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Intermenstrual and post-coital bleeding
CASE-BASED LEARNING
Intermenstrual and post-coital bleeding
in women attending with unscheduled vaginal bleeding. In many women no cause for bleeding is identified and it may resolve without intervention. Unscheduled bleeding is often accompanied by other menstrual disorders including menorrhagia, dysmenorrhoea or dyspareunia (Tables 1 and 2).
Sinead Morgan Shreelata Datta
Assessment of women with intermenstrual or post-coital bleeding Unscheduled vaginal bleeding has a myriad of causes and the different pathologies can co-exist. A thorough gynaecological history and careful examination is an essential aid to diagnosis and will guide the need for further investigation. In younger women malignancy is uncommon and unscheduled bleeding is more commonly associated with hormonal contraceptive use and is generally termed “breakthrough bleeding”. With increasing age fibroids and polyps are more commonly seen and abnormal bleeding in these women should arouse suspicion of malignancy. Women with unscheduled bleeding who warrant referral to secondary care include Women over the age of 45 with IMB Women under the age of 45 with IMB and risk factors for endometrial cancer Women over the age of 35 with PCB for over 4 weeks Persistent IMB and negative examination findings Persistent PCB or IMB bleeding at any age Failure of previous treatment Abnormal appearance to cervix or vagina on speculum examination Cervical pathology not suspicious of cancer that may require treatment (polyp/ectropion) Pelvic mass
Abstract Intermenstrual and post-coital bleeding are very common presenting complaints among women of reproductive age. The majority of cases of unscheduled bleeding in premenopausal women result from benign conditions such as endometrial polyps, infection or from oral contraceptive use. Cervical and endometrial cancers however are associated with abnormal bleeding and therefore it is essential that women with these symptoms are evaluated carefully. The single most important stage in the assessment of women with unscheduled bleeding is a vaginal speculum examination; the presence of bleeding should not delay this essential investigation. Women with risk factors for endometrial malignancy or symptoms suggestive of gynaecological pathology may warrant ultrasound examination and/or endometrial biopsy. This review discusses three common causes of intermenstrual and postcoital bleeding and outlines some of the important considerations in the assessment and management of these patients.
Keywords cervical cancer; contraception; endometrial polyp; intermenstrual bleeding; postcoital
Introduction Unscheduled vaginal bleeding is a common indication for women to seek medical advice in their reproductive years. It has been estimated that almost one quarter of premenopausal women experience intermenstrual bleeding with almost 8% experiencing post-coital bleeding at some time. In women under the age of 35 unscheduled bleeding is more commonly associated with contraceptive use, in older women benign gynaecological conditions such as polyps and fibroids are more commonly seen and malignancy is more prevalent. Although malignancy is rare in premenopausal women, menstrual irregularities can be one of the first symptoms of gynaecological cancer. The association between abnormal bleeding and cancer can be a source of significant anxiety for patients. Intermenstrual bleeding (IMB) is defined as bleeding at any time during a woman’s cycle other than during menstruation. Postcoital bleeding (PCB) is non-menstrual bleeding occurring during, immediately or shortly after intercourse. IMB and PCB often coexist and therefore the causes of both must be considered
Causes of intermenstrual bleeding Physiological Vaginal Cervical
Uterine
Ovarian Hormonal
Sinead Morgan MBBS BSc (Hons) MRCOG is a Specialist Registrar in Obstetrics and Gynaecology at Princess Royal University Hospital, King’s College Hospital NHS Foundation Trust, London, UK. Conflicts of interest: none declared.
Other
Shreelata Datta MBBS BSc (Hons) LLM MRCOG MD is a Consultant Obstetrician and Gynaecologist at King’s College Hospital NHS Foundation Trust, London, UK. Conflicts of interest: none declared.
OBSTETRICS, GYNAECOLOGY AND REPRODUCTIVE MEDICINE --:-
Ovulation Adenosis Vaginal cancer Cervical polyp Cervical ectropion Cervical cancer Infection (chlamydia, gonorrhoea) Condylomata Endometrial polyp Fibroids Endometritis Adenomyosis Endometrial cancer Caesarean scar defect Malpositioned IUCD Hormone secreting tumours Hormonal contraceptive use Poor compliance with hormonal contraceptive Perimenopausal hormonal changes Drug use (Tamoxifen, anticoagulants) Drug interaction with hormonal contraceptives
Table 1
1
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CASE-BASED LEARNING
delayed while waiting for a smear test result. Vaginal swabs should be taken in those at risk of infection. In patients with concurrent menorrhagia a full blood count should be performed to assess for anaemia. Transvaginal ultrasound is useful to assess fibroids and endometrial abnormalities. Endometrial cavity abnormalities are best assessed on a post-menstrual ultrasound and saline sonography may aid diagnosis of endometrial polyps where there is uncertainty. Endometrial cancer is rare in young women particularly when there are no additional risk factors however the incidence rises sharply after the age of 40 and therefore endometrial biopsy should be considered in these women. Endometrial biopsy is indicated in women over 45 with IMB, women with persistent IMB and in cases where treatment has failed to improve symptoms. Endometrial sampling can be performed as a blind procedure or under hysteroscopic guidance. Hysteroscopy is particularly useful when a focal endometrial lesion is suspected on ultrasound and directed biopsy is needed or to allow the removal of polyps or submucous fibroids. Risk factors for endometrial cancer include: Elevated BMI Age over 45 Polycystic ovarian syndrome Perimenopausal women with anovulatory cycles Oestrogen secreting ovarian tumours Tamoxifen use Systemic oestrogen use Diabetes Personal or family history of breast, endometrial or colorectal cancer (Lynch syndrome) Previous endometrial hyperplasia
Causes of post-coital bleeding Vaginal Cervical
Uterine Other
Vaginal cancer Vaginitis Cervical ectropion Cervical polyp Cervical cancer Infection Endometrial polyp Trauma
Table 2
History taking In the first instance pregnancy must be excluded in any patient presenting with unscheduled bleeding. A comprehensive menstrual history should be taken and details of cycle length and regularity should be elicited. The pattern of abnormal bleeding in relation to the menstrual cycle should be outlined; for example, regular mid-cycle bleeding may suggest bleeding in association with ovulation which is experienced by 1e2% of women. The presence of other gynaecological symptoms such as menorrhagia, dyspareunia, dysmenorrhoea, vaginal discharge and temperature should be sought and details of past deliveries and pregnancies should be obtained. A contraceptive history should be taken including current and past contraceptive use, compliance with contraception and the concurrent use of medication that may have resulted in a drug interaction. A detailed sexual history is particularly important in women under the age of 25 or those who have a new sexual partner as these women are at higher risk of sexually transmitted infections (STI). A past smear history is essential and should include information regarding the most recent smear test result as well as details of past smear abnormalities, previous colposcopy and treatments. A family or personal history of gynaecological, breast or gastrointestinal malignancy should be elicited and smoking status should be ascertained.
