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Heavy menstrual bleeding
REVIEW
Heavy menstrual bleeding
Prevalence Between 4% and 51% of women experience HMB depending on their country of origin and clinical settings where data had been collected. Heavy menstrual bleeding affects one in three women of reproductive age. In the UK, almost 1.5 million women per year consult their GP with menstrual complaints and the annual treatment cost exceeds £65 m.
Rashda Bano Shreelata Datta Tahir A Mahmood
Abstract
Causes of heavy menstrual bleeding
Heavy menstrual bleeding is defined as excessive menstrual blood loss which interferes with the woman’s physical, emotional, social and material quality of life, and which can occur alone or in combination with other symptoms. All interventions should aim to improve quality of life rather than focussing on menstrual blood loss alone. An accurate history may indicate the cause of the bleeding. Indications for endometrial biopsy include persistent intermenstrual bleeding as well as heavy menstrual bleeding, in women aged 45 and over and those where there is evidence of treatment failure. First line treatment includes tranexamic acid or nonsteroidal anti-inflammatory drugs or combined oral contraceptives. Second line treatment options include, levonorgestrel-releasing intrauterine system (provided long-term use is anticipated), oral norethisterone or injectable long-acting progestogens. In women with HMB alone who have failed to respond to the above treatment options: with uterus no bigger than a 10-week pregnancy, endometrial ablation should be considered in preference to hysterectomy. Where hysterectomy is indicated, the route of hysterectomy should be considered in the following order: first-line vaginal; second-line abdominal/laparoscopic.
Fibroids, polyps, coagulopathy, endometrial/cervical malignancy, thyroid disease, pelvic infection especially by Chlamydia, and arteriovenous malformations are the possible causes of HMB. Iatrogenic causes include use of anticoagulants etc. Submucosal and intramural fibroids are particularly associated with HMB, although about 50% of fibroids cause no symptoms. Coagulopathy should be considered in women who fail to respond to medical management or women who present at a young age. Coagulopathy may be inherited or acquired and most common inherited disorder is von Willebrand’s disease. Endometrial and cervical carcinomas are potential causes of intermenstrual and post coital bleeding and rarely HMB. Untreated hypothyroidism may be associated with HMB. Chronic endometrial infection may cause intermenstrual bleeding or HMB. Chlamydia trachomatis has been proposed as a cause of HMB. Arteriovenous malformations (AVM) in the uterus may be congenital or acquired and are a rare cause of HMB. Acquired AVM may occur following uterine curettage after pregnancy. Colour Doppler imaging is a useful diagnostic modality if AVM malformation is suspected. Acute heavy bleeding from an AVM may be required to be managed with uterine artery embolization. Iatrogenic causes include the use of anticoagulants in women with thromboembolic disease and copper IUD. Table 1 summarises the main causes of HMB.
Keywords abnormal uterine bleeding; endometrial ablation; heavy menstrual bleeding; hormonal treatment; hysterectomy; long acting injectable progestogens
Obesity and HMB Introduction
Obesity is associated with abnormal uterine bleeding. There is clear association between obesity, endometrial polyps, endometrial hyperplasia and ovulatory dysfunction. As PCOs are associated with obesity and obesity augments its development, many of the effects of obesity on menstrual disorders are manifested through PCOs. A survey of pre-menopausal women with endometrial polyps found that 82% reported abnormal uterine bleeding. In obese women particularly in combination with hypertension, there is an increase risk for polyp development. In addition, in infertility patients, Body Mass Index (BMI) was an independent risk factor for the development of endometrial polyps. Obese women would therefore appear to be at an increased risk of developing endometrial polyps although the basis for this is not known. Obesity also increases the risk of malignancy developing within an endometrial polyp. In one study it is reported that 86% of women with complex hyperplasia were obese. Histological examination of pre-menopausal endometrial biopsies found that women with hyperplasia had a significantly higher BMI than those without hyperplasia. In another study the median BMI in the hyperplastic group was 38 kg/m2 compared with 30 kg/m2 in the non-hyperplastic group.
Heavy menstrual bleeding (HMB) is defined as excessive menstrual blood loss which interferes with a woman’s physical, social, emotional and/or material quality of life. It can occur alone or in combination with other symptoms. The term heavy menstrual bleeding has replaced the term menorrhagia. The objective definition of HMB is no longer used except for research purposes.
Rashda Bano MRCOG is a Specialist Registrar in Obstetrics and Gynaecology at Victoria Hospital, Kirkcaldy, Scotland. Conflicts of interest: none declared. Shreelata Datta MRCOG LLM is a Locum Consultant Obstetrician & Gynaecologist at St Helier’s Hospital, Carshalton, Surrey, UK. Conflicts of interest: none declared. Tahir A Mahmood MD FRCOG FRCPI MBA FACOG is a Consultant Obstetrician and Gynaecologist at Victoria Hospital, Kirkcaldy, Scotland. Conflicts of interest: none declared.
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REVIEW
suggested by history of excessive bleeding since menarche, postpartum haemorrhage, surgery related bleeding, or a history of two or more of following: bruising greater than 5 cm, epistaxis once a month, frequent bleeding or a family history of bleeding disorders. According to NICE guideline, 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. If the history suggests HMB without structural or histological abnormality, pharmaceutical treatment can be started without carrying out a physical examination or other investigations at initial consultation at primary care unless treatment chosen is LNG-IUS. Measuring menstrual blood loss either directly (alkaline haematin) or indirectly (‘Pictorial blood loss assessment chart’) is not routinely recommended for HMB.
Summary of causes of HMB Classification
Subtype
Local uterine pathology
Uterine fibroids Uterine polyps Chronic endometrial infection Uterine cancer Endometrial hyperplasia Arteriovenous malformation Polycystic ovaries (PCOs) Hypothyroidism Coagulopathy e.g. Von Willebrand’s disease Anticoagulation therapy IUCD
Local pelvic pathology Systemic disorders
Iatrogenic causes
Table 1
Examination Women with complex endometrial hyperplasia are more frequently obese. In addition, BMI is predictive of endometrial thickness on an ultrasound scan and this is predictive of hyperplasia. Obese women are thus at increased risk of developing endometrial hyperplasia. A raised BMI is associated with earlier menarche and menstrual irregularities during adolescence. A raised BMI will certainly impact on endometrial function in the context of an increased risk of endometrial hyperplasia and endometrial carcinoma. Raised circulating oestrogen levels, as a consequence of peripheral conversion of androgens by adipose tissue aromatase, enzyme have been implicated in the increased proliferative activity of endometrial cells. Circulating adipokines have also been associated with increased angiogenesis as well as cell proliferation. HMB is a common complaint among those women who are premenopausal and who are subsequently diagnosed with endometrial cancer. It would therefore not be unlikely if a raised BMI was found to impact on the volume of menstrual blood loss.
A general physical examination should be performed to exclude signs of anaemia, evidence of systemic coagulopathy and thyroid disease. An abdominal examination should be performed to exclude a pelvic mass especially if there is a history of pressure symptoms (fibroid or ovarian enlargement); a speculum examination should be performed to assess vulva, vagina and cervix (this may reveal sources of bleeding, such as a tumour, polyp or a discharge suggesting infection). A bimanual examination should be performed to elicit uterine enlargement. A physical examination should be carried out before All LNG-IUS fittings. All investigations for structural abnormalities All investigations for histological abnormalities. Women with fibroids that are palpable abdominally or who have Intracavity fibroids and/or whose uterine length as measured at ultrasound or hysteroscopy is greater than 12 cm would require further assessment in a hospital setting.
Bleeding of endometrial origin
Investigations (Table 2)
In the majority of cases of HMB, the precise cause of heavy bleeding lies at level of the endometrium. This was previously termed as DUB or dysfunctional uterine bleeding and it is a diagnosis of exclusion.
Laboratory tests A full blood count test should be carried out on all women with HMB. This should be done in parallel with any HMB treatment offered. Testing for coagulation disorders (for example, von Willebrand’s disease) should be considered in women who have had HMB since menarche and have personal or family history suggesting a coagulation disorder. A serum ferritin test, LH, FSH should not routinely be carried out on women with HMB. Thyroid testing should be carried out only when other signs and symptoms of thyroid disease are present.
