What are the causes and treatment options for a woman of reproductive age experiencing intermenstrual bleeding (bleeding between periods)?

Intermenstrual Bleeding in Reproductive-Age Women

For a woman of reproductive age experiencing bleeding between periods, first rule out pregnancy, then systematically evaluate for structural causes (polyps, fibroids, adenomyosis, malignancy) and non-structural causes (contraceptive-related, coagulopathy, ovulatory dysfunction, STDs) using the PALM-COEIN classification system, with transvaginal ultrasound as the primary imaging modality. 1, 2

Initial Assessment and Diagnostic Workup

Pregnancy testing is mandatory in all reproductive-age women presenting with intermenstrual bleeding to exclude pregnancy-related causes before proceeding with further evaluation. 1, 2

Key History Elements to Obtain:

• Contraceptive use: Intermenstrual bleeding is common with hormonal contraceptives, particularly during the first 3-6 months of use or with inconsistent pill-taking. 3
• Bleeding pattern: Assess frequency, duration, regularity, and volume using FIGO System 1 descriptors. 4
• Medication history: Check for anticoagulants, antiplatelet agents, or drug interactions that may contribute to bleeding. 3
• Sexual history: Post-coital bleeding warrants testing for Chlamydia trachomatis and other STDs. 3
• Risk factors for endometrial cancer: Age, obesity, diabetes, hypertension, unopposed estrogen exposure, tamoxifen use, Lynch syndrome. 2

Physical Examination:

• Speculum examination to visualize the cervix and vagina, excluding cervical or vaginal sources of bleeding. If a visible ulcerating or fungating lesion is present, urgent referral for malignancy evaluation is required. 3, 2
• Bimanual examination to assess uterine size, contour, mobility, and adnexal masses. 2

Laboratory and Imaging Studies:

• Complete blood count to assess for anemia from chronic blood loss. 2
• Thyroid-stimulating hormone and prolactin levels to evaluate for endocrine causes. 2
• Coagulation studies if coagulopathy is suspected (particularly in adolescents with heavy bleeding since menarche). 1
• Transvaginal ultrasound with Doppler is the first-line imaging study to identify structural causes including polyps, adenomyosis, leiomyomas, and endometrial hyperplasia/malignancy. 1, 2
• Saline infusion sonohysterography has 96-100% sensitivity and 94-100% negative predictive value for uterine pathology and can distinguish between leiomyomas and polyps with 97% accuracy. 2

Classification Using PALM-COEIN System

The PALM-COEIN framework systematically categorizes causes: 1, 2, 4

Structural Causes (PALM):

• Polyp: Common in women over 40, diagnosed via ultrasound or hysteroscopy. 2
• Adenomyosis: Frequently coexists with fibroids, presents with dysmenorrhea and dyspareunia, common in women in their 40s. 1, 2
• Leiomyoma (fibroids): Most common structural cause in women under 40 with heavy menstrual bleeding. 2
• Malignancy/hyperplasia: Most serious etiology, particularly in postmenopausal women; endometrial thickness <4mm on ultrasound has nearly 100% negative predictive value for cancer. 2

Non-Structural Causes (COEIN):

• Coagulopathy: Consider in adolescents or women with lifelong heavy bleeding. 1
• Ovulatory dysfunction: Common in adolescents (immature hypothalamic-pituitary-ovarian axis) and perimenopausal women. 5
• Endometrial: Primary endometrial disorders affecting hemostasis. 2
• Iatrogenic: Hormonal contraceptives, IUDs, anticoagulation therapy (approximately 70% of women on anticoagulation experience heavy bleeding). 2

Management Based on Etiology

For Contraceptive-Related Intermenstrual Bleeding:

If the patient is using hormonal contraceptives and experiencing unscheduled bleeding, first assess for inconsistent use, drug interactions, or smoking, then provide reassurance that bleeding typically decreases after 3-6 months of use. 3

• Rule out underlying gynecological problems: STDs, pregnancy, new pathologic uterine conditions (polyps, fibroids). 3
• If no underlying problem is found and treatment is desired:
  • NSAIDs for 5-7 days during bleeding episodes. 3
  • Short-term hormonal treatment with low-dose combined oral contraceptives or estrogen for 10-20 days (if medically eligible). 3
  • For extended/continuous combined hormonal contraceptive users: Consider a 3-4 day hormone-free interval (not during first 21 days, not more than once monthly). 3

For Non-Contraceptive-Related Intermenstrual Bleeding:

Intermenstrual bleeding in women not using oral contraceptives is usually due to structural or inflammatory lesions and requires investigation with transvaginal ultrasound. 5

• Test for Chlamydia trachomatis and treat if positive, particularly if post-coital bleeding is present. 3
• If structural lesions are identified: Refer to gynecology for hysteroscopy, polypectomy, or other surgical management. 2
• If ovulatory dysfunction is diagnosed:
  • Combined hormonal contraceptives are effective for ovulatory dysfunction bleeding. 1
  • Oral progestins for 21 days per month reduce menstrual blood loss in women with cyclic heavy bleeding. 1
  • Levonorgestrel-releasing IUD reduces menstrual blood loss by 71-95% and is the most effective first-line medical treatment. 1, 6

Special Populations and Contraindications

Women with Cardiovascular Disease or Hypertension:

• Avoid NSAIDs and tranexamic acid due to increased risk of MI and thrombosis. 1, 6
• Progestin-only contraceptives are first-line as they show no increased cardiovascular risk. 6
• Combined hormonal contraceptives are absolutely contraindicated due to 6-9 fold increased MI risk and 8-15 fold increased stroke risk. 6
• Levonorgestrel IUD is preferred due to minimal systemic absorption and high efficacy. 1, 6

Women on Antiplatelet Therapy:

• Reassess indication for ongoing antiplatelet therapy and discontinue if appropriate before initiating treatment. 1
• Progestin-eluting IUDs are preferred due to minimal systemic absorption. 1

When to Refer to Gynecology

Refer to gynecology for: 2

• Failed medical management
• Endometrial sampling showing hyperplasia or malignancy
• Postmenopausal bleeding with endometrial thickness ≥4mm
• Persistent bleeding despite treatment requiring hysteroscopy to diagnose focal lesions potentially missed by endometrial sampling

Common Pitfalls to Avoid

• Do not perform unscheduled Pap smears outside the screening program for evaluation of intermenstrual bleeding. 3
• Do not rely on endometrial biopsy alone to rule out focal lesions, as it has variable sensitivity. 1
• Do not normalize heavy menstrual bleeding or iron deficiency, as both adversely impact quality of life, cognitive function, and work/school performance. 7
• Ensure adequate diagnostic workup per PALM-COEIN classification before attributing bleeding to ovulatory dysfunction. 6