Abnormal Uterine Bleeding: Differential Diagnosis

So, you’ve seen a patient who has abnormal uterine bleeding and used the 10 targeted AUB questions to gather a comprehensive history. You know what’s normal. Now comes the part that actually helps you figure out what’s wrong.

Abnormal uterine bleeding (AUB) isn’t a final diagnosis—it’s a symptom. And when someone walks into your office with heavy, irregular, or unexpected bleeding, the question isn’t “What’s the name of the condition?” It’s “What systems could be at play here?”

First, you’ve got to do a physical exam, including a pelvic exam. I know. You don’t like doing them. You’re not comfortable with them. Someone told you they did a research study, and patients said they didn’t want them. True story: I worked at an facility where the ED staff would frequently cite this as a get-out-if-jail-free card for pelvic exams. But we don’t do this with any other part of the body. Can you imagine seeing a patient someone with chest pain and ordering an echo without a heart and lung exam or seeing a patient with a headache and jumping directly to a neurology referral and an MRI? I could write a thesis about how underlying societal misogyny leads us to feel that women’s* health concerns are not worth investing in, researching, evaluating or teaching properly, but that’s a different post for another day. For now, I’ll simply say that 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 I’ve already shared examples of patients who endured long waits only to find that they had a problem that could been diagnosed and treated easily the first time they came in or they were in the wrong place and needed to wait longer for a more appropriate referral.

So, offer the exam. Let your patient know it could provide key information to figure out what’s going on. I break down what to look for on bimanual and speculum exam and how to make it less uncomfortable here. Clients may decline if they are bleeding (or for any other reason), although you should inform them that this is not a contraindication. If the client is due for cervical cancer screening and if they are sexually active and interested in STI testing, you can collect those specimens during your exam. If they have any unusual discharge or itching, you can also test for common infections that are not linked to sex like bacterial vaginosis or yeast infections. If the patient had any of the following in their history: age>35, obesity, diabetes, family history of colon or uterine cancer, tamoxifen use, consider an endometrial biopsy if that is part of your practice. A pregnancy test should be obtained for anyone who is at risk for pregnancy (having penetrative sex where they encounter semen) and if it is positive, that’s calls for a different evaluation that we will discuss elsewhere.

This is where we stop chasing zebras, resist the urge to blindly order an ultrasound, and start grouping possible causes into one of 5 meaningful categories for more diagnostic clarity, and a plan that helps you get your patient answers fast. Let’s break it down:

If the bleeding is regular and excessive (heavy or prolonged):

This means the normal menstrual cycle is intact with normal ovulation. This means you are on the lookout for things that can increase the amount of bleeding in a normal cycle. The client might have: 

• Structural causes

  i.e. a physical growth or anomaly causing the bleeding. Think fibroids (leiomyomas), adenomyosis, endometrial or cervical polyps. The uterus may feel enlarged, irregularly shaped or globular on exam if fibroids or adenomyosis are present. Your patient may also have a history of painful periods (dysmenorrhea). You might see a cervical polyp (or an endometrial polyp if it is large enough to prolapse through the cervix) on speculum exam. Cancers and pre-cancers (hyperplasia) of the uterus — especially the endometrium — can also present with heavy bleeding. Arteriovenous malformations are a rare possibility to consider if the bleeding started or worsened after a uterine surgery like a D&C.  

• Hormonal causes

  Like thyroid disease. The patient may also be experiencing weight changes, palpitations, hair loss, heat or cold intolerance, or fatigue. You might notice an enlarged thyroid gland on exam.

  Patient in the early menopause transition may also notice changes in their menses.

• Bleeding disorders

  This is more common among young clients who have had consistently heavy or prolonged periods since menarche, but can also be an issue in older clients. The client may have had nosebleeds, increased bruising, or excessive bleeding in other situations (injury, surgery, oral hygiene). Petechiae may be present on exam.

• Medication side effects

  Common culprits are anticoagulants, antiplatelet therapy or copper IUDs

Must-have tests: A complete blood count to assess for anemia or low platelets, thyroid stimulating hormone (TSH) (for most adults its routine screening anyway), follicle stimulating hormone (FSH, performed on cycle day 3*), and a pelvic ultrasound for the structural stuff.

Case-by-case: Coagulation studies and tests for bleeding disorders like von-willebrand’s disease if you suspect a bleeding disorder. Endometrial biopsy for patients with risk factors (age>35, obesity, diabetes, family history of colon or uterine cancer, tamoxifen use) if or if your suspicion is high and EMB is part of your practice.

If the bleeding is regular and lighter than usual:

This suggests something is decreasing the amount of lining that is produced and shed during the normal menstrual cycle or blocking its flow out of the uterus

• Structural causes

  Either scar tissue obstructing the cervix (cervical stenosis) or the endometrial cavity itself (Asherman syndrome). Both of these are more likely in a patient who has had recent instrumentation of the cervix or uterus, although any form of inflammation could potentially procedure scar tissue.

• Medication Side Effects

  Hormonal birth control may decrease menstrual flow. This side effect can be advantageous for patients with heavy menses, but patients who started hormones purely for birth control or other indications may be surprised by the effect on their periods.

 Case-by-case: Consider imaging studies or procedures to look inside the uterus and cervix. A sonohystogram or saline-infused sonogram may reveal an irregular endometrial cavity.

If the patient has normal periods are normal with additional intermenstrual bleeding (including bleeding with intercourse):

This also suggests that the normal cycle of ovulation and menstruation is intact, and something else is causing additional bleeding. Consider:

• Structural causes

  Polyps of the cervix or endometrium (if they are big enough to prolapse through the cervix) may be visible on exam or they may be detected on pelvic ultrasound. Cervical ectropion where normal columnar cells of the endocervix are visible on the exocervix, may case either irregular spotting or post-coital spotting/bleeding. This condition is benign. There may be a central red or pink, fuzzy patch visible on the cervix during speculum exam A malpositioned IUD can also cause post-coital or irregular bleeding.

