Abnormal Uterine Bleeding

Use of progestogens in the treatment of menorrhagia

- Norethiserone 5 mg TDS from day 5-26 or injected LA progestogens such as Depo every 12 weeks - Oral progestogens used to be the most common drugs used to treat menorrhagia, but may not be the most effective. - Early studies showed an improvement in subjective MBL but objective studies have shown no statistical improvement. - They are most effectively used in anovulatory menorrhagia to gain cycle control.

How do we diagnose menorrhagia?

- Subjective assessment - Pictorial blood loss assessment charts - Objective assessment. Only half of women complaining of heavy periods will have menorrhagia, so relying on subjective assessment alone will mean that many women are treated for a condition that they do not have. A visual method of assessing menstrual blood loss using pictorial charts has been shown to be more effective at diagnos- ing menorrhagia than subjective assessment alone. This considers the degree to which each item of sanitary protection is soiled with blood as well as the quantity used, but, interestingly, the charts are not frequently used in practice. Objective measurement of menstrual blood loss is rarely performed and usually only during clinical trials. This is because collecting and storing soiled sanitary protection for measurement of menstrual blood loss requires time and is inconvenient for most patients.

Use of antifibrinolytics and hemostatics in treating menorrhagia

- Tranexamic acid is an antifibrinolytic that inhibits the activation of plasminogen to plasmin. It reduces the excessive fibrinolytic activity found in the endometrium of menorrhagic women. - Can reduce by up to 50%, most effective with IUCDs, fibroids and bleeding diathesis - It is widely used for the treatment of heavy periods as it is effective for a substantial proportion of women. - Its most important side effect is the risk of thrombosis, although uncommon. Discontinue if changes to color vision. can also cause N/V/D

Use of the combined pill in the treatment of menorrhagia

- When taken in a cyclical fashion, the COCP inhibits ovulation and produces regular shedding of a thin endometrium. - Suppresses production of gonadotrophins and is thought to reduce menstrual blood loss by up to 50%. - Can improve dysmenorrhea, regulate cycle and improve premenstrual symptoms, reduce risk of PID, and protective against cancer - This makes it an effective long-term medical treatment for some women with menorrhagia. - Thrombogenic side effects should be discussed with older women and smokers who are considering using COCP for therapeutic reasons.

Urinary tract damage and hysterectomy

Damage to the ureter occurs in approximately 1 in every 200 hysterectomies. The ureter is likely to be damaged at the infundibulopelvic ligament, beneath the uterine artery and adjacent to the cervix. Predisposing factors to ureteric damage include congenital anomaly of the renal tracts and distortion of normal anatomy from pelvic inflammatory disease, endometriosis and malignancy. Trauma to the bladder occurs in approximately 1 in 100 hysterectomies and is much higher following vagi- nal hysterectomy. Predisposing factors include previous surgery and obesity.

Use of Danazol in the treatment of menorrhagia

Danazol is a testosterone derivative producing a num- ber of effects on the hypothalamic-pituitary-ovarian axis. It is not commonly used. The optimum dosage in the treatment of menorrhagia appears to be 200 mg daily, significantly reducing mean MBL as well as reducing dysmenorrhoea. The androgenic proper- ties of danazol produce unacceptable side effects in some women.

Hysterectomy

Hysterectomy can be vaginal, laparoscopic or abdominal, depending on the uterine findings. Total abdominal hysterectomy is useful for women with large uteri, multiple large fibroids, adenomyosis, pelvic adhesions and endometriosis. Hysterectomy can be a 'subtotal' procedure, where the cervix is left behind and can include removing the ovaries, to reduce the risk of ovarian cancer (oophorectomy). If the cervix is left behind, cervical smears must be continued Hysterectomy is not first-line surgical management for DUB. Only consider when: - Other treatments have failed, are contra-indicated or declined. - There is desire for amenorrhoea. - The woman is fully informed and requests it. - There is no desire to retain the uterus and fertility.

Overview: management of menorrhagia

If history and FBC are reassuring medical treatment should be considered and can be done in primary care. Refer to secondary care = pesistent intermenstrual bleeding, no improvement with medical management, >45 with heavy menstrual bleeding, abnormality after physical examination, risk for endometrial cancer/hyprplasia First line is LNG-IUS-Mirena; LT left in for 12 months Second line is tranexamic axid, mefenamic acid, for COCP. Third line is progestogens (norethiserone 5 mg TDS from day 5-26 or injected LA progestogens such as Depo every 12 weeks).

Define menorrhagia

Menorrhagia (heavy menstrual bleeding) is defined as heavy cyclical periods, which interferes with physical, social and emotional quality of life. It can occur alone or in combination with other symptoms. Only about half of women complaining of heavy periods actually have menorrhagia, which is defined as more than 80 mL of menstrual blood loss (MBL) per period. This represents two standard deviations above the mean MBL, which is about 40 mL per period. Two-thirds of women with genuine menorrhagia will have iron- deficiency anaemia.

