Is Irregular Bleeding Always Hormonal? What to Rule Out First

A Medical Exploration of Causes, Misconceptions, and Clinical Approach to Abnormal Uterine Bleeding
When a patient walks into your clinic with the complaint of irregular bleeding, the default assumption is often, “It’s probably hormonal.” While hormonal imbalances are indeed common—especially among adolescents, perimenopausal women, and those with polycystic ovary syndrome (PCOS)—not all irregular bleeding stems from disrupted endocrine signals.

In reality, abnormal uterine bleeding (AUB) can be the first clinical sign of a broad spectrum of conditions, ranging from uterine abnormalities and bleeding disorders to malignant or iatrogenic causes.

As clinicians, prematurely labeling the cause as “hormonal” may result in missed diagnoses, delayed interventions, and inappropriate hormonal treatment.

This article will clarify the clinical definition of irregular bleeding, present a structured overview of non-hormonal causes that must be ruled out first, and offer a rational, evidence-guided approach to managing AUB across various age groups.

1. Defining Irregular Bleeding: What Do Patients Actually Mean?

Patients use the term “irregular bleeding” imprecisely. Understanding their description is crucial.

They may be referring to:

• Menorrhagia: Excessive or prolonged periods
  
  
• Metrorrhagia: Bleeding between cycles
  
  
• Oligomenorrhea: Infrequent menstruation
  
  
• Polymenorrhea: Cycles shorter than 21 days
  
  
• Postcoital bleeding: Bleeding following intercourse
  
  
• Postmenopausal bleeding: Any vaginal bleeding after menopause
  

Step one in every case: clearly identify the bleeding pattern. Document cycle timing, flow duration, volume, associated symptoms, and how it affects quality of life.

2. PALM-COEIN Classification: A Systematic Framework

The FIGO classification for AUB in reproductive-aged women provides an excellent diagnostic scaffold.

Structural causes (PALM):

• Polyp
  
  
• Adenomyosis
  
  
• Leiomyoma
  
  
• Malignancy or hyperplasia
  

Non-structural causes (COEIN):

• Coagulopathy
  
  
• Ovulatory dysfunction
  
  
• Endometrial disorders
  
  
• Iatrogenic (drugs, devices)
  
  
• Not yet classified
  

When approaching AUB, remember: ovulatory dysfunction is only one among many causes.

3. Start with the Basics: Rule Out These First

Before attributing bleeding to hormonal imbalance, prioritize ruling out:

a) Pregnancy and complications
Pregnancy-related bleeding remains a crucial differential—even in “regular” cycles.

Includes:

• Ectopic pregnancy
  
  
• Threatened miscarriage
  
  
• Molar pregnancy
  

Order β-hCG testing in every reproductive-age female.

b) Structural abnormalities
Common structural causes:

• Uterine polyps: Intermenstrual or postcoital bleeding
  
  
• Submucosal fibroids: Heavy and prolonged periods
  
  
• Adenomyosis: Enlarged uterus, pain, heavy bleeding
  
  
• Endometrial hyperplasia or malignancy: Especially in women >45 or those with risk factors
  

First-line imaging: pelvic ultrasound. Hysteroscopy or biopsy if suspicion persists.

c) Cervical pathology
Consider:

• Cervicitis or sexually transmitted infections
  
  
• Cervical dysplasia or carcinoma
  
  
• Ectropion, especially with OCP use
  

Use: Speculum exam, Pap smear, cervical swabs.

d) Coagulopathies
Especially in:

• Adolescents with early menorrhagia
  
  
• Patients with easy bruising or family bleeding history
  

Suspect:

• Von Willebrand disease
  
  
• Platelet function abnormalities
  

Order: CBC, PT, aPTT, bleeding time, and Von Willebrand profile as needed.

4. When Is Irregular Bleeding Truly Hormonal?

Hormonal (ovulatory) causes are common—but must be a diagnosis of exclusion.

Scenarios suggestive of hormonal etiology:

• Adolescents post-menarche (immature HPO axis)
  
  
• Perimenopause with erratic anovulation
  
  
• PCOS-related chronic anovulation
  
  
• Hypothalamic dysfunction from stress or caloric deficit
  
  
• Thyroid disorders or hyperprolactinemia
  

Typical features:

• Infrequent cycles followed by heavy bleeding
  
  
• Lack of ovulatory signs
  
  
• Associated findings: acne, weight changes, hirsutism, galactorrhea
  

Investigations:

• TSH
  
  
• Prolactin
  
  
• FSH, LH, estradiol (if amenorrheic)
  
  
• Androgens and insulin (for PCOS)
  

5. Age-Based Differential Approach

Adolescents:

• Exclude bleeding disorders early
  
  
• Expect some anovulatory cycles initially
  
  
• Screen for PCOS if persistent >2 years
  

Reproductive-age women:

• Rule out pregnancy first
  
  
• Assess anatomy via ultrasound
  
  
• Consider medication effects or endocrine causes
  

Perimenopausal women:

• Anovulatory bleeding more likely
  
  
• Increased risk of hyperplasia or cancer
  
  
• Biopsy for frequent, heavy, or prolonged bleeding
  

Postmenopausal women:

• Any bleeding is abnormal
  
  
• Rule out malignancy or atrophy
  
  
• Endometrial thickness >4 mm warrants biopsy
  

6. Iatrogenic Causes: A Commonly Overlooked Factor

Medications often contribute to irregular bleeding. Culprits include:

• Hormonal contraceptives (especially new users or non-compliance)
  
  
• IUDs (initial bleeding phase)
  
  
• Anticoagulants (e.g., DOACs)
  
  
• SSRIs and antipsychotics (via prolactin changes)
  

Always inquire about:

• New or missed medications
  
  
• IUD insertion
  
  
• herbal remedies
  

7. What About Endometrial Causes?

Even in patients with ovulatory cycles and normal hormone profiles, local endometrial abnormalities can cause bleeding.

Examples:

• Dysregulated fibrinolysis
  
  
• Prostaglandin imbalances
  
  
• Vascular fragility
  

This diagnosis is often reached by exclusion. Therapeutic options: NSAIDs, tranexamic acid, or endometrial ablation.

8. Workup Summary: Practical Flow

When approaching any case of irregular bleeding:

• Define the specific bleeding pattern
  
  
• Exclude pregnancy
  
  
• Perform full pelvic and cervical assessment
  
  
• Order pelvic ultrasound
  
  
• Screen for infections when indicated
  
  
• Order TSH, prolactin, FSH/LH, and androgen panel
  
  
• Review medication history and life stressors
  
  
• Biopsy endometrium if age >45 or high-risk features
  

If all else is normal, a hormonal cause becomes more plausible.

9. When to Refer or Escalate

Refer to gynecology if:

• Suspicious imaging (complex masses, thick endometrium)
  
  
• Abnormal Pap smear
  
  
• Poor response to conservative treatment
  
  
• Need for hysteroscopy, D&C, or surgical intervention
  

Refer to hematology if:

• Recurrent bleeding with normal pelvic findings
  
  
• Family history of coagulopathy
  
  
• Abnormal hemostatic labs
  

10. Final Word: Don’t Let Hormonal Be a Lazy Diagnosis

“Hormonal” isn’t a standalone diagnosis—it’s one piece of a much broader puzzle.

Irregular bleeding could indicate anything from benign endocrine shifts to early-stage malignancy. Precision matters.

Before blaming hormones, ensure the uterus, cervix, endometrium, coagulation, and iatrogenic influences are evaluated—and don’t forget the possibility of pregnancy.

In clinical medicine, assumptions without investigation risk not just mismanagement but harm.