Why do aromatase inhibitors (anastrozole or letrozole) cause joint pain?

If you are being treated for breast cancer with Aromatase inhibitors like Anastrozole or Letrozole, you may experience joint pain or stiffness. This is known as "aromatase inhibitor-associated arthralgia," and it is a common side effect. While these medications play a crucial role in reducing the risk of cancer recurrence, the discomfort can affect quality of life, making it important to understand why it happens and how to manage it effectively.

Aromatase inhibitors work by blocking the enzyme aromatase, which is responsible for converting androgens into estrogen in postmenopausal women. By lowering estrogen levels, Aromatase inhibitors reduce the growth stimulus for estrogen receptor-positive breast cancers. However, estrogen is also essential for joint and bone health.

The exact reasons Aromatase inhibitors cause joint pain and stiffness are not completely understood, but several theories exist:

  • Reduced estrogen impact: Estrogen helps maintain the balance of inflammation in the body and contributes to the health of cartilage and connective tissue in joints. Lower estrogen levels from AIs may increase inflammation, leading to joint pain and stiffness.
  • Changes in joint fluid: Estrogen also helps maintain lubrication in the joints. Reduced estrogen may lead to less joint fluid, resulting in stiffness and discomfort.
  • Nervous system sensitization: Some studies suggest that lower estrogen levels may make the body’s pain receptors more sensitive, leading to heightened pain response in joints.


Joint pain related to Aromatase inhibitors typically starts within a few months of beginning treatment, although it can appear at any time during therapy. For some people, symptoms are mild, while for others, they can be more pronounced, affecting the fingers, wrists, knees, hips, and other joints. Patients often report that the stiffness is worse in the morning or after periods of inactivity.

While joint symptoms are more likely to appear early in the treatment, they may improve over time, although this varies from person to person.

The duration of joint pain can vary. Some patients may experience relief over time as their body adjusts to the medication. However, for others, symptoms may persist for as long as they are taking the Aromatase inhibitors. In some cases, symptoms may linger even after discontinuing the medication but typically decrease in intensity over time.