicated for women who prefer long term contraception (5 years) (Bednarek & Jensen, 2009; Lethaby, Cooke, & Rees, 2010) (Grade A, High Certainty)
- Proved to be effective and well tolerated in the short-/mid-term treatment of fibroid-related heavy menstrual bleeding, the symptomatic treatment of endometriosis and adenomyosis, as well as in cases of endometrial hyperplasia (Heikinheimo & Gemzell-Danielsson, 2012) (Grade B, Moderate Certainty)
- Reduces HMB 88.4% by 1 year (Ghazizadeh et al., 2011) (Grade A, Moderate Certainty)
- More cost effective than hysterectomy or ablation (Lethaby, Cooke, & Rees, 2010; Sweet et al., 2012) (Grade A, High Certainty)
- Reduces incidence of hysterectomy (Lethaby, Cooke, & Rees, 2010; Sweet et al., 2012) (Grade A, High Certainty)
- Minimally invasive (Lethaby, Cooke, & Rees, 2010; Sweet et al., 2012) (Grade A, High Certainty)
- Preserves fertility, good option for younger women (Bednarek & Jensen, 2009; Sweet et al., 2012) (Grade A, Moderate Certainty)
- Systemic side effects: breast tenderness, acne, mood changes, headaches, and bloating (Ghazizadeh et al., 2011) (Grade A, High Certainty)
- Most common side effect is spotting (Ghazizadeh et al., 2011) (Grade A, High Certainty)
- Combined Oral Contraceptives (COCs)
- Indicated for patients who require contraception but do not wish to use an intrauterine device (IUD) (Kiley & Shulman, 2011; Sweet et al., 2012) (Grade A, Moderate Certainty)
- Greater reductions in blood loss than placebo (Fraser et al., 2011) (Grade B, Moderate Certainty)
- Also increases in hemoglobin, hematocrit, and ferritin levels (Fraser et al., 2011) (Grade B, Moderate Certainty)
- Cost effective (Kiley & Shulman, 2011; Sweet et al., 2012) (Grade A, High Certainty)
- Conditions which contraindicate use include:
- History of breast cancer
- History of or current deep venous thrombosis/pulmonary embolism (DVT/PE) or cerebrovascular accident (CVA)
- Diabetes: insulin-dependent; with nephropathy/retinopathy/neuropathy or other vascular disease; or of >20 years' duration
- Blood pressure systolic ≥160 mmHg, diastolic ≥100; vascular disease
- Current and history of ischemic heart disease
- Complicated valvular heart disease
- History of peripartum cardiomyopathy
- Less than 21 days postpartum
- Smokers ≥35 years
- Thrombogenic mutations
- Systemic lupus erythematosus, only with positive (or unknown) phospholipids antibodies
- History of migraines without aura, age ≥35; migraines with aura, any age
- Medically treated or current gallbladder disease
- Hepatocellular adenoma or malignant liver tumor
- Severe, decompensated cirrhosis
- Complicated solid organ transplantation (graft failure [acute or chronic], rejection, cardiac allograft vasculopathy) ("Committee opinion no. 505," 2011) (Grade A, High Certainty)
- Also good option for younger women to preserve fertility (Fraser et al., 2011) (Grade A, High Certainty)
- Oral/Injected/Implanted (Implanon) Progesterone
- Indicated for women who have a history of venous thromboembolism (VTE) or Factor V Leiden carrier (Lethaby, Irvine, & Cameron, 2009) (Grade A, Moderate Certainty)
- Not shown to reduce bleeding as much as IUD (Lethaby, Irvine, & Cameron, 2009; Sweet et al., 2012) (Grade A, High Certainty)
- Oral progesterone only given during the luteal phase should not be used for the treatment of HMB (Lethaby, Irvine, & Cameron, 2009) (Grade B, Moderate Certainty)
Non-Hormonal Agents
- Tranexamic Acid (Lysteda)
- Begin first day of menses and continue for 5 days (Roy & Bhattacharya, 2004; Sweet et al., 2012) (Grade B, Moderate Certainty)
- Can be adjunct therapy to non-steroidal anti-inflammatory drugs (NSAIDs) (Roy & Bhattacharya, 2004) (Grade B, Moderate Certainty)
- Shown to reduce menstrual blood loss by 45%-60% through preventing activation of plasminogen (Edlund, 2011; Fraser et al., 2008; Lethaby, Farquhar, & Cooke, 2010; Lukes et al., 2010; Roy & Bhattacharya, 2004; Sweet et al., 2012) (Grade B, High Certainty)
- Contraindicated if patient has active intravascular clotting or subarachnoid hemorrhage (Sweet et al., 2012) (Grade D, High Certainty)
- Caution in patients with a risk for or history of thromboembolic or renal disease (Roy & Bhattacharya, 2004; Sweet et al., 2012) (Grade C, High Certainty)
- No evidence of increased incidence of thromboembolic events during treatment with tranexamic acid (Fraser et al., 2008; Roy & Bhattacharya, 2004; Sweet et al., 2012) (Grade B, Moderate Certainty)