Endometrial polyp Case 1 A 38-year-old nulliparous woman is referred to the gynaecology clinic with a 12-month history of IMB. Her last smear test was 6 months ago and was normal. She has a regular sexual partner and uses condoms for contraception. An infection screen arranged by her GP was normal. She has no significant past medical or surgical history and does not take regular medication.
Examination Assessment of body mass index (BMI) is important due to the association between endometrial cancer and elevated BMI. Abdominal examination may reveal a pelvic mass in patients with large fibroids. Bimanual and speculum examination are mandatory in women with unscheduled bleeding. Findings suggestive of cervical malignancy are contact bleeding, ulceration, friable tissue or a craggy irregular cervix. The presence of vaginal discharge and cervical excitation is suggestive of infection and the cervix may appear red, congested or oedematous on speculum examination. A cervical ectropion or endocervical polyp may be seen. The vulva and vaginal walls should be carefully examined. Consideration should be given to extra-genital areas as unscheduled bleeding can arise from the bladder or rectum.
How would you assess this patient? A full gynaecological history should be taken; in this case there was no relationship between her intermenstrual bleeding and the stage of her menstrual cycle. Her periods were regular but heavy and painful. Abdominal examination did not identify a pelvic mass. Bimanual and speculum examination did not reveal any abnormality. In this case further investigation with ultrasound is indicated due to her persistent symptoms and absence of other identifiable cause. See Table 1 for differential diagnoses. Ultrasound findings An ultrasound scan was performed on day 3 of her menstrual cycle. The report describes the uterus as retroverted with an endometrial thickness of 9.7 mm. The midline endometrial echo was disrupted by an 8 6 6 mm homogenous structure consistent with an endometrial polyp. There was a single feeding vessel on colour Doppler examination. Both ovaries appeared normal.
Investigations A cervical smear test should be performed if not up to date. If the cervix appears abnormal referral to colposcopy should not be
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CASE-BASED LEARNING
periods are not heavy or painful, she has had a recent negative sexual health screen and uses condoms for contraception. She has no significant past medical or surgical history. She is anxious regarding the possibility of cervical cancer as she has been told she is too young for cervical screening.
Transvaginal ultrasound is the first line imaging modality for endometrial assessment. Endometrial polyps appear as hyperechoic areas within the endometrial cavity and are best visualised in the early follicular phase of the cycle when the endometrium is thin. Saline can be instilled into the endometrial cavity to aid visualization.
How would you assess this patient? After taking a detailed gynaecological and sexual history, pregnancy must be excluded. The presence of post-coital bleeding warrants speculum and bimanual examination to assess a local cause of bleeding. See Table 2 for differential diagnoses. The pertinent point in this case is that this patient is not yet part of the National Health Service cervical screening programme (NHSCP) and the concern is that of missing a diagnosis of cervical cancer. The current age range for cervical screening in the UK is 25e64 with 3 yearly screening until aged 49 and 5 yearly thereafter. A review by the Advisory Committee on Cervical Screening found that the number of cervical cancer cases diagnosed in 20e24 year olds does not appear to be increasing and may be expected to fall with the advent of the national human papilloma virus (HPV) vaccination programme. Screening is not recommended in this age group as it does not reduce the incidence of or mortality from cervical cancer. Screening in younger women is also thought to have the potential to cause more harm than good. HPV infection is common in women under 25 and there is good evidence that minor cellular changes occur frequently in these women but appear to regress spontaneously. Screening these women would result in a high number of colposcopy referrals and subsequent treatments which in addition to causing undue anxiety could increase the risk of pre-term labour in future pregnancies. There are approximately 50 cases per year of cervical cancer in women aged 20e24 resulting in 0e5 deaths. A significant contributing factor in these deaths was a delay in diagnosis due to a delay in gynaecological examination as abnormal bleeding was ascribed to dysfunctional uterine bleeding or contraceptive use. Abnormal vaginal bleeding is very common in women aged 20e24 with 1 in 600 describing PCB and up to 1% describing IMB. Both these symptoms could arise as a result of cervical cancer and therefore young women with these symptoms require thorough assessment. A speculum examination should be performed in any woman presenting with PCB or persistent IMB and where appropriate, a cervical smear should be taken. If the cervix appears abnormal a 2-week wait referral to colposcopy should be arranged without awaiting the result of cervical cytology. If the cervix appears normal screening should be arranged for STIs and appropriate treatment and full sexual health screening offered if necessary. If symptoms persist despite appropriate treatment gynaecological referral is indicated. Most invasive cervical cancers that cause PCB will be visible on speculum examination. The incidence of cervical cancer is low in the UK due to the presence of a national screening programme. The risk of cancer is particularly low in women who have had a recent normal smear test (0.6%). The incidence of invasive cancer in
Pathophysiology of endometrial polyps Endometrial polyps are focal overgrowths of endometrial glands and stroma covered by surface epithelium and can vary in size from a few millimetres up to several centimetres, they can be single or multiple. They are common in both pre and postmenopausal women and many are asymptomatic. They are usually benign but hyperplastic or malignant change can be seen within polyps. The prevalence of endometrial polyps in the general population has been reported at 7.8%. The incidence of polyps increases with age and malignancy is more likely in older women and in women with symptomatic polyps. The prevalence of malignant polyps has been reported at 1.7% in women of reproductive age compared to 5.4% in post-menopausal women. Polyps are associated with a number of symptoms including IMB, PCB, postmenopausal bleeding, vaginal discharge, menorrhagia and infertility. What are the management options for this patient? The high prevalence of asymptomatic endometrial polyps has called into question the causal relationship between endometrial polyps and unscheduled bleeding and this must be borne in mind when counselling patients. Management depends on symptoms, age, fertility wishes