In a 50‑year‑old woman with irregular uterine bleeding, an endometrial biopsy showing early proliferative endometrium and an endocervical biopsy showing cervicitis, what is the most likely cause and how should it be managed?

Perimenopausal Anovulatory Bleeding with Benign Histology

In this 50-year-old woman, the most likely cause is anovulatory bleeding due to perimenopausal hormonal instability, and management should focus on hormonal regulation with combined oral contraceptives or cyclic progestins after confirming the absence of structural lesions on transvaginal ultrasound. 1

Understanding the Clinical Picture

The combination of irregular bleeding, early proliferative endometrium, and cervicitis in a 50-year-old woman points strongly toward anovulatory cycles as the primary mechanism. 2, 3

• Early proliferative endometrium indicates estrogen stimulation without subsequent progesterone effect—the hallmark of anovulation—rather than malignancy or hyperplasia. 1
• Endocervical cervicitis is an incidental finding that may contribute to contact bleeding but does not explain the irregular uterine bleeding pattern. 3
• At age 50, this patient is in the perimenopausal window when declining and erratic ovarian function leads to unopposed estrogen exposure and irregular shedding. 2, 3

Diagnostic Confirmation Before Treatment

Before initiating hormonal therapy, transvaginal ultrasound combined with transabdominal imaging must be performed to exclude structural causes (polyps, fibroids, adenomyosis) that could be masked by hormonal treatment. 1, 4

• The American College of Radiology assigns TVUS the highest appropriateness rating (7–9) for evaluating abnormal uterine bleeding in this age group. 1
• If TVUS shows a focal lesion or endometrial thickness ≥10 mm, proceed to saline infusion sonohysterography (sensitivity 96–100%) to characterize polyps or submucous fibroids. 1, 4
• If the endometrium is thin and uniform on ultrasound, the benign biopsy result is reassuring and hormonal management can proceed. 1

Laboratory work-up should include:

• TSH and prolactin to identify reversible endocrine causes of anovulation. 4, 5
• Complete blood count and ferritin to assess for anemia and iron depletion from chronic blood loss. 5
• Pregnancy test (β-hCG) in all reproductive-age women, even at age 50. 4, 5

First-Line Medical Management

Combined hormonal contraceptives (CHCs) or cyclic progestins are the recommended first-line therapies for perimenopausal anovulatory bleeding. 2, 3, 6

Option 1: Combined Oral Contraceptives

• Use low-dose CHCs (20–35 mcg ethinyl estradiol) if the patient is a nonsmoker, normotensive, and has no history of thromboembolism, stroke, or migraine with aura. 2, 6
• CHCs provide contraception, cycle regulation, and endometrial protection against unopposed estrogen. 2, 6
• This is particularly appropriate for perimenopausal women who remain at risk of pregnancy. 2

Option 2: Cyclic Progestin Therapy

• Medroxyprogesterone acetate 10 mg daily for 10–14 days per month for at least 3–6 months is the standard regimen for women who cannot use estrogen. 2, 6, 7
• Cyclic progestin opposes estrogen-driven endometrial proliferation and establishes a predictable withdrawal bleed. 2, 7
• This approach is safer in women with cardiovascular risk factors or contraindications to estrogen. 2

Option 3: Levonorgestrel Intrauterine System

• The LNG-IUS is highly effective for reducing menstrual blood loss and provides long-term endometrial suppression. 2, 6, 8
• It is the most effective medical treatment for heavy menstrual bleeding and may induce amenorrhea. 6, 8

Management of the Cervicitis

• Treat the endocervical cervicitis based on infectious etiology if identified (e.g., chlamydia, gonorrhea). 3
• If no pathogen is identified, the cervicitis is likely reactive or inflammatory and does not require specific antimicrobial therapy. 3
• Cervicitis alone does not explain the irregular uterine bleeding pattern and should not delay hormonal management of anovulation. 3

When to Escalate Evaluation

Persistent bleeding despite appropriate medical therapy mandates further investigation. 1

• If bleeding continues after 3–6 months of hormonal treatment, perform hysteroscopy with directed biopsy to exclude focal lesions (polyps, submucous fibroids) missed by blind sampling. 1, 8
• Office endometrial biopsy has a 10% false-negative rate, so a negative result does not rule out pathology in symptomatic patients. 1
• Never accept a benign biopsy as definitive if symptoms persist—escalate to hysteroscopy or fractional D&C. 1

Surgical Options for Refractory Cases

If medical management fails or is not tolerated, consider:

• Endometrial ablation (second-generation techniques: thermal balloon, microwave, radiofrequency) for women who have completed childbearing. 1, 8
• Hysterectomy is the most definitive treatment and provides complete resolution of symptoms. 1, 2, 8

Critical Pitfalls to Avoid

• Do not initiate hormonal therapy without imaging to exclude structural causes that could be masked by treatment. 1, 4
• Do not assume the cervicitis explains the irregular bleeding—anovulation is the primary driver in this perimenopausal patient. 3
• Do not overlook anemia and iron deficiency—measure hemoglobin and ferritin even if the patient is asymptomatic. 5
• Do not accept a benign biopsy as reassuring if bleeding persists—the 10% false-negative rate mandates further evaluation. 1