Bowel damage and hysterectomy

The incidence of bowel trauma is approximately 1 in 200 hysterectomies. Risk factors predisposing to bowel damage are obesity, previous laparotomy, adhesions, intrinsic bowel problems (e.g. chronic inflammatory bowel disease) and irradiation. Bowel dysfunction following hysterectomy is well documented, with constipation occurring in up to half the patients during the first 2 weeks of the abdominal approach. One in five patients will continue to experi- ence constipation in the first three postoperative months.

Incidence of menorrhagia

The incidence of menorrhagia is reported to be 9-15% of population samples in Western Europe; however, as many as one-third of women regard their menstrual loss as heavy. Early menarche, late menopause, reduction in family size with concurrent reduction in periods of lactational amenorrhoea have all contributed to an almost tenfold increase in the number of periods that women experience during their reproductive life. This has meant that excessive menstrual bleeding has become one of the most common causes of concern for health in women.

LT complications of hysterectomy

When the uterus is removed, the pelvic floor and its nerve supply are disrupted. This can predispose to pelvic floor laxity with subsequent prolapse, as well as bladder and bowel dysfunction. Even when the ovaries are con- served, disruption of their blood supply can interfere with their function, and might even predispose to pre- mature ovarian failure, a risk factor for cardiovascular disease and osteoporosis.

Endometrial ablation

Endometrial ablation is a day-case procedure which reduces menstrual blood loss by producing an 'iatro- genic' Asherman's syndrome. Endometrium is destroyed using laser, resection, thermal or microwave ablation techniques and the ensuing intrauterine adhesions reduce endometrial regrowth from deep within crypts or glands. It is therefore not suitable for women wishing to conceive. Although this does not guarantee amenorrhoea as hysterectomy does, advantages include speed of surgery, quicker recovery, rapid return to work and the use of local as opposed to general anaesthesia. Following endometrial ablation, MBL has been shown to be reduced by up to 90%. - Recommended 1st line if uterus is <10 weeks of gestation on palpation (can also do hysteroscopic myomectomy) - Day case procedure, involves removing the full thickness of the endometrium together with the superficial myometrium and the basal glands thought to be the focus of endometrial growth - Contraindicated in large fibroids or suspected malignancy or those wishing to conceive - Types radiofrequency ablation, balloon thermal ablation, microwave ablation, free fluid thermal ablation, rollerball ablation, transcervical resection of endometrium (for small fibroids) - The ensuing intrauterine adhesions reduce endometrial regrowth from deep within crypts or glands - Contraception is still advised even though fertility is not usually retained

More on local pathology

Fibroids increase menstrual loss in 2 ways 1. They enlarge the uterine cavity, thereby increasing the surface area of the endometrium from which menstruation occurs 2. They may produce prostaglandins, which have been implicated in the aetiology of menorrhagia. In a similar way, endometrial polyps increase the sur- face area of the endometrium and are also hormonally active. Menstrual blood loss in the presence of pelvic pathology, such as endometriosis and PID, is variable and often in the normal range. Menorrhagia is therefore associated with, but not necessarily caused by, these conditions. Dysfunctional uterine bleeding (DUB) is the most common cause of menorrhagia and is the term used when there are no apparent local or systemic causes for menorrhagia. It is therefore a diagnosis made by exclusion. Altered endometrial prostaglandin metabo- lism seems to have an important role in the aetiology of DUB. This is supported by the fact that prostaglandin inhibitors decrease menstrual blood loss in women with DUB. Premalignant and malignant endometrium may pre- sent with menorrhagia and must always be excluded.

Use of GnRH agonists in the treatment of menorrhagia

GnRH agonists suppress pituitary-ovarian function and effectively produce a temporary, reversible menopausal state. Because of the subsequent bone density loss their long-term use as a primary medical treatment for menorrhagia is limited unless add-back hormone therapy is given (if continued for >6 months). This relegates their clinical use to that of preoperative aid (3-4 months), allowing: - correction of IDA - reduction of size of fibroids - reduction in surgical blood loss

Use of PG inhibitors in the treatment of menorrhagia

Several NSAIDS, including naproxen, ibuprofen (these 2 less effective than tranexamic) and mefenamic acid, inhibit the cyclo-oxygenase enzyme system, which controls the production of cyclic endoperoxides from arachidonic acid. NSAIDs improve: • Reduces menstrual loss by 25% in ¾ women. • dysmenorrhoea • menstrual headaches. NSAIDS are taken during menstruation, so side effects are usually better tolerated than with drugs that are taken throughout the menstrual cycle.

Classify the complications of hysterectomy

Short term complications: • Fever • Haemorrhage requiring transfusion Unintended major surgery because of: • Urinary tract damage • Bowel damage Long-term complications, e.g. pain, regret.

Use of intrauterine systems in the treatment of menorrhagia

- Intrauterine contraceptive systems with either progesterone or levonorgestrel dramatically reduce MBL as well as acting as contraception. The Mirena intrauterine sys- tem releases 20 mg of levonorgestrel every 24 h into the endometrium from a silicone barrel. - As a result of minimal systemic absorption, side effects are usually limited to irregular spotting in the initial year of use. Amenorrhoea occurs in up to 50% of long-term users because of endometrial atrophy. - Contraceptively, it is as effective as sterilization, although fertility returns almost immediately once it is removed. - Since it was granted its license in the UK for the treatment of menorrhagia for up to 5 years per system the use of the Mirena IUS for the treatment of heavy periods has increased dramatically. - Summ: for 12 months, more effective than oral treatments and more acceptable LT.

