What are the side effects of anastazole (Aromatase Inhibitor)?

Side Effects of Anastrozole

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 among the most common and bothersome side effects, affecting 25-30% of patients:

• Joint stiffness and arthralgias occur frequently and are a leading cause of treatment discontinuation 1, 2
• Arthritis is reported in over 10% of patients 3
• Musculoskeletal pain appears related to the profound estrogen suppression caused by anastrozole 4, 5

Risk factors that increase likelihood of joint symptoms include: 6

• Previous hormone replacement therapy use (40.6% vs 28.4% without prior HRT)
• Obesity (BMI >30 kg/m²: 37.2% incidence)
• Prior chemotherapy exposure (37.8% vs 31.3% without chemotherapy)
• Hormone receptor-positive tumors

Bone Health Complications

Anastrozole significantly increases bone loss and fracture risk, which is the most serious quality-of-life threatening side effect:

• Decreased bone mineral density in both lumbar spine and hip occurs compared to baseline 1, 3
• Increased fracture risk, particularly of spine, hip, and wrist 1, 3
• Fracture rates are significantly higher than with tamoxifen (7.1% vs 4.1% after 37 months) 2
• Severe osteoporosis (T-score <-4 or >2 vertebral fractures) is a relative contraindication to anastrozole use 1

Mandatory bone protection measures include: 1, 2

• Baseline bone mineral density measurement before starting treatment
• Regular calcium and vitamin D supplementation
• Weight-bearing exercise
• Consider bisphosphonates or RANKL inhibitors in patients with moderate bone loss

Vasomotor Symptoms

Hot flashes and night sweats are very common:

• Occur in both anastrozole and tamoxifen users, though both drugs cause these symptoms 1
• Hot flashes are the most common reason for treatment discontinuation in clinical trials 3
• Vasomotor symptoms were significantly increased with anastrozole in the IBIS-II trial 1

Cardiovascular Effects

Hypertension is a notable side effect:

• Reported in >10% of patients 3
• Increased frequency of hypertension specifically noted with anastrozole 1

Regarding ischemic cardiovascular events: 3

• No statistical difference in overall population (4% anastrozole vs 3% tamoxifen)
• However, in women with pre-existing ischemic heart disease, angina pectoris occurred more frequently (11.6% vs 5.2% with tamoxifen)

Genitourinary and Ophthalmologic Effects

Vaginal dryness and dry eyes are common complaints:

• Both symptoms should be discussed before initiating therapy 1, 2
• Dyspareunia (painful intercourse) occurs more frequently with anastrozole than tamoxifen 1

Other Common Side Effects (>10% incidence)

3

• Asthenia (weakness)
• Pain (general and back pain)
• Depression
• Nausea and vomiting
• Rash
• Insomnia
• Headache
• Peripheral edema (leg/ankle swelling)
• Increased cough and dyspnea
• Pharyngitis
• Lymphedema (in affected arm after breast cancer surgery)

Rare but Serious Side Effects

The following require immediate medical attention: 3

• Skin reactions: lesions, ulcers, or blisters (stop drug immediately)
• Severe allergic reactions: facial/lip/tongue/throat swelling, difficulty swallowing or breathing
• Liver problems: jaundice, right upper quadrant pain, general malaise (stop drug and notify physician)

Metabolic Effects

• Increased blood cholesterol may occur, requiring monitoring 3
• Weight gain is reported, though less common than with megestrol 7

Critical Counseling Points

Before starting anastrozole, patients must understand: 1, 2

1. The drug only works in truly postmenopausal women—serial hormone testing may be needed to confirm menopausal status 2
2. Bone protection is mandatory, not optional
3. Joint symptoms are common but may improve with continued use or require switching to alternative endocrine therapy
4. Regular bone density monitoring is essential throughout treatment

Common pitfall to avoid: Do not use anastrozole in premenopausal women or those with treatment-induced amenorrhea where ovarian function cannot be reliably assessed, as the drug will be ineffective and expose patients to unnecessary side effects 1, 2