and risk of malignancy. Small polyps (<1 cm) may regress spontaneously particularly in premenopausal women while large polyps are more likely to be symptomatic. Conservative management may be considered in premenopausal women with asymptomatic small polyps as the risk of malignancy in these cases is low. This group of women should however be encouraged to report any abnormal bleeding as this may warrant surgical treatment. The presence of an endometrial polyp and abnormal bleeding increases the risk of malignancy from 2.16% to 4.15% and therefore polypectomy is usually recommended both to detect endometrial malignancy and to improve abnormal bleeding. This is best done via operative hysteroscopy to allow complete resection of the polyp, this can be achieved under local or general anaesthesia depending on the clinical circumstances. Patients should be counselled regarding the surgical risks of operative hysteroscopy in addition to the recurrence risk of endometrial polyps which has been reported to be as high as 15%. Polyp resection may also be appropriate in subfertile patients as increased pregnancy rates have been reported after polypectomy although further research is needed to see if this improves live birth rates.
Cervical ectropion Case 2 A 22-year-old woman attended with post-coital bleeding for 4 months. She has an otherwise regular menstrual cycle and her
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CASE-BASED LEARNING
women with PCB is higher than that of asymptomatic women and therefore colposcopic assessment should be arranged without delay if there are concerns regarding the appearance of the cervix. Other more common causes of post-coital bleeding may be identified on speculum examination (Table 2). In this case this patient was found to have a cervical ectropion.
local treatment. Once infection and malignancy have been excluded cryocauterisation or diathermy may be performed under colposcopic guidance.
Bleeding associated with contraceptive use Case 3 A 27-year-old nulliparous woman attends gynaecology clinic with a 6-month history of intermenstrual bleeding. She has been taking the combined oral contraceptive pill for 8 months. She has no significant past medical or surgical history. Her last cervical smear test was 18 months ago and was normal. Figure 1.
What are the management options? Cervical ectropion is a benign condition where cervical eversion results in the columnar epithelium of the endocervix being seen on the endocervix. It characteristically appears as a red ring around the cervical os. It is considered a normal physiological process as a result of exposure to oestrogens. It is therefore seen in young women, during pregnancy and in combined oral contraceptive users. It is usually asymptomatic but can result in vaginal discharge or post-coital bleeding. Exposure of the columnar epithelium to vaginal secretions results in squamous metaplasia and this often produces a resolution of symptoms, therefore conservative management may be appropriate in some cases. In patients on the combined oral contraceptive pill changing to a non-oestrogen containing contraceptive may be beneficial. In symptomatic patients in whom conservative measures have failed consideration may be given to
How would you assess this patient? A detailed gynaecological and contraceptive history is essential in this case to aid diagnosis. The possibility of pregnancy should be considered and a pregnancy test should be performed on sexually active women using hormonal contraception with unscheduled bleeding. A detailed menstrual history should be taken with particular attention to her bleeding pattern prior to starting oral contraception. The current type of oral contraception and compliance should be ascertained. The use of any concurrent prescribed, over the counter or herbal preparations needs to be outlined due
Summary of management of unscheduled bleeding in hormonal contraceptive users • Assess compliance with contraception • Consider STI screening • Review smear history and screen if due • Assess for other gynaecolgical symptoms • Consider speculum and bimanual examination • Endometrial assessment for high risk groups • Smoking cessation advice
Combined oral contraceptive pill
Progesterone only pill
• Allow 3 month trial of pill before changing
• Consider switching desogestrel users to a traditional POP
• Advise against cycling packets
• Mefanamic or tranexamic acid may shorten duration of a bleeding episode
• Increase dose of ethinylestradiol up to 35 micrograms
Progesterone implant, IUS or DMPA
used either continuously or cyclically • No evidence to support reducing injection interval in DMPA users • Mefanamic acid or tranexamic acid may shorten duration of bleeding episode in DMPA users
• Try alternative COCP • Combined vaginal ring may improve cycle control
Figure 1
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CASE-BASED LEARNING
control. The combined vaginal ring has also been shown to improve cycle control compared to the combined oral contractive pill and so can be offered as an alternative.
to the possibility of a drug interaction. A history of illness that may have interfered with the absorption of medication should be assessed. A sexual history should be taken and screening for infections particularly Chlamydia trachomatis and Neisseria gonorrhoea should be performed in women under 25, women of any age with a new partner and women with more than one partner in the past year. Single vaginal swabs are available to screen for both infections or vaginal self-swabs can be used, urinary testing for STIs is no longer recommended. A cervical screening history should be taken and a smear test performed if it is due. Other gynaecological symptoms such as dyspareunia, vaginal discharge or post-coital bleeding should be elicited to assess whether the cause for bleeding is related to hormonal contraceptive use. A smoking history should be elicited as breakthrough bleeding is more prevalent among smokers. Women should be advised prior to starting hormonal contraceptives that unscheduled bleeding in the first 3 months is not uncommon and usually settles with continued use. Unscheduled bleeding for the first 6 months with the progesterone IUS or implant may be considered normal. The presence of PCB always warrants a speculum and bimanual examination. Where it is IMB only, for less than 3 months, with a normal smear history, no risk factors for STIs and no symptoms suggestive of gynaecological pathology, a conservative approach without examination could be considered with a follow up review arranged. If her bleeding had continued for more than 3 months, she had not had up to date cervical screening, or if she had any other gynaecological symptoms or requested examination then bimanual and speculum examination should be performed. In women over the age of 45 with persistent unscheduled bleeding or a change in bleeding pattern and younger women with risk factors for endometrial cancer, endometrial assessment with ultrasound scan endometrial biopsy should be considered.