Fever and hysterectomy

This is the most common complication following hys- terectomy, with one in three women experiencing this following the abdominal approach. In one-quarter of cases the source of infection is not identifiable; the most common identifiable infection is urinary tract infection, followed by wound or vaginal cuff infection. The use of prophylactic antibiotics is associated with a lower rate of infection of the urinary tract, abdominal wound and vaginal cuff.

Post-menopausal bleeding: define, list the possible causes and how do you manage it.

Vaginal bleeding after 12 months of amenorrhea (in a woman of the age where menopause can be expected or in younger women with premature ovarian failure/menopause) MAIN PRIORITY IS TO EXCLUDE MALIGNANCY Etiology 1) Vaginal atrophy: most common 2) Use of HRT 3) Endometrial hyperplasia 4) Endometrial cancer - 10% will have cancer, but 90% of those with cancer present with PMB 5) Endometrial polyps 6) Cervical polyps 7) Cervical cancer 8) Uterine srcoma 9) Ovarian carcinoma = think estrogen secreting theca cell tumors 10) Vaginal cancer 11) Vulval cancer 12) Trauma 13) Bleeding disoder Investigations - Appropriate first line Ix is TVUS, assess thickness (threshold >5mm) - If suspicious proceed to do hysteroscopy and biopsy (GA, outpatient) - There are some one stop clinics in the country where they will do all this Manage - according to cause

Surgical options for treating menorrhagia

• Intrauterine pathology such as endometrial polyps and submucous fibroids should be removed hyster- oscopically. This reduces MBL by 75%. • Open myomectomy may be required for large fibroids, where the uterus is to be conserved. • Endometrial ablative methods are becoming in- creasingly popular due to rapid recovery and the possibility of outpatient treatment. • Hysterectomy - this is reserved for women who con- tinue to experience menorrhagia despite trying other treatments and is discussed below in detail.

More on Ix

• blood tests - a full blood count should be performed in all cases. Thyroid function and clotting studies should only be performed if clinically indicated • ultrasound - a pelvic ultrasound will identify uterine enlargement caused by fibroids and adnexal masses. Endometrial polyps or submucous fibroids should be suspected if the endometrial thickness is excessive for the time of the menstrual cycle • an endometrial biopsy - should be performed on all women aged over 45 years and in women under 45 years if there are risk factors in the history such as persistent intermenstrual bleeding or suspicious findings on ultrasound scan. This can be performed either in the outpatient clinic or under general anaesthesia. It might show endometrium inappropriate to the menstrual cycle secondary to anovulation, endometrial hyperplasia or carcinoma. A cervical smear should also be performed where this is due, or sooner if there is a history of intermenstrual or postcoital bleeding • current methods of endometrial sampling - for example pipelle biopsy. These appear to be at least as accurate as D&C, have high levels of patient acceptability, lower complication rates and do not require inpatient admission or general anaesthesia. However, they may miss benign and malignant endometrial pathology and must therefore be con- sidered inadequate for the further investigation of menorrhagia that has persisted despite medical therapy. In this instance, a hysteroscopy plus sampling should be performed either as an outpatient or under general anaesthesia depending on facilities and patient preference • diagnostic hysteroscopy - the most effective way of excluding intrauterine pathology. This can be per- formed in the outpatient setting without analgesia and will identify endometrial polyps, submucous fibroids, endometritis and most endometrial carcinomas. Where appropriate, laparoscopy will be indicated to exclude pelvic pathology. NB - Evidence suggests that a blind D&C, used as a diagnostic or therapeutic tool in the management of menorrhagia, is inadequate when used alone. Abnormal bleeding before the age of 40 does not usually require endometrial sampling unless the patient is at high risk of endometrial hyperplasia, e.g. PCOS and increased BMI.

Complications of endometrial ablation

• uterine perforation - this commonly occurs where the uterine wall is thinnest, such as the cornual regions and the cervical canal. It is associated with fluid overload, trauma to the gastrointestinal and genitourinary tracts and major blood vessels result- ing in peritonitis or haemorrhage. • fluid overload - the use of non-electrolytic solutions, such as 1.5% glycine, for electrosurgery and the pressures needed to distend the uterine walls pre-dispose to the absorption of large quantities of fluid, which can result in hyponatraemia due to dilutional effects of the irrigating fluid. Congestive cardiac failure, hypertension, neurological symptoms, haemolysis and coma occur. • haemorrhage - this can occur if the myometrium is resected too deeply or if the uterus is perforated. • infection - the true incidence of pelvic infection fol;owing endometrial ablation is difficult to quantify. Infection can be overwhelming and might cause long-term pelvic pain. - vaginal discharge, increased period pain (even if no further bleeding), need for additional surgery Rarely, deaths have occurred after endometrial ablation; these have been due to air embolism during laser ablation, toxic shock following endometrial resection, sepsis from bowel perforation and from haemorrhage following major pelvic vessel transection.