History, examination and investigations for HMB A history should be taken from the woman that should cover the nature of bleeding and related symptoms that might suggest structural or histological abnormality, impact on the quality of life and other factors that may determine treatment options (such as presence of co morbidity). The range and natural variability in menstrual cycles and blood loss should be taken into account when diagnosing HMB. A menstrual diary is often helpful to determine the amount and timing of the bleeding. Flooding and clots indicate significant loss. Inter menstrual and post coital bleeding are suggestive of an anatomical cause, whereas pressure symptoms, including bowel and urinary symptoms, can indicate the presence of a large fibroid. A coagulation disorder may be
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Endometrial biopsy Dilatation and Curettage should not be used at all in the management of HMB. If appropriate, a biopsy should be taken to exclude endometrial cancer or atypical hyperplasia. Indications for a biopsy include, for example, persistent intermenstrual bleeding, and in women aged 45 and over treatment failure or ineffective
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Summary of investigations for HMB and their benefits Investigation type
Specific investigation
Indication
Blood test
FBC, TFTs Coagulation screen
Histology Imaging
Endometrial biopsy Transvaginal and transabdominal ultrasound
To exclude anaemia and hypothyroidism, where thyroid symptoms exist To exclude a clotting disorder where a positive family history or other symptoms exist To exclude endometrial atypia or carcinoma To identify uterine structural abnormalities such as polyps and fibroids
Table 2
Summary of pharmaceutical treatments available for menorrhagia and their outcomes Pharmaceutical treatment
Mechanism of action
Effect on menstrual bleeding
Is it a contraceptive?
Side effects
Levonorgestrel-releasing intrauterine system (LNGIUS)
Prevents endometrial proliferation
Bleeding reduced by up to 95%; full benefit may take upto 6 months
Yes
Tranexamic acid, two tablets 3e4 times a day orally for up to 4 days during menses Nonsteroidal antiinflammatory drugs (NSAIDs), taken during menses
It is an antifibrinolytic
Bleeding reduced by up to 58%
No
Irregular bleeding; hormonal problems such as breast tenderness, acne or headaches, uterine perforation at the time of insertion (rare) Indigestion; diarrhoea; headaches
Reduces production of prostaglandin
Bleeding reduced by up to 49%
No
Combined oral contraceptives (COCs), taken daily for 21 days, followed by a 7 day break
Prevents endometrial proliferation
Bleeding reduced by 43%
Yes
Oral progestogen (norethisterone), 15 mg from day 5 to day 26 of cycle Injected or implanted progestogen, injected every 12 weeks or implant for 3 years use
Prevents endometrial proliferation
Bleeding reduced by up to 83%
Yes
Prevents endometrial proliferation
Bleeding is likely to stop completely
Yes
Gonadotrophin-releasing hormone analogue (GnRH-a), given as a monthly injection for 3e6 months
Stops oestrogen and progesterone production
Bleeding stopped completely in 89% of women
No
Indigestion; diarrhoea, worsening of asthma in sensitive individuals; peptic ulcers with possible bleeding and peritonitis Mood changes; headaches; nausea; fluid retention; breast tenderness, deep vein thrombosis; stroke; heart attacks Weight gain; bloating; breast tenderness; headaches; acne
Weight gain; irregular bleeding; amenorrhoea; premenstrual-like syndrome (including bloating, fluid retention, breast tenderness), loss of bone mineral density, Menopausal symptoms (such as hot flushes, increased sweating, vaginal dryness)
Adapted from Heavy Menstrual Bleeding NICE Clinical Guidelines, No. 44.National Collaborating Centre for Women’s and Children’s Health (UK) London: RCOG Press; 2007.
Table 3
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A summary of various interventions for the treatment of HMB Surgical treatment
Mechanism of action
Impact on future fertility?
Side effects
Endometrial ablation
Destroys endometrial lining
Yes
Transcervical resection of fibroids (hysteroscopic myomectomy) Open myomectomy (fibroids >3 cm)
Surgical resection of submucosal fibroids Surgical resection of subserosal or intramural fibroids Surgical removal of uterus removal of ovaries
No
Vaginal discharge, period pain or cramping, infection , perforation (rare) Adhesions, perforation, haemorrhage, recurrence, infection Infection, haemorrhage, thrombosis, recurrence, pain, adhesions Infection, haemorrhage, urinary tract infection, bowel damage, thrombosis, menopausal symptoms with oophorectomy Adhesions, perforation, recurrence, infection, haemorrhage
Hysterectomy
Uterine artery embolization
Injection into blood vessels to reduce blood flow to a fibroid uterus
No Yes
Potentially
Table 4
Norethisterone (15 mg) daily from days 5 to 26 of the menstrual cycle, or injected long-acting progestogens. Other treatment options include GnRH analogue. Danazol, Ethamsylate and Gestrinone are no longer recommended for use in treatment of HMB owing to their unacceptable side effects.
treatment. Blind sampling methodologies (outpatient endometrial biopsy) are reasonable screening techniques but they are ineffective at diagnosing focal lesions. Hysteroscopy and endometrial biopsy can be performed. Role of imaging Ultrasound is the first line diagnostic tool for identifying structural abnormalities. Hysteroscopy and Magnetic resonance imaging (MRI) should not be used as a first line diagnostic tool. Saline infusion sonography should not be used as first line diagnostic tool.
Non-hormonal treatments: these treatments can be used if hormonal treatments are not acceptable to the woman or while investigations and definitive treatment is being organized. Antifibrinolytics e antifibrinolytics such as Tranexamic acid reduce blood loss by upto 50% by inhibiting endometrial fibrinolysis. Side effects are rare but may include indigestion, diarrhoea or headache. Cochrane reviews concluded that antifibrinolytic therapy causes a greater reduction in objective measurements of heavy menstrual bleeding when compared to placebo or other medical therapies (NSAIDS, oral luteal phase progestagens and ethamsylate). This treatment is not associated with an increase in side effects compared to placebo, NSAIDS, oral luteal phase progestagens or ethamsylate. Flooding, leakage and sex life is significantly improved after tranexamic acid therapy when compared with oral luteal progestogens but no other measures of quality of life were assessed. Prostaglandin synthetase inhibitor e non-steroidal anti-inflammatory drugs are an example of prostaglandin synthetase inhibitor and act by inhibiting endometrial prostaglandin production leading to reduction in menstrual blood loss. Mefenamic acid is the most frequently used agent and reduces blood loss by approximately 25%. This medicine has to be taken during menstruation and is associated with gastrointestinal side effects such as indigestion, diarrhoea, worsening of asthma and peptic ulcer disease. When HMB coexists with dysmenorrhoea, NSAIDs should be preferred to Tranexamic acid. There have been isolated reports of NSAID-associated reversible female infertility and probable mechanism is ovulatory failure due to non-rupture of mature follicle.
Treatment for HMB HMB has a major impact on a woman’s quality of life. Treatment and care should take into account the woman’s needs and preferences. Women with HMB should have the opportunity to make informed decisions about their care and treatment, in partnership with their healthcare professionals. Women should be given information about mode of action, duration of action, side effects and impact on fertility of different treatment options available. Treatment can be either medical or surgical; medical management does not impact on future fertility in the long-term. Table 3 summarises the pharmacological treatments available, together with their outcomes, whilst Table 4 considers surgical interventions for menorrhagia and their benefits. Pharmaceutical treatments Pharmaceutical treatment should be considered where no structural or histological abnormality is present, or for fibroids less than 3 cm in diameter which do not distort the uterine cavity. Hormonal and non-hormonal treatments are available and should be considered in the following order. Levonorgestrel-releasing intrauterine system (LNG-IUS) provided long-term (at least 12 months) use is anticipated. Tranexamic acid or non-steroidal anti-inflammatory drugs (NSAIDs) or combined oral contraceptives (COCs).
