Women treated with aromatase inhibitors often experience joint pain and musculoskeletal aching --severe enough, in some cases, to make them stop the treatment.

Two researchers, David T. Felson, of Boston University Clinical Epidemiology Unit, and Steven R. Cummings, of California Pacific Medical Center Research Institute and University of California, San Francisco, have thoroughly examined the evidence linking aromatase inhibitors and, more broadly, estrogen deprivation joint pain.

" Estrogen's effects on inflammation within the joint are not well known," Felson and Cummings observe. Yet, as they note, estrogen has well-established tissue-specific effects on inflammatory cytokines. Estrogen's role in joint inflammation could account for the increased sensitivity to pain that some women suffer with estrogen depletion.

Aromatase inhibitors have been linked to higher rates of joint and muscle pain than Tamoxifen and placebo in various clinical trials for breast cancer treatment and prevention.

In a National Cancer Institute of Canada study, 5,187 postmenopausal women who completed a 5-year course of Tamoxifen therapy for breast cancer were randomized to a further 5 years receiving the aromatase inhibitor Letrozole ( Femara ) or a placebo. 21 percent of women taking Letrozole reported joint pain compared with 16 percent of the women receiving placebo.

In a study of Leuprolide ( Lupron ), a hormonal agent used to treat infertility and a variety of gynecological disorders, 102 premenopausal women experienced symptoms of estrogen deprivation, such as vaginal dryness, after 2 weeks of treatment, and suffered joint pain between weeks 3 and 7 of treatment. Overall, 25 percent of the women developed persistent joint pain, affecting the knees, elbows, ankles, and other areas, during the study.
The pain was resolved in all women between 2 and 12 weeks after stopping the leuprolide therapy.

In a postmenopausal estrogen/progestin intervention trial, women who received estrogen had a significantly decrease chance of musculoskeletal symptoms--between 32 and 38 percent--compared with women randomly assigned placebo.
Symptoms reported in the placebo group included joint pain, muscle stiffness, and skull and neck aching. In other studies, however, estrogen replacement therapy had no beneficial effect on musculoskeletal pain.

Felson and Cummings also highlight recent data showing that Asian women undergoing menopause have lower estradiol levels than Caucasian women and seem to be more vulnerable to a syndrome commonly known as "menopausal arthritis."
They also note the high rate of both osteoarthritis and rheumatoid arthritis in postmenopausal women.
Authors have concluded by stressing the need for further research into the contribution of estrogen deficiency to arthritis, as well as for recognizing the risks of musculoskeletal syndrome when prescribing aromatase inhibitors and other estrogen-depleting treatments.

Source: Arthritis & Rheumatism, 2005


XagenaMedicine2005