In this article Katelyn Tondo-Steele, DO and Karen McLean, MD, PhD discuss the current evidence for managing hot flashes and joint pain. Hot flashes and joint pain are common side effects of menopause inducing surgery, and hormone inhibitor therapy in low-grade serous cancer.
Hot flashes
Hot flashes and night sweats, also known as vasomotor symptoms, are caused by abnormal temperature regulation due to estrogen withdrawal.
Non-pharmacological Management
Lifestyle changes, such as identifying and avoiding triggers and keeping your body temperature cool, are the first-line therapies for mild hot flashes. Smoking can worsen hot flashes and therefore it is also recommended to avoid smoking. Other behavioral interventions that have shown benefit include relaxation training, cognitive behavioral therapy, acupuncture, and clinical hypnosis.
Medication Management
Most of our management approaches for hot flashes come from studies with breast cancer patients on hormone therapy. The most studied agents for include antidepressants such as selective serotonin reuptake inhibitors (SSRI) or serotonin-norepinephrine reuptake inhibitors (SNRI), as well as gabapentin and clonidine. Several SSRIs, including paroxetine, fluoxetine, sertraline and citalopram, have been shown to be more effective than placebo in reducing hot flashes.
SSRI/SNRIs
The SSRI paroxetine (7.5 mg daily) is the only FDA-approved medication for the treatment of hot flashes. Other non-FDA approved medications include the SNRIs, venlafaxine and desvenlafaxine, which have been demonstrated in clinical studies to be more effective than placebo in the treatment of hot flashes. The dose of venlafaxine in most studies is 75 mg daily. Of note, there is some concern that SSRI/SNRIs may interfere with the efficacy of tamoxifen, so this should be discussed with your provider if you are taking tamoxifen.
Gabapentin
Gabapentin, a medication commonly used for epilepsy and chronic pain, has also been shown to be efficacious for hot flashes. Gabapentin (900 mg daily) was shown to be effective in decreasing hot flash severity. Clonidine, a treatment for high blood pressure, has also been studied and appears to have a moderate effect in the treatment of hot flashes. The typical dose is 0.1 mg/day of transdermal clonidine or 0.1 mg/day oral clonidine.
Supplements – caution advised
No over-the-counter dietary supplement or herbal therapy has been found to be effective for hot flashes. Some studies suggest phytoestrogens may reduce vasomotor symptoms, however, this is not recommended in low grade serous ovarian cancer due to the estrogen responsiveness of the cancer.
Examples of phytoestrogens include soy products and flax seed. Similarly, there are no randomized, controlled studies to support black cohosh, primrose oil, or vitamin E supplements.
Other proposed symptom management approaches that have insufficient data at this time are hydroxychloroquine, tart cherry, and antihistamines. One study on bee pollen noted improvements in hot flashes, however it may cause increased estrogen levels and therefore is not recommended.
Joint and musculoskeletal pain
The musculoskeletal symptoms associated with aromatase inhibitor (AI) therapy have been termed aromatase inhibitor musculoskeletal syndrome (AIMSS) or aromatase inhibitor related arthralgias (AIA).
Common Symptoms
The most common symptoms are arthralgias (joint stiffness), myalgias (muscle ache and pain), tendinopathies (tendon pain and swelling) and stiffness. A number of risk factors for developing symptoms have been reported including younger age, prior paclitaxel chemotherapy and the presence of pain at the start of treatment with AI therapy.
First-Line Treatment
The first-line treatments for AIMSS include nonsteroidal anti-inflammatory drugs (NSAIDS) and exercise. NSAIDS may be used for short-term pain relief. Exercise has demonstrated in clinical studies a reduction in pain severity and a lower pain score. Other non-pharmacologic therapies include acupuncture; women receiving 12 weeks of acupuncture had improvement in pain that lasted for one year.
Medical Management
Duloxetine, an SNRI, has been shown to improve joint pain compared to placebo. The most common dose is 30 mg daily for one week and then increased to 60 mg daily. This study noted a greater improvement of pain following use of duloxetine in obese patients. SSRIs and gabapentin have also been shown to improve AIMSS in gynecologic cancer patients.
[Cure Our Ovarian Cancer’s Side Note: Some people with low-grade serous ovarian cancer also comment that an anti-histamine such as Claritin can be helpful.]Supplements
A study on omega-3 fatty acids also noted an improvement of pain scores. However, in this study, the improvement was only statistically beneficial in obese patients. There have been several studies investigating the potential of vitamin D supplementation to improve AIMSS symptoms, although the findings have been inconsistent. If you are having symptoms, you can consider discussing with your provider potential vitamin D level testing and supplementation.
Changing Therapies
If you are experiencing significant musculoskeletal side effects on your AI, another option is to discuss with your provider switching from one endocrine therapy to another. Multiple studies suggest exemestane is associated with an increased likelihood of musculoskeletal side effects. Some people are able to tolerate a different AI even though they discontinued the first AI because of side effects.
Authors:
Katelyn Tondo-Steele DO and Karen McLean, MD, PhD of the University of Michigan.
In 2020 Dr McLean co-authored a study investigating aromotaste inhibitor use, side effects and discontinuation in gynaecological oncology patients.
Disclaimer:
The information in this article is not intended to be a replacement for medical advice. If you are considering any of the recommendations in this article – please discuss them with your cancer specialist first.
References
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