As a Trainee, postmenopausal bleeding is considered a bread-and-butter topic, as the investigation and management is relatively straightforward. Interestingly, there is a paucity of guidelines worldwide. However, most importantly, any bleeding postmenopause necessitates further evaluation and referral.
Postmenopausal bleeding (PMB) accounts for five per cent of office gynaecology presentations.1 Its definition is self-explanatory, as any bleeding from the genital tract occurring in the postmenopausal period, arising after 12 months of amenorrhoea in a women of menopausal age.2 Generally, four to 11 per cent of postmenopausal women will experience bleeding.1 The chance of this occurring reduces as time since menopause increases.1
Postmenopausal bleeding aetiology
While the most common cause for PMB is atrophy, the diagnostic algorithm for PMB is designed to detect cancer, particularly endometrial cancer.1 Vaginal, endometrial and urogenital atrophy is par for the course with postmenopausal hypoestrogenism.1 Atrophy accounts for 60–80 per cent of all causes of PMB, while endometrial hyperplasia and cancer each account for ten per cent of cases.1,3
The remaining causes are attributed to endometrial or cervical polyps (two to 12 per cent); exogenous oestrogen (15–25 per cent); cervical cancer (one per cent) and factors such as vaginal trauma, anticoagulants and bleeding from non-gynaecological sites.1,3 See Table 1 for a summary of these causes.
Table 1. Origin of postmenopausal bleeding incidence.
Modified from Goodman A. Postmenopausal bleeding. UpToDate Accessed June 2014 and Brand A. The women with postmenopausal bleeding. Aust Family Physician 2007.
History and examination
Like any other presentation in gynaecology, and more broadly medicine, the evaluation of PMB starts with a thorough history and physical examination. This will usually be first encountered with a presentation to a patient’s general practitioner; however, presentations to emergency departments also occur.
Salient history surrounding the bleeding includes: when it started, duration, pattern, amount, frequency and any associated trauma.1 Changes in bladder or bowel function and associated factors such as pain and weight loss are also important to ascertain.1
It is imperative to determine the use of hormone replacement therapy (HRT), the type of HRT (continuous, cyclical, oestrogen and progesterone or oestrogen only), duration of use and whether the patient has had a hysterectomy. It cannot be highlighted too strongly that any woman who is on HRT and has a uterus requires progesterone for endometrial protection.
Details of the patient’s past gynaecological, obstetric, medical, surgical, medication and family history are also essential.1 In particular, and often forgotten, is a thorough list of all over-the-counter medications, especially phytoestrogens.1,3 Phytoestrogens in brief are plant derivatives from, for example, soy, alfalfa and red clovers, that have an oestrogenic effect.4 They are often taken to relieve vasomotor symptoms of menopause as an alternative to traditional HRT preparations.4
Tamoxifen, a medication used to reduce the risk of breast cancer recurrence in patients who have had breast cancer, is also worth a mention. Tamoxifen has been associated with changes to the endometrium including polyps, hyperplasia and cancer.1,3,5 Thus it is important to establish a patient’s personal history of breast cancer and treatments undertaken, as well as a family history of this disease and other cancers such as colon and endometrial.1
In terms of physical examination, this should begin with general appearance and establishing body mass index, as obesity is a well-recognised risk factor for the development of endometrial cancer.1,3 An abdominal examination should focus on palpation for discernible masses.1,3 A systematic pelvic examination may yield the cause of the PMB.1 Examination should include a detailed inspection of the vulva and vagina, particularly looking for atrophy, suspicious lesions, trauma and a foreign body.1 A speculum examination should be performed in order to evaluate the cervix for polyps and cancer.3 It is imperative a pap smear is taken at this time.3 A bimanual examination to evaluate uterine size, mobility and the adnexae as well as a rectal examination completes the assessment of the pelvis.3
Postmenopausal bleeding investigations
The investigation of PMB is relatively straightforward, involving a pelvic ultrasound and tissue biopsy.1,3 Depending on the findings of physical examination, this biopsy may be from the vulva, vagina or cervix, but most commonly the evaluation needs to include an endometrial biopsy.1,3 Women should be referred to a gynaecologist for ongoing investigation of PMB.3
The majority of women referred to outpatient gynaecological services have had pelvic ultrasound in order to evaluate the endometrial thickness and assess for pelvic pathology. Transvaginal ultrasound (TVUS) is considered an acceptable initial investigation in women with PMB.1,6 In this group of women, as distinct from women with an incidental finding of thickened endometrium or fluid without bleeding, an endometrial thickness of 4–5mm typically correlates with low risk for endometrial disease.7 As the endometrial thickness increases to 20mm so too does the risk of endometrial cancer.7 It is important to remember that there is no accepted agreement on the cut-off for normal endometrial thickness and, thus, any women with risk factors and symptoms require endometrial sampling.3
There have been many studies looking at the sensitivity and specificity of TVUS in detecting endometrial cancer in women with PMB.7 This varies depending on the endometrial thickness used. For example, a sensitivity and specificity of 96 and 53 per cent respectively for an endometrial thickness of 4mm and 96 and 61 per cent respectively for endometrial thickness of 5mm.7 It was the consensus of the UpToDate article that an endometrial thickness less than 5mm on TVUS usually excluded endometrial cancer, however solitary use of ultrasound is not recommended in the exclusion of cancer.7
An endometrial biopsy is considered the gold standard for evaluation of PMB.3,7 Endometrial biopsy can be obtained with an endometrial pipelle in the outpatient setting, or by hysteroscopy and curettage (with or without dilatation) in either the outpatient or inpatient setting.7
Overall, the endometrial pipelle has been shown to adequately sample the endometrium.7 It is considered the more sensitive device in identifying hyperplasia or cancer compared to other sampling devices.7 The sensitivity of the pipelle endometrial sampling in the detection of endometrial hyperplasia and cancer was 99.6 and 81 per cent, respectively, in postmenopausal women.7 It is important to remember pipelle sampling of the endometrium may miss pathology, as often less than 50 per cent of the endometrium is sampled, thus it is most useful with greater than 50 per cent of the endometrium is involved with disease.7
Potential complications of endometrial pipelle biopsy include uterine perforation and infection.3 Patients should be counselled regarding the possibility of insufficient or non-diagnostic sampling, which may necessitate further investigation.
