Joint Pain from Aromatase Inhibitors

What is Aromatase Inhibitor Joint Pain?

Aromatase inhibitor joint pain, also called aromatase inhibitor-associated arthralgia, is joint pain and stiffness caused by this class of breast cancer medicine. Aromatase inhibitors lower estrogen in postmenopausal women with hormone receptor-positive breast cancer, and joint pain is one of their main side effects.^[1] Up to half of women taking them report joint pain.^[2]

Common symptoms

The pain is usually felt in several joints at once, often the hands, wrists and knees, together with stiffness.^{[2, 3]} Loss of hand grip strength, tendon and joint-lining changes, carpal tunnel symptoms and fluid in the joints have been reported in aromatase inhibitor users.^[3]

Joint symptoms are often a reason women stop taking the medicine early. Up to 20% stop taking it as prescribed because of the pain.^[2]

Causes and risk factors

Aromatase inhibitors (anastrozole, letrozole and exemestane) reduce estrogen, and the loss of estrogen is thought to be the underlying reason for the joint symptoms, although the exact pathway is unknown.^{[1, 3]} One hypothesis involves the growth hormone and insulin-like growth factor pathway, and in one study, grip strength loss differed with body mass index.^[3]

Because the causes are not fully understood, researchers have not established clear predictors of who will be affected.^[2]

How it is diagnosed and treated conventionally

Joint pain on an aromatase inhibitor is a clinical diagnosis made by your oncology team after other causes, such as arthritis, bone problems or cancer spread, have been considered. It is managed together with them.^[1] There is no established, effective standard treatment, and current advice includes lifestyle changes and pain-relieving medicines depending on how severe the symptoms are.^{[2, 4]}

Systematic reviews of the many strategies tried found no definitive evidence in favor of any single one, largely because of weaknesses in the studies.^[5]

Why Aromatase Inhibitor Joint Pain calls for a whole-person approach

This joint pain has a hormonal trigger but shows up in the joints and tendons and affects quality of life and whether women stay on treatment, so care that looks at only one of these may miss part of the picture.^{[2, 3]} For a condition like this, we ask that you are under a physician's care for it and that your treating team knows you are receiving complementary care.

Care that also addresses movement, body weight, bone health and the stress of cancer treatment can sit alongside what your oncology team prescribes.

Estrogen loss and the joints

Estrogen suppression is considered the root of the symptoms, and fluid retention and tendon-sheath changes have been described in affected joints.^[3] Exactly how this produces pain is not settled.^[2]

Movement and exercise

A review of exercise for this condition found that a mixed program of aerobic and resistance exercise was feasible and safe and may be of most benefit for joint pain, function and quality of life. Yoga was linked with better physical function and tai chi with better mental health. The review recommended larger trials, and the pain has no established treatment.^[4]

Bone health and other effects of estrogen loss

Aromatase inhibitors also cause bone mineral density loss, osteoporosis and fractures, as well as hot flashes, so joint pain is one of several effects that need monitoring.^[1] Your oncology team follows these.

Staying on treatment

Joint pain is a leading reason women stop aromatase inhibitors early, and stopping early could raise the chance of cancer recurrence.^{[2, 4]} Easing the pain is therefore not only a comfort measure but may help women continue their prescribed treatment.^[5]

Acupuncture for Aromatase Inhibitor Joint Pain

What the research shows

Acupuncture appears to give modest pain relief, and a network meta-analysis ranked it first among the treatments compared for this problem.^[6] The largest trial randomized 226 postmenopausal women with early-stage breast cancer to true acupuncture, sham acupuncture or a waitlist. Worst pain scores fell by about 2.05 points on a 10-point scale with true acupuncture at 6 weeks, compared with 1.07 with sham and 0.99 with waitlist. The authors judged the clinical importance of the difference uncertain.^[7]

In the 52-week follow-up of this trial, women who had 12 weeks of true acupuncture still had about 1 point lower worst pain than the sham and waitlist groups.^[8]

Smaller trials point the same way, with caveats. In a trial of 43 women, worst pain at 6 weeks was 3.0 with true acupuncture and 5.5 with sham.^[9] In a trial of 67 women, electroacupuncture lowered pain more than a waitlist, but sham acupuncture lowered it by a similar amount.^[10]

A meta-analysis of 7 trials with 603 patients found less pain, with no severe adverse events.^[11] An earlier analysis of 5 real-versus-sham trials found only non-significant trends toward less pain and stiffness.^[12] A review of systematic reviews considered the overall confidence in acupuncture for this problem low, while still finding that it eased pain more than waiting-list controls.^[13] A network meta-analysis of 17 trials ranked acupuncture first for pain intensity among the treatments compared.^[6]

How acupuncture may work

How acupuncture eases aromatase inhibitor joint pain is not known, and no settled explanation has been established. Sham acupuncture also eased pain considerably in the trials, which suggests part of the benefit may come from non-specific effects of treatment.^{[7, 10, 11]}

What treatment involves

Treatment uses fine, sterile, single-use needles placed on the hands, wrists, knees and other painful joints and sometimes at points elsewhere on the body, with sessions lasting about 20 to 40 minutes. The large trial used twice-weekly sessions for 6 weeks, then weekly sessions for 6 weeks.^[7] We reassess after a short course of visits.

