What causes breakthrough bleeding?

Causes of Breakthrough Bleeding

Breakthrough bleeding is most commonly caused by hormonal imbalances, particularly related to estrogen and progesterone levels, with specific mechanisms including estrogen withdrawal, sustained estrogen production, and progestin-related vascular changes.

Hormonal Causes

Hormonal Contraceptives

• Combined hormonal contraceptives (CHCs):

  • Occurs in approximately 10% of users 1
  • More common during the first 3 months of use, with 91% of cases occurring in this period 2
  • Lower doses of ethinyl estradiol (15-20 μg) are associated with longer time to establish regular bleeding patterns compared to higher doses (30 μg) 3
  • Typically resolves within 3 months at higher estrogen doses 3

• Progesterone-only pills (POPs):

  • Higher incidence of breakthrough bleeding (approximately 40% of users) compared to CHCs 1
  • Progestins can cause vascular changes in the endometrium similar to those seen in women using long-term, low-dose progestogen-only contraceptives 4

Hormone Replacement Therapy (HRT)

• Common problem in postmenopausal women taking HRT 4
• Often the most important factor deterring women from continuing or starting HRT 4
• Typically occurs when progestin is added to estrogen therapy, usually 2-3 years after starting pubertal induction with estrogen 5

Pathophysiological Mechanisms

Estrogen-Related Mechanisms

1. Estrogen withdrawal bleeding:

   • Occurs when estrogen levels suddenly drop 6
   • Common in cyclic hormonal regimens

2. Estrogen breakthrough bleeding:

   • Results from inappropriately sustained estrogen production 6
   • Common in women with chronic anovulation 6
   • Can lead to endometrial hyperplasia if untreated 6

Progestin-Related Mechanisms

• Progestins affect endometrial vasculature, which can lead to fragility and subsequent bleeding 4
• In hereditary angioedema patients, progestins have been shown to affect Factor XII, kallikrein, and kinin concentrations, which may influence bleeding patterns 5

Other Causes

Pregnancy-Related

• Placental abnormalities:
  • Placenta previa (affects approximately 1 in 200 pregnancies) 5
  • Placental abruption (affects approximately 1% of pregnancies) 5
  • Vasa previa (affects approximately 1 in 2,500 to 1 in 5,000 deliveries) 5

Pathological Causes

• Endometrial polyps
• Cervical lesions (cervicitis, cervical polyps)
• Uterine fibroids (leiomyomas) 7
• Adenomyosis 7
• Endometrial or myometrial malignancies 7

Bleeding Disorders

• Bleeding disorders of unknown cause (BDUC) can present with abnormal uterine bleeding despite normal standard laboratory tests of hemostasis 5
• Inherited platelet function defects 5

Diagnostic Approach

Initial Evaluation

• Assess bleeding pattern: timing, duration, amount, and associated symptoms
• Evaluate for pregnancy in women of reproductive age
• Consider transvaginal ultrasound as first-line imaging with 90-99% sensitivity for detecting uterine abnormalities 7
• MRI when ultrasound is inconclusive, particularly for differentiating adenomyosis from leiomyomas 7

Laboratory Assessment

• Complete blood count to assess for anemia
• Coagulation studies (PT, aPTT) to rule out bleeding disorders 5
• Hormonal evaluation when appropriate

Management Considerations

For Hormonal Contraceptive-Related Bleeding

• Consider changing to a higher estrogen dose formulation if using low-dose products 3
• If using progesterone-only methods, consider switching to combined hormonal contraceptives to reduce breakthrough bleeding (from 40% to 10%) 1
• Reassurance that bleeding typically improves after 3 months of use 2

For Hormone Replacement Therapy

• For postmenopausal women on HRT with endometrial hyperplasia concerns, adding progesterone is essential (200 mg per day for 12 days per 28-day cycle) 8
• For breakthrough bleeding during anticoagulant therapy, evaluate for underlying causes and consider switching to LMWH over DOAC therapy 5

For Bleeding Disorders

• Tranexamic acid is favored for prophylaxis for minor/major surgeries and during pregnancy in patients with bleeding disorders 5

Important Caveats

• Breakthrough bleeding in postmenopausal women must always be appropriately evaluated due to increased risk of endometrial adenocarcinoma 4
• Persistence of breakthrough bleeding beyond 3-6 months of hormonal therapy warrants further investigation
• Breakthrough bleeding is a major reason for discontinuation of hormonal therapies, with approximately 25% of women stopping pill use due to this side effect 1
• In certain cultural or religious contexts, breakthrough bleeding may have significant implications for adherence to contraception 1

Remember that while breakthrough bleeding is often benign and related to hormonal fluctuations, it can sometimes signal underlying pathology that requires thorough evaluation.