Progesterone only pill (POP) The POP is a more suitable alternative to the COCP in women who are breastfeeding, women over 35 years of age, in smokers and in women in whom oestrogens are contraindicated. The pattern of bleeding can vary between the different types of POP. Women taking the desogestrel POP (Cerazette Ò) can be advised to try a different POP but it should be explained that they may still experience bleeding but the pattern may be different and this may be more or less acceptable to some women. 50% of women taking Cerazette Ò will be amenorrhoeic or have infrequent bleeding after one year, the other 50% will have frequent or prolonged bleeding. Traditional POP preparations are associated with less amenorrhoea and less prolonged bleeding but frequent irregular bleeding is common. There is no evidence that taking two POPs a day improves bleeding. Progesterone only implant, depot medroxyprogesterone acetate (DMPA) or IUS The addition of a first line COCP containing 30e35 mg of ethinylestradiol for 3 months may help reduce unscheduled bleeding in this group of women although it is not licenced for this indication. Evidence that this is beneficial is available for users of the progesterone IUS and implant but evidence of its benefit is lacking for patients using DMPA although its use is nevertheless advised. The COCP can be given cyclically or in a continuous pattern and can be repeated as often as needed provided there are no contraindications to oestrogen use. For women using DMPA there is no evidence that reducing the interval between injections improves bleeding. Mefenamic acid or tranexamic acid may be beneficial in the short term by reducing the length of bleeding episodes in women using DMPA but evidence of similar benefit has not been found in users of the implant or IUS.
Conclusion
What are the management options for this patient? After excluding others causes for unscheduled bleeding the management depends on the type of contraception used.
Unscheduled bleeding in premenopausal women is usually as a result of benign disease but consideration must be given to the possibility of malignancy in all cases. Further investigation to exclude malignancy is warranted in women over the age of 45 and in younger women with additional risk factors. Prolonged symptoms or persistent symptoms despite treatment should prompt the need for further evaluation to exclude malignancy. There is considerable overlap in symptomatology in conditions associated with IMB and PCB and history taking is an essential tool in the diagnosis of these patients. Bimanual and speculum examination is indicated in almost all cases of unscheduled vaginal bleeding and a delay in performing these important tests has been shown to result in an unacceptable delay in diagnosis, thereby increasing the morbidity and mortality associated with gynaecological cancers. A
Combined oral contraceptives (COCP) General principles in the management of irregular bleeding with oral contraception include ensuring adherence to pill taking and avoiding cycling of packets in COCP users as this can result in breakthrough bleeding. Smoking cessation advice should be offered as smoking is linked to a higher incidence of breakthrough bleeding. Unscheduled bleeding is less common with the COCP compared to the progesterone only pill (POP). The COCP with the lowest dose of ethinylestradiol to achieve cycle control is usually prescribed for contraceptive purposes. In cases of unscheduled bleeding trying an alternative COCP with a different oestrogen or progestogen component may help. Increasing the dose of ethinylestradiol up to a maximum of 35 mg often improves cycle
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CASE-BASED LEARNING
FURTHER READING Department of Health. Clinical practice guidance for the assessment of young women aged 20e24 with abnormal vaginal bleeding, 2010. NICE Clinical Guideline. Heavy menstrual bleeding, January 2007. Lumsden MA, Gebbie A, Holland C. Managing unscheduled bleeding in non-pregnant premenopausal women. BMJ 2013 Jun 4; 346: f3251. https://doi.org/10.1136/bmj.f3251. Management of unscheduled bleeding in women using hormonal contraception. Faculty of Sexual and Reproductive Healthcare, 2009. NHS Cervical Screening Programme. Colposcopy and Programme Management, NHSCSP Publication number 20, Third edition March 2016.
Practice points C
C
C
C
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C
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Pregnancy must be excluded in any woman of reproductive age presenting with unscheduled bleeding. The first symptom of gynaecological cancer can be a change in menstrual pattern, including unscheduled vaginal bleeding, these symptoms therefore should prompt the need for bimanual and vaginal speculum examination. Women with symptoms suggestive of cervical cancer including post-coital bleeding, persistent vaginal discharge and intermenstrual bleeding should undergo gynaecological examination and be referred for colposcopy if cancer is suspected. Women with unscheduled bleeding and a previous negative smear result have a greatly reduced risk of cervical cancer however a previous negative smear result should not delay referral to colposcopy if there is a clinical suspicion of cervical cancer on examination. Women aged under 25 with abnormal vaginal bleeding who are found to have a normal cervix on examination should be screened for infection and treated appropriately. Persistent symptoms (6e8 weeks) should prompt gynaecological referral. Endometrial biopsy is indicated in women over 45 with persistent intermenstrual bleeding and in younger women with risk factors. Unscheduled bleeding is common in the first 3 months with hormonal contraception but persistent symptoms, the presence of risk factors or the other gynaecological symptoms warrants further investigation.
