DYSFUNCTIONAL UTERINE BLEEDING (DUB at a glance (• Menorrhagia is the…
DYSFUNCTIONAL UTERINE BLEEDING
diagnosis of exclusion and is defined as any abnormal uterine bleeding in the absence of pregnancy, genital tract pathology, or systemic disease
Menorrhagia is the commonest symptom and DUB will ultimately be the cause in 50–60% of women with this symptom.
Menorrhagia is responsible for 15–20% of gynaecological referrals to hospital and an even higher proportion of GP gynae consultations.
Objective measures of blood loss >80mL are clinically meaningless and should not be used outside research. If periods are reported as unacceptably heavy, then they are!
DUB at a glance
• Menorrhagia is the commonest gynaecological symptom you will see, and most of these women will have DUB.
• DUB is an umbrella term and only diagnosed after exclusion of pathology.
• Women under 45 can safely be treated without investigation in the absence of erratic bleeding.
• TVS is the first-line investigation if the woman is >45yrs with failed medical therapy to identify endometrial polyps + fibroids (i.e. focal pathology).
• In the presence of erratic bleeding in women >45yrs an endometrial biopsy is required.
• The majority of women will respond to medical therapy, especially tranexamic ± mefenamic acid.
• The Mirena IUS® is an excellent treatment that significantly reduces the number of women requiring surgery.
• Surgery should only be used in women who have completed their family and have had failed adequate medical therapy.
• Endometrial ablation: microwave endometrial ablation (MEA), balloon ablation, or Novasure are easy to perform and should be offered before hysterectomy.
• Hysterectomy has higher morbidity and cost, but is a guaranteed cure, and long-term satisfaction rates are high.
The exact causes of DUB are unknown. Proposed mechanisms at the endometrial level include:
• Abnormal PG ratios (+ other inflammatory mediators) favouring vasodilatation and platelet non-aggregation.
• Excessive fibrinolysis.
• Defects in expression/function of matrix metalloproteinases (MMPs), vascular growth factors, and endothelins.
• Aberrant steroid receptor function.
• Defects in the endomyometrial junctional zone.
• Heavy and/or prolonged vaginal bleeding (with clots and flooding): irregular, heavy periods usually occur at the extremes of reproductive life (post-menarche and peri-menopausal).
• May be associated with dysmenorrhoea.
• Systemic symptoms of anaemia and disruption of life due to bleeding.
• A smear history and contraceptive use are vital information.
Totally erratic bleeding, IMB, or PCB should prompt a search for cervical or endometrial pathology.
• Abdomino-pelvic examination is usually normal. If the uterus is significantly enlarged, fibroids are likely.
Differential diagnosis for DUB
• Submucous fibroids.
• Endometrial polyps, hyperplasia, or cancer.
• Very rarely, hypothyroidism or coagulation defects.
• FBC (Hb + MCV).
• Ferritin, TFTs, and clotting screens are not routine investigations—only consider if clinically indicated.
• Cervical smears are not done opportunistically if smear history normal.
• STI screen including Chlamydia.
• The risk of endometrial pathology in women <45yrs is very small so no further investigation required—treat and await clinical response.
• If >45yrs, with risk factors for endometrial disease, or no clinical response:
• TVS USS—is good for identifying fibroids and polyps, and measuring endometrial thickness. The risk of endometrial pathology with a normal TVS USS is small, but it may be less accurate during menstruation
• pipelle endometrial biopsy to exclude hyperplasia or cancer
• hysteroscopy and biopsy (preferably outpatient) may be appropriate as above or if there is no response to initial medical treatment
• hysteroscopy is mandatory with erratic bleeding in a woman >45yrs if USS reveals focal pathology, e.g. polyp, or is unable to assess the whole endometrium, biopsy is inadequate, or bleeding is persistent or repeated.
• Releases measured doses of levonorgestrel into the endometrial cavity for 5yrs inducing an atrophic endometrium. Blood loss ↓ by up to 90% and ~30% will be amenorrhoeic at 12mths.
• Provides contraception.