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Cochrane reviews concluded that NSAIDs reduce HMB when compared with placebo but are less effective than tranexamic acid, danazol or LNG IUS. In the limited number of small studies suitable for evaluation, no significant difference in efficacy was demonstrated between NSAIDs and other medical treatments such as oral luteal progestogen, ethamsylate, COC or another type of intrauterine system, Progestasert. Use of NSAIDs and/or Tranexamic acid should be stopped if it does not improve symptoms within three menstrual cycles.
leading to amenorrhoea. Use of a Gonadotropin-releasing hormone analogue could be considered prior to surgery or when all other treatment options for uterine fibroids, including surgery or uterine artery embolization, are contraindicated. If this treatment is to be used for more than 6 months or if adverse effects are experienced then hormone replacement therapy (HRT) as ‘addback’ therapy is recommended. Danazol: Cochrane reviews concluded that Danazol appears to be an effective treatment for heavy menstrual bleeding compared to other medical treatments. The use of Danazol may be limited by its side effect profile, its acceptability to women and the need for continuing treatment. The small number of trials, and the small sample sizes of the included trials limit the recommendations for clinical care. Further studies are unlikely in the future and this review will not be updated unless further studies are identified. There is no reliable evidence available from randomized controlled trials regarding the benefits or harms of the use of danazol for treating uterine fibroids. Obesity and Treatment options: one clear effect of obesity is that the management of HMB amongst women with a raised BMI is a challenge. The treatments available for HMB may be limited although data showing treatment outcome in relation to BMI are lacking. Raised BMI is associated with poor efficacy of hormonal contraception suggesting an effect or obesity on bioavailability or action of steroids. Hysterectomy will have additional complications in the presence of a raised BMI. A recent publication reported that patients with a BMI of greater than 34 showed a trend towards failure with this intervention. Some options seem to be suited to obese women. The levonorgestrel-releasing intrauterine system (LNG-IUS) is considered a “first time” treatment option for management of HMB. It also protects against endometrial hyperplasia in ovulatory dysfunction. A recent study amongst adolescent women undergoing bariatric surgery showed a high acceptance rate of this method for management of menstrual complaints.
Hormonal treatments: Combined oral contraceptive pills e the ombined oral contraceptive pill (OCP) is considered effective in the management of HMB. Evidence from one randomized controlled trial of the COCP (Ethinyl oestradiol 30 mcg and levonorgestrel 150 mcg for 21 days) found a reduction in blood loss of 43%. Side effects include nausea, mood changes, breast tenderness and rarely thromboembolic disease (risk increases in smokers, obese and older women). A Cochrane review found one small study which found no significant difference between groups treated with OCP, mefenamic acid, low dose danazol or naproxen. Overall, the evidence from the one study is not sufficient to adequately assess the effectiveness of OCP. Oral progestogens e norethisterone acetate (5 mg, three times daily) taken from day 5 to day 26 of the menstrual cycle, is effective in treating HMB. Side effects include weight gain, bloating, breast tenderness, headache, acne and depression. Cochrane reviews concluded that Progestogens administered from day 15 or 19 to day 26 of the cycle offer no advantage over other medical therapies such as danazol, tranexamic acid, nonsteroidal anti-inflammatory drugs (NSAIDs) and the IUS in the treatment of menorrhagia in women with ovulatory cycles. Progestogen therapy for 21 days of the cycle results in a significant reduction in menstrual blood loss, although women found the treatment less acceptable than intrauterine levonorgestrel. This regimen of progestogen may have a role in the short-term treatment of menorrhagia. Injectable long acting progestogens e it is well recognized that amenorrhoea occurs in many women when long acting progestogens are used for contraception, and they can also be used for the treatment of HMB. Side effects include irregular bleeding, weight gain, amenorrhoea and less commonly bone density loss. Levonorgestrel releasing intrauterine system (LNG IUS) e LNG IUS is an excellent alternative to surgery for women with HMB who also seek reliable long-term contraception. It releases the hormone at a rate of 20 mg per day and acts locally by causing thinning and atrophy of endometrium. There is very little systemic absorption of the hormone so progestogen related side effects are much less than with oral agents. Side effects include breast tenderness, headache, acne or uterine perforation at time of insertion. RCTs show that the LNG IUS reduces menstrual loss by up to 96% after one year but that the full benefit may not be seen for first 6 months. Women should be fully counselled that they are likely to experience unscheduled spotting/bleeding in first 5 to 6 months. Gonadotropin releasing hormone analogues e GnRHa act by down regulating the HPO axis and induce ovarian suppression,
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Surgical treatment for HMB Typically, surgical management is only considered in women who have completed their family, with the exception of polypectomy and myomectomy where fertility can be retained. In the early 1990s, it was estimated that at least 60% of women presenting with HMB went on to have a hysterectomy. This was often the only treatment offered. Since the 1990s the number of hysterectomies has been decreasing rapidly. This reduction in hysterectomy rates is considered to reflect not only the introduction of successful treatment options, such as the LNG-IUS, but also having access to endometrial ablation techniques. Dilatation and curettage should not be used as a treatment option in any clinical situation. Table 4 summarizes surgical and radiological treatments for HMB. Polypectomy: endocervical polyps can be avulsed in the outpatient setting. Endometrial polyps can be removed blindly under general anaesthetic, or by hysteroscopic resection either under general anaesthetic, or in the outpatient setting. Endometrial ablation: endometrial ablation is targeted destruction of endometrium. It should be considered where bleeding is having a severe impact on a woman’s quality of life, and she does
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not wish to conceive in the future. Endometrial ablation should be considered in women with HMB who have a uterus no bigger than a 10-week pregnancy and also those with small uterine fibroids (less than 3 cm in diameter). First generation techniques include hysteroscopic transcervical resection of endometrium, using an electrical diathermy loop and roller ball ablation. These techniques offer treatment for uterine cavities with sub mucous fibroids. Second generation techniques have been developed for smoother and smaller cavities. These include fluid filled thermal balloon ablation, microwave ablation and impedance controlled endometrial ablation. These procedures can be performed as a day case. Women who undergo this procedure should be advised to use effective contraception. Pre ablation endometrial histology should be obtained and hysteroscopy should be performed before and after the procedure to exclude endometrial perforation. Post operatively, patients may complain of transient crampy abdominal pain and a watery brown discharge for between 3 and 4 weeks. Potential complications include device failure at time of procedure, endometritis, haematometra, fluid overload due to absorption of distension medium, uterine perforation and intra abdominal injury including visceral burns. As a general rule, of all the women undergoing endometrial ablation with a second generation technique, 40e50% will become amenorrhoeic, 40 e60% will have markedly reduced menstrual loss and 20% will have no difference in their bleeding. Long term trials show that while most women are initially satisfied, many subsequently choose or require repeat endometrial ablation or hysterectomy. About 15% women would require hysterectomy during a 10-year follow up following ablation independent of a technique used. Cochrane reviews concluded Endometrial ablation techniques offer a less invasive surgical alternative to hysterectomy. The rapid development of new methods of endometrial destruction has made systematic comparisons between methods and with the ’gold standard’ first generation techniques difficult. Most of the newer techniques are technically easier than hysteroscopy-based methods to perform but technical difficulties with new equipment need to be ironed out. Overall, the existing evidence suggests that success rates and complication profiles of newer techniques of ablation compare favourably with hysteroscopic techniques. Endometrial resection and ablation offers an alternative to hysterectomy as a surgical treatment for heavy menstrual bleeding. Both procedures are effective and satisfaction rates are high. Although hysterectomy is associated with a longer operating time, a longer recovery period and higher rates of postoperative complications, it offers permanent relief from heavy menstrual bleeding. The initial cost of endometrial destruction is significantly lower than hysterectomy but, since re-treatment is often necessary, the cost difference narrows over time.
