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Recent Evidence Suggests Caution In Prescribing Hormone Therapy For Breast Cancer And Sheds New Light On 'Menopausal Arthritis'

September 2, 2005
John Wiley & Sons, Inc.
A study published in the September 2005 issue of Arthritis & Rheumatism examines the evidence linking aromatase inhibitors and, more broadly, estrogen deprivation joint pain.

One of the most effective new treatments for breast cancer is a hormonetherapy. Aromatase inhibitors work by powerfully blocking theconversion of androgen precursors into estrogens, which lowersestradiol levels in the bloodstream and estrogen levels in peripheraltissues. Because aromatase inhibitors reduce the rates of recurrence inwomen with early-stage postmenopausal breast cancer, these agents arenot only becoming widely used in breast cancer treatment, but alsobeing explored for their potential to prevent the disease in women athigh risk. While focusing on this therapy's promise, advocates havetended to downplay one of its drawbacks. Women treated with aromataseinhibitors often experience joint pain and musculoskeletalaching--severe enough, in some cases, to make them stop the treatment.

Two noted researchers, David T. Felson, M.D., of Boston UniversityClinical Epidemiology Unit, and Steven R. Cummings, M.D., of CaliforniaPacific Medical Center Research Institute and University of California,San Francisco, have thoroughly examined the evidence linking aromataseinhibitors and, more broadly, estrogen deprivation joint pain. In theSeptember 2005 issue of Arthritis & Rheumatism (,they share their insights to alert oncologists, primary carephysicians, and other health care professionals to this widelyoverlooked, potential problem for women.

"Estrogen's effects on inflammation within the joint are not wellknown," Dr. Felson and Dr. Cummings observe. Yet, as they note,estrogen has well-established tissue-specific effects on inflammatorycytokines. Estrogen's role in joint inflammation could account for theincreased sensitivity to pain that some women suffer with estrogendepletion. Citing studies of pharmacological suppression of estrogenand studies of natural menopause, the authors offer a look atcompelling evidence associating estrogen deprivation with joint pain,including:

  • Aromatase inhibitors have been linked to higher ratesof joint and muscle pain than tamoxifen and placebo in various clinicaltrials for breast cancer treatment and prevention. One example: In aNational Cancer Institute of Canada study, 5,187 postmenopausal womenwho completed a 5-year course of tamoxifen therapy for breast cancerwere randomized to a further 5 years receiving the aromatase inhibitorletrozole or a placebo. 21 percent of women taking letrozole reportedjoint pain compared with 16 percent of the women receiving placebo.
  • In a study of leuprolide, a hormonal agent used totreat infertility and a variety of gynecological disorders, 102premenopausal women experienced symptoms of estrogen deprivation, suchas vaginal dryness, after 2 weeks of treatment, and suffered joint painbetween weeks 3 and 7 of treatment. Overall, 25 percent of the womendeveloped persistent joint pain, affecting the knees, elbows, ankles,and other areas, during the study. The pain was resolved in all womenbetween 2 and 12 weeks after stopping the leuprolide therapy.
  • In a postmenopausal estrogen/progestin interventiontrial, women who received estrogen had a significantly decrease chanceof musculoskeletal symptoms--between 32 and 38 percent--compared withwomen randomly assigned placebo. Symptoms reported in the placebo groupincluded joint pain, muscle stiffness, and skull and neck aching. Inother studies, however, estrogen replacement therapy had no beneficialeffect on musculoskeletal pain.

    Dr. Felson and Dr. Cummings also highlight recent data showing thatAsian women undergoing menopause have lower estradiol levels thanCaucasian women and seem to be more vulnerable to a syndrome commonlyknown as "menopausal arthritis." They also note the high rate of bothosteoarthritis and rheumatoid arthritis in postmenopausal women. Theyconclude by stressing the need for further research into thecontribution of estrogen deficiency to arthritis, as well as forrecognizing the risks of musculoskeletal syndrome when prescribingaromatase inhibitors and other estrogen-depleting treatments.


    Article: "AromataseInhibitors and the Syndrome of Arthralgias With Estrogen Deprivation,"David T. Felson and Steven R. Cummings, Arthritis & Rheumatism,September 2005; 52:9; pp. 2594-2598.

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    John Wiley & Sons, Inc.. "Recent Evidence Suggests Caution In Prescribing Hormone Therapy For Breast Cancer And Sheds New Light On 'Menopausal Arthritis'." ScienceDaily. ScienceDaily, 2 September 2005. <>.
    John Wiley & Sons, Inc.. (2005, September 2). Recent Evidence Suggests Caution In Prescribing Hormone Therapy For Breast Cancer And Sheds New Light On 'Menopausal Arthritis'. ScienceDaily. Retrieved April 22, 2024 from
    John Wiley & Sons, Inc.. "Recent Evidence Suggests Caution In Prescribing Hormone Therapy For Breast Cancer And Sheds New Light On 'Menopausal Arthritis'." ScienceDaily. (accessed April 22, 2024).

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