Epidemiology

• Self-reported intermenstrual bleeding (IMB) and postcoital bleeding (PCB) have an annual cumulative incidence of 17% and 6% respectively in menstruating women from a questionnaire study based on subjects within an urban English, general practice setting.¹
• PCB occurs in 0.7-39% of women with cervical cancer. The risk of a woman seen in the community with PCB having cervical cancer is approximately 1 in 44,000 in 20-24 year olds and 1 in 2,400 in 45-54 year olds.²
• In another English study, looking at pathological findings from a group of women referred to colposcopy for PCB but with a negative previous cervical smear, a third had an ectropion, 12% had cervical polyps, 7% had cervical intraepithelial neoplasia (CIN), 2% had chlamydia but nobody in this study had invasive cancer.³
• Only 2% of endometrial cancers occur before 40 years old. Risk factors for endometrial cancer include: nulliparity, diabetes, obesity, polycystic ovary syndrome, unopposed oestrogen therapy, chronic anovulatory cycles and the use of tamoxifen. Women with risk factors and IMB should be fully investigated.

Aetiology⁴

Causes of postcoital bleeding (PCB)

• Infection
• Cervical or endometrial polyps
• Vaginal cancer
• Cervical cancer
• Trauma

Causes of intermenstrual bleeding (IMB)

• Pregnancy-related including ectopic pregnancy and gestational trophoblastic disease
• Physiological - 1-2% spot around ovulation
• Iatrogenic
  • Combined oral contraceptive pill (COCP) - either in too low dose or in combination with an enzyme-inducing drug
  • Progesterone-only pill
  • Contraceptive depot injections
  • Intrauterine systems (IUS)⁵ or implant
  • Emergency contraception⁶
  • Tamoxifen
  • Following smear or treatment to the cervix
  • Caesarean section scars⁷
  • Drugs altering clotting parameters, e.g. anticoagulants, SSRIs, corticosteroids
  • Alternative remedies, e.g. ginseng, ginkgo, soy supplements, and St John's wort⁸
• Vaginal causes:
  • Adenosis
  • Vaginitis (bleeding uncommon before the menopause)
  • Tumours
• Cervical causes:
  • Infection - chlamydia, gonorrhoea
  • Cancer (but bleeding is most often postcoital)
  • Cervical polyps
  • Cervical ectropion
  • Condylomata acuminata of the cervix
• Uterine causes:
  • Endometrial polyps
  • Cancer (endometrial adenocarcinoma, adenosarcoma⁹ and leiomyosarcoma)
  • Adenomyosis (usually only symptomatic in later reproductive years)
  • Endometritis
  • Fibroids
• Oestrogen-secreting ovarian cancers

Presentation

Given the wide differential for non-menstrual vaginal bleeding, a careful history and examination is paramount.

History

• Menstrual history:
  • Last menstrual period - was the last period a 'normal' period?
  • Regularity and cycle length
  • Duration of abnormal bleeding - prolonged versus recent change?
  • Presence of menorrhagia
  • Timing of bleeding in the menstrual cycle
  • Associated symptoms, e.g. abdominal pain, fever, vaginal discharge, dyspareunia,
  • Factors that aggravate bleeding, e.g. exercise, intercourse
• Obstetric history
  • Previous pregnancies and deliveries, including time since last delivery/miscarriage/termination
  • Current breast-feeding
  • Risk of current pregnancy - increased, for example, with unprotected intercourse, forgotten pills, gastroenteritis or antibiotics used with the COCP
  • Risk factors for ectopic pregnancy - for example, a history of pelvic inflammatory disease or endometriosis, IVF treatment, use of an intrauterine contraceptive device (IUCD) or the progestogen-only pill (POP)
• Gynaecological history:
  • Current use of contraception
  • Smears - most recent test results, any previous smear abnormalities, colposcopy, treatment for abnormalities, etc.
  • Previous gynaecological investigations or surgery
• Sexual history - risk factors for sexually transmitted infection (STI) (those aged <25 years, or at any age with a new partner, or more than one partner in the last year), past history and treatment for STIs.
• Medical history - e.g. bleeding disorders, diabetes
• Current medication (including unprescribed)

