What are the side effects of Anastrazole (aromatase inhibitor)?

Anastrozole Side Effects

Anastrozole causes several important side effects that directly impact quality of life, with musculoskeletal symptoms and bone loss being the most clinically significant concerns requiring proactive monitoring and management. 1

Musculoskeletal Side Effects

Joint-related symptoms are the leading cause of treatment discontinuation and occur in 25-30% of patients. 1

• Joint stiffness, arthralgias, and arthritis are well-documented effects of anastrozole, appearing related to profound estrogen suppression 1, 2
• Arthralgia and myalgia occur more frequently with anastrozole compared to tamoxifen 3
• These symptoms may improve with continued use or require switching to alternative endocrine therapy 1

Bone Health Complications (Most Serious Quality-of-Life Threatening Effect)

Anastrozole significantly increases bone loss and fracture risk, with decreased bone mineral density occurring in both lumbar spine and hip compared to baseline. 1

• Fracture rates are significantly higher than with tamoxifen (7.1% vs 4.1% after 37 months) 1
• The FDA label confirms that anastrozole lowers estrogen levels, causing bones to become thinner and weaker, increasing fracture risk especially of spine, hip, and wrist 4
• Clinical trial data demonstrate mean decreases in lumbar spine and total hip BMD compared to baseline 4
• Severe osteoporosis (T-score <-4 or >2 vertebral fractures) is a relative contraindication to anastrozole use 1, 2

Mandatory Bone Protection Measures

All patients require baseline bone mineral density measurement before starting treatment, regular calcium and vitamin D supplementation, weight-bearing exercise, and consideration of bisphosphonates or RANKL inhibitors in patients with moderate bone loss. 1, 2, 4

Cardiovascular Effects

• Increased stroke risk compared to tamoxifen 3
• Hypertension is a common side effect 2, 4
• In women with pre-existing ischemic heart disease, the incidence of ischemic cardiovascular events was 17% with anastrozole versus 10% with tamoxifen 4

Vasomotor Symptoms

Hot flashes and night sweats are very common, occurring in both anastrozole and tamoxifen users, though vasomotor symptoms are significantly increased with anastrozole. 3, 1, 2

• Hot flashes are the most common adverse reaction leading to discontinuation of therapy 4

Genitourinary and Ophthalmologic Effects

Vaginal dryness and dry eyes are common complaints that should be discussed before initiating therapy. 1

• Dyspareunia (painful intercourse) occurs more frequently with anastrozole than tamoxifen 1
• Dry eyes are a recognized side effect 2, 4

Metabolic Effects

• Hypercholesterolemia occurs more frequently with anastrozole than tamoxifen 3, 2
• The FDA label recommends blood tests to check cholesterol during treatment 4

Other Common Side Effects

• Depression occurs in a significant proportion of patients 1, 4
• Peripheral edema (leg/ankle swelling) 1, 4
• Weakness (asthenia) 4
• Nausea and vomiting 4
• Headache 4
• Back pain 4
• Increased cough and shortness of breath 4
• Rash 4
• Gastrointestinal disturbances (29-33% incidence) 5

Serious But Rare Side Effects

Stop anastrozole immediately and seek medical attention for: 4

• Skin reactions including lesions, ulcers, or blisters
• Severe allergic reactions with swelling of face, lips, tongue, or throat causing difficulty swallowing or breathing
• Liver problems with symptoms including general feeling of not being well, yellowing of skin or eyes, or right-sided abdominal pain

Critical Counseling Points Before Starting Treatment

Patients must understand that: 1

• Anastrozole only works in truly postmenopausal women 1, 2
• Bone protection is mandatory, not optional 1, 2
• Joint symptoms are common but may improve with continued use 1
• The drug should not be taken with tamoxifen or other estrogen-containing medications as this causes antagonistic effects 4