intervention in an attempt to reduce the vascularity of the fibroids. Immediate complications include excessive blood loss and a blood transfusion may be necessary. Difficulty achieving haemostasis may result in hysterectomy so patients should be counselled pre operatively about this risk. Other risks include infection. Uterine Artery Embolization: uterine artery embolization is carried out by interventional radiologist, usually under local anaesthetic with or without sedation for fibroid related menorrhagia. The femoral artery is canalized on one or both sides and fed into the iliac and then the uterine artery. Angiography is carried out to confirm the correct position before introduction of the embolic agent. Blockage of both uterine arteries results in fibroids becoming avascular and shrinking in size. As the normal myometrium subsequently derives its blood supply from the vaginal and ovarian vasculature, UAE is thought to have no permanent effect on the rest of the uterus. In the immediate postoperative period, patients may experience ischaemic pain and small risk of sepsis is acknowledged. Occasionally, fibroids may be expelled vaginally after UAE. Rarely, subserosal fibroids can become adherent to the bowel and UAE can lead to bowel necrosis and peritonitis. There is a small risk of premature ovarian failure but a recent study has shown that there is no evidence of a deterioration of ovarian function after 1 year. This procedure is currently not recommended for women who wish to maintain their fertility. Hysterectomy: hysterectomy should only be considered when a woman has completed her family and when medical and less invasive surgical options have failed or are inappropriate. Vaginal hysterectomy e vaginal hysterectomy is appropriate for women with HMB with a small uterus and adequate cervical descent. Advantages of the vaginal route include the absence of abdominal wound and minimal disturbance of the intestines. This results in less post-operative pain, earlier mobilization and earlier discharge from the hospital. Risks related to this approach are bladder damage, bleeding, infection and bowel damage. Abdominal hysterectomy e abdominal hysterectomy is indicated in women with a uterine size greater than 12 weeks of pregnancy, endometriosis or a history of pelvic inflammatory disease, previous c/section, or a long vagina and a narrow sub pubic arch, making the vaginal approach technically difficult. A subtotal abdominal hysterectomy may be performed according to patient preference or if surgery is technically difficult owing to adhesions or endometriosis. Patient must be warned of 15% risk of residual bleeding from the cervix. In young patients with HMB, the ovaries are usually conserved but a bilateral salpingo oophorectomy may be carried out simultaneously after detailed discussion with the patient, with particular attention to family history. Women should be counselled as regards 1:72 lifelong risk of developing ovarian cancer if the ovaries have been retained at hysterectomy. Laparoscopic hysterectomy e laparoscopic hysterectomy could be laparoscopic assisted vaginal hysterectomy, laparoscopic total or subtotal hysterectomy. There is opportunity to diagnose and treat other pelvic disease and to carry out other adnexal surgery. There is less post-operative pain, less analgesia
Myomectomy: myomectomy is the surgical removal of intramural and subserosal fibroids from the uterine walls with conservation of the uterus. In women with multiple fibroids or a significantly enlarged uterus, the abdominal approach is most appropriate. Laparoscopic myomectomy may be performed in selected cases. If a fibroid protrudes into the uterine cavity (submucous), it may be removed hysteroscopically. GnRH analogue therapy is often used for three months prior to surgical
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Care pathway for heavy menstrual bleeding Woman presenting with HMB Take history Take full blood count
No structural or histological abnormality suspected
Structural or histological abnormality suspected Physical exam
No abnormality/fibroids less than 3 cm in diameter
Pharmaceutical treatment
Consider endometrial biopsy for persistent intermenstrual bleeding, and in women over 45 treatment failure or ineffective treatment
Uterus is palpable abdominally or pelvic mass
Consider physical exam Consider second pharmaceutical treatment if first fails
Consider imaging, first-line ultrasound Provide information to woman and discuss treatment options
Severe impact on quality of life + no desire to conceive + normal uterus ± small fibroids (<3cm diameter)
Endometrial ablation
• • • •
Other treatments have failed, are contraindicated or declined Desire for amenorrhoea Fully informed woman requests it No desire to retain uterus and fertility
Hysterectomy Don’t remove healthy ovaries
Myomectomy
Severe impact on quality of life Fibroids (>3 cm diameter)
Uterine artery embolisation
Care Pathway adapted from NICE Guideline and Models of Care in women’s health (RCOG)
Figure 1
among women who are obese, who have significant pathology, who have had previous surgery or who have pre-existing medical conditions.
requirement, earlier mobilization and earlier discharge from hospital. However this approach requires skills in advanced laparoscopic surgery. Operating time tends to be longer during the early stages of acquiring these skills, and complication rates such as haemorrhage, bowel and bladder injury and a higher chance of conversion of procedure to open technique tends to be higher. These risks tend to be higher among women who are obese, with associated co-morbidities such as endometriosis, Pelvic Inflammatory Disease, previous caesarean sections, adhesions and previous abdominal and pelvic surgery (Figure 1).
Serious risks The overall risk of serious complications from abdominal hysterectomy is approximately four women in every 100. Damage to the bladder and/or the ureter (seven women in every 1000) and or long-term disturbance to the bladder function. Damage to the bowel: four women in every 10 000. Haemorrhage requiring blood transfusion, 23 women in every 1000. Return to theatre because of bleeding/wound dehiscence, and so on: seven women in every 1000.
Risks related to various routes for hysterectomy It is recommended that clinicians should counsel women as regards risks associated with surgery which tend to be higher
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Pelvic abscess/infection: two women in every 1000. Venous thrombosis or pulmonary embolism, four women in every 1000. Risk of death within 6 weeks, 32 women in every 100 000.
Shankar M, Lee CA, Sabin CA, et al. von Willebrand disease in women with menorrhagia: a systematic review. BJOG 2004; 111: 734e40. Wedisinghe L, Lumsden MA. Heavy menstrual bleeding. In: Mahmood T, Templeton A, Dhillon C, eds. Models of care in women’s health. London: RCOG Press, 2009; 67e80.
Frequent risk Frequent risks include wound infection, pain, delayed wound healing, keloid formation, numbness, tingling or burning sensation around the scar, frequency of micturition, urinary tract infection and premature ovarian failure.
Practice points
Severe acute heavy menstrual bleeding Severe acute HMB can occur as a result of a coagulopathy (most commonly von Willebrand’s disease), prolapsed fibroids, AVMs, or anti coagulation. Initial management is based on haemodynamic stability followed by treatment of the specific condition.A
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FURTHER READING Critchley HOD, Colin Duncan W, Brito-Mutunayagam S, Reynolds RM. Obesity and menstrual disorders. In: Mahmood T, Arulkumaran S, eds. Obesity e a ticking time bomb for reproductive health. London: Elsevier Insights Series, 2013; 525e36. Darlow KL, Horne AW, Critchley HO, et al. Management of vascular uterine lesions associated with persistent low level HCG. J Fam Plann Reprod Health Care 2008 Apr; 34: 118e20. Lethaby AE, Cooke I, Rees M. Progesterone or progestogen releasing intrauterine systems for heavy menstrual bleeding. Cochrane Database Syst Rev 2005; CD002126. McGurgan P, O’Donovan P. Second generation endometrial ablation: an overview. Best Pract Res Clin Obstet Gynaecol 2007 Dec; 21: 931e45 [Epub 2007 May 23]. National Collaborative Centre for Women’s and Children’s Health. Heavy menstrual bleeding. London: RCOG Press, 2007. http://guidance.nice. org.uk/CG44. Rashid S, Khaund A, Murray LS, et al. The effects of UAE and surgical treatment on ovarian function in women with uterine fibroids. BJOG 2010; 117: 985e9.
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The term menorrhagia should be replaced by heavy menstrual bleeding. HMB may have a major impact on a woman’s quality of life and any intervention should aim to improve this rather than focussing on menstrual blood loss. The initial management should take place within a primary care setting following an abdominal and pelvic examination and measurement of full blood count. If history or clinical findings are suggestive of structural abnormality, ultrasound should be the primary investigation backed up by hysteroscopy. Endometrial biopsy is indicated in cases of prolonged or persistent inter menstrual bleeding and in cases of treatment failure in women over 45 years. Endometrial ablation is cheap safe and effective for relief of HMB and may be offered as a first line treatment for women who decline medical options. Long term satisfaction is high with hysterectomy, but it is associated with significant morbidity and mortality and should be offered only if simpler alternatives have failed. Healthy ovaries should not be removed at hysterectomy and the route for hysterectomy should be determined by assessment of individual patients, as well as by the skill and experience of the individual clinician.
