Postmenopausal Bleeding: Differential Diagnosis
So, you’ve seen a patient who has abnormal uterine bleeding and used the 8 targeted PMB questions to gather a comprehensive history. You know that post menopausal bleeeding is never normal. Now we can go from accurately noting the symptom (bleeding) to figuring out the diagnosis.
First: If the patient has never had 12 full months without a period, by definition you are not dealing with post-menopausal bleeding!!! Check out the article on getting a targeted history for AUB and formulating a differential .
Next, you’ve got to do a physical exam, including a pelvic exam. There’s no other part of the body a patient could tell you was bleeding and you would place a referral without considering exam. So let’s not do it with that vaginas. Remember: anyone with concerning bleeding from their vagina deserves to have it looked at. Sure, you could just refer to gynecology, but you and I both know the patient will likely wait for that appointment for months, and we don’t want a patient to wait all that time only to find they were in the wrong place or that they had a problem that could been diagnosed and treated easily the first time they came in. No blind ultrasounds. No reflexive referrals to gynecology.
I structure a differential diagnosis for PMB slightly differently than I do for AUB in reproductive-age patients for one main reason: the threat of endometrial cancer. Endometrial cancer is rare overall (affecting 3% of people with uteruses in the United States), but over 70% of cases occur in patients over the age of 55, and >90% present with post menopausal bleeding (1). EC can also present in a variety of ways, so it doesn’t matter as much if the bleeding is heavy, light, spotting or situational. It goes without saying that a missed or delayed diagnosis can be devastating, so every postmenopausal patient who walks into my office with bleeding gets a transvaginal ultrasound or endometrial biopsy to evaluate for endometrial cancer, and then I use the history and exam to rule out other potential causes. Let’s get into it:
If the patient still has their uterus:
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Although endometrial cancer is uncommon, any patient with postmenopausal bleeding who still has their uterus needs to be evaluated for endometrial cancer or hyperplasia.
Cervical cancer (or dysplasia) can also cause postmenopausal bleeding.
Cancers of the ovaries, fallopian tube, vulva,and vagina may present with bleeding as well. A thorough pelvic exam is an essential part of the evaluation for PMB. Follow up ultrasound may be indicated if endometrial biopsy is negative or exam findings are concerning for intraabdominal pathology.
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Polyps (cervical or endometrial), fibroids,and adenomyosis (for patients on hormone therapy) can also cause bleeding in the postmenopausal period.
In the absence of other findings, consider trauma from foreign objects (including other body parts, toys, pessaries etc).
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Similar to the reproductive years, hormonal therapy can lead to cyclic or irregular bleeding. However, evaluation for endometrial cancer should be considered if bleeding persists beyond the intial few months of hormone therapy.
Tamoxifen therapy for patients with a personal or family history of breast cancer increases the risk of endometrial cancer or hyperplasia. Routine assessment is not recommended, but any bleeding should prompt an evaluation.
Anticoagulant or antiplatelet medications and some herbs or supplements may also precipitate postmenopausal bleeding. These medications can still cause bleeding even if the uterus and/or cervix are absent, but I’ll include them here with the other medications.
Must-have tests: A transvaginal ultrasound or endometrial biopsy to evaluate for endometrial cancer. An endometrial thickness <5mm is reassuring for the absence of endometrial cancer. However, ultrasound may be less sensitive in some patients, including among Black patients and patients with fibroids. I offer both, explaining that tissue diagnosis is the more sensitive and the better way to actually know what the cells of the uterine lining are doing, but an ultrasound is a reasonable first option and we can return to biopsy if the ultrasound is abnormal or bleeding persists and we don’t find another cause. A pelvic exam may reveal cervical polyps or large endometrial polyps or even cervical masses consistent with cancer.
Case-by-case: Unless they’ve had a pap test in the last year or so, I offer a diagnostic pap (as opposed to routine screening) pap to any of my patients with post-menopausal bleeding, especially if they have had a history of abnormal paps in the past.
If the patient has vulvovaginal itching, discharge, or pain (including pain with intercourse):
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Part of the genitourinary syndrome of menopause (GUSM), this is the most common cause of post-menopausal bleeding. The drop in estrogen levels that accompany cessation of menses also lead to decreased lubrication of the vulva and vagina and breakdown of the epithelium that can cause bleeding.
Vaginal tissues will look pale and dry on exam with decreased rugae, there may even be visible breaks or fissures. Vaginal estrogen is a great option for these patients, provided you have ruled out endometrial cancer or hyperplasia.
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Vaginitis, sexually transmitted infections, and endometritis can present with bleeding.
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Inflammatory conditions of the vulvar skin like lichen (sclerosus, planus or simplex chronicus), vulvar dermatitis, and other skin conditions can all cause bleeding. Perform a thorough physical exam to look for associated skin changes.
Must-have tests: A pelvic exam will provide key findings to guide further testing and referrals. You may find skin changes consistent with atrophy, prolapse or erosion of the urethral meatus, or signs of STIs. This is not the time for a blind urine test for gonorrhea and chlamydia or a hand wave to discuss estrogen the next time the patient sees their gynecologist. During your exam, offer testing for yeast infections and bacterial vaginosis.
Case-by-case: If the patient is sexually active, also offer testing for gonorrhea, chlamydia, and trichomonas (an oft-forgotten STI). Look for signs of herpes on exam and test for that if appropriate. Careful not to mix up the isolated ulcers of herpes with the overall tissue changes from atrophy as Halle Berry’s provider (in)famously did. (Not that I understand how that even happens).
If the patient has bowel or bladder symptoms:
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Urinary tract infections can actually become more common in the menopausal period due to hypoestrogenic changes of the urethra and surrounding tissues.
If a urinalysis is negative for other signs of infection, but positive for blood, consider bladder or urethral cancers as a possible bleeding source.
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Hemorrhoids, diverticulitis, colon cancer, and inflammatory bowel conditions like Chron’s disease can all manifest with bleeding. Diverticulitis can even cause bowel fistulas to the uterus that then result in bleeding. If the patient has a change in bowel habits and there is no apparent vulvovaginal or uterine cause, don’t assume atrophy and call it a day. Consider testing for rectal bleeding and a proper investigation of their GI symptoms.
Must-have tests: A thorough pelvic exam including an exam of the urinary and gastrointestinal neighbors to the vulva. I know I talk about this is a lot, but it is really difficult to overstress the importance of an exam for pelvic complaints.
Case-by-case: Urinalysis and urine culture if there are symptoms consistent with UTI. Fecal occult blood testing (or referral for colonoscopy if the patient is due) and consider a GI referral for concerning bowel symptoms.
Now you have what the tools complete a comprehensive initial evaluation for post menopausal bleeding. With our strategic line of questioning, you can now make smart decisions about which tests to order to determine if the source falls under one of 6 categories: structural (Dysplasia), structural (benign), infection, urinary tract / gastrointestinal, atrophy, or other dermatologic.
Thanks for reading! Have thoughts, questions, suggestions for future posts, or your own story to share? Drop a comment below - I’d love to hear from you.