• Hormonal causes

  If bleeding predictably occurs mid-cycle, it may be due to a sudden normal drop in estrogen that occurs with ovulation. Individuals on hormonal birth control can experience irregular menses or a regular period with occasional breakthrough bleeding.

• Inflammation (including infection)

  of the cervix (cervicitis) or the endometrium (endometritis) can cause spotting or slightly heavier bleeding. Vaginal discharge, pelvic pain, dyspareunia or fever may be present. Cervical motion tenderness of uterine tenderness may be noted on exam.

Must-have tests: Your history and exam are the keys to finding these causes. I personally offer testing for vaginitis (such as yeast infections) during every exam for irregular or intermenstrual bleeding.

Case-by-case: Offer STI testing to anyone who is sexually active. Consider an ultrasound to rule out endometrial polyps and assess IUD position for patients who have them in place. Endometrial biopsy for patients with risk factors (age>35, obesity, diabetes, family history of colon or uterine cancer, tamoxifen use) if or if your suspicion is high and EMB is part of your practice.

If the bleeding is irregular:

This suggests ovulation is not happening consistently. Causes are usually:

• Hormonal

  Postmenarche

  Anovulatory or oligo-ovulatory cycles are common in the first few years after onset of menses. Clients may experience both skipped menses and periods of spotting or heavy bleeding. Moliminal symptoms are usually absent. Labs are often normal.

  Thyroid disease

  Changes in thyroid hormone levels can influence levels of gonadotropin stimulating hormone in the hypothalamus, which in turn has an effect on the levels of follicle stimulating hormone produced in the pituitary gland.  It is more common to have regular periods with changes in the amount of bleeding with thyroid dysfunction, but irregular periods can happen as well.

  Hyperprolactinemia

  Affected individuals sometimes have bilateral nipple discharge or visual filed defects. Prolactin levels may be elevated with prolactin-producing tumors or breastfeeding. It can also be a side effect of common mood stabilizing medications, especially antipsychotics.

  Perimenopause or premature ovarian insufficiency

  In the late menopausal transition, ovulation starts to occur irregularly. Patients may skip periods for several months at a time, mixed in with periods of regular menses. Symptoms of menopause (vaginal dryness, hot flashes) may be present. Cycles may either been less frequent or more frequent than prior.

  With POI (i.e menopause prior to age 40), clients may initially present with infertility. FSH and estradiol levels should be assessed on cycle day 3*. Estradiol levels may be low or normal (<100pg/ml). FSH levels can also vary, but high FSH levels (>25IU/L) in a patient under 40 indicate likely POI. Assays can be repeated in one month to confirm.

  Hyperandrogenism

  • Polycystic ovarian syndrome. Hirsutism and acanthosis nigricans may be present on exam. As clients may remove hair, it is important to ask if they use any hair removal techniques especially on the face, back, or chin. PCOS is a clinical diagnosis but testosterone or DHEA-S levels may be mildly elevated and pelvic ultrasound may reveal multiple peripheral follicles.

  • Nonclassical congenital adrenal hyperplasia (CAH) may present with acne and/or hirsutism. 17-hydroxyprogesterone levels over 1500ng/dl are diagnostic of nonclassical CAH.

  • Androgen-secreting tumors are rare but should be suspected if signs of virilization (deepening voice, male-pattern balding, clitoromegaly) are present.

  Exogenous hormones (medication side effect)

  Hormonal contraception (birth control) can cause Intermenstrual bleeding, decreased menstrual flow, or amenorrhea. If the patient recently stopped hormonal contraception or switched methods, it can take some time for cycles to return to normal. FSH and estradiol levels may be affected by recent hormone use, making lab tests more difficult to interpret in this scenario.

Must-have tests: Thyroid stimulating hormone (TSH), day 3 follicle stimulating hormone (FSH), and prolactin are my standard tests for irregular periods. If prolactin is elevated, it’s a good idea to have the patient repeat the test on a day when they can avoid any nipple stimulation (from bathing, intercourse, or breastfeeding) beforehand to ensure it is not falsely elevated.

Case-by-case: Testosterone and dehydroepiandrosterone (DHEA-S) if the patient has excess acne or hair growth. Consider 17-hydroxyprogesterone (17-OHP) if virilization is severe or testosterone has been normal in the past. Refer to gynecology if any of these come back abnormal. Testosterone levels >150ng/dl or DHEAS >700mcg/dl are suggestive of adrenal tumors and require follow up imagine (CT scan and a referral to endocrinology). If the 17-OHP level is between 200-1500ng/dl is strongly suggestive of CAH, you can order an ACTH stimulation test with the referral to speed things along. Day 3 estradiol may be helpful for possible POI patients who are also worried about infertility. Endometrial biopsy for patients with risk factors (age>35, obesity, diabetes, family history of colon or uterine cancer, tamoxifen use) if or if your suspicion is high and EMB is part of your practice.

Now you have what you need to complete a comprehensive initial evaluation for abnormal uterine bleeding. With our strategic line of questioning, you can determine if your patient is having regular but excessive bleeding, regular with intermentrsual bleeding, or irregular. Based on the characterization of the bleeding, you can now make smart decisions about which tests to order to elucidate if the source falls under one of 5 categories: structural, hormonal, inflammatory, bleeding disorder, or medication side effect.

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.

💡Want a printable version?

Support with a free subscription or upgrade for unlimited access to quick-reference flowsheets, checklists and to printable tools you can bring straight to clinic. Or purchase tools individually.