Case 6 A 58-year-old woman with postmenopausal bleeding

 Case 6 A 58-year-old woman with

postmenopausal bleeding

Luisa Riglinski is 58-year-old cook at a local secondary

school. She thinks her last menstrual period was about

6–7 years ago. Two months ago she had a few days of

vaginal bleeding which was like the end of period and since

then she has continued to spot most days. This is dark red

or brown and she has taken to wearing panty liners. She

has no pain or any associated symptoms. Initially she

thought that her periods had restarted but a friend told her

that she should see her GP. She has no pain or any other

symptoms. She has never been on hormone replacement

therapy (HRT).

What are the most likely causes

of her bleeding?

• Endometrial cancer

• Atrophic vaginitis

• Local cervical lesion

• Cervical cancer

• Iatrogenic

• Chlamydia infection

What further questions would help to

establish the diagnosis?

History of bleeding

Postmenopausal bleeding (PMB) is defined as bleeding

more than 12 months since a woman ' s last normal menstrual period so you need to establish when this was. You

should ask about the amount and duration of bleeding

and any associated symptoms. Try to clarify the site of

bleeding to confirm that it is vaginal and not rectal or in

her urine. Some women may find this very difficult to

define.

Smear history

You need to check if she has attended for cervical screening and the result of her last smear test.

Drug history

Iatrogenic causes are important so you need to take a

drug history. HRT is a common cause of PMB and if she

is taking HRT, you need to ask about unscheduled bleeds;

bleeding not at the time of the withdrawal bleed for

women in taking a cyclical preparation or bleeding on

continuous combined preparations. Check if she has had

any problems with compliance, absorption (e.g. gastrointestinal upset) or metabolism (see Case 8 ).

Women currently or previously on tamoxifen are at

increased risk of endometrial polyps, endometrial cancer

and endometrial sarcoma although vaginal bleeding is a

common side - effect.

Sexual history

Although Chlamydia infection is less common in older

women, you should not ignore this as a possible cause.

You do not need to take a full sexual history but you

should ask if she has changed her sexual partner in the

last 12 months.

Obstetrics and Gynaecology: Clinical Cases Uncovered.

By M. Cruickshank and A. Shetty. Published 2009 by Blackwell

Publishing. ISBN 978-1-4051-8671-1.

KEY POINT

Women who continue to have periods after the age of

55 years also need to be investigated as for PMB.

Mrs Riglinski tells you that she has never been on HRT or

tamoxifen (Box 6.1). She has no history of breast cancer.

She had regular smears with normal results until the age

of 55 but she declined the last invitation to attend. She

did not want to be a ‘difficult patient’ but she found the

examination to be too uncomfortable. Her husband is 68

years old and has been in a nursing home for the last

year following a stroke. He had another stroke 2 months

ago and she is worried that the stress of this event hasCase 6 53

PART 2: CASES

caused her to bleed. She has not been sexually active

since.

What would you look for on

examination to aid your diagnosis?

Abdominal examination

There are unlikely to be any findings that will aid your

diagnosis. Endometrial cancer usually presents with early

stage disease which is confined to the uterus. It is rare for

endometrial cancer to present at an advanced stage when

there may be an omental cake (from tumour infiltration),

peritoneal disease, liver enlargement or ascites.

Genital examination

It is important to look for local causes for bleeding including examination of the vulva. It is essential to perform a

speculum examination to inspect the vagina and cervix.

The finding of a clinical cervical cancer will prompt you to

make an urgent referral. A bimanual examination may

not be revealing. The uterus is small in postmenopausal

women. Uterine enlargement may be incidental (e.g.

caused by old calcified fibroids) and the uterus is not

usually enlarged with a very early stage endometrial

cancer. Less common are ovarian cysts, fibrothecomas,

which produce oestrogen which causes endometrial

hyperplasia and possible cancer. These ovarian tumours

are benign and have the consistency of a fibroid on palpation. They are firm, well defined and mobile. However, it

may be difficult to palpate the adenexa in postmenopausal women who find vaginal examinations uncomfortable. Obesity will also make pelvic examination

difficult and you may not be able to feel the uterus clearly.

On examination, her vulva is normal and she has mild

atrophic changes of her vagina and her cervix. She has some

laxity of the vaginal walls but no significant prolapse. She

has a small anteverted mobile uterus. You are unable to feel

any adnexal masses.

Now review the possible causes of

postmenopausal bleeding

• Endometrial cancer. You cannot exclude endometrial

cancer from the history and examination and you need

to consider further investigations.