- More expensive than other therapies (Roy & Bhattacharya, 2004; Sweet et al., 2012) (Grade B, High Certainty)
- Non-steroidal Anti-inflammatory Drugs (NSAIDs)
- Ibuprofen, naproxen sodium, and mefenamic acid have been widely studied (Edlund, 2011; Fraser et al., 2008; Roy & Bhattacharya, 2004; Sweet et al., 2012) (Grade B, High Certainty)
- Begin the first day of menses and continue for 5 days or until menses cease (Sweet et al., 2012) (Grade B, High Certainty)
- Can be adjunct therapy to COCs, intrauterine contraceptive devices, and tranexamic acid (Fraser et al., 2008; Roy & Bhattacharya, 2004) (Grade B, Moderate Certainty)
- Shown to reduce menstrual blood loss by 20%-50% through decreasing prostaglandin levels (Edlund, 2011; Fraser et al., 2008; Roy & Bhattacharya, 2004; Sweet et al., 2012) (Grade B, High Certainty)
- May also improve dysmenorrhea (Fraser et al., 2008; Roy & Bhattacharya, 2004; Sweet et al., 2012)
- Caution in patients with gastrointestinal risk factors such as history of gastrointestinal (GI) bleed, peptic ulcer disease, or chronic alcohol abuse (Edlund, 2011; Fraser et al., 2008; Roy & Bhattacharya, 2004; Sweet et al., 2012) (Grade C, High Certainty)
Referral Treatment Options
- Endometrial ablation (American College of Obstetricians and Gynecologists, 2008; Apgar et al. 2007; Middleton et al., 2010; Sweet et al., 2012; Stovall, 2011) (Grade A, High Certainty)
- Magnetic-resonance imaging (MRI)-guided focused ultrasound (Fennessy et al., 2007; Stovall, 2011) (Grade B, Moderate Certainty)
- Uterine fibroid embolization (Sweet et al., 2012; Stovall, 2011) (Grade A, High Certainty)
- Myomectomy (Geidam et al., 2011; Sweet et al., 2012) (Grade B, Moderate Certainty)
- Hysterectomy/oophorectomy (Apgar et al., 2007; Bhavnani & Clarke, 2003; Sweet et al., 2012) (Grade C, High Certainty)
Definitions:
Grading of Recommendations (Based on U.S. Preventive Services Task Force [USPSTF] Ratings)
A. The USPSTF strongly recommends that clinicians provide the service to eligible patients. The USPSTF found good evidence that the service improves important health outcomes and concludes that benefits substantially outweigh harms.
B. The USPSTF recommends that clinicians provide this service to eligible patients. The USPSTF found at least fair evidence that the service improves important health outcomes and concludes that benefits outweigh harms.
C. The USPSTF makes no recommendation for or against routine provision of the service. The USPSTF found at least fair evidence that the service can improve health outcomes but concludes that the balance of benefits and harms is too close to justify a general recommendation.
D. The USPSTF recommends against routinely providing the service to asymptomatic patients. The USPSTF found at least fair evidence that the service is ineffective or that harms outweigh benefits.
I. The USPSTF concludes that the evidence is insufficient to recommend for or against routinely providing the service. Evidence that the service is effective is lacking, of poor quality, or conflicting, and the balance of benefits and harms cannot be determined.
Quality of Evidence (Based on USPSTF Ratings)
High: The available evidence usually includes consistent results from well-designed, well-conducted studies in representative primary care populations. These studies assess the effects of the preventive service on health outcomes. This conclusion is therefore unlikely to be strongly affected by the results of future studies.
Moderate: The available evidence is sufficient to determine the effects of the preventive service on health outcomes, but confidence in the estimate is constrained by such factors as:
- The number, size, or quality of individual studies
- Inconsistency of findings across individual studies
- Limited generalizability of findings to routine primary care practice
- Lack of coherence in the chain of evidence
As more information becomes available, the magnitude or direction of the observed effect could change, and this change may be large enough to alter the conclusion.
Low: The available evidence is insufficient to assess effects on health outcomes. Evidence is insufficient because of:
- The limited number or size of studies
- Important flaws in study design or methods
- Inconsistency of findings across individual studies
- Gaps in the chain of evidence
- Findings not generalizable to routine primary care practice
- Lack of information on important health outcomes
More information may allow estimation of effects on health outcomes.