Serious problems from acupuncture are rare. In prospective studies, about 9 in 100 patients had a minor reaction such as bleeding, soreness or redness at a needle site, and serious events occurred in about 1 in 10,000 patients.^[14] In the large trial, grade 1 bruising was more common with true acupuncture than sham (47% vs 25%).^[7] Tell the practitioner first if you have a bleeding disorder, take blood thinners, have a low blood count, or have a pacemaker (relevant to electroacupuncture). Women who have had lymph nodes removed should tell us which side, so that needles are placed with care.

Ayurvedic medicine for Aromatase Inhibitor Joint Pain

The Ayurvedic view

Ayurveda describes joint pain and stiffness as a disorder of Vata, the principle said to govern movement, in the joints (Sandhigata Vata), often with a build-up of ama, or undigested residue. In this traditional framework, aging, dryness and the effects of illness and treatment are thought to disturb Vata. These are traditional categories, not biomedical diagnoses.

Therapies that may be used

Care is chosen for the individual and traditionally combines:

• Warm, nourishing meals and regular daily routine intended to calm Vata
• Gentle warm oil massage and local heat over the painful joints
• Gentle yoga and breathing exercises
• Herbs traditionally used for joint pain, prescribed individually and only after your oncology team has been informed

Panchakarma procedures are not appropriate during active cancer treatment without your oncologist's agreement, during acute illness, in frailty or in pregnancy.

What the research shows

No clinical trials of Ayurvedic treatment for aromatase inhibitor joint pain were found. A PubMed search for Ayurvedic treatments, ashwagandha, Boswellia or guggul for this problem found only one study of a Boswellia-containing supplement, which is discussed under herbal medicine.

Yoga is an Ayurveda-adjacent practice with some direct evidence. In a crossover trial of 60 breast cancer survivors with knee pain from aromatase inhibitors, a 6-week yoga program reduced knee pain more than massage.^[15] The trial was small, and exercise reviews call for larger trials.^{[4, 15]}

Herbal medicine for Aromatase Inhibitor Joint Pain

Herbs and formulas that have been studied

Studies in this condition include traditional Chinese medicine, curcumin (from turmeric) and a combination supplement containing Boswellia, alpha-lipoic acid, methylsulfonylmethane and bromelain.^{[16, 17, 18]}

What the research shows

The evidence is limited. A meta-analysis of 4 trials of traditional Chinese medicine (the abstract does not say which treatments, so acupuncture-type therapies may be included) in women with aromatase inhibitor musculoskeletal symptoms reported lower worst pain and pain interference, and better physical quality of life, but no effect on stiffness or bone density. Adverse events were minimal, and the authors called for more safety data.^[16] A network meta-analysis ranked multicomponent herbal medicine below acupuncture but above exercise, while single natural products did worse than inactive controls.^[6]

A placebo-controlled pilot trial of nanoemulsion curcumin in 42 women found no significant differences from placebo in symptoms or grip strength, though the study was too small to be conclusive.^[17] A single-group study of 53 women using a Boswellia-containing supplement reported less pain, but without a control group it cannot show the supplement caused the change.^[18]

Safety and herb-drug interactions

Herbs are active substances and can interact with medicines, including cancer medicines. Tell your oncology team and us about every herb and supplement before starting it.

Women taking aromatase inhibitors should be cautious with herbs thought to have estrogen-like activity, since the medicines work by lowering estrogen. For black cohosh, a systematic review found no association with higher breast cancer risk, but also a lack of evidence that it works for hot flashes in women with breast cancer.^[19] Herbs should be prescribed individually after a review of your medicines.

In one study, about one fifth of Ayurvedic products bought online contained detectable lead, mercury or arsenic.^[20] Herbs should come from tested sources. Tell us if you have liver or kidney disease, take blood thinners, or have surgery planned.

Translating traditional medicine into modern biological language

The links drawn here are interpretation, not equivalence. Chinese medicine describes joint pain as blocked flow of qi and blood in the channels, sometimes with cold or dampness, and often with kidney deficiency after menopause. Researchers studying aromatase inhibitor joint pain look at things that loosely parallel this picture: estrogen loss, tendon-sheath changes and fluid retention in the joints.^{[2, 3]}

Ayurveda's aggravated Vata in the joints describes stiff, dry, painful joints that worsen with cold and rest. No study has shown that a dosha or traditional pattern corresponds to a specific biological process.

How this care fits with your medical care

Integrative care for aromatase inhibitor joint pain is complementary. Keep your oncologist, and do not stop or change your aromatase inhibitor or other prescribed medicines without talking to your oncology team, because stopping early may raise the chance of recurrence.^[2] We do not diagnose the cause of joint pain, so new or worsening pain should be reviewed by your oncology team.

Please bring your diagnosis, a full list of medicines and supplements, your latest blood counts and bone density results, and details of any surgery, radiation or lymph node removal.

When to seek urgent medical care

Most aromatase inhibitor joint pain is not an emergency, but some symptoms point to infection, a fracture or other serious problems.^[1]

• A joint that is suddenly hot, red and swollen, especially with fever or chills
• Severe or sudden bone pain, or inability to bear weight after a fall
• New, severe or one-sided pain, especially at night or in the back, hip or ribs, as bone problems and cancer spread need medical review
• New weakness, numbness or loss of bladder or bowel control
• Chest pain, shortness of breath or swelling of one leg

If any of these occur, call 911 or go to the nearest emergency department.