Does Femara (Letrozole) Cause Carpal Tunnel Syndrome?
Yes, Femara (letrozole) can cause carpal tunnel syndrome, as documented in FDA post-marketing surveillance reports, though the exact incidence rate is not well-established. 1
Evidence from FDA Drug Label
The FDA label for letrozole explicitly lists carpal tunnel syndrome and trigger finger as identified adverse reactions during post-approval use, though these reactions are reported voluntarily from a population of uncertain size, making it difficult to reliably estimate their frequency. 1
Comparative Evidence from Aromatase Inhibitor Class
While direct large-scale trial data for letrozole specifically is limited, substantial evidence exists for other aromatase inhibitors in the same drug class:
Anastrozole (another aromatase inhibitor) caused carpal tunnel syndrome in 2.6% of patients compared to 0.7% with tamoxifen in the ATAC trial after 100 months of follow-up (P < .0001). 2
Anastrozole in the prevention trial showed 3.4% incidence versus 1.6% with placebo (odds ratio 2.16, P < .001), with surgical intervention required in 0.9% versus 0.3% (odds ratio 3.06, P = .018). 3
Exemestane (a steroidal aromatase inhibitor like letrozole) caused carpal tunnel syndrome in 2.8% of patients versus 0.6% with tamoxifen (odds ratio 5.23, P < .0001), with 69% of affected patients requiring surgical release. 4
Clinical Characteristics of Aromatase Inhibitor-Induced CTS
Most cases occur early in treatment and are of mild to moderate intensity. 2
Approximately 46-53% of cases are bilateral, and surgical release may be necessary in the majority of symptomatic cases. 4
The condition can greatly affect daily-life activities in approximately 36% of cases. 4
Very few patients discontinue treatment due to carpal tunnel syndrome alone. 4, 2
Risk Factors for AI-Induced CTS
Beyond aromatase inhibitor use itself, additional risk factors include:
High body mass index is significantly associated with increased CTS risk. 3
Prior hormone replacement therapy use increases risk (P = .007). 2
Prior chemotherapy increases risk (P = .01). 2
Musculoskeletal symptoms reported after trial entry predict higher CTS risk. 3
Younger age (under 60 years) is associated with higher risk compared to older patients. 2
Clinical Implications
Monitor patients on Femara for symptoms of median nerve compression, including pain, paresthesias, and weakness in the thumb, index finger, middle finger, and radial half of the ring finger. 5 Classic examination findings include positive Phalen maneuver, median nerve compression test, and the "flick sign." 5
Initial conservative management should include nocturnal wrist splinting in neutral position, which is effective for symptoms that worsen at night. 6, 5 Local corticosteroid injection can provide relief for more than one month and delay the need for surgery. 5
Surgical decompression should be offered if symptoms are severe at presentation or if conservative therapy fails after 4-6 months. 5 Endoscopic and open techniques are equally effective, though patients return to work approximately one week earlier with endoscopic repair. 5
Common Pitfall
Do not assume that musculoskeletal symptoms, including carpal tunnel syndrome, indicate better cancer outcomes. While unadjusted analysis suggested improved disease-free survival, after adjustment for confounding factors, musculoskeletal symptoms were not independently associated with improved disease-free survival (HR 0.96, P = 0.67) or overall survival (HR 1.02, P = 0.82). 4