Can anastrozole (aromatase inhibitor) be used in women to prevent estradiol conversion?

Can Anastrozole Be Used in Women to Prevent Estradiol Conversion?

Yes, anastrozole can be used in postmenopausal women to prevent estradiol conversion by inhibiting the aromatase enzyme, but it is absolutely contraindicated in premenopausal women. 1

Mechanism and Efficacy

Anastrozole is a selective non-steroidal aromatase inhibitor that blocks the conversion of adrenal androgens (androstenedione and testosterone) to estrone and estradiol in peripheral tissues. 2

• In postmenopausal women, anastrozole 1 mg daily reduces estradiol by approximately 70% within 24 hours and by 80% after 14 days of treatment. 2
• Suppression of serum estradiol is maintained for up to 6 days after cessation of therapy. 2
• Intratumoral estrogen levels are suppressed by 89% for estradiol, 83% for estrone, and 73% for estrone sulfate. 3
• Plasma estrogen levels are reduced by 84-94% with standard dosing. 3

Critical Menopausal Status Requirement

Premenopausal women should never receive anastrozole outside of clinical trials. 1

• Aromatization of adrenal androgens is not a significant source of estradiol in premenopausal women, so anastrozole would not effectively lower estradiol levels in this population. 2
• Anastrozole does not adequately suppress ovarian estrogen synthesis in women with functioning ovaries. 1
• Women who become amenorrheic with chemotherapy may still have continued ovarian estrogen production despite absent menses. 1
• Serial assessment of luteinizing hormone, follicle-stimulating hormone, and estradiol is mandatory to confirm true postmenopausal status before initiating anastrozole. 1

Approved Clinical Uses in Postmenopausal Women

Breast Cancer Risk Reduction

• Anastrozole 1 mg daily for 5 years should be discussed as an option to reduce invasive breast cancer risk in postmenopausal women at increased risk. 1
• Women most likely to benefit have atypical hyperplasia, LCIS, 5-year BCRAT risk ≥3%, or 10-year Tyrer-Cuzick risk ≥5%. 1

Adjuvant Breast Cancer Treatment

• Postmenopausal women with hormone receptor-positive early breast cancer should receive an aromatase inhibitor as initial adjuvant therapy, sequential with tamoxifen, or as extended therapy. 1

Mandatory Pre-Treatment Evaluation

Before initiating anastrozole, clinicians must evaluate baseline fracture risk and measure bone mineral density. 1, 4

• Women with severe osteoporosis (T-score <-4 or more than two vertebral fractures) should not receive anastrozole. 1, 4
• Use anastrozole with caution in postmenopausal women with moderate bone mineral density loss. 1
• Consider bone-protective agents such as bisphosphonates or RANKL inhibitors if anastrozole is used in women with moderate bone loss. 1, 4

Essential Bone Protection Strategy

All patients receiving anastrozole require comprehensive bone protection: 1, 4

• Calcium and vitamin D supplementation is mandatory. 1, 4
• Regular weight-bearing exercise should be encouraged. 1, 4
• Anastrozole significantly increases fracture risk compared to tamoxifen (7.1% vs 4.1% after 37 months). 1
• Increased bone resorption markers and decreased spine and hip BMD occur with anastrozole treatment. 1

Common Side Effects to Counsel Patients About

Patients must be informed of the following adverse effects: 1, 4

• Joint stiffness and arthralgias (very common) 1, 4
• Vasomotor symptoms (hot flashes) 1, 4
• Hypertension 1, 4
• Dry eyes and vaginal dryness 1, 4
• Gastrointestinal disturbances (29-33% incidence, generally mild and transient) 5

Critical Pitfall to Avoid

Never prescribe anastrozole to premenopausal women for breast cancer risk reduction or treatment outside of clinical trials. 1 The drug is ineffective in this population because ovarian estrogen production remains the primary source of circulating estradiol, which anastrozole cannot adequately suppress. 2