• Atrophic vaginitis. You have found atrophic changes

but you still need to exclude other pathology before

you can attribute her symptoms to this. This can be

treated by topical (intravaginal cream or pessary)

oestrogens.

• Local cervical lesion. You have excluded local lesions

such as a cervical polyp on your examination. Remember

that ‘ ectopy ’ is related to high oestrogen levels and you

should be suspicious of such a finding in a postmenopausal patient.

• Cervical cancer. Although she did not attend for her

last smear, she has a previous negative screen history and

you have not found a clinical cancer. As you have to

perform a speculum examination, you should ask her if

Box 6.1 Tamoxifen

Tamoxifen is a non-steroidal oestrogen antagonist which

is used widely as adjuvant treatment for women who

have oestrogen receptor positive breast carcinoma. It

reduces the risk of recurrence particularly during

the first 5 years of treatment, decreases the overall

progression of the disease and prevents disease in

the contralateral breast. Long-term tamoxifen use is

controversial because of its oestrogenic effects on the

endometrium. Although it acts as an anti-oestrogen on

breast cancer cells, it has a mild oestrogenic effect on the

endometrium, bone and cardiovascular system.

Long-term use is associated with proliferative

endometrium and a spectrum of benign and malignant

changes of the endometrium have been reported

including hyperplasia, polyps and carcinoma. The

incidence of endometrial carcinoma in the postmenopausal women taking tamoxifen is significantly

higher than women not on tamoxifen. Overall, the

benefits of tamoxifen against breast cancer recurrence are

greater than the risks of developing endometrial cancer.

EB is appropriate as the first line of investigation but

you need to remember that a negative result is not

conclusive. This will require further investigation by

hysteroscopy. TV US appearances can be misleading as

tamoxifen can give a sonotranslucent effect on both the

endometrial stroma and myometrium. This results in false

positive reports in cases of cystic atrophy which appears

as thickened cystic endometrium on scan. Histology will

confirm multiple cystic spaces lined by atrophic

epithelium.

Hysteroscopy is the investigation of choice for women

with PMB and a history of tamoxifen usage. It allows

direct inspection of the endometrium and full-thickness

biopsies using a resectoscope can be taken at the same

procedure.54 Part 2: Cases

PART 2: CASES

you can take a smear to keep her screening up to date

(not to diagnose cancer).

• Iatrogenic. She has not taken any medication that may

cause vaginal bleeding.

• Chlamydia infection. You do not need to pursue this

as she has not been sexually active in the last year.

• Stress (as suggested by M rs R iglinski). Although some

woman may relate bleeding to a stressful event, this does

not cause PMB.

What further investigations must you

now consider?

Women with PMB can be investigated effectively as

outpatients.

Transvaginal ultrasound scanning

Transvaginal ultrasound (TV US) is an accurate method

of excluding endometrial cancer. TV US identifies those

women who need further investigation by endometrial

biopsy (EB) on the basis of the scan findings. Findings

that require further investigation by EB:

• Women with an endometrial thickness >4 – 5 mm (the

exact cut - off will depend on local protocols)

• An irregular endometrial outline

• Fluid in the uterine cavity

Fifty percent of postmenopausal women scanned for the

investigation of PMB will have a thin regular endometrium and can be reassured at this first visit that no further

investigation is required. The negative predictive value is

almost 100% in excluding endometrial cancer. This

reduces the need for further intervention and allows you to

provide reassurance for those women with a normal result.

Report of TV US results for Mrs Riglinski (Fig. 6.1). The

uterus contains a regular thickening measuring 8mm in

thickness. This could represent a polyp. Neither ovary can

be identified and there are no adnexal masses or free

fluid.

What do you do next?

As her endometrial thickness is >4 mm, she requires

further investigation. It is often not possible to clearly

delineate normal atrophic postmenopausal ovaries. The

aim of the scan is to look at the endometrial thickness

and outline, although the sonographer may comment on

other pelvic structures.

1 Endometrial biopsy. There are a number of different

devices for obtaining an outpatient EB. If the scan finding

represents a polyp, it is unlikely to be removed by EB.

KEY POINT

You need to identify the tubal cornuae to confirm that the

hysterocope is in the uterine cavity.

Figure 6.1 Transvaginal ultrasound scan result for Mrs Riglinski.

2 Hysteroscopy. Hysteroscopy is often used to investigate PMB as it allows direct inspection of the endometrium. It can detect intrauterine abnormalities and is a

sensitive means of identifying polyps and submucous

macroscopic findings. It can be used in the outpatient

setting using a paracervical block for anaesthetic. Outpatient hysteroscopy is highly acceptable to women. Alternatively, it can be performed under general anaesthetic.