Crown Copyright Ó 2017 Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Morgan S, Datta S, Intermenstrual and post-coital bleeding, Obstetrics, Gynaecology and Reproductive Medicine (2017), https://doi.org/10.1016/j.ogrm.2017.10.003
Intermenstrual and post-coital bleeding
in women attending with unscheduled vaginal bleeding. In many women no cause for bleeding is identified and it may resolve without intervention. Unscheduled bleeding is often accompanied by other menstrual disorders including menorrhagia, dysmenorrhoea or dyspareunia (Tables 1 and 2).
Sinead Morgan Shreelata Datta
Assessment of women with intermenstrual or post-coital bleeding Unscheduled vaginal bleeding has a myriad of causes and the different pathologies can co-exist. A thorough gynaecological history and careful examination is an essential aid to diagnosis and will guide the need for further investigation. In younger women malignancy is uncommon and unscheduled bleeding is more commonly associated with hormonal contraceptive use and is generally termed “breakthrough bleeding”. With increasing age fibroids and polyps are more commonly seen and abnormal bleeding in these women should arouse suspicion of malignancy. Women with unscheduled bleeding who warrant referral to secondary care include Women over the age of 45 with IMB Women under the age of 45 with IMB and risk factors for endometrial cancer Women over the age of 35 with PCB for over 4 weeks Persistent IMB and negative examination findings Persistent PCB or IMB bleeding at any age Failure of previous treatment Abnormal appearance to cervix or vagina on speculum examination Cervical pathology not suspicious of cancer that may require treatment (polyp/ectropion) Pelvic mass
Abstract Intermenstrual and post-coital bleeding are very common presenting complaints among women of reproductive age. The majority of cases of unscheduled bleeding in premenopausal women result from benign conditions such as endometrial polyps, infection or from oral contraceptive use. Cervical and endometrial cancers however are associated with abnormal bleeding and therefore it is essential that women with these symptoms are evaluated carefully. The single most important stage in the assessment of women with unscheduled bleeding is a vaginal speculum examination; the presence of bleeding should not delay this essential investigation. Women with risk factors for endometrial malignancy or symptoms suggestive of gynaecological pathology may warrant ultrasound examination and/or endometrial biopsy. This review discusses three common causes of intermenstrual and postcoital bleeding and outlines some of the important considerations in the assessment and management of these patients.
Keywords cervical cancer; contraception; endometrial polyp; intermenstrual bleeding; postcoital
Introduction Unscheduled vaginal bleeding is a common indication for women to seek medical advice in their reproductive years. It has been estimated that almost one quarter of premenopausal women experience intermenstrual bleeding with almost 8% experiencing post-coital bleeding at some time. In women under the age of 35 unscheduled bleeding is more commonly associated with contraceptive use, in older women benign gynaecological conditions such as polyps and fibroids are more commonly seen and malignancy is more prevalent. Although malignancy is rare in premenopausal women, menstrual irregularities can be one of the first symptoms of gynaecological cancer. The association between abnormal bleeding and cancer can be a source of significant anxiety for patients. Intermenstrual bleeding (IMB) is defined as bleeding at any time during a woman’s cycle other than during menstruation. Postcoital bleeding (PCB) is non-menstrual bleeding occurring during, immediately or shortly after intercourse. IMB and PCB often coexist and therefore the causes of both must be considered
Causes of intermenstrual bleeding Physiological Vaginal Cervical
Uterine
Ovarian Hormonal
Sinead Morgan MBBS BSc (Hons) MRCOG is a Specialist Registrar in Obstetrics and Gynaecology at Princess Royal University Hospital, King’s College Hospital NHS Foundation Trust, London, UK. Conflicts of interest: none declared.
Other
Shreelata Datta MBBS BSc (Hons) LLM MRCOG MD is a Consultant Obstetrician and Gynaecologist at King’s College Hospital NHS Foundation Trust, London, UK. Conflicts of interest: none declared.
OBSTETRICS, GYNAECOLOGY AND REPRODUCTIVE MEDICINE --:-
Ovulation Adenosis Vaginal cancer Cervical polyp Cervical ectropion Cervical cancer Infection (chlamydia, gonorrhoea) Condylomata Endometrial polyp Fibroids Endometritis Adenomyosis Endometrial cancer Caesarean scar defect Malpositioned IUCD Hormone secreting tumours Hormonal contraceptive use Poor compliance with hormonal contraceptive Perimenopausal hormonal changes Drug use (Tamoxifen, anticoagulants) Drug interaction with hormonal contraceptives
Table 1
1
Crown Copyright Ó 2017 Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Morgan S, Datta S, Intermenstrual and post-coital bleeding, Obstetrics, Gynaecology and Reproductive Medicine (2017), https://doi.org/10.1016/j.ogrm.2017.10.003
CASE-BASED LEARNING
delayed while waiting for a smear test result. Vaginal swabs should be taken in those at risk of infection. In patients with concurrent menorrhagia a full blood count should be performed to assess for anaemia. Transvaginal ultrasound is useful to assess fibroids and endometrial abnormalities. Endometrial cavity abnormalities are best assessed on a post-menstrual ultrasound and saline sonography may aid diagnosis of endometrial polyps where there is uncertainty. Endometrial cancer is rare in young women particularly when there are no additional risk factors however the incidence rises sharply after the age of 40 and therefore endometrial biopsy should be considered in these women. Endometrial biopsy is indicated in women over 45 with IMB, women with persistent IMB and in cases where treatment has failed to improve symptoms. Endometrial sampling can be performed as a blind procedure or under hysteroscopic guidance. Hysteroscopy is particularly useful when a focal endometrial lesion is suspected on ultrasound and directed biopsy is needed or to allow the removal of polyps or submucous fibroids. Risk factors for endometrial cancer include: Elevated BMI Age over 45 Polycystic ovarian syndrome Perimenopausal women with anovulatory cycles Oestrogen secreting ovarian tumours Tamoxifen use Systemic oestrogen use Diabetes Personal or family history of breast, endometrial or colorectal cancer (Lynch syndrome) Previous endometrial hyperplasia
Causes of post-coital bleeding Vaginal Cervical
Uterine Other
Vaginal cancer Vaginitis Cervical ectropion Cervical polyp Cervical cancer Infection Endometrial polyp Trauma
Table 2
History taking In the first instance pregnancy must be excluded in any patient presenting with unscheduled bleeding. A comprehensive menstrual history should be taken and details of cycle length and regularity should be elicited. The pattern of abnormal bleeding in relation to the menstrual cycle should be outlined; for example, regular mid-cycle bleeding may suggest bleeding in association with ovulation which is experienced by 1e2% of women. The presence of other gynaecological symptoms such as menorrhagia, dyspareunia, dysmenorrhoea, vaginal discharge and temperature should be sought and details of past deliveries and pregnancies should be obtained. A contraceptive history should be taken including current and past contraceptive use, compliance with contraception and the concurrent use of medication that may have resulted in a drug interaction. A detailed sexual history is particularly important in women under the age of 25 or those who have a new sexual partner as these women are at higher risk of sexually transmitted infections (STI). A past smear history is essential and should include information regarding the most recent smear test result as well as details of past smear abnormalities, previous colposcopy and treatments. A family or personal history of gynaecological, breast or gastrointestinal malignancy should be elicited and smoking status should be ascertained.
