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Home , Anovulation, Heavy menstrual bleeding, Intermenstrual bleeding

CLINICAL PRACTICE • Clinical update Dysfunctional uterine

Elizabeth Farrell, MBBS, FRANZCOG, FRCOG, is Head, Clinic, Monash Medical Centre, and a Director and consultant, The Jean Hailes Foundation, Melbourne, Victoria.

BACKGROUND Dysfunctional uterine bleeding (DUB) is 10% of working women were absent from Dysfunctional uterine bleeding (DUB) is defined as excessively heavy, prolonged or work because of excessive bleeding.1 the major cause of heavy menstrual frequent bleeding of uterine origin that is not There are two types of DUB: ovulatory bleeding and impacts on women’s health due to or any recognisable pelvic and anovulatory. Ovulatory DUB accounts for both medically and socially. or systemic disease. It is, therefore, a diagno- about 80% of cases. In ovulatory DUB the sis of exclusion. The mechanisms for the is regular, preceded by ovula- OBJECTIVE abnormal bleeding and the site from which it tion and heavy but of normal duration. It is This article reviews the management of DUB. arises are largely unknown. Menstruation is a most common in women in their 30s. very complex process involving oestrogen Anovulatory DUB is more likely to occur at DISCUSSION and and their receptors, the beginning and end of the reproductive Dysfunctional uterine bleeding is defined as endometrial vasculature, endometrial vasoac- years. The is irregular and heavy menstrual uterine bleeding not due to tive substances, processes of tissue the bleeding is heavy and may be prolonged. any recognisable cause and is therefore a breakdown and remodelling, and endometrial Polycystic syndrome may be associ- diagnosis of exclusion. Other conditions such repair and regeneration. ated with chronic . as uterine fibroids, endometrial polyps and Dysfunctional uterine bleeding is the diag- systemic diseases should be excluded by nosis in 40–60% of women with excessive Differential diagnosis appropriate investigations. In the adolescent, menstrual bleeding which is defined as In women with abnormal uterine bleeding investigations for a coagulopathy should be greater than 80 mL blood loss (normal men- both uterine (endometrial and myometrial) performed. The pathophysiology of DUB is strual loss <80 mL). Heavy menstrual and systemic causes need to be excluded largely unknown but occurs in both ovulatory bleeding may affect a woman’s health both before DUB can be diagnosed. and anovulatory menstrual cycles. Medical medically and socially, causing problems Uterine causes treatments include nonsteroidal anti- such as deficiency anaemia and social inflammatory drugs or antiprostaglandins, phobia respectively. Dysfunctional uterine Endometrial polyps, hyperplasia, and rarely , the releasing bleeding is the commonest cause of iron endometrial carcinoma, may cause heavy , combined oral deficiency in the developed world and of menstrual bleeding but also may present contraceptive pills, and other hormonal chronic illness in the developing world.1 with . Uterine therapies. As no medical treatment is In the reproductive years, one in five fibroids, in particular submucous fibroids, superior to another, each woman should be women in Australasia are affected by DUB.2 may have increased vascularity with large individually assessed as to appropriate It is estimated that the United Kingdom vessels on the uterine surface that rupture management. Surgical treatments include spends £800 million per year to treat women during the menses. , which and . with menorrhagia, and in a Swedish study simplistically is in the

906Reprinted from Australian Family Physician Vol. 33, No. 11, November 2004 Clinical practice: Dysfunctional uterine bleeding

