Abnormal uterine bleeding

Contributed by Mr Antonios V Antoniou, consultant gynaecologist and lead in minimal access surgery and urogynaecology, Newham University Hospital and London Independent Hospital, London

Section 1: Epidemiology and aetiology
Abnormal menstruation includes menorrhagia (blood loss greater than 80ml), intermenstrual bleeding (IMB), postcoital bleeding (PCB, defined as bleeding occurring during or immediately after sexual intercourse at a time distinct from menstruation), oligomenorrhoea and amenorrhoea.

Periods can also be irregular and prolonged (metrorrhagia).

NICE defines menorrhagia as excessive menstrual blood loss that interferes with a woman's physical, emotional, social and material quality of life.1

Menorrhagia is the predominant complaint in women with abnormal uterine bleeding. One in 20 women aged between 30 and 49 years will consult their GP each year with menorrhagia.2

These bleeding disturbances are classified as dysfunctional when no pathologic abnormality can be demonstrated. Amenorrhoea will not be discussed in this article.

Prevalence
Prevalence rates in the population vary from 4 to 27 per cent.1

Abnormalities in menstrual bleeding are a common cause of consultation in general practice as well as specialist referral to hospital.3

Aetiology
The causes of abnormal uterine bleeding are many and include complications of pregnancy, benign and malignant lesions, as well as dysfunctional uterine bleeding. The majority of women can be reassured that there is no pathology.

Uterine bleeding in very young girls before expected menarche may be caused by trauma (such as straddle injury or abuse), a foreign body (such as toys), precocious puberty or exogenous hormones.

Irregular periods are common during adolescence. The most common cause is anovulation or reduced ovulation due to the noncyclic release of follicle-stimulating hormone (FSH) and luteinising hormone (LH), which is itself due to a relatively immature hypothalamic-pituitary-ovarian axis.4 This can last for a couple of years after menarche.

It is advisable to screen women with menorrhagia for inherited coagulation defects, when there is a family history of bleeding diathesis and no obvious pelvic pathology.

Menstrual irregularities such as very light periods and secondary amenorrhoea are more common in female athletes.5

Submucous fibroids or intramural fibroids in close relation to the uterine cavity are found in 40 per cent of patients with heavy and/or prolonged menstrual bleeding.5 Fibroids are more common in African-Caribbean women than in Caucasians.

The evidence for any association between thyroid disorders and menstrual abnormality is not compelling.1

The most common finding in women who have heavy menstrual bleeding is dysfunctional uterine bleeding. Uterine fibroids and polyps are the most common form of pathology found.1

Section 2: Diagnosis
Enquiry should be made as to the woman's medical and medication history; recent weight changes, stress and exercise.

Specific questions to elicit features of a bleeding disorder include a history of menorrhagia since menarche, recurrent epistaxis, bleeding after dental extraction, operations or childbirth, and family history. Assessment of clotting factors should be requested.

endometrial polyp

Ask about use of HRT, and if the patient has breast cancer whether she is taking tamoxifen. Unopposed estrogen therapy and tamoxifen both increase the risk of endometrial carcinoma.

Family history of cancers should also be obtained, with particular reference to breast, ovarian, uterine and bowel cancer. Age, nulliparity, late menopause, obesity, diabetes, polycystic ovarian syndrome and hypertension are all associated risk factors for cancer of the endometrium. The majority of women with endometrial cancer will present with postmenopausal bleeding.

Patients should be asked to keep a menstrual diary.

Differential diagnosis
Pelvic inflammatory disease (PID) should be suspected in any young woman who presents with low abdominal tenderness, pain, abnormal bleeding, fever and cervical tenderness on examination.

Pelvic pain and pressure effects such as urgency of micturition may indicate the presence of fibroids.

IMB may result from an endometrial or fibroid polyp, fibroid, endometrial hyperplasia or carcinoma. Check for symptoms of anaemia, and request an FBC if necessary.

It is mandatory in all cases to ask about the last cervical smear test result.

A contraceptive history should be taken, as recent-onset menorrhagia (as well as IMB) may be explained by the cessation of the combined oral contraceptive pill (COC).

