What is the role of Arimadex (anastrozole) in Hormone Replacement Therapy (HRT) with testosterone?

Anastrozole (Arimadex) in Hormone Replacement Therapy with Testosterone

Anastrozole is not recommended for routine use in testosterone-based hormone replacement therapy (HRT) as there are no established guidelines supporting its use in this context. 1

Mechanism of Action and Effects

• Anastrozole is a selective non-steroidal aromatase inhibitor that works by inhibiting the enzyme aromatase, which converts androgens (primarily androstenedione and testosterone) to estrogens 2
• In postmenopausal women, anastrozole significantly lowers serum estradiol concentrations by approximately 70% within 24 hours and by approximately 80% after 14 days of daily dosing 2
• In men, anastrozole can increase endogenous testosterone production while decreasing estradiol levels, maintaining estradiol within the normal male range 3

Approved Indications vs. Off-Label Use

• Anastrozole is FDA-approved for:

  • Breast cancer treatment in postmenopausal women 2
  • Breast cancer risk reduction in postmenopausal women at increased risk 1

• Anastrozole is NOT approved for:

  • Management of estrogen levels in patients on testosterone therapy 1
  • Use in premenopausal women for hormone management 1

Evidence in Male Hormone Management

• Studies have shown that anastrozole (1 mg daily) can increase bioavailable testosterone from 99±31 to 207±65 ng/dl in elderly men with low testosterone levels 3
• Total testosterone levels increased from 343±61 to 572±139 ng/dl with daily anastrozole treatment in elderly men 3
• Serum estradiol levels decreased from 26±8 to 17±6 pg/ml with anastrozole treatment, remaining within the normal male range 3
• In subfertile hypoandrogenic men, anastrozole improved endocrine parameters in approximately 95% of treated patients 4

Side Effects and Safety Considerations

• Common side effects of anastrozole include:

  • Joint stiffness and arthralgias (reported in 35.6% of patients) 5, 6
  • Bone loss and increased risk of fractures 6
  • Vasomotor symptoms (hot flashes, night sweats) 6
  • Hypertension 6
  • Dry eyes 6
  • Hypercholesterolemia 6

• Short-term administration of anastrozole in elderly men with mild hypogonadism does not appear to adversely affect:

  • Lipid profiles 7
  • Inflammatory markers of cardiovascular risk 7
  • Insulin resistance 7

Monitoring Recommendations

• Prior to initiating anastrozole:

  • Evaluate baseline fracture risk 1
  • Measure bone mineral density 1
  • Use caution in patients with moderate bone mineral density loss 1

• During treatment:

  • Monitor testosterone levels 1
  • Monitor hematocrit 1
  • Monitor liver function 1
  • Consider bone density monitoring 6

Clinical Considerations

• Anastrozole should not be used in premenopausal individuals as it does not adequately suppress ovarian estrogen synthesis 5
• History of osteoporosis or severe bone loss is a relative contraindication for anastrozole use 1
• All patients receiving aromatase inhibitors should be encouraged to exercise regularly and take adequate calcium and vitamin D supplements 6
• For patients with moderate loss of bone mineral density, consider using bone-protective agents such as bisphosphonates 6

Conclusion for Clinical Practice

• While anastrozole can effectively increase testosterone levels in men with low testosterone, its use in testosterone-based HRT should be limited to specific clinical scenarios where estrogen-related side effects are problematic 3
• The decision to use anastrozole should be based on careful consideration of the risk-benefit profile, particularly regarding bone health 6, 1
• Regular monitoring of hormone levels and potential side effects is essential when anastrozole is used off-label for hormone management 1