Endometrial polyp Case 1 A 38-year-old nulliparous woman is referred to the gynaecology clinic with a 12-month history of IMB. Her last smear test was 6 months ago and was normal. She has a regular sexual partner and uses condoms for contraception. An infection screen arranged by her GP was normal. She has no significant past medical or surgical history and does not take regular medication.
Examination Assessment of body mass index (BMI) is important due to the association between endometrial cancer and elevated BMI. Abdominal examination may reveal a pelvic mass in patients with large fibroids. Bimanual and speculum examination are mandatory in women with unscheduled bleeding. Findings suggestive of cervical malignancy are contact bleeding, ulceration, friable tissue or a craggy irregular cervix. The presence of vaginal discharge and cervical excitation is suggestive of infection and the cervix may appear red, congested or oedematous on speculum examination. A cervical ectropion or endocervical polyp may be seen. The vulva and vaginal walls should be carefully examined. Consideration should be given to extra-genital areas as unscheduled bleeding can arise from the bladder or rectum.
How would you assess this patient? A full gynaecological history should be taken; in this case there was no relationship between her intermenstrual bleeding and the stage of her menstrual cycle. Her periods were regular but heavy and painful. Abdominal examination did not identify a pelvic mass. Bimanual and speculum examination did not reveal any abnormality. In this case further investigation with ultrasound is indicated due to her persistent symptoms and absence of other identifiable cause. See Table 1 for differential diagnoses. Ultrasound findings An ultrasound scan was performed on day 3 of her menstrual cycle. The report describes the uterus as retroverted with an endometrial thickness of 9.7 mm. The midline endometrial echo was disrupted by an 8 6 6 mm homogenous structure consistent with an endometrial polyp. There was a single feeding vessel on colour Doppler examination. Both ovaries appeared normal.
Investigations A cervical smear test should be performed if not up to date. If the cervix appears abnormal referral to colposcopy should not be
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periods are not heavy or painful, she has had a recent negative sexual health screen and uses condoms for contraception. She has no significant past medical or surgical history. She is anxious regarding the possibility of cervical cancer as she has been told she is too young for cervical screening.
Transvaginal ultrasound is the first line imaging modality for endometrial assessment. Endometrial polyps appear as hyperechoic areas within the endometrial cavity and are best visualised in the early follicular phase of the cycle when the endometrium is thin. Saline can be instilled into the endometrial cavity to aid visualization.
How would you assess this patient? After taking a detailed gynaecological and sexual history, pregnancy must be excluded. The presence of post-coital bleeding warrants speculum and bimanual examination to assess a local cause of bleeding. See Table 2 for differential diagnoses. The pertinent point in this case is that this patient is not yet part of the National Health Service cervical screening programme (NHSCP) and the concern is that of missing a diagnosis of cervical cancer. The current age range for cervical screening in the UK is 25e64 with 3 yearly screening until aged 49 and 5 yearly thereafter. A review by the Advisory Committee on Cervical Screening found that the number of cervical cancer cases diagnosed in 20e24 year olds does not appear to be increasing and may be expected to fall with the advent of the national human papilloma virus (HPV) vaccination programme. Screening is not recommended in this age group as it does not reduce the incidence of or mortality from cervical cancer. Screening in younger women is also thought to have the potential to cause more harm than good. HPV infection is common in women under 25 and there is good evidence that minor cellular changes occur frequently in these women but appear to regress spontaneously. Screening these women would result in a high number of colposcopy referrals and subsequent treatments which in addition to causing undue anxiety could increase the risk of pre-term labour in future pregnancies. There are approximately 50 cases per year of cervical cancer in women aged 20e24 resulting in 0e5 deaths. A significant contributing factor in these deaths was a delay in diagnosis due to a delay in gynaecological examination as abnormal bleeding was ascribed to dysfunctional uterine bleeding or contraceptive use. Abnormal vaginal bleeding is very common in women aged 20e24 with 1 in 600 describing PCB and up to 1% describing IMB. Both these symptoms could arise as a result of cervical cancer and therefore young women with these symptoms require thorough assessment. A speculum examination should be performed in any woman presenting with PCB or persistent IMB and where appropriate, a cervical smear should be taken. If the cervix appears abnormal a 2-week wait referral to colposcopy should be arranged without awaiting the result of cervical cytology. If the cervix appears normal screening should be arranged for STIs and appropriate treatment and full sexual health screening offered if necessary. If symptoms persist despite appropriate treatment gynaecological referral is indicated. Most invasive cervical cancers that cause PCB will be visible on speculum examination. The incidence of cervical cancer is low in the UK due to the presence of a national screening programme. The risk of cancer is particularly low in women who have had a recent normal smear test (0.6%). The incidence of invasive cancer in
