How should a reproductive‑age woman with regular menstrual cycles, light pink vaginal spotting two weeks before her expected period, no hormonal contraception, no intercourse‑related bleeding, and an overdue Pap smear be evaluated and managed?

Evaluation and Management of Mid-Cycle Spotting in a Reproductive-Age Woman

This patient requires a pregnancy test first, followed by cervical cancer screening (overdue Pap smear), and if both are negative with no other concerning features, reassurance that mid-cycle spotting is likely ovulatory bleeding and does not require treatment. 1

Immediate Diagnostic Steps

Mandatory First Test

• Obtain a urine β-hCG pregnancy test immediately to exclude pregnancy-related complications such as implantation bleeding, threatened miscarriage, or ectopic pregnancy, even though she denies hormonal contraception use. 1

Cervical Screening (Overdue)

• Perform Pap smear with HPV co-testing now, as her last screening was 1 year ago and current guidelines recommend screening every 3 years for cytology alone or every 5 years for co-testing in women aged 30-65. 1
• Cervical pathology (dysplasia, polyps, or malignancy) can present as intermenstrual spotting and must be excluded. 1

Additional Laboratory Evaluation

• Screen for sexually transmitted infections (gonorrhea and chlamydia) because pelvic inflammatory disease can cause intermenstrual bleeding even without post-coital symptoms. 1
• Measure thyroid-stimulating hormone and prolactin levels to rule out thyroid disease or hyperprolactinemia that may cause anovulation and irregular bleeding patterns. 1
• Coagulation studies are not indicated in this case because she describes only light spotting (not soaking through pads), no clots, and unchanged regular menstrual flow—none of which suggest heavy menstrual bleeding or an underlying bleeding disorder. 2, 3

Differential Diagnosis Using PALM-COEIN Classification

The PALM-COEIN system differentiates structural from non-structural causes of abnormal uterine bleeding. 1, 4

Structural Causes (PALM)

• Polyps: Endometrial polyps may produce irregular intermenstrual bleeding. 1
• Leiomyoma (fibroids): Can cause intermenstrual spotting, though typically associated with heavier flow. 1
• Malignancy/Hyperplasia: Rare in reproductive-age women with regular cycles but must be excluded via Pap smear. 1

Non-Structural Causes (COEIN)

• Ovulatory dysfunction: The most likely diagnosis in this patient is mid-cycle ovulatory bleeding, which occurs in up to 5% of women with regular cycles due to the estrogen drop at ovulation. 4, 5
• Coagulopathy: Excluded by the absence of heavy bleeding, clots, or flooding. 1, 2
• Endometrial disorders: Primary endometrial hemostatic defects are unlikely given the minimal bleeding volume. 1
• Iatrogenic causes: She denies hormonal contraception or other medications. 1

Imaging Considerations

• Transvaginal ultrasound is NOT indicated at this initial visit unless the pelvic examination reveals abnormalities, she has risk factors for structural pathology (obesity, chronic anovulation), or symptoms persist despite reassurance. 1
• If ultrasound becomes necessary and findings are inconclusive, saline-infusion sonohysterography has 96-100% sensitivity for detecting intracavitary lesions. 1, 4

Management Algorithm

If Pregnancy Test and Pap Smear Are Negative

Reassurance is the primary intervention for mid-cycle ovulatory spotting in a woman with otherwise regular cycles and no concerning features. 1, 5

• Explain that light pink spotting 2 weeks before menses (mid-cycle) is physiologic ovulatory bleeding caused by transient estrogen withdrawal at ovulation and does not indicate pathology. 4, 5
• No medical treatment is required unless the patient finds the spotting bothersome or it increases in volume. 1

If Patient Desires Treatment Despite Benign Etiology

• First-line: NSAIDs (ibuprofen, naproxen, or mefenamic acid 500 mg three times daily) for 5-7 days during spotting episodes can reduce bleeding by 20-60%. 1
• Second-line: Combined oral contraceptives (30-35 µg ethinyl estradiol with levonorgestrel or norgestimate) suppress ovulation and eliminate mid-cycle bleeding. 1, 4
• Avoid aspirin, as it may paradoxically increase menstrual bleeding. 1

If Spotting Persists or Worsens After 3-6 Months

• Obtain transvaginal ultrasound to evaluate for structural pathology (polyps, fibroids, endometrial thickening). 1, 4
• Reassess for underlying gynecological problems including new STD exposure, medication interactions, or pathologic uterine conditions. 6, 1

Red-Flag Indicators Requiring Urgent Further Investigation

• Persistent pelvic pain despite adequate NSAID therapy. 1
• Dyspareunia or non-cyclic pelvic pain. 1
• Abnormal findings on pelvic examination (cervical motion tenderness, adnexal masses, cervical lesions). 1
• Heavy menstrual bleeding requiring pad/tampon change every 1-2 hours, or clots ≥1 inch diameter. 1, 2
• Abrupt change from regular cycles to amenorrhea or significantly heavier flow. 6, 1

Common Pitfalls to Avoid

• Do not assume structural pathology is absent without performing the overdue Pap smear and pelvic examination. 1
• Do not initiate hormonal therapy before excluding pregnancy—this is a mandatory first step. 1, 4
• Do not order extensive coagulation studies for light spotting in a woman with normal regular menses and no personal or family history of bleeding disorders. 2, 3
• Do not perform endometrial biopsy in a reproductive-age woman with regular cycles and light intermenstrual spotting unless specific risk factors are present (obesity, chronic anovulation, failure of medical therapy). 4

Follow-Up

• No routine follow-up visit is required if pregnancy test and Pap smear are negative and the patient is reassured. 6
• Advise the patient to return if spotting increases in volume, becomes associated with pain, occurs after intercourse, or if her regular menstrual pattern changes. 6, 1