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Heavy menstrual bleeding
Prevalence Between 4% and 51% of women experience HMB depending on their country of origin and clinical settings where data had been collected. Heavy menstrual bleeding affects one in three women of reproductive age. In the UK, almost 1.5 million women per year consult their GP with menstrual complaints and the annual treatment cost exceeds £65 m.
Rashda Bano Shreelata Datta Tahir A Mahmood
Abstract
Causes of heavy menstrual bleeding
Heavy menstrual bleeding is defined as excessive menstrual blood loss which interferes with the woman’s physical, emotional, social and material quality of life, and which can occur alone or in combination with other symptoms. All interventions should aim to improve quality of life rather than focussing on menstrual blood loss alone. An accurate history may indicate the cause of the bleeding. Indications for endometrial biopsy include persistent intermenstrual bleeding as well as heavy menstrual bleeding, in women aged 45 and over and those where there is evidence of treatment failure. First line treatment includes tranexamic acid or nonsteroidal anti-inflammatory drugs or combined oral contraceptives. Second line treatment options include, levonorgestrel-releasing intrauterine system (provided long-term use is anticipated), oral norethisterone or injectable long-acting progestogens. In women with HMB alone who have failed to respond to the above treatment options: with uterus no bigger than a 10-week pregnancy, endometrial ablation should be considered in preference to hysterectomy. Where hysterectomy is indicated, the route of hysterectomy should be considered in the following order: first-line vaginal; second-line abdominal/laparoscopic.
Fibroids, polyps, coagulopathy, endometrial/cervical malignancy, thyroid disease, pelvic infection especially by Chlamydia, and arteriovenous malformations are the possible causes of HMB. Iatrogenic causes include use of anticoagulants etc. Submucosal and intramural fibroids are particularly associated with HMB, although about 50% of fibroids cause no symptoms. Coagulopathy should be considered in women who fail to respond to medical management or women who present at a young age. Coagulopathy may be inherited or acquired and most common inherited disorder is von Willebrand’s disease. Endometrial and cervical carcinomas are potential causes of intermenstrual and post coital bleeding and rarely HMB. Untreated hypothyroidism may be associated with HMB. Chronic endometrial infection may cause intermenstrual bleeding or HMB. Chlamydia trachomatis has been proposed as a cause of HMB. Arteriovenous malformations (AVM) in the uterus may be congenital or acquired and are a rare cause of HMB. Acquired AVM may occur following uterine curettage after pregnancy. Colour Doppler imaging is a useful diagnostic modality if AVM malformation is suspected. Acute heavy bleeding from an AVM may be required to be managed with uterine artery embolization. Iatrogenic causes include the use of anticoagulants in women with thromboembolic disease and copper IUD. Table 1 summarises the main causes of HMB.
Keywords abnormal uterine bleeding; endometrial ablation; heavy menstrual bleeding; hormonal treatment; hysterectomy; long acting injectable progestogens
Obesity and HMB Introduction
Obesity is associated with abnormal uterine bleeding. There is clear association between obesity, endometrial polyps, endometrial hyperplasia and ovulatory dysfunction. As PCOs are associated with obesity and obesity augments its development, many of the effects of obesity on menstrual disorders are manifested through PCOs. A survey of pre-menopausal women with endometrial polyps found that 82% reported abnormal uterine bleeding. In obese women particularly in combination with hypertension, there is an increase risk for polyp development. In addition, in infertility patients, Body Mass Index (BMI) was an independent risk factor for the development of endometrial polyps. Obese women would therefore appear to be at an increased risk of developing endometrial polyps although the basis for this is not known. Obesity also increases the risk of malignancy developing within an endometrial polyp. In one study it is reported that 86% of women with complex hyperplasia were obese. Histological examination of pre-menopausal endometrial biopsies found that women with hyperplasia had a significantly higher BMI than those without hyperplasia. In another study the median BMI in the hyperplastic group was 38 kg/m2 compared with 30 kg/m2 in the non-hyperplastic group.
Heavy menstrual bleeding (HMB) is defined as excessive menstrual blood loss which interferes with a woman’s physical, social, emotional and/or material quality of life. It can occur alone or in combination with other symptoms. The term heavy menstrual bleeding has replaced the term menorrhagia. The objective definition of HMB is no longer used except for research purposes.
Rashda Bano MRCOG is a Specialist Registrar in Obstetrics and Gynaecology at Victoria Hospital, Kirkcaldy, Scotland. Conflicts of interest: none declared. Shreelata Datta MRCOG LLM is a Locum Consultant Obstetrician & Gynaecologist at St Helier’s Hospital, Carshalton, Surrey, UK. Conflicts of interest: none declared. Tahir A Mahmood MD FRCOG FRCPI MBA FACOG is a Consultant Obstetrician and Gynaecologist at Victoria Hospital, Kirkcaldy, Scotland. Conflicts of interest: none declared.
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suggested by history of excessive bleeding since menarche, postpartum haemorrhage, surgery related bleeding, or a history of two or more of following: bruising greater than 5 cm, epistaxis once a month, frequent bleeding or a family history of bleeding disorders. According to NICE guideline, 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. If the history suggests HMB without structural or histological abnormality, pharmaceutical treatment can be started without carrying out a physical examination or other investigations at initial consultation at primary care unless treatment chosen is LNG-IUS. Measuring menstrual blood loss either directly (alkaline haematin) or indirectly (‘Pictorial blood loss assessment chart’) is not routinely recommended for HMB.
Summary of causes of HMB Classification
Subtype
Local uterine pathology
Uterine fibroids Uterine polyps Chronic endometrial infection Uterine cancer Endometrial hyperplasia Arteriovenous malformation Polycystic ovaries (PCOs) Hypothyroidism Coagulopathy e.g. Von Willebrand’s disease Anticoagulation therapy IUCD
Local pelvic pathology Systemic disorders
Iatrogenic causes
Table 1
Examination Women with complex endometrial hyperplasia are more frequently obese. In addition, BMI is predictive of endometrial thickness on an ultrasound scan and this is predictive of hyperplasia. Obese women are thus at increased risk of developing endometrial hyperplasia. A raised BMI is associated with earlier menarche and menstrual irregularities during adolescence. A raised BMI will certainly impact on endometrial function in the context of an increased risk of endometrial hyperplasia and endometrial carcinoma. Raised circulating oestrogen levels, as a consequence of peripheral conversion of androgens by adipose tissue aromatase, enzyme have been implicated in the increased proliferative activity of endometrial cells. Circulating adipokines have also been associated with increased angiogenesis as well as cell proliferation. HMB is a common complaint among those women who are premenopausal and who are subsequently diagnosed with endometrial cancer. It would therefore not be unlikely if a raised BMI was found to impact on the volume of menstrual blood loss.
A general physical examination should be performed to exclude signs of anaemia, evidence of systemic coagulopathy and thyroid disease. An abdominal examination should be performed to exclude a pelvic mass especially if there is a history of pressure symptoms (fibroid or ovarian enlargement); a speculum examination should be performed to assess vulva, vagina and cervix (this may reveal sources of bleeding, such as a tumour, polyp or a discharge suggesting infection). A bimanual examination should be performed to elicit uterine enlargement. A physical examination should be carried out before All LNG-IUS fittings. All investigations for structural abnormalities All investigations for histological abnormalities. Women with fibroids that are palpable abdominally or who have Intracavity fibroids and/or whose uterine length as measured at ultrasound or hysteroscopy is greater than 12 cm would require further assessment in a hospital setting.
Bleeding of endometrial origin
Investigations (Table 2)
In the majority of cases of HMB, the precise cause of heavy bleeding lies at level of the endometrium. This was previously termed as DUB or dysfunctional uterine bleeding and it is a diagnosis of exclusion.
Laboratory tests A full blood count test should be carried out on all women with HMB. This should be done in parallel with any HMB treatment offered. Testing for coagulation disorders (for example, von Willebrand’s disease) should be considered in women who have had HMB since menarche and have personal or family history suggesting a coagulation disorder. A serum ferritin test, LH, FSH should not routinely be carried out on women with HMB. Thyroid testing should be carried out only when other signs and symptoms of thyroid disease are present.