It is important to exclude non-gynaecological causes of bleeding (rectal and/or urethral) by specific questioning. If the patient has been wearing pads, ask whether the bleed is on the front, middle or back of the pad and, if suspected upon examination, refer to the appropriate team.

PCB must be considered a sign of cervical cancer until proven otherwise, and referral to the colposcopy clinic should be made in patients above the age of 35 years.

Examination
Abdominal palpation may detect a grossly enlarged fibroid uterus; vaginal examination may reveal an enlarged uterus consistent with fibroids, polyps extending to the cervix, or more rarely possible signs of malignancy such as a flush cervix with a mass that may be contiguous with the vagina and/or rectum, or a fungating mass. Examination with a speculum may reveal an ectropion, cervical polyp, cervicitis secondary to an infection, or a frank cancer, and allows swabs and a biopsy to be taken.

Investigations
Pregnancy needs to be excluded in all women with abnormal uterine bleeding.

A pipelle biopsy should be taken for histological diagnosis and a pelvic ultrasound scan arranged. This can detect fibroids and measure endometrial thickness.

Many units now have a 'one stop' hysteroscopy clinic (including an ultrasound scan facility), with local pathways that allow a fast-track service for possible cancer cases.

Recent developments include the use of a bipolar resectoscope that allows for 'see and treat' in cases of endometrial polyps (see picture above) or small fibroids.

Endometrial hyperplasia may present with menorrhagia, IMB or PCB and is classified as simple, complex or atypical. Simple and complex hyperplasias carry a 1-3 per cent risk of malignant transformation,6 and atypical hyperplasia (simple and complex) a 23-29 per cent risk.6

Referral to hysteroscopy clinic
Referral criteria for outpatient hysteroscopy clinic5
  • Postmenopausal bleeding
  • Persistent (≥ 3-6 months duration) unscheduled bleeding while taking HRT or tamoxifen treatment
  • Persistent (≥ 3-6 months duration) IMB in premenopausal women ≥ 40 years of age
  • ≥ 40 years with regular heavy periods who have failed to respond to ≥ 3-6 months of medical treatment eg tranexamic acid, COC
  • Irregular heavy periods, failed response to at least six months treatment (eg COC)

Section 3: Medical management
Management of menstrual irregularity depends on the underlying pathology. Where no pathology is found, treatment may be conservative in women with normal haemoglobin.

If the abnormality persists then repeat scan and pipelle biopsy or hysteroscopy may be warranted after six to 12 months. Otherwise medical therapy should form the mainstay of treatment, and is dependent on the patient's desire for fertility.

Appropriate antibiotic therapy is prescribed in the treatment of PID.

An energy loss in women whose energy expenditure exceeds dietary intake appears to be the primary factor affecting GnRH suppression in athletes.5 Increasing calorific intake may be sufficient to reverse menstrual dysfunction as well as stimulate bone density.7

In women not trying to conceive, anovulation may be treated using the oral contraceptive pill for cycle control. Oral contra- ceptives are associated with a statistically significant reduction in risk of cancer of the endo-metrium, ovary and large bowel (with a very small increased risk of cervical cancer).8

Patients with anovulation trying to conceive should be referred to the infertility clinic after exclusion of any pathology.

Treatments
Treatments for menorrhagia include the levonorgestrel intra-uterine system (LNG-IUS), NSAIDs, antifibrinolytic drugs (tranexamic acid), progestogens and oral contraceptives. The side-effects of danazol have limited its popularity.

NICE recommends the LNG-IUS as first-line treatment provided long-term use (at least 12 months) is anticipated.1 It can produce irregular spotting in early months but should reduce blood loss by up to 80 per cent.

There is now evidence indicating that the LNG-IUS significantly improves dysmenorrhoea and dyspareunia associated with endometriosis and adenomyosis - the latter also being associated with menorrhagia.

If the patient has regular cycles and declines the LNG-IUS or OCP, tranexamic acid (with mefenamic acid, particularly if pain is a feature) may be taken during menstruation.

Iron supplements should also be given to anaemic patients.

Section 4: Surgical therapy
Surgery is usually reserved for patients unresponsive to medical treatment and should be as conservative as possible.

