Gab Kovacs1 and Paula Briggs2
(1)
Department of Obstetrics and Gynaecology, Monash University, Clayton, Victoria, Australia
(2)
Sexual and Reproductive Health, Southport and Ormskirk Hospital, Southport, UK
Definition
Incidence
Aetilogy and Pathogenesis
Clinical Assessment
History
Examination
Investigations
Treatment (NICE Clinical Guideline 44 “guidance.nice.org.uk/cg44”)
Medical
Surgical
Complications
Prognosis
Intermenstrual Bleeding (IMB)
Definition
Incidence
Aetilogy and Pathogenesis
Clinical Assessment
Treatment
Complications
Prognosis
Postcoital Bleeding (PCB)
Definition
Incidence
Aetilogy and Pathogenesis
Clinical Assessment
Treatment
Post Menopausal Bleeding (PMB)
Definition
Incidence
Aetilogy and Pathogenesis
Clinical Assessment
Treatment
Complications
Prognosis
A number of different types of bleeding problem fall under the umbrella of AUB.
Definition
· Heavy menstrual bleeding (HMB) is excessive menstrual bleeding.
· Intermenstrual bleeding (IMB) is bleeding between periods.
· Post coital bleeding (PCB) is bleeding after sex.
· Post menopausal bleeding is bleeding at least 1 year after the last menstrual period.
Incidence
AUB is one of the commonest reasons for referral to see a gynaecologist.
Aetilogy and Pathogenesis
Using the “pathological shopping list” all possible potential aetiological factors will be covered. To make this more logical, from a clinical perspective, possible factors will be considered in order of frequency.
· Degenerative – The peri-menopause could be considered, “a degenerative condition of ovulation”, with subsequent deficiency in progesterone resulting in disruption of the menstrual cycle with possible HMB.
· Neoplastic Benign – Leiomyomata or fibroids are a common cause of HMB. These benign growths are composed of fibromuscular tissue. The propensity for fibroids to cause HMB is dependent upon the position of the tumour in the uterus (see Fig. 13). Fibroids are classically described as sub-serous (on the outer aspect of the uterus), intramural (embedded in the muscle) or submucous (distorting the uterine cavity). As a result of the proximity to and the associated distortion of the endometrial cavity, submucous fibroids are the most likely fibroids to be associated with HMB.
· Congenital – Any congenital abnormality that increases the surface area of the uterine cavity can result in an increase in the amount of endometrium shed, e.g. bicornuate uterus.
· Traumatic – The introduction of a foreign body, for example an intrauterine device (IUD) can be associated with HMB, particularly in the first few months following insertion.
· Inflammatory/Infective – Pelvic Inflammatory Disease (PID) can result in increased blood flow to the uterus, with possible HMB.
· Vascular/Haematological – Any abnormality of coagulation has the potential to result in excessive bleeding at the time of menstruation. Although rare, a vascular malformation in the uterus, can result in HMB.
· Neoplastic Malignant – Endometrial cancer may present as HMB, and needs to be excluded, particularly if there are risk factors present. Potential risk factors include, nulliparity, polycystic ovarian syndrome, obesity and diabetes. Endometrial cancer is becoming commoner in association with the global rise in obesity.
Ovarian cancer can also be associated with HMB, although the presenting symptom is more commonly pain and abdominal distension.
· Endocrine – Hypothyroidism can be associated with HMB.
· Psychogenic – The mind can have a wide and varied effect on body systems, and it is possible that stress may be associated with HMB.
· Iatrogenic – This means a cause due to medical intervention. HMB after the insertion of an IUD would be considered iatrogenic. Administration of exogenous hormones may also a cause HMB.
Clinical Assessment
History
It can be difficult to assess the extent of the bleeding suffered by an individual woman. Some women who have significant blood loss don’t complain of HMB, whereas other women who perceive that they have HMB, do not actually lose all that much blood when assessed quantitatively. For this reason, NICE Clinical Guideline 44 stresses that if the woman feels that her blood loss is excessive, then it is. Measuring the amount of blood lost is regarded as old fashioned and is no longer considered relevant as it has no place in clinical management. Questions which might be helpful when trying to determine the impact of bleeding on the individual woman include enquiring as to whether clots are passed, and whether the patient has to use more than one method of sanitary protection e.g. towels and tampons.