Mrs Riglinski agrees to have an outpatient hysteroscopy

with a paracervical block. At hysteroscopy, the cervical

canal is normal, the uterine cavity is smooth and regular

with a fundal polyp. Both uterine coruna are seen. The

polyp is removed using biopsy forceps and sent for histology

(Fig. 6.2).

The report from the pathology laboratory confirms a simple

endometrial polyp with no evidence of hyperplasia or

malignancy.

What further management is required?

Mrs Riglinski does not require any further treatment.

Polyp formation after the menopause can be related to

tamoxifen or oestrogens. As she is not on HRT this may

be related to obesity because of peripheral conversion of

androgens (androstenidione) in subcutaneous fat to oestrogens. Polyps may recur but there is no need for follow -Case 6 55

PART 2: CASES

up. You should advise Mrs Riglinski to contact her GP if

she has further PMB occurring 6 months after her investigations for polyp removal. Remember to warn Mrs

Riglinski that it is normal to have some spotting or discharge following the removal of the polyp.

What would have been the management

if she was found to have an

endometrial cancer?

Women with endometrial cancer confined to the uterus

are usually curable by surgery and most women present

with early stage disease. The treatment of choice is total

abdominal hysterectomy and bilateral salpingo -

oopherectomy (TAH/BSO) with peritoneal washings

taken on opening the abdominal cavity for staging

cytology.

When there is deep myometrial invasion or grade 3

disease, the prognosis with standard surgery alone is

poorer because of the risk of spread to pelvic lymph

nodes and recurrence. Endometrial cancer is radiosensitive and cure can still be achieved in early stage disease.

Radiotherapy may also be given following surgery for

women considered at increased risk of recurrent disease.

Adjuvant radiotherapy is given to treat the pelvis by

external beam with a caesium insertion to the vaginal

vault and/or chemotherapy.

Women with endometrial cancer are often elderly

with other medical problems and preoperative assessment for fitness for an anaesthetic and surgery is

essential.

Figure 6.2 Hysteroscopic findings of the endometrial cavity

containing a polyp.

the absence of endometrial pathology. Hysteroscopy

should also be performed if an endometrial polyp is

suspected on TV US.

Women with a history of taking tamoxifen, especially

for longer than 5 years, are at increased risk of

endometrial polyps, cancer and sarcoma. However, the

effects on the endometrium and myometrium mean

that TV US is not reliable and a hysteroscopy and

full - thickness biopsy are essential to exclude cancer.

Women who are asymptomatic on tamoxifen do not need

to be investigated or screened for endometrial

cancer.

Once endometrial cancer has been excluded, any local

causes can be treated. Often reassurance is all that is

required. Following investigation, women should be re -

referred for further investigation if they continue to

experience PMB after 6 months.

CASE REVIEW

Postmenopausal bleeding is defined as bleeding more than

12 months since a woman ' s last normal period. However,

women who continue to menstruate after the age of 55

years, who have unscheduled bleeds on cyclical HRT or

continue to bleed more than 6 months after starting

continuous combined HRT also need to be investigated.

Transvaginal ultrasound scan should be the first line

investigation as it allows good views of the pelvis and the

endometrium. Transabdominal scanning may be used for

the few women who cannot tolerate the intravaginal probe.

Women with an endometrium measuring 5 mm or greater

are at increased risk of endometrial cancer and require an

endometrial biopsy. This can be performed at the same

visit using an endometrial sampler. However,

if the specimen is inadequate for histology, cancer has not

been excluded and a hysteroscopy and biopsy

are required to obtain an adequate biopsy or confirm56 Part 2: Cases

PART 2: CASES

• Women with a endometrial thickness >5mm or an

irregular contour require further investigation by

endometrial biopsy +/− hysteroscopy

• Women with unscheduled bleeds on HRT need to be

investigated

• Women on continuous combined HRT may initially have

irregular bleeding but need to be investigated if this

continues beyond 6 months

• The benefits of tamoxifen in breast cancer treatment

outweigh the risks but any abnormal vaginal bleeding

while on tamoxifen requires full investigation

KEY POINTS

• Women with PMB need to be investigated to exclude

endometrial cancer

• About 8–10% of women with PMB will have

endometrial cancer

• A further 1–2% will have a malignancy at another site,

e.g. cervix, vulva, bladder or anus

• Visual inspection of the cervix is essential to identify

cervical cancer

• TV US is an accurate method of excluding endometrial

cancer and provides rapid reassurance to women with a

thin and regular endometrium

Further reading

Investigation of Post Menopausal Bleeding. SIGN Guideline Publication 61.ISBN 1899893 13 X. September 2002 .