What is the safest hormone therapy for a 45‑year‑old woman with a recent cerebrovascular accident who has abnormal uterine bleeding due to endometrial hyperplasia?

Safest Hormone Therapy in a 45-Year-Old with Recent Stroke and Abnormal Uterine Bleeding from Endometrial Hyperplasia

A levonorgestrel-releasing intrauterine device (LNG-IUD, 20 μg/day) is the safest hormone therapy option for this patient, as it provides local endometrial protection with minimal systemic absorption and avoids the stroke risk associated with systemic hormone therapy. 1

Critical Contraindication: Systemic Hormone Therapy After Stroke

Active stroke or history of stroke is an absolute contraindication to systemic estrogen-progestogen therapy. 2 The National Comprehensive Cancer Network explicitly identifies "active arterial thromboembolic disease, such as stroke or myocardial infarction, or history of these conditions" as an absolute contraindication to systemic progesterone therapy. 2 The American Heart Association stroke prevention guidelines confirm that a history of stroke contraindicates hormone replacement therapy. 1

For every 10,000 women taking combined estrogen-progestin for one year, there are 8 additional strokes, and this risk emerges within the first 1–2 years of therapy. 3 In women with prior stroke, the recurrence risk is unacceptably high with systemic hormones. 1

Recommended Treatment: Levonorgestrel-Releasing IUD

Primary Evidence for LNG-IUD Safety

The American Heart Association's scientific statement on spontaneous coronary artery dissection (SCAD) provides the most relevant guidance for managing abnormal uterine bleeding in women with recent cardiovascular events. Among medical therapies for heavy menstrual bleeding, progestin-eluting intrauterine devices such as the levonorgestrel 20 μg/day-releasing device may be useful for controlling bleeding and protect against pregnancy. 1

Systemic progesterone levels increase minimally with these intrauterine devices, but the main effect is at the endometrial level. 1 This local action is critical for a patient with recent stroke, as it avoids the systemic thrombotic risks of oral or transdermal hormones.

Efficacy for Endometrial Hyperplasia

The levonorgestrel 20 μg/day-releasing device is the most effective approach (comparable to the efficacy of endometrial ablation), resulting in 71% to 95% reduction in menstrual blood loss. 1 It is the only progestin intrauterine device that has been evaluated specifically for treatment of abnormal uterine bleeding. 1

For endometrial hyperplasia specifically, the ESMO endometrial cancer guidelines note that progestin-loaded IUD is an option for fertility-sparing therapy in endometrial conditions. 1 While these guidelines focus on early endometrial cancer, the same local progestin effect provides robust endometrial protection in hyperplasia.

Advantages Over Systemic Progestins

Oral progestins (medroxyprogesterone acetate or micronized progesterone) would typically be first-line for endometrial hyperplasia, but systemic progesterone therapy carries the same stroke contraindication as estrogen. 2 The National Comprehensive Cancer Network explicitly lists "active arterial thromboembolic disease, such as stroke" as an absolute contraindication to progesterone therapy. 2

Cyclic oral progestin treatment reduces bleeding by 87% 1, but this requires systemic absorption that poses unacceptable stroke risk in this patient. The LNG-IUD achieves comparable efficacy without systemic exposure.

Alternative Consideration: Endometrial Ablation

If the LNG-IUD is not tolerated or fails to control bleeding, second-generation endometrial ablation techniques (thermal balloon, microwave, radiofrequency) may be considered. 1 The American Heart Association notes that "the long-term efficacy of conservative surgical treatment for heavy menstrual bleeding such as second-generation endometrial ablation techniques is greater than that of oral medical treatment." 1

Advantages of ablative procedures include effectiveness in managing bleeding, reduction of pregnancy risk, and the ability to perform the procedure without systemic hormone exposure. 1 This is particularly relevant for patients with cardiovascular contraindications to hormones.

Treatments to Avoid

Systemic Estrogen-Progestogen Therapy

Absolutely contraindicated. History of stroke is an absolute contraindication to combined hormone therapy. 1, 2, 3

Oral or Injectable Progestins

High-dose oral or injectable progestin-only medications may be considered for the short term in hemodynamically unstable women 1, but for ongoing management, systemic progestins carry stroke risk. 2 The patient's recent stroke makes even progestin-only systemic therapy relatively contraindicated.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

Nonhormonal, noncontraceptive options such as nonsteroidal anti-inflammatory drugs should generally be avoided in women with cardiovascular disease given their association with MI and thrombosis. 1

Tranexamic Acid

Tranexamic acid should generally be avoided given its association with thrombosis. 1 This is particularly important in a patient with recent stroke.

Monitoring and Follow-Up

After LNG-IUD insertion:

• Assess bleeding pattern at 3 and 6 months to confirm adequate control. 1
• Endometrial sampling is not routinely required with the LNG-IUD unless breakthrough bleeding develops, as the local progestin effect provides robust endometrial protection. 1
• Monitor for IUD expulsion or displacement, which occurs in approximately 5% of users in the first year.

Clinical Algorithm

1. Confirm stroke history and timing – Recent stroke is an absolute contraindication to systemic hormones. 1, 2
2. Assess severity of bleeding – If hemodynamically unstable, consider urgent gynecologic consultation for possible ablation or hysterectomy. 1
3. Insert levonorgestrel 20 μg/day IUD as first-line therapy for stable patients. 1
4. If LNG-IUD fails or is not tolerated → Consider endometrial ablation. 1
5. If ablation fails or patient desires definitive treatment → Hysterectomy may be appropriate. 1

Common Pitfalls to Avoid

• Do not prescribe oral micronized progesterone or medroxyprogesterone acetate despite their efficacy for hyperplasia, as stroke history contraindicates systemic progestins. 2
• Do not assume "progestin-only" therapy is safe after stroke – the National Comprehensive Cancer Network explicitly contraindicates systemic progesterone in patients with history of stroke. 2
• Do not delay treatment – Untreated endometrial hyperplasia can progress to cancer, and the LNG-IUD provides immediate local therapy without systemic risk. 1
• Do not use combined oral contraceptives – These contain estrogen and are absolutely contraindicated. 1, 2