Hysteroscopy and curettage is typically saved for cases where office sampling was insufficient or not possible owing to patient discomfort or cervical stenosis.3 The advantage to hysteroscopy is it provides the ability to see the entire endometrial cavity and is particularly useful in detecting and removing focal lesions such as polyps.7 Again, this can be performed on an outpatient basis, avoiding the complications of general anaesthesia; however, appropriate patient selection is essential.7 Risks involved in this procedure include infection, bleeding, uterine perforation and, again, insufficient sampling.7
A diagnostic Pap smear in any women presenting with PMB should also be undertaken.1 This can help provide a differential between an endocervical and endometrial cause of PMB.1
Postmenopausal bleeding management
After a thorough evaluation for PMB and arrival at a diagnosis, the question arises as to what to do next. For women with cervical or endometrial cancer, prompt referral to the gynaecological oncology service is imperative for definitive management.3 A gynaecologist in conjunction with the patient’s general practitioner typically manages other causes. Causes such as cervical or endometrial polyps may have already been managed and removed in the work up of PMB. As long as benign histopathology is confirmed, no further investigation or treatment is required. In such situations, patient education is paramount, as patients should be informed that any further episodes of PMB require re-evaluation.
A diagnosis of vulvovaginal or urogenital atrophy is not cause for treatment unless women are experiencing symptoms.8 Additionally, treatment of atrophy may be recommended in the context of vulvovaginal surgery or in cases of pelvic organ prolapse and urinary incontinence.8 Aside from vaginal bleeding or spotting, symptoms of atrophy typically include vaginal dryness, burning, pruritis and dyspareunia.8
An approach to management of vulvovaginal atrophy includes vaginal moisturisers and lubricants, as well as topical vaginal oestrogens.8 Generally, topical vaginal oestrogen is more successful than vaginal moisturisers and lubricants.8 Topical vaginal oestrogen preparations in Australia include Vagifem (oestradiol) and Ovestin (oestriol). A typical regimen for these products is daily for two weeks, then twice weekly thereafter.8 Topical vaginal oestrogen is the treatment of choice over systemic HRT for women where atrophy is the predominant symptom.8
There are many preparations of commercially available vaginal moisturisers and lubricants, including products such as Replens and Sylk.8 These are designed for regular use, typically a few times per week, not just at the time of sexual intercourse.8 The composition of vaginal moisturisers and lubricants can vary, including water, silicone and oil, and there can be some trial and error until a patient finds the product to suit their requirements.8
Endometrial hyperplasia is defined as proliferation of endometrial glands and consequentially an increased gland to stroma ratio.9 Endometrial hyperplasia can be sub-classified into simple or complex with or without atypia.9 The importance of endometrial hyperplasia is each sub-category has a corresponding risk of progression to endometrial cancer for simple or complex hyperplasia with or without atypia the risks are one, three, eight and 29 per cent, respectively.9 An overview to the management of endometrial hyperplasia in postmenopausal women can be summarised into treatment with progestins or hysterectomy.10 The decision of treatment modality is usually based upon the presence of atypia, as this increases the risk of progression to endometrial cancer.10
- Goodman A. Postmenopausal uterine bleeding. UpToDate. Accessed online June 2014.
- PMB [Internet]. Patent.co.uk. Accessed June 16 2014. Available from www.patent.co.uk/ .
- Brand A. The women with postmenopausal bleeding. Australian Family Physician 2007;36:116-120.
- Lethaby A, Marjoribanks J, Kronenberg F, Roberts H, Eden J, Brown J. Phytoestrogens for menopausal vasomotor symptoms. Cochrane Database of Systematic Reviews 2013, Issue 12. Art. No CD001395. DOI:10.1002/14651858.CD001395.pub4.
- Chin J, Konje JC, Hickey M. Levonorgestral intrauterine system for endometrial protection in women with breast cancer on tamoxifen. Cochrane Database of Systematic Reviews 2009, Issue 4. Art No. CD007245. DOI: 10.1002/14651858. CD007245.pub2.
- Smith-Bindman R, Weiss E, Feldstein V. How thick is too thick? When endometrial thickness should prompt biopsy in postmenopausal women without vaginal bleeding. Ultrasound Obstet Gynaecol 2004; 24:558-565.
- Feldman S. Evaluation of the endometrium for malignant and premalignant disease. UpToDate. Accessed online June 2014.
- Bachmann G, Santen R. Treatment of vaginal atrophy. UpToDate. Accessed online June 2014.
- Giuntoli RL, Zacur HA. Classification and diagnosis of endometrial hyperplasia. UpToDate. Accessed online June 2014.
- Giuntoli RL, Zacur HA. Management of endometrial hyperplasia. UpToDate. Accessed online June 2014.