Pathophysiology of endometrial polyps Endometrial polyps are focal overgrowths of endometrial glands and stroma covered by surface epithelium and can vary in size from a few millimetres up to several centimetres, they can be single or multiple. They are common in both pre and postmenopausal women and many are asymptomatic. They are usually benign but hyperplastic or malignant change can be seen within polyps. The prevalence of endometrial polyps in the general population has been reported at 7.8%. The incidence of polyps increases with age and malignancy is more likely in older women and in women with symptomatic polyps. The prevalence of malignant polyps has been reported at 1.7% in women of reproductive age compared to 5.4% in post-menopausal women. Polyps are associated with a number of symptoms including IMB, PCB, postmenopausal bleeding, vaginal discharge, menorrhagia and infertility. What are the management options for this patient? The high prevalence of asymptomatic endometrial polyps has called into question the causal relationship between endometrial polyps and unscheduled bleeding and this must be borne in mind when counselling patients. Management depends on symptoms, age, fertility wishes and risk of malignancy. Small polyps (<1 cm) may regress spontaneously particularly in premenopausal women while large polyps are more likely to be symptomatic. Conservative management may be considered in premenopausal women with asymptomatic small polyps as the risk of malignancy in these cases is low. This group of women should however be encouraged to report any abnormal bleeding as this may warrant surgical treatment. The presence of an endometrial polyp and abnormal bleeding increases the risk of malignancy from 2.16% to 4.15% and therefore polypectomy is usually recommended both to detect endometrial malignancy and to improve abnormal bleeding. This is best done via operative hysteroscopy to allow complete resection of the polyp, this can be achieved under local or general anaesthesia depending on the clinical circumstances. Patients should be counselled regarding the surgical risks of operative hysteroscopy in addition to the recurrence risk of endometrial polyps which has been reported to be as high as 15%. Polyp resection may also be appropriate in subfertile patients as increased pregnancy rates have been reported after polypectomy although further research is needed to see if this improves live birth rates.
Cervical ectropion Case 2 A 22-year-old woman attended with post-coital bleeding for 4 months. She has an otherwise regular menstrual cycle and her
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women with PCB is higher than that of asymptomatic women and therefore colposcopic assessment should be arranged without delay if there are concerns regarding the appearance of the cervix. Other more common causes of post-coital bleeding may be identified on speculum examination (Table 2). In this case this patient was found to have a cervical ectropion.
local treatment. Once infection and malignancy have been excluded cryocauterisation or diathermy may be performed under colposcopic guidance.
Bleeding associated with contraceptive use Case 3 A 27-year-old nulliparous woman attends gynaecology clinic with a 6-month history of intermenstrual bleeding. She has been taking the combined oral contraceptive pill for 8 months. She has no significant past medical or surgical history. Her last cervical smear test was 18 months ago and was normal. Figure 1.
What are the management options? Cervical ectropion is a benign condition where cervical eversion results in the columnar epithelium of the endocervix being seen on the endocervix. It characteristically appears as a red ring around the cervical os. It is considered a normal physiological process as a result of exposure to oestrogens. It is therefore seen in young women, during pregnancy and in combined oral contraceptive users. It is usually asymptomatic but can result in vaginal discharge or post-coital bleeding. Exposure of the columnar epithelium to vaginal secretions results in squamous metaplasia and this often produces a resolution of symptoms, therefore conservative management may be appropriate in some cases. In patients on the combined oral contraceptive pill changing to a non-oestrogen containing contraceptive may be beneficial. In symptomatic patients in whom conservative measures have failed consideration may be given to
How would you assess this patient? A detailed gynaecological and contraceptive history is essential in this case to aid diagnosis. The possibility of pregnancy should be considered and a pregnancy test should be performed on sexually active women using hormonal contraception with unscheduled bleeding. A detailed menstrual history should be taken with particular attention to her bleeding pattern prior to starting oral contraception. The current type of oral contraception and compliance should be ascertained. The use of any concurrent prescribed, over the counter or herbal preparations needs to be outlined due
Summary of management of unscheduled bleeding in hormonal contraceptive users • Assess compliance with contraception • Consider STI screening • Review smear history and screen if due • Assess for other gynaecolgical symptoms • Consider speculum and bimanual examination • Endometrial assessment for high risk groups • Smoking cessation advice
Combined oral contraceptive pill
Progesterone only pill
• Allow 3 month trial of pill before changing
• Consider switching desogestrel users to a traditional POP
• Advise against cycling packets
• Mefanamic or tranexamic acid may shorten duration of a bleeding episode
• Increase dose of ethinylestradiol up to 35 micrograms
Progesterone implant, IUS or DMPA
used either continuously or cyclically • No evidence to support reducing injection interval in DMPA users • Mefanamic acid or tranexamic acid may shorten duration of bleeding episode in DMPA users
• Try alternative COCP • Combined vaginal ring may improve cycle control
Figure 1
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CASE-BASED LEARNING
control. The combined vaginal ring has also been shown to improve cycle control compared to the combined oral contractive pill and so can be offered as an alternative.