A lifelong history of HMB (since menarche) in association with excessive bleeding during other operations e.g. on tooth extractions, or easy bruising may suggest an inherited coagulopathy such as von Willebrands Disease. This is a rare condition, but von Willebrand factor should be checked for if the history is suggestive.
Examination
Pallor of skin and conjunctivae can assess the possibility and degree of anaemia, although this can only be reliably determined by measuring a full blood count (FBC). Otherwise examination is directed towards determining any of the aetiological factors described above. The size of the uterus, and any localised enlargements due to fibroids may be detected on bimanual examination.
Investigations
Haematology – Full Blood Count.
Coagulation profile is only indicated if there is a chronic history of bleeding, or a family history of a coagulation defect. Liaison with a haematologist may be helpful.
Ultrasound examination of the uterus (preferably transvaginal TV U/S) is the most helpful investigation. It can be used to exclude intrauterine pathology, and accurately detect any uterine abnormality including structural defects such as the presence of fibroids.
The introduction of a negative contrast medium e.g. saline, can be used to facilitate the detection of endometrial polyps.
Endometrial biopsy – this can be done using a variety of samplers with the patient awake. All of the available sampling techniques are based on suction. In association with TV U/S, endometrial sampling is as sensitive as hysteroscopy, historically viewed as the gold standard investigation for HMB.
Hysteroscopy – if ultrasound suggests a uterine abnormality, hysteroscopy may be considered to allow visual inspection and possible treatment, by removal of any pathology identified.
Dilatation and curettage (D & C). This is a far less common procedure now, due to the development of out patient investigation using U/S and hysteroscopy.
Treatment (NICE Clinical Guideline 44 “guidance.nice.org.uk/cg44”)
Medical
Intra-uterine the insertion of a levonorgesterel intrauterine system (LNG-IUS) Mirena® is the first line recommended treatment. This is fitted like any other intrauterine device, but delivers levonorgestrel directly to the endometrium, causing it to become atrophic. The majority of women will continue to ovulate, but will benefit from this “end organ” effect. This can be inserted in a variety of different settings including General Practice and its availability since 1995 has changed gynaecological practice dramatically. It has become increasingly possible to manage women in an out patient setting. The use of the LNG-IUS has revolutionised the treatment of HMB and has made hysterectomy a far less common procedure. It is effective in the majority of women and its triple license means that it can be used to provide contraception, to manage HMB and to provide endometrial protection for women who require hormone replacement therapy (HRT). This can facilitate bleed free HRT in the perimenopause and has the potential to reduce symptoms during the menopause transition. Occasionally women using a LNG-IUS to control HMB have troublesome persistent unscheduled bleeding, requiring default to one of the surgical options, starting with the least invasive procedure.
The combined oral contraceptive pill (COC) can be considered.
Oestradiol valerate combined with dienogest, in a variable dosing regime, marketed as Qlaira® has a license to manage HMB in women also requiring contraception. This will be dependent on a risk assessment to exclude contraindications to oestrogen e.g. a history of focal migraine, a family history of venous thromboembolism, hypertension, smoking over the age of 35, obesity and concomitant use of enzyme inducing medication.
Qlaira® results in an 88 % reduction in medial menstrual blood loss, as compared with an average reduction of 90 % with Mirena®. As a class effect the combined oral contraceptive pill results in a 40 % reduction in bleeding.
Where there is a contraindication to oestrogen, progestogens alone can be used. Historically in the UK, norethisterone has been given in a dose of 5 mg three times daily during days 5–26 of the cycle, although this treatment could be given continuously, until such time as a more definitive treatment can be provided. Other progestogens, such as Provera (10 mg two to three times daily), can also be used for this purpose.
Injectable long acting progestogens, such depot medroxyprogesterone acetate, can also be used. This is commonly associated with amenorrhoea, but can cause troublesome side effects such as weight gain.
Other Medical Treatments
· Non steroidal anti inflammatory drugs (NSAIDS) may be administered just before and during menstruation.
This not only reduces bleeding due to the effect on the prostaglandin receptor, but also has the added benefit of reducing pain (dysmenorrhea), which may be associated with HMB.