Endometrial ablation allows conservation of the uterus and may now be performed via a variety of techniques including resection, microwave ablation, thermablation and radiofrequency ablation. Women must have completed childbearing and have a benign cause for the menorrhagia.

NovaSure (radiofrequency ablation) has a good safety profile, is easy to learn and has an average treatment time of 90 seconds. It can be performed under local anaesthesia in the outpatient 'one stop' clinic, or as a day case with good results.

A recent study, with a seven-year follow up, revealed over 90 per cent amenorrhoea rate, and 8 per cent of patients requiring a hysterectomy, with low complications.9

Hyperplasia
Simple hyperplasia may be treated conservatively in women wishing to retain their uterus. The LNG-IUS has been used successfully; however, patients require close follow up with repeat hysteroscopy and biopsy.

Those with atypical hyperplasia are best advised to have a hysterectomy because of the high risk of developing endometrial cancer.

Fibroids
Patients diagnosed with large submucosal fibroids and patients who cannot tolerate the outpatient procedure may be admitted as day cases for resection of fibroids.

New developments include the use of bipolar resectoscopes that allow the safe resection of larger submucosal fibroids.

Submucosal fibroids are diagnosed as type O, I or II, depending on how much they project into the uterine cavity (see figure above). The significance being that the type II may require a two-stage procedure necessitating admission on separate occasions. This allows the uterus to contract to squeeze the fibroid further into the cavity. This effectively treats menorrhagia, and can improve fertility.

Patients with a grossly enlarged fibroid uterus may require a myomectomy or a hysterectomy, depending on whether the woman has completed her family or wishes to retain her fertility.

The use of GnRH analogues such as goserelin may result in shrinkage of fibroids, such that a mid-line incision may be converted to a transverse one, or in the case of a less grossly enlarged uterus allow a laparoscopic approach.

Advantages of the laparoscopic approach to a myomectomy, or hysterectomy, include day stay, less pain, faster recovery, fewer adhesions, better cosmetic outcome, and faster return to work.

Fibroids or the uterus may be removed via the laparoscopic port or via an incision in the vagina (colpotomy).

The hysterectomy may be performed (as at laparotomy) as a total or subtotal depending on the need to remove the cervix and the woman's wishes.

Fibroids can recur and patients must be warned that repeat surgery is associated with a higher complication rate, particularly after a laparotomy requiring a mid-line incision.

Factors taken into account at consultation for such repeat surgery for open myomectomy, include the patients' age and chances of spontaneous conception, since they may be best advised to opt for hysterectomy.

References

1. NICE clinical guideline 44. Heavy menstrual bleeding. London: NICE, 2007.

2. Vessey M P, Villard-Mackintosh L, McPherson K, Coulter A, Yeates D. The epidemiology of hysterectomy: findings in a large cohort study. Br J Obstet Gynaecol 1992; 99(5): 402-7.

3. Palep-Singh M, Prentice A. Epidemiology of abnormal uterine bleeding. Best Pract Res Clin Obstet Gynaecol 2007; 21(6): 887-90.

4. Gidwani G P. Vaginal bleeding in adolescents. J Reprod Med 1984; 29(6): 417-20.

5. Clark T J, Gupta J K. Handbook of outpatient hysteroscopy. Hodder Education, 2005.

6. Kurman R J, Kaminski P F, Norris H J. The behaviour of endometrial hyperplasia. A long-term study of 'untreated' hyperplasia in 170 patients. Cancer 1985; 56(2): 403-12.

7. Kadir R A, Economides D L, Sabin C A, Owens D, Lee CA. Frequency of inherited bleeding disorders in women with menorrhagia. Lancet 1998; 351(9101): 485-9.

8. Hannaford P C, Selvaraj S, Elliot A M, Angus V, Iversen L, Lee A J. Cancer risk among users of oral contraceptives: cohort data from the Royal College of General Practitioner's oral contraception study. BMJ 2007; 335(7621): 651.

9. Fulop T, Rakoczi I, Barna I. NovaSure impedance controlled endometrial ablation: long term follow-up results. J Minim Invasive Gynecol 2007; 14(1): 85-90.

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