• Side effects: insertional issues, irregular PV bleeding for first 4–6mths (usually abates); progestagenic side effects are rare due to minimal systemic absorption.
This IUS has resulted in a major ↓ in number of hysterectomies.
• Antifibrinolytics: tranexamic acid 1g tds days 1–4 (40% ↓ in loss):
• safe, non-hormonal, non-contraceptive
• side effects—leg cramps, minor GI upset. Caution in cardiac disease
• NSAIDS: mefenamic acid 500mg tds days 1–5 (20–30% ↓ in loss and significant ↓ in dysmenorrhoea):
• safe, non-hormonal/contraceptive.
• side effects—GI upset including ulceration, renal impairment. Caution if asthmatic, CV disease, renal impairment, peptic ulcer.
• COCP: 20–30% ↓ loss and improvement in dysmenorrhoea:
• provides contraception
• Oral progestagens: are generally of no benefit in regular menorrhagia other than—short term continuous treatment to stop bleeding.
• Mirena IUS®: as above.
• Tranexamic and mefenamic acid are useful to ↓ loss during periods.
• COCP will also regulate an irregular cycle (safe up to the menopause if no other cardiovascular risk factors).
• Cyclical (days 5–26) Norethisterone 5mg tds or medroxyprogesterone acetate 5–10mg tds:
• regulates cycle, but little evidence to suggest ↓ in loss
• side effects—bloating, headache
Where first-line therapy has failed, further medical treatment may be used in very anaemic women, bleeding continuously, having their life disrupted, or who have cautions or contraindications to surgery.
• GnRH analogues can achieve amenorrhoea quickly by inducing a medical menopausal state: side effects—vasomotor symptoms and use limited to 6–12mths maximum due to bone loss.
• High-dose progestagens: medroxyprogesterone acetate 10mg tds continuously will induce amenorrhoea, but may be time-limited due to side effects as before.
Danazol and ethamsylate are no longer indicated.
Anaemia should be corrected by treating the underlying cause of bleeding and using ferrous sulphate (or equivalent) to replace lost iron stores.
Dysfunctional uterine bleeding
Surgery should be reserved for the minority of women who fail to respond to medical management.Surgery should be reserved for the minority of women who fail to respond to medical management.
Women have to be certain their families are complete before surgery.
Destruction of the endometrium down to the basalis layer is effective for most women and should be offered to all for consideration.
• Microwave (MEA).
• Thermal balloon (Thermachoice).
• Novasure (electrical impedance).
Hysteroscopic resection, or rollerball ablation, are now used much less often due to ↑ operative complications.
Endometrial ablation is less effective if the endometrial cavity is >10cm.
Typical endometrial ablation results in normal size cavities:
• 80–90% of women are significantly improved.
• 30% will become amenorrhoeic.
• 20% will need a second procedure by 5yrs.
• The newer procedures above are generally very safe and straightforward; however, there is a small risk of bleeding, infection, uterine perforation, and failed procedure.
• They are generally carried out under GA, but may occasionally be done under cervical block.
• Hysterectomy is the only guaranteed cure for DUB, but RCTs have shown higher morbidity, longer recovery, and financial costs compared to endometrial ablation.
• Complications include haemorrhage; infection; and bladder, ureteric, or bowel injury (<1%). Death is extremely rare.
• Long-term satisfaction rates for hysterectomy are generally very high and regardless of method most women report improved sexual function—as one patient put it, ‘I actually have sex now I’m not bleeding all the time’.
• Vaginal hysterectomy is the route of choice over abdominal, where possible, as recovery, post-operative pain, and cost are reduced.
• Laparoscopic-assisted vaginal hysterectomy (LAVH) takes longer than abdominal or vaginal, and has higher rates of urinary tract injury. No evidence supports routine use of this method.
• Subtotal hysterectomy is quicker and has a lower risk of bladder injury, but the possible improved sexual satisfaction rates are as yet unproven. There is a small risk of continuing light menstruation if residual endometrial cells are left, and women will continue to require smear tests.