to the possibility of a drug interaction. A history of illness that may have interfered with the absorption of medication should be assessed. A sexual history should be taken and screening for infections particularly Chlamydia trachomatis and Neisseria gonorrhoea should be performed in women under 25, women of any age with a new partner and women with more than one partner in the past year. Single vaginal swabs are available to screen for both infections or vaginal self-swabs can be used, urinary testing for STIs is no longer recommended. A cervical screening history should be taken and a smear test performed if it is due. Other gynaecological symptoms such as dyspareunia, vaginal discharge or post-coital bleeding should be elicited to assess whether the cause for bleeding is related to hormonal contraceptive use. A smoking history should be elicited as breakthrough bleeding is more prevalent among smokers. Women should be advised prior to starting hormonal contraceptives that unscheduled bleeding in the first 3 months is not uncommon and usually settles with continued use. Unscheduled bleeding for the first 6 months with the progesterone IUS or implant may be considered normal. The presence of PCB always warrants a speculum and bimanual examination. Where it is IMB only, for less than 3 months, with a normal smear history, no risk factors for STIs and no symptoms suggestive of gynaecological pathology, a conservative approach without examination could be considered with a follow up review arranged. If her bleeding had continued for more than 3 months, she had not had up to date cervical screening, or if she had any other gynaecological symptoms or requested examination then bimanual and speculum examination should be performed. In women over the age of 45 with persistent unscheduled bleeding or a change in bleeding pattern and younger women with risk factors for endometrial cancer, endometrial assessment with ultrasound scan endometrial biopsy should be considered.
Progesterone only pill (POP) The POP is a more suitable alternative to the COCP in women who are breastfeeding, women over 35 years of age, in smokers and in women in whom oestrogens are contraindicated. The pattern of bleeding can vary between the different types of POP. Women taking the desogestrel POP (Cerazette Ò) can be advised to try a different POP but it should be explained that they may still experience bleeding but the pattern may be different and this may be more or less acceptable to some women. 50% of women taking Cerazette Ò will be amenorrhoeic or have infrequent bleeding after one year, the other 50% will have frequent or prolonged bleeding. Traditional POP preparations are associated with less amenorrhoea and less prolonged bleeding but frequent irregular bleeding is common. There is no evidence that taking two POPs a day improves bleeding. Progesterone only implant, depot medroxyprogesterone acetate (DMPA) or IUS The addition of a first line COCP containing 30e35 mg of ethinylestradiol for 3 months may help reduce unscheduled bleeding in this group of women although it is not licenced for this indication. Evidence that this is beneficial is available for users of the progesterone IUS and implant but evidence of its benefit is lacking for patients using DMPA although its use is nevertheless advised. The COCP can be given cyclically or in a continuous pattern and can be repeated as often as needed provided there are no contraindications to oestrogen use. For women using DMPA there is no evidence that reducing the interval between injections improves bleeding. Mefenamic acid or tranexamic acid may be beneficial in the short term by reducing the length of bleeding episodes in women using DMPA but evidence of similar benefit has not been found in users of the implant or IUS.
Conclusion
What are the management options for this patient? After excluding others causes for unscheduled bleeding the management depends on the type of contraception used.
Unscheduled bleeding in premenopausal women is usually as a result of benign disease but consideration must be given to the possibility of malignancy in all cases. Further investigation to exclude malignancy is warranted in women over the age of 45 and in younger women with additional risk factors. Prolonged symptoms or persistent symptoms despite treatment should prompt the need for further evaluation to exclude malignancy. There is considerable overlap in symptomatology in conditions associated with IMB and PCB and history taking is an essential tool in the diagnosis of these patients. Bimanual and speculum examination is indicated in almost all cases of unscheduled vaginal bleeding and a delay in performing these important tests has been shown to result in an unacceptable delay in diagnosis, thereby increasing the morbidity and mortality associated with gynaecological cancers. A
Combined oral contraceptives (COCP) General principles in the management of irregular bleeding with oral contraception include ensuring adherence to pill taking and avoiding cycling of packets in COCP users as this can result in breakthrough bleeding. Smoking cessation advice should be offered as smoking is linked to a higher incidence of breakthrough bleeding. Unscheduled bleeding is less common with the COCP compared to the progesterone only pill (POP). The COCP with the lowest dose of ethinylestradiol to achieve cycle control is usually prescribed for contraceptive purposes. In cases of unscheduled bleeding trying an alternative COCP with a different oestrogen or progestogen component may help. Increasing the dose of ethinylestradiol up to a maximum of 35 mg often improves cycle
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FURTHER READING Department of Health. Clinical practice guidance for the assessment of young women aged 20e24 with abnormal vaginal bleeding, 2010. NICE Clinical Guideline. Heavy menstrual bleeding, January 2007. Lumsden MA, Gebbie A, Holland C. Managing unscheduled bleeding in non-pregnant premenopausal women. BMJ 2013 Jun 4; 346: f3251. https://doi.org/10.1136/bmj.f3251. Management of unscheduled bleeding in women using hormonal contraception. Faculty of Sexual and Reproductive Healthcare, 2009. NHS Cervical Screening Programme. Colposcopy and Programme Management, NHSCSP Publication number 20, Third edition March 2016.
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Pregnancy must be excluded in any woman of reproductive age presenting with unscheduled bleeding. The first symptom of gynaecological cancer can be a change in menstrual pattern, including unscheduled vaginal bleeding, these symptoms therefore should prompt the need for bimanual and vaginal speculum examination. Women with symptoms suggestive of cervical cancer including post-coital bleeding, persistent vaginal discharge and intermenstrual bleeding should undergo gynaecological examination and be referred for colposcopy if cancer is suspected. Women with unscheduled bleeding and a previous negative smear result have a greatly reduced risk of cervical cancer however a previous negative smear result should not delay referral to colposcopy if there is a clinical suspicion of cervical cancer on examination. Women aged under 25 with abnormal vaginal bleeding who are found to have a normal cervix on examination should be screened for infection and treated appropriately. Persistent symptoms (6e8 weeks) should prompt gynaecological referral. Endometrial biopsy is indicated in women over 45 with persistent intermenstrual bleeding and in younger women with risk factors. Unscheduled bleeding is common in the first 3 months with hormonal contraception but persistent symptoms, the presence of risk factors or the other gynaecological symptoms warrants further investigation.
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