Examination

• Establish that the bleeding is from the vagina, not the rectum or in the urine. Any doubt can be eliminated by inserting a tampon which will confirm presence of blood in the vagina.
• BMI - high BMI is an independent risk factor for endometrial cancer.
• Abdominal examination noting the presence/absence of pelvic masses.
• PV examination (speculum and bimanual) looking for obvious genital tract pathology. Note whether any contact bleeding occurs, friability of tissue, cervical 'excitation' or tenderness, presence of ulceration, polyps or discharge and any other lower genital tract sites of bleeding. Common findings include:
  • Cervical ectropion (or erosion) - appears as a red ring around the external os due to extension of the endocervical columnar epithelium over the ectocervix.
  • Cervical polyp - mass arising from the endocervix, usually protruding through the external os into the vagina. They can be avulsed and sent to histology. Occasionally, endometrial polyps can be seen extruding through the cervix. In a Danish study, polyps were found in 5.8% of premenopausal women but only 9% of those under the age of 30 years.¹⁰
  • Cervicitis - the cervix appears red, congested and sometimes oedematous. There may be purulent discharge and the cervix is usually tender to palpation. The most common causes of infection currently is Chlamydia trachomatis. Neisseria gonorrhoeae as a cause of cervicitis should not be forgotten. A rarer cause is Trichomonas vaginalis where the cervix is friable, with prominent papillae and punctate haemorrhages, and is commonly described as a 'strawberry cervix'. Herpetic cervicitis gives rise to multiple ulcerated regions.

Investigations

• FBC
• Clotting
• Thyroid function
• FSH/LH levels (if onset of menopause suspected)

Referral for further investigation:

• With persistent IMB (usually taken as more than three months):
  • Transvaginal ultrasound - this is the investigation of choice to look for structural abnormality. Ultrasound should ideally be done immediately postmenstrually as the endometrium at its thinnest and polyps and cystic areas tend to be more obvious. An endometrial thickness of 8 mm or less is significantly less likely to be associated with a malignant pathology.¹² Evidence of endometrial thickening should prompt referral for biopsy. Even by an experienced operator, pathology can be missed on ultrasound in the presence of an IUCD due to reflections and shadowing.¹³
  • Endometrial biopsy may be done as a surgery or clinic-based procedure using the Pipelle® device or Vabra® aspirator.¹⁴ Their disadvantage is that they miss up to 18% of focal lesions.⁴ Hysteroscopy with biopsy is the current gold standard for investigating the uterine cavity, allowing direct visualisation and tissue diagnosis.¹⁵
    

    Who should be referred with persistent intermenstrual bleeding (IMB) and negative clinical findings for endometrial biopsy?11,16 Older women (>45 years) Women aged <45 years with risk factors for endometrial cancer if IMB persists after the first three months of starting a contraceptive method or who present with a change in bleeding pattern.

  • For postcoital bleeding (PCB):
    • Colposcopy - despite the low rate of serious pathologies seen in referred PCB cases with a negative recent smear, there is a concern that these women are nonetheless at an increased risk of CIN and continue to warrant colposcopy referral.¹⁷

Management

Management is dependent on the cause of the bleeding.

Suspected cancer

If gynaecological cancer is suspected, refer urgently for investigation.

Infection

• Antibiotic treatment will depend on the organism involved and local patterns of sensitivity.
• Contact tracing and treatment of sexual partners should be initiated.
• Electrocautery of secondarily infected Nabothian follicles is sometimes performed for chronic cervicitis.

Hormonal contraception¹¹

• Warn women that unscheduled bleeding in the first three months after starting a new hormonal contraceptive method is common, and that up to six months' unscheduled bleeding with the IUS and progestogen-only implant may be considered normal. Indeed the Royal College of Obstetricians and Gynaecologists' guidelines suggest that genital examination is not required within this time frame if, after taking a clinical history, there are no risk factors for STIs or symptoms suggestive of other underlying causes, and the woman is participating in a National Cervical Screening Programme.
• However, follow-up should be planned, as bleeding may persist beyond this time.
• For persistent bleeding beyond the first three months' use, or where there is a change in bleeding pattern, or where a woman has not participated in a National Cervical Screening Programme, a speculum +/- bimanual examination should be performed.
• Where clinical findings are normal, there are no other associated symptoms, the women is 45 years or under and has no risk factors for endometrial cancer, reassurance or medical treatment is appropriate.

Strategies for treating unscheduled bleeding in those using hormonal contraception:

• For COCP users:
  • Stick with the same pill for a trial of at least three months, as bleeding may settle.
  • Use a pill with a dose of ethinylestradiol sufficient to provide the best cycle control - consider increasing to a maximum of 35 micrograms.
  • May try a different COCP, or a different dose or type of progestogen.
• For POP users:
  • Try a different POP (although little evidence that changing the progestogen type or increasing the dose improves bleeding)
  • No evidence that desogestrel-only pills (e.g. Cerazette®) have better bleeding patterns than traditional POPs.
  • No evidence that doubling to two pills per day improves bleeding.
• For progestogen-only implants, depots and IUS users:
  • A first-line COCP (with 30-35 micrograms ethinylestradiol) may be considered for up to three months continuously or in the usual cyclical regimen. Note this is an unlicensed indication.
  • There is no evidence that reducing the injection interval for depot progestogen injections improves bleeding but some try bringing this forward by up to two weeks.
  • Mefenamic acid can be used to reduce the duration of bleeding for women on depot progestogen injections.