History, examination and investigations for HMB A history should be taken from the woman that should cover the nature of bleeding and related symptoms that might suggest structural or histological abnormality, impact on the quality of life and other factors that may determine treatment options (such as presence of co morbidity). The range and natural variability in menstrual cycles and blood loss should be taken into account when diagnosing HMB. A menstrual diary is often helpful to determine the amount and timing of the bleeding. Flooding and clots indicate significant loss. Inter menstrual and post coital bleeding are suggestive of an anatomical cause, whereas pressure symptoms, including bowel and urinary symptoms, can indicate the presence of a large fibroid. A coagulation disorder may be
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Endometrial biopsy Dilatation and Curettage should not be used at all in the management of HMB. If appropriate, a biopsy should be taken to exclude endometrial cancer or atypical hyperplasia. Indications for a biopsy include, for example, persistent intermenstrual bleeding, and in women aged 45 and over treatment failure or ineffective
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Summary of investigations for HMB and their benefits Investigation type
Specific investigation
Indication
Blood test
FBC, TFTs Coagulation screen
Histology Imaging
Endometrial biopsy Transvaginal and transabdominal ultrasound
To exclude anaemia and hypothyroidism, where thyroid symptoms exist To exclude a clotting disorder where a positive family history or other symptoms exist To exclude endometrial atypia or carcinoma To identify uterine structural abnormalities such as polyps and fibroids
Table 2
Summary of pharmaceutical treatments available for menorrhagia and their outcomes Pharmaceutical treatment
Mechanism of action
Effect on menstrual bleeding
Is it a contraceptive?
Side effects
Levonorgestrel-releasing intrauterine system (LNGIUS)
Prevents endometrial proliferation
Bleeding reduced by up to 95%; full benefit may take upto 6 months
Yes
Tranexamic acid, two tablets 3e4 times a day orally for up to 4 days during menses Nonsteroidal antiinflammatory drugs (NSAIDs), taken during menses
It is an antifibrinolytic
Bleeding reduced by up to 58%
No
Irregular bleeding; hormonal problems such as breast tenderness, acne or headaches, uterine perforation at the time of insertion (rare) Indigestion; diarrhoea; headaches
Reduces production of prostaglandin
Bleeding reduced by up to 49%
No
Combined oral contraceptives (COCs), taken daily for 21 days, followed by a 7 day break
Prevents endometrial proliferation
Bleeding reduced by 43%
Yes
Oral progestogen (norethisterone), 15 mg from day 5 to day 26 of cycle Injected or implanted progestogen, injected every 12 weeks or implant for 3 years use
Prevents endometrial proliferation
Bleeding reduced by up to 83%
Yes
Prevents endometrial proliferation
Bleeding is likely to stop completely
Yes
Gonadotrophin-releasing hormone analogue (GnRH-a), given as a monthly injection for 3e6 months
Stops oestrogen and progesterone production
Bleeding stopped completely in 89% of women
No
Indigestion; diarrhoea, worsening of asthma in sensitive individuals; peptic ulcers with possible bleeding and peritonitis Mood changes; headaches; nausea; fluid retention; breast tenderness, deep vein thrombosis; stroke; heart attacks Weight gain; bloating; breast tenderness; headaches; acne
Weight gain; irregular bleeding; amenorrhoea; premenstrual-like syndrome (including bloating, fluid retention, breast tenderness), loss of bone mineral density, Menopausal symptoms (such as hot flushes, increased sweating, vaginal dryness)
Adapted from Heavy Menstrual Bleeding NICE Clinical Guidelines, No. 44.National Collaborating Centre for Women’s and Children’s Health (UK) London: RCOG Press; 2007.
Table 3
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A summary of various interventions for the treatment of HMB Surgical treatment
Mechanism of action
Impact on future fertility?
Side effects
Endometrial ablation
Destroys endometrial lining
Yes
Transcervical resection of fibroids (hysteroscopic myomectomy) Open myomectomy (fibroids >3 cm)
Surgical resection of submucosal fibroids Surgical resection of subserosal or intramural fibroids Surgical removal of uterus removal of ovaries
No
Vaginal discharge, period pain or cramping, infection , perforation (rare) Adhesions, perforation, haemorrhage, recurrence, infection Infection, haemorrhage, thrombosis, recurrence, pain, adhesions Infection, haemorrhage, urinary tract infection, bowel damage, thrombosis, menopausal symptoms with oophorectomy Adhesions, perforation, recurrence, infection, haemorrhage
Hysterectomy
Uterine artery embolization
Injection into blood vessels to reduce blood flow to a fibroid uterus
No Yes
Potentially
Table 4
Norethisterone (15 mg) daily from days 5 to 26 of the menstrual cycle, or injected long-acting progestogens. Other treatment options include GnRH analogue. Danazol, Ethamsylate and Gestrinone are no longer recommended for use in treatment of HMB owing to their unacceptable side effects.
treatment. Blind sampling methodologies (outpatient endometrial biopsy) are reasonable screening techniques but they are ineffective at diagnosing focal lesions. Hysteroscopy and endometrial biopsy can be performed. Role of imaging Ultrasound is the first line diagnostic tool for identifying structural abnormalities. Hysteroscopy and Magnetic resonance imaging (MRI) should not be used as a first line diagnostic tool. Saline infusion sonography should not be used as first line diagnostic tool.
Non-hormonal treatments: these treatments can be used if hormonal treatments are not acceptable to the woman or while investigations and definitive treatment is being organized. Antifibrinolytics e antifibrinolytics such as Tranexamic acid reduce blood loss by upto 50% by inhibiting endometrial fibrinolysis. Side effects are rare but may include indigestion, diarrhoea or headache. Cochrane reviews concluded that antifibrinolytic therapy causes a greater reduction in objective measurements of heavy menstrual bleeding when compared to placebo or other medical therapies (NSAIDS, oral luteal phase progestagens and ethamsylate). This treatment is not associated with an increase in side effects compared to placebo, NSAIDS, oral luteal phase progestagens or ethamsylate. Flooding, leakage and sex life is significantly improved after tranexamic acid therapy when compared with oral luteal progestogens but no other measures of quality of life were assessed. Prostaglandin synthetase inhibitor e non-steroidal anti-inflammatory drugs are an example of prostaglandin synthetase inhibitor and act by inhibiting endometrial prostaglandin production leading to reduction in menstrual blood loss. Mefenamic acid is the most frequently used agent and reduces blood loss by approximately 25%. This medicine has to be taken during menstruation and is associated with gastrointestinal side effects such as indigestion, diarrhoea, worsening of asthma and peptic ulcer disease. When HMB coexists with dysmenorrhoea, NSAIDs should be preferred to Tranexamic acid. There have been isolated reports of NSAID-associated reversible female infertility and probable mechanism is ovulatory failure due to non-rupture of mature follicle.
Treatment for HMB HMB has a major impact on a woman’s quality of life. Treatment and care should take into account the woman’s needs and preferences. Women with HMB should have the opportunity to make informed decisions about their care and treatment, in partnership with their healthcare professionals. Women should be given information about mode of action, duration of action, side effects and impact on fertility of different treatment options available. Treatment can be either medical or surgical; medical management does not impact on future fertility in the long-term. Table 3 summarises the pharmacological treatments available, together with their outcomes, whilst Table 4 considers surgical interventions for menorrhagia and their benefits. Pharmaceutical treatments Pharmaceutical treatment should be considered where no structural or histological abnormality is present, or for fibroids less than 3 cm in diameter which do not distort the uterine cavity. Hormonal and non-hormonal treatments are available and should be considered in the following order. Levonorgestrel-releasing intrauterine system (LNG-IUS) provided long-term (at least 12 months) use is anticipated. Tranexamic acid or non-steroidal anti-inflammatory drugs (NSAIDs) or combined oral contraceptives (COCs).