· Tranexamic acid, administered during menstruation, in a dose of 1 G tds for 4 days, can also be effective in reducing blood loss for some women.
Surgical
Minor
Endometrial ablation destroys the endometrium. The early techniques required elctrocoagulation and resection using either a resecting loop or roller ball. Newer methods of ablation, either using a balloon filled with saline solution that has been heated to 85 °C (thermal balloon ablation, Thermachoice® – takes 8 min to complete) or Novasure®, an automated technique using diathermy, which takes less than 90 s to complete, are safer and do not require general anaesthesia. Novasure® is contraindicated where there is significant distortion of the endometrial cavity. It may be possible to use Thermachoice® in women with endometrial distortion due to fibroids, although this is a less effective method of ablating the endometrium.
Major
This would entail hysterectomy. Total hysterectomy means removal of the uterine body and cervix, whereas sub-total hysterectomy means removal of the uterus with conservation of the cervix. Hysterectomy can be performed abdominally, laparoscopically or vaginally.
Complications
The major complication of HMB is anaemia due to blood loss and consequent iron deficiency. This can be counteracted by recommending iron supplements to women with HMB, as part of their treatment. Some women may require blood transfusion.
Prognosis
There are a number of effective treatments available for women with HMB. One of the greatest challenges is providing treatment early, before women suffer potential complications. Anaemia can cause depression and this can adversely affect the whole family.
Intermenstrual Bleeding (IMB)
Definition
This is bleeding at any time except during menstruation.
Incidence
It is not uncommon as an isolated occurrence, but if persistent, it needs to be investigated.
If it occurs whilst using hormonal contraception it is called unscheduled bleeding.
Aetilogy and Pathogenesis
· Neoplastic – This is the most likely cause
· Benign – cervical or endometrial polyp
· Malignant – cancer of endometrium or cervix
· Iatrogenic – Administration of exogenous hormones, either as part of a contraceptive regime or as a treatment of AUB.
· Traumatic – this can occur in association with an intrauterine contraceptive device.
· Inflammatory/Infective – this is an unlikely cause.
· Vascular/Haematological – a cervical vascular lesion could cause IMB.
· Congenital – NIL
· Degenerative – NIL
· Endocrine – NIL
· Psychogenic – NIL
· Toxic – NIL
Clinical Assessment
History
· How long has it been present?
· How often does it occur?
· Any precipitating cause (if it occurs after sexual intercourse), it is postcoital bleeding (PCB)- see below
Examination
Abdominal palpation should always precede vaginal examination
· Speculum examination- the cervix should be visualised and polyps, or other lesions excluded.
· Bimanual examination- whilst this should be performed, it is unlikely to help with the diagnosis.
Investigations
A cervical smear test may be indicated as dictated by the national screening programme. Referral directly to colposcopy may be deemed more appropriate if the cervix has a suspicious appearance.
Transvaginal ultrasound is not always helpful in detecting endometrial polyps or other endometrial lesions. The introduction of a negative contrast medium can be useful to clarify potential endometrial pathology.
Hysteroscopy allows direct visualisation of the uterine cavity and would be regarded as the gold standard investigation.
Endometrial sampling or curettage may be undertaken to allow histological examination of the endometrium.
Treatment
Medical
Hormonal- If there is no pathology detected, the bleeding is likely to be due to a hormone imbalance. The use of combined hormonal contraception, or administering a progestogen can be tried. The commonly administered progestogens are Norethisterone 5 mg tds or Provera 10 mg bd.
In the case of unscheduled bleeding occurring whilst using hormonal contraception, potential causes include poor absorption, increased metabolism or missing pills. Changing either the hormonal content or the delivery route may help, although this is not always the case. For some women it is necessary to change the method altogether e.g. changing from the combined pill to an intrauterine device.
Other medical – there are no other available treatment options.
Surgical
· Minor – if a cervical polyp is detected this should be removed using polyp forceps and a TV U/S undertaken to determine whether there is a suspicion of any endometrial polyps. Endometrial polyps can be removed during out patient hysteroscopy if they are small. Larger polyps are removed under general anaesthetic. Newer technology such as Myosure®, has simplified polypectomy. This is a form of morcelator which “gobbles” up polyps and submucous fibroids and can be used in an out patient setting.