, can cause heavy painful is a possible cause in the adolescent woman, the appropriate first line therapy for ovulatory periods and . It is difficult to diag- a screen or function tests DUB.2 nose but features may be seen on ultrasound should be performed when appropriate. Progestogen releasing intrauterine device and directly at and laparoscopy. Other tests such as function tests, Heavy bleeding can occur in the presence of renal investigations or autoantibodies such as The (LNG) releasing intrauterine an intrauterine device (IUD), usually a nonhor- lupus coagulant should be performed if device (IUD) releases LNG at a low dose of 20 monal releasing IUD. organic disease is suspected. A transvaginal µg per day leading to endometrial atrophy and ultrasound (except in the adolescent woman) thickened cervical mucus. There is a major Systemic causes will aid in excluding pelvic causes of heavy reduction in blood loss up to 97% after 12 has been reported bleeding. Hysteroscopy with dilation and months of use. The IUD is suitable in both ovu- with . Coagulopathy is consid- curettage or , or latory and anovulatory DUB. Irregular light ered to be a rare cause, but studies have shown laparoscopy if there is associated pain, will be bleeding can be a troublesome side effect par- an increase in the prevalence of Von Willebrand diagnostic but not curative for DUB. ticularly in the first 3 months but decreases disease. A systemic review of 11 studies from with time in most cases. The IUD is also contra- Europe and the USA showed an overall preva- Management ceptive and its duration of action is 5 years.2 lence of 13% with the range from 5–24%.3 In Before any treatment other pathology must be The LNG releasing IUD is available on the adolescents, investigation for a coagulopathy excluded. Where there is systemic disease, Pharmaceutical Benefits Scheme for contracep- may be more relevant. In chronic renal disease, treat accordingly or refer on to the appropriate tion, but not for treatment of DUB specifically. heavy menstrual bleeding may occur but is not specialist. Iron therapy, usually oral, is pre- Combined likely to be an initial presentation. scribed if iron deficiency anaemia is diagnosed. In small studies, both the 30 µg and 50 µg Medical treatment Assessment combined oral contraceptive pills (COCP) Clinical assessment is most important in Nonsteroidal anti-inflammatory drugs have reduced menstrual blood loss signifi- determining the cause of heavy menstrual (NSAIDs) or antiprostaglandins reduce cantly by up to 50%. The COCP probably acts bleeding. A careful history and examination prostaglandin levels which are excessive in by inducing a thin endometrial layer and has should be performed to exclude organic heavy menstrual bleeding, but the mecha- the added advantages of reducing dysmenor- disease and to determine the extent of nism of action is not fully understood. Blood rhoea and providing contraception. lifestyle impairment, what previous treat- flow is reduced by about 30% and menstrual Progestogens ments have been used, and the woman’s pain is also reduced. All the major NSAIDs expectations from treatment. available have been shown to be effective. The progestogens, or progestins, are usually The assessment of heavy menstrual is prescribed for the heavy used cyclically but can be used continuously. bleeding is quite subjective and women may days of the menses in a dose of 1 g three They are the first line treatment in anovulatory over or underestimate their menstrual loss. times per day. Side effects of NSAIDs DUB and are prescribed in the from The symptoms and signs that may signify include headaches and gastrointestinal symp- about day 15 to day 25. In ovulatory DUB, the heavy menstrual bleeding include: toms such as nausea, vomiting, diarrhoea progestogen is prescribed from day 5 to day 25. • an unusual increase in blood loss and dyspepsia. Contraindications include For emergency suppression of heavy men- • more than 7 days of bleeding acute gastrointestinal disorders such as strual bleeding noresthisterone 15 mg per day • bleeding or flooding not contained within ulcers, intolerance to NSAIDs, or asthma. or greater, or medroxyprogesterone acetate pads or (particularly if wearing 30 mg per day or greater, is prescribed until Tranexamic acid the largest size) bleeding ceases; a maintenance dose should • clots greater than 3 cm, and Tranexamic acid (cyklokapron) is an antifibri- be continued until the woman has 3–4 weeks • the presence of signs of anaemia or iron nolytic agent that reduces the endometrial free of bleeding. Ceasing the progestogen will deficiency on blood testing. fibrinolytic enzymes that are increased in result in a withdrawal bleed. Investigations DUB. Menstrual blood loss is reduced by 45–60%. Tranexamic acid is prescribed on Other therapies Clinical examination should include a routine only the heavy days of the menses, usually Pap test. A full blood examination should be during the first 5 days. The dose prescribed is has been found to effectively reduce performed if anaemia is suspected or a 1 g 3–4 times per day. Side effects are infre- heavy menstrual bleeding but its use has been serum ferritin to detect iron deficiency. As a quent but include nausea and leg cramps. limited because of its recommended short coagulopathy such as Thrombosis is a rare risk. Tranexamic acid is term use and side effects including headaches,

Reprinted from Australian Family Physician Vol. 33, No. 11, November 2004  907 Clinical practice: Dysfunctional uterine bleeding

acne, depression, weight gain, oily hair and competent and experienced operator is the voice changes. Danazol is also used as a 6 most appropriate technique with less morbidity. week treatment before endometrial ablation. is similar to danazol but is a Conclusion twice per week dose. Gonadotropin releasing Dysfunctional uterine bleeding is a common hormone (GnRH) agonists have a very limited problem in women in the 30–50 years age role in the treatment of DUB but are used as group. The pathophysiology is not fully under- pretreatment for endometrial ablation, and stood and it is complex. Dysfunctional or endometriosis surgery. Treatment bleeding is a diagnosis of exclusion. Uterine the GNRH agonists is limited to 6 months and systemic causes must be excluded before because of bone demineralisation due to the the diagnosis is made. occurs in temporary ‘chemical menopause’ induced. about 80% of women with DUB. Dysfunctional uterine bleeding also occurs at the extremes of Surgical treatment the reproductive years; in the adolescent, coag- The decision to perform surgery for the treat- ulopathies should be excluded. Management is ment of DUB will depend on a number of initially with medical treatments. Surgical pro- factors including: cedures are performed only if other treatments • failure of medical therapies prove ineffective.4 • other associated symptoms such as pain, and Conflict of interest: Dr Farrell is a current • the woman’s request for surgery and investigator of a menopause related pharma- what she expects the outcome of the pro- ceutical company funded research project. cedure will be. References In deciding on the appropriate form of surgi- 1. The initial management of menorrhagia: evidence cal treatment, outcomes need to be taken based clinical guidelines. No. 1. Royal College of into account such as whether the relief of Obstetricians and Gynaecologists, 1998. symptoms will be temporary or permanent, 2. Guidelines for the management of heavy men- strual bleeding. National Health Committee potential complications of the surgery, recov- New Zealand, 1998. ery time with loss of work, total cost of the 3. Shankar M, Lee CA, Sabin CA, Evonomides DL, procedure, and patient satisfaction. Dilation Kadir RA. Von Willebrand disease in women with menorrhagia: a systematic review. BJOG and curettage with hysteroscopy is a diag- 2004;111:734–740. nostic investigation not a treatment for DUB. 4. Bongers MY, Mol BW, Brolmann HA. Current Endometrial ablation or resection is a pro- treatment of dysfunctional uterine bleeding. cedure to destroy the by either Maturitas 2004;47:159–174.

a form of diathermy or removal. First genera- AFP tion techniques (including laser ablation, roller Correspondence ball diathermy or resection) and second gen- Email: [email protected] eration techniques including microwave ablation are all very effective when per- formed by the appropriately trained specialist. Although the procedure is not contraceptive, it should not be performed if a woman wishes to have further . Hysterectomy leads to guaranteed amenor- rhoea but does have a significant morbidity rate. However, the complication rate may be less with an experienced operator. There are three types of hysterectomy: laparoscopically assisted, vaginal, and abdominal. The laparo- scopically assisted hysterectomy by a

908Reprinted from Australian Family Physician Vol. 33, No. 11, November 2004