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Cochrane reviews concluded that NSAIDs reduce HMB when compared with placebo but are less effective than tranexamic acid, danazol or LNG IUS. In the limited number of small studies suitable for evaluation, no significant difference in efficacy was demonstrated between NSAIDs and other medical treatments such as oral luteal progestogen, ethamsylate, COC or another type of intrauterine system, Progestasert. Use of NSAIDs and/or Tranexamic acid should be stopped if it does not improve symptoms within three menstrual cycles.
leading to amenorrhoea. Use of a Gonadotropin-releasing hormone analogue could be considered prior to surgery or when all other treatment options for uterine fibroids, including surgery or uterine artery embolization, are contraindicated. If this treatment is to be used for more than 6 months or if adverse effects are experienced then hormone replacement therapy (HRT) as ‘addback’ therapy is recommended. Danazol: Cochrane reviews concluded that Danazol appears to be an effective treatment for heavy menstrual bleeding compared to other medical treatments. The use of Danazol may be limited by its side effect profile, its acceptability to women and the need for continuing treatment. The small number of trials, and the small sample sizes of the included trials limit the recommendations for clinical care. Further studies are unlikely in the future and this review will not be updated unless further studies are identified. There is no reliable evidence available from randomized controlled trials regarding the benefits or harms of the use of danazol for treating uterine fibroids. Obesity and Treatment options: one clear effect of obesity is that the management of HMB amongst women with a raised BMI is a challenge. The treatments available for HMB may be limited although data showing treatment outcome in relation to BMI are lacking. Raised BMI is associated with poor efficacy of hormonal contraception suggesting an effect or obesity on bioavailability or action of steroids. Hysterectomy will have additional complications in the presence of a raised BMI. A recent publication reported that patients with a BMI of greater than 34 showed a trend towards failure with this intervention. Some options seem to be suited to obese women. The levonorgestrel-releasing intrauterine system (LNG-IUS) is considered a “first time” treatment option for management of HMB. It also protects against endometrial hyperplasia in ovulatory dysfunction. A recent study amongst adolescent women undergoing bariatric surgery showed a high acceptance rate of this method for management of menstrual complaints.
Hormonal treatments: Combined oral contraceptive pills e the ombined oral contraceptive pill (OCP) is considered effective in the management of HMB. Evidence from one randomized controlled trial of the COCP (Ethinyl oestradiol 30 mcg and levonorgestrel 150 mcg for 21 days) found a reduction in blood loss of 43%. Side effects include nausea, mood changes, breast tenderness and rarely thromboembolic disease (risk increases in smokers, obese and older women). A Cochrane review found one small study which found no significant difference between groups treated with OCP, mefenamic acid, low dose danazol or naproxen. Overall, the evidence from the one study is not sufficient to adequately assess the effectiveness of OCP. Oral progestogens e norethisterone acetate (5 mg, three times daily) taken from day 5 to day 26 of the menstrual cycle, is effective in treating HMB. Side effects include weight gain, bloating, breast tenderness, headache, acne and depression. Cochrane reviews concluded that Progestogens administered from day 15 or 19 to day 26 of the cycle offer no advantage over other medical therapies such as danazol, tranexamic acid, nonsteroidal anti-inflammatory drugs (NSAIDs) and the IUS in the treatment of menorrhagia in women with ovulatory cycles. Progestogen therapy for 21 days of the cycle results in a significant reduction in menstrual blood loss, although women found the treatment less acceptable than intrauterine levonorgestrel. This regimen of progestogen may have a role in the short-term treatment of menorrhagia. Injectable long acting progestogens e it is well recognized that amenorrhoea occurs in many women when long acting progestogens are used for contraception, and they can also be used for the treatment of HMB. Side effects include irregular bleeding, weight gain, amenorrhoea and less commonly bone density loss. Levonorgestrel releasing intrauterine system (LNG IUS) e LNG IUS is an excellent alternative to surgery for women with HMB who also seek reliable long-term contraception. It releases the hormone at a rate of 20 mg per day and acts locally by causing thinning and atrophy of endometrium. There is very little systemic absorption of the hormone so progestogen related side effects are much less than with oral agents. Side effects include breast tenderness, headache, acne or uterine perforation at time of insertion. RCTs show that the LNG IUS reduces menstrual loss by up to 96% after one year but that the full benefit may not be seen for first 6 months. Women should be fully counselled that they are likely to experience unscheduled spotting/bleeding in first 5 to 6 months. Gonadotropin releasing hormone analogues e GnRHa act by down regulating the HPO axis and induce ovarian suppression,
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Surgical treatment for HMB Typically, surgical management is only considered in women who have completed their family, with the exception of polypectomy and myomectomy where fertility can be retained. In the early 1990s, it was estimated that at least 60% of women presenting with HMB went on to have a hysterectomy. This was often the only treatment offered. Since the 1990s the number of hysterectomies has been decreasing rapidly. This reduction in hysterectomy rates is considered to reflect not only the introduction of successful treatment options, such as the LNG-IUS, but also having access to endometrial ablation techniques. Dilatation and curettage should not be used as a treatment option in any clinical situation. Table 4 summarizes surgical and radiological treatments for HMB. Polypectomy: endocervical polyps can be avulsed in the outpatient setting. Endometrial polyps can be removed blindly under general anaesthetic, or by hysteroscopic resection either under general anaesthetic, or in the outpatient setting. Endometrial ablation: endometrial ablation is targeted destruction of endometrium. It should be considered where bleeding is having a severe impact on a woman’s quality of life, and she does
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not wish to conceive in the future. Endometrial ablation should be considered in women with HMB who have a uterus no bigger than a 10-week pregnancy and also those with small uterine fibroids (less than 3 cm in diameter). First generation techniques include hysteroscopic transcervical resection of endometrium, using an electrical diathermy loop and roller ball ablation. These techniques offer treatment for uterine cavities with sub mucous fibroids. Second generation techniques have been developed for smoother and smaller cavities. These include fluid filled thermal balloon ablation, microwave ablation and impedance controlled endometrial ablation. These procedures can be performed as a day case. Women who undergo this procedure should be advised to use effective contraception. Pre ablation endometrial histology should be obtained and hysteroscopy should be performed before and after the procedure to exclude endometrial perforation. Post operatively, patients may complain of transient crampy abdominal pain and a watery brown discharge for between 3 and 4 weeks. Potential complications include device failure at time of procedure, endometritis, haematometra, fluid overload due to absorption of distension medium, uterine perforation and intra abdominal injury including visceral burns. As a general rule, of all the women undergoing endometrial ablation with a second generation technique, 40e50% will become amenorrhoeic, 40 e60% will have markedly reduced menstrual loss and 20% will have no difference in their bleeding. Long term trials show that while most women are initially satisfied, many subsequently choose or require repeat endometrial ablation or hysterectomy. About 15% women would require hysterectomy during a 10-year follow up following ablation independent of a technique used. Cochrane reviews concluded Endometrial ablation techniques offer a less invasive surgical alternative to hysterectomy. The rapid development of new methods of endometrial destruction has made systematic comparisons between methods and with the ’gold standard’ first generation techniques difficult. Most of the newer techniques are technically easier than hysteroscopy-based methods to perform but technical difficulties with new equipment need to be ironed out. Overall, the existing evidence suggests that success rates and complication profiles of newer techniques of ablation compare favourably with hysteroscopic techniques. Endometrial resection and ablation offers an alternative to hysterectomy as a surgical treatment for heavy menstrual bleeding. Both procedures are effective and satisfaction rates are high. Although hysterectomy is associated with a longer operating time, a longer recovery period and higher rates of postoperative complications, it offers permanent relief from heavy menstrual bleeding. The initial cost of endometrial destruction is significantly lower than hysterectomy but, since re-treatment is often necessary, the cost difference narrows over time.