Cervical ectropions

• These may resolve spontaneously if the COCP is stopped, or following pregnancy
• They can be treated conservatively or cauterised with silver nitrate.
• Other treatment options include thermal cautery and diathermy, cryosurgery, laser or microwave therapy.¹⁹

Cervical polyps

• Polyps should be avulsed and sent for histology.
• They are accompanied by endometrial polyps in about 25%,²⁰ so further investigation (ultrasound +/- hysteroscopy), particularly in older women, can be indicated.

Document references

1. Shapley M, Jordan K, Croft PR; An epidemiological survey of symptoms of menstrual loss in the community. Br J Gen Pract. 2004 May;54(502):359-63. [abstract]
2. Shapley M, Jordan J, Croft PR; A systematic review of postcoital bleeding and risk of cervical cancer. Br J Gen Pract. 2006 Jun;56(527):453-60. [abstract]
3. Sahu B, Latheef R, Aboel Magd S; Prevalence of pathology in women attending colposcopy for postcoital bleeding with negative cytology. Arch Gynecol Obstet. 2007 Nov;276(5):471-3. Epub 2007 Apr 12. [abstract]
4. Albers JR, Hull SK, Wesley RM; Abnormal uterine bleeding. Am Fam Physician. 2004 Apr 15;69(8):1915-26. [abstract]
5. Guttinger A, Critchley HO; Endometrial effects of intrauterine levonorgestrel. Contraception. 2007 Jun;75(6 Suppl):S93-8. Epub 2007 Mar 23. [abstract]
6. Gainer E, Kenfack B, Mboudou E, et al; Menstrual bleeding patterns following levonorgestrel emergency contraception. Contraception. 2006 Aug;74(2):118-24. Epub 2006 Apr 27. [abstract]
7. Tahara M, Shimizu T, Shimoura H; Preliminary report of treatment with oral contraceptive pills for intermenstrual vaginal bleeding secondary to a cesarean section scar. Fertil Steril. 2006 Aug;86(2):477-9. Epub 2006 Jun 12. [abstract]
8. Murphy PA, Kern SE, Stanczyk FZ, et al; Interaction of St. John's Wort with oral contraceptives: effects on the pharmacokinetics of norethindrone and ethinyl estradiol, ovarian activity and breakthrough bleeding. Contraception. 2005 Jun;71(6):402-8. [abstract]
9. Abu J, Ireland D, Brown L; Adenosarcoma of an endometrial polyp in a 27-year-old nulligravida: a case report. J Reprod Med. 2007 Apr;52(4):326-8. [abstract]
10. Dreisler E, Stampe Sorensen S, Ibsen PH, et al; Prevalence of endometrial polyps and abnormal uterine bleeding in a Danish Ultrasound Obstet Gynecol. 2009 Jan;33(1):102-8. [abstract]
11. Management of Unscheduled Bleeding in Women Using Hormonal Contraception, Faculty of Sexual and Reproductive Healthcare (2009)
12. Getpook C, Wattanakumtornkul S; Endometrial thickness screening in premenopausal women with abnormal uterine bleeding. J Obstet Gynaecol Res. 2006 Dec;32(6):588-92. [abstract]
13. Pitkin J; Dysfunctional uterine bleeding. BMJ. 2007 May 26;334(7603):1110-1.
14. Brooks PG; In the management of abnormal uterine bleeding, is office hysteroscopy preferable to sonography? The case for hysteroscopy. J Minim Invasive Gynecol. 2007 Jan-Feb;14(1):12-4. [abstract]
15. Naim NM, Mahdy ZA, Ahmad S, et al; The Vabra aspirator versus the Pipelle device for outpatient endometrial sampling. Aust N Z J Obstet Gynaecol. 2007 Apr;47(2):132-6. [abstract]
16. Heavy menstrual bleeding, NICE Clinical Guideline (January 2007)
17. Abu J, Davies Q, Ireland D; Should women with postcoital bleeding be referred for colposcopy? J Obstet Gynaecol. 2006 Jan;26(1):45-7. [abstract]
18. Referral for suspected cancer, NICE Clinical Guideline (2005)
19. Yang K, Li J, Liu Y, et al; Microwave therapy for cervical ectropion. Cochrane Database Syst Rev. 2007 Oct 17;(4):CD006227. [abstract]
20. Stamatellos I, Stamatopoulos P, Bontis J; The role of hysteroscopy in the current management of the cervical polyps. Arch Gynecol Obstet. 2007 Oct;276(4):299-303. Epub 2007 Jul 25. [abstract]

Internet and further reading

• FP Notebook Cervix anatomy; Images of normal cervix and ectropion
• Chandran L; Cervicitis. eMedicine, March 2009.