Occasionally the appearance of columnar epithelium on the ectocervix, an ectropian (erronously called an erosion) may cause IMB, or PCB. This can be treated using cauterisation, although it is likely to recur and therefore this form of treatment is not recommended by all clinicians.
· Major – this is not indicated
Complications
Endometrial polyps may develop malignant change, although this is uncommon.
Prognosis
Polyps may recur.
Postcoital Bleeding (PCB)
Definition
Vaginal bleeding following sexual intercourse.
Incidence
This is a common symptom, and although it could be the presentation of cervical cancer, this is rarely the case.
Aetilogy and Pathogenesis
· Neoplastic
· Benign
o Cervical ectropion
o Cervical polyp
· Malignant – Cervical cancer
· Endocrine – Could be IMB
· Traumatic – Could be due to friction associated with vigorous sexual intercourse
· Inflammatory/Infective – an inflamed cervix is more vascular and therefore more likely to bleed
· Vascular/Haematogenous – a cervical haemanagioma may cause PCB, but this is rare
· Denegenerative – NIL
· Psychogenic – NIL
· Congenital – NIL
· Iatrogenic – NIL
· Toxic – NIL
Clinical Assessment
History
Bleeding/spotting after sexual intercourse.
Examination
Speculum examination and visualisation of the cervix.
Investigations
Cervical smear test, if indicated by the relevant screening programme or referral to colposcopy if the cervix has a suspicious appearance. If referring to colposcopy in the UK, the recommendation is not to take a cervical smear test prior to referral.
Ultrasound
An endometrial sample may be indicated, particularly for women over the age of 45.
Hysteroscopy, dependent upon any potential intrauterine pathology noted on U/S examination.
Treatment
Hormonal
Rarely needed or helpful.
Other Medical
NIL.
Surgical
· Minor – polypectomy, cauterisation of cervix if indicated
· Major – NIL
· Complications – Unlikely
· Prognosis – Following treatment it is possible that the problem will recur
Post Menopausal Bleeding (PMB)
Definition
Vaginal bleeding, 12 months or longer after the last menstrual period.
Incidence
It is the commonest presentation of endometrial carcinoma, which is becoming commoner. Endometreial cancer is the third most common cause of death from a female cancer.
Aetilogy and Pathogenesis
· Neoplastic
· Benign- cervical polyp
· Malignant – endometrial cancer – PMB is endometrial cancer until proven otherwise.
· Vascular/Haematogenous – a cervical haemanagioma may cause PMB, but is rare.
· Iatrogenic – Intermittent administration of oestrogens may result in PMB.
· Traumatic – Could be due to atrophic changes
· Degenerative – Atrophic vaginitis may result in PMB, especially after trauma/sexual intercourse.
· Endocrine – NIL
· Inflammatory/Infective – Unlikely, although this can occur in association with atrophic vaginitis
· Psychogenic – NIL
· Congenital – NIL
· Toxic – NIL
Clinical Assessment
History
· Date of last menstrual period (LMP)
· Duration, frequency and quantity of PMB
· Any medication used, including Hormone Replacement Therapy (HRT)
· Any precipitating causes
Examination
· Abdominal palpation – unlikely to be helpful
· Speculum examination – looking for local lesions, e.g. cervical polyp
· Bimanual examination – unlikely to be helpful
Investigations
· Ultrasound – the endometrium should be 3–5 mm or less in a post menopausal woman and it is important that there are no suspicious features.
· Endometrial sampling – If there is concern an endometrial sample should be taken.
· Hysteroscopy if either of the above fail to reassure.
Treatment
Medical
· Hormonal – If the PMB is thought to be due to “atrophic” changes, local oestrogen can be used. This can be provided in a variety of different forms, including creams, pessaries and via a vaginal ring impregnated with oestrogen.
· Other medical – NIL
Surgical
· Minor: D & C – to obtain tissue for histology. This is only likely to be undertaken if endometrial sampling is not possible as an out patient.
· Major: If endometrial cancer is detected, the treatment is total abdominal hysterectomy with bilateral oophorectomy (TAH BSO).
Complications
Disseminated cancer.
Prognosis
The cause can almost always be found, and managed with appropriate treatment. The prognosis is dependent upon the underlying cause and the length of time that it has been present prior to diagnosis.