intervention in an attempt to reduce the vascularity of the fibroids. Immediate complications include excessive blood loss and a blood transfusion may be necessary. Difficulty achieving haemostasis may result in hysterectomy so patients should be counselled pre operatively about this risk. Other risks include infection. Uterine Artery Embolization: uterine artery embolization is carried out by interventional radiologist, usually under local anaesthetic with or without sedation for fibroid related menorrhagia. The femoral artery is canalized on one or both sides and fed into the iliac and then the uterine artery. Angiography is carried out to confirm the correct position before introduction of the embolic agent. Blockage of both uterine arteries results in fibroids becoming avascular and shrinking in size. As the normal myometrium subsequently derives its blood supply from the vaginal and ovarian vasculature, UAE is thought to have no permanent effect on the rest of the uterus. In the immediate postoperative period, patients may experience ischaemic pain and small risk of sepsis is acknowledged. Occasionally, fibroids may be expelled vaginally after UAE. Rarely, subserosal fibroids can become adherent to the bowel and UAE can lead to bowel necrosis and peritonitis. There is a small risk of premature ovarian failure but a recent study has shown that there is no evidence of a deterioration of ovarian function after 1 year. This procedure is currently not recommended for women who wish to maintain their fertility. Hysterectomy: hysterectomy should only be considered when a woman has completed her family and when medical and less invasive surgical options have failed or are inappropriate. Vaginal hysterectomy e vaginal hysterectomy is appropriate for women with HMB with a small uterus and adequate cervical descent. Advantages of the vaginal route include the absence of abdominal wound and minimal disturbance of the intestines. This results in less post-operative pain, earlier mobilization and earlier discharge from the hospital. Risks related to this approach are bladder damage, bleeding, infection and bowel damage. Abdominal hysterectomy e abdominal hysterectomy is indicated in women with a uterine size greater than 12 weeks of pregnancy, endometriosis or a history of pelvic inflammatory disease, previous c/section, or a long vagina and a narrow sub pubic arch, making the vaginal approach technically difficult. A subtotal abdominal hysterectomy may be performed according to patient preference or if surgery is technically difficult owing to adhesions or endometriosis. Patient must be warned of 15% risk of residual bleeding from the cervix. In young patients with HMB, the ovaries are usually conserved but a bilateral salpingo oophorectomy may be carried out simultaneously after detailed discussion with the patient, with particular attention to family history. Women should be counselled as regards 1:72 lifelong risk of developing ovarian cancer if the ovaries have been retained at hysterectomy. Laparoscopic hysterectomy e laparoscopic hysterectomy could be laparoscopic assisted vaginal hysterectomy, laparoscopic total or subtotal hysterectomy. There is opportunity to diagnose and treat other pelvic disease and to carry out other adnexal surgery. There is less post-operative pain, less analgesia
Myomectomy: myomectomy is the surgical removal of intramural and subserosal fibroids from the uterine walls with conservation of the uterus. In women with multiple fibroids or a significantly enlarged uterus, the abdominal approach is most appropriate. Laparoscopic myomectomy may be performed in selected cases. If a fibroid protrudes into the uterine cavity (submucous), it may be removed hysteroscopically. GnRH analogue therapy is often used for three months prior to surgical
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Care pathway for heavy menstrual bleeding Woman presenting with HMB Take history Take full blood count
No structural or histological abnormality suspected
Structural or histological abnormality suspected Physical exam
No abnormality/fibroids less than 3 cm in diameter
Pharmaceutical treatment
Consider endometrial biopsy for persistent intermenstrual bleeding, and in women over 45 treatment failure or ineffective treatment
Uterus is palpable abdominally or pelvic mass
Consider physical exam Consider second pharmaceutical treatment if first fails
Consider imaging, first-line ultrasound Provide information to woman and discuss treatment options
Severe impact on quality of life + no desire to conceive + normal uterus ± small fibroids (<3cm diameter)
Endometrial ablation
• • • •
Other treatments have failed, are contraindicated or declined Desire for amenorrhoea Fully informed woman requests it No desire to retain uterus and fertility
Hysterectomy Don’t remove healthy ovaries
Myomectomy
Severe impact on quality of life Fibroids (>3 cm diameter)
Uterine artery embolisation
Care Pathway adapted from NICE Guideline and Models of Care in women’s health (RCOG)
Figure 1
among women who are obese, who have significant pathology, who have had previous surgery or who have pre-existing medical conditions.
requirement, earlier mobilization and earlier discharge from hospital. However this approach requires skills in advanced laparoscopic surgery. Operating time tends to be longer during the early stages of acquiring these skills, and complication rates such as haemorrhage, bowel and bladder injury and a higher chance of conversion of procedure to open technique tends to be higher. These risks tend to be higher among women who are obese, with associated co-morbidities such as endometriosis, Pelvic Inflammatory Disease, previous caesarean sections, adhesions and previous abdominal and pelvic surgery (Figure 1).
Serious risks The overall risk of serious complications from abdominal hysterectomy is approximately four women in every 100. Damage to the bladder and/or the ureter (seven women in every 1000) and or long-term disturbance to the bladder function. Damage to the bowel: four women in every 10 000. Haemorrhage requiring blood transfusion, 23 women in every 1000. Return to theatre because of bleeding/wound dehiscence, and so on: seven women in every 1000.
Risks related to various routes for hysterectomy It is recommended that clinicians should counsel women as regards risks associated with surgery which tend to be higher
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Pelvic abscess/infection: two women in every 1000. Venous thrombosis or pulmonary embolism, four women in every 1000. Risk of death within 6 weeks, 32 women in every 100 000.
Shankar M, Lee CA, Sabin CA, et al. von Willebrand disease in women with menorrhagia: a systematic review. BJOG 2004; 111: 734e40. Wedisinghe L, Lumsden MA. Heavy menstrual bleeding. In: Mahmood T, Templeton A, Dhillon C, eds. Models of care in women’s health. London: RCOG Press, 2009; 67e80.
Frequent risk Frequent risks include wound infection, pain, delayed wound healing, keloid formation, numbness, tingling or burning sensation around the scar, frequency of micturition, urinary tract infection and premature ovarian failure.
Practice points
Severe acute heavy menstrual bleeding Severe acute HMB can occur as a result of a coagulopathy (most commonly von Willebrand’s disease), prolapsed fibroids, AVMs, or anti coagulation. Initial management is based on haemodynamic stability followed by treatment of the specific condition.A
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FURTHER READING Critchley HOD, Colin Duncan W, Brito-Mutunayagam S, Reynolds RM. Obesity and menstrual disorders. In: Mahmood T, Arulkumaran S, eds. Obesity e a ticking time bomb for reproductive health. London: Elsevier Insights Series, 2013; 525e36. Darlow KL, Horne AW, Critchley HO, et al. Management of vascular uterine lesions associated with persistent low level HCG. J Fam Plann Reprod Health Care 2008 Apr; 34: 118e20. Lethaby AE, Cooke I, Rees M. Progesterone or progestogen releasing intrauterine systems for heavy menstrual bleeding. Cochrane Database Syst Rev 2005; CD002126. McGurgan P, O’Donovan P. Second generation endometrial ablation: an overview. Best Pract Res Clin Obstet Gynaecol 2007 Dec; 21: 931e45 [Epub 2007 May 23]. National Collaborative Centre for Women’s and Children’s Health. Heavy menstrual bleeding. London: RCOG Press, 2007. http://guidance.nice. org.uk/CG44. Rashid S, Khaund A, Murray LS, et al. The effects of UAE and surgical treatment on ovarian function in women with uterine fibroids. BJOG 2010; 117: 985e9.
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The term menorrhagia should be replaced by heavy menstrual bleeding. HMB may have a major impact on a woman’s quality of life and any intervention should aim to improve this rather than focussing on menstrual blood loss. The initial management should take place within a primary care setting following an abdominal and pelvic examination and measurement of full blood count. If history or clinical findings are suggestive of structural abnormality, ultrasound should be the primary investigation backed up by hysteroscopy. Endometrial biopsy is indicated in cases of prolonged or persistent inter menstrual bleeding and in cases of treatment failure in women over 45 years. Endometrial ablation is cheap safe and effective for relief of HMB and may be offered as a first line treatment for women who decline medical options. Long term satisfaction is high with hysterectomy, but it is associated with significant morbidity and mortality and should be offered only if simpler alternatives have failed. Healthy ovaries should not be removed at hysterectomy and the route for hysterectomy should be determined by assessment of individual patients, as well as by the skill and experience of the individual clinician.
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