What is an alternative to transdermal estradiol for managing menopausal symptoms in a 40-year-old white female with surgical menopause?

When Veozah Would Be Used Instead of Transdermal Estradiol in a 40-Year-Old with Surgical Menopause

Veozah (fezolinetant) should NOT be used as first-line therapy in this patient—transdermal estradiol is the appropriate treatment for a 40-year-old with surgical menopause unless absolute contraindications to estrogen exist. 1, 2

Why Estrogen Therapy is Preferred in This Patient

Age and Timing Considerations

• Women with surgical menopause before age 45-50 should start hormone replacement therapy immediately post-surgery and continue until at least the average age of natural menopause (51 years), then reassess 1
• The benefit-risk profile of HRT is most favorable for women under 60 or within 10 years of menopause onset 1, 3
• At age 40, this patient has 11 years until the average age of natural menopause, making estrogen therapy medically indicated for both symptom management and prevention of long-term health consequences 1

Health Consequences of Untreated Surgical Menopause

• Women with surgical menopause before age 45 have a 32% increased risk of stroke (95% CI, 1.43-2.07) compared to those with natural menopause at typical ages 1
• The accelerated decline in estradiol levels causes rapid rises in LDL cholesterol, declines in HDL cholesterol, and increases in blood pressure 1
• Estrogen supplementation provides a 27% reduction in nonvertebral fractures and prevents accelerated bone loss (2% annually in first 5 years post-menopause) 1

Optimal Estrogen Regimen for This Patient

• Transdermal estradiol 50 μg patch applied twice weekly is first-line therapy because it bypasses hepatic first-pass metabolism, reducing cardiovascular and thromboembolic risks compared to oral formulations 1, 4, 5
• Since she has no uterus (surgical menopause), estrogen-alone therapy can be used safely without progestin 1, 3
• Estrogen-alone therapy shows no increased breast cancer risk and may even be protective (RR 0.80) 1, 2

Absolute Contraindications When Veozah Would Be Considered

Veozah would only be appropriate if this patient has absolute contraindications to estrogen therapy, including: 1, 6

Cardiovascular Contraindications

• History of myocardial infarction or coronary heart disease 1, 6
• History of stroke 1, 6
• History of deep vein thrombosis or pulmonary embolism 1, 6
• Thrombophilic disorders 1, 6
• Spontaneous coronary artery dissection (SCAD) 6

Malignancy Contraindications

• History of breast cancer or hormone-sensitive malignancies 1, 6
• Known or suspected estrogen-dependent neoplasia 1, 6

Other Absolute Contraindications

• Active liver disease 1, 6
• Antiphospholipid syndrome or positive antiphospholipid antibodies 1, 6
• Unexplained abnormal vaginal bleeding 6

Critical Clinical Pitfalls to Avoid

Do Not Delay Estrogen Therapy

• Do not delay HRT initiation in women with surgical menopause before age 45 who lack contraindications—the window of opportunity for cardiovascular protection is time-sensitive 1
• Failing to initiate estrogen therapy in this young patient exposes her to unnecessary long-term cardiovascular, bone, and cognitive risks 1

Do Not Use Non-Hormonal Therapy as First-Line

• Non-hormonal alternatives (including Veozah) are second-line options reserved for patients with contraindications to estrogen 6, 3
• For a 40-year-old with surgical menopause, the benefits of estrogen therapy far exceed the risks in the absence of contraindications 1, 3

Smoking Consideration

• If this patient smokes, smoking cessation is the single most important intervention for reducing cardiovascular risk 1
• Smoking in women over age 35 significantly amplifies cardiovascular and thrombotic risks with HRT, though at age 40 with surgical menopause, the benefits of estrogen still typically outweigh risks if she can quit smoking 1

Algorithm for Decision-Making

1. Screen for absolute contraindications to estrogen therapy (cardiovascular disease, thromboembolism, hormone-sensitive cancer, active liver disease, antiphospholipid syndrome) 1, 6

2. If NO contraindications exist: Prescribe transdermal estradiol 50 μg patch twice weekly (estrogen-alone since no uterus) 1, 4

3. If absolute contraindications exist: Consider Veozah or other non-hormonal alternatives (SSRIs, gabapentin, cognitive behavioral therapy) 1, 6

4. Continue estrogen therapy until at least age 51, then reassess necessity and symptoms 1, 2

5. Annual clinical review focusing on compliance, ongoing symptom burden, and emergence of any new contraindications 1