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 ovarian 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

There is no strong evidence that lifestyle changes, such as identifying and avoiding triggers and keeping your body temperature cool, improve vasomotor symptoms but anecdotally these may help with mild symptoms. Some non-pharmacological interventions that have shown benefit include cognitive behavioral therapy and clinical hypnosis, as well as weight loss. Smoking can worsen hot flashes and therefore it is recommended to avoid smoking.

Medication management

Most of our management approaches for hot flashes come from studies with breast cancer patients on hormone therapy. The most studied agents include antidepressants such as selective serotonin reuptake inhibitors (SSRI) or serotonin-norepinephrine reuptake inhibitors (SNRI), as well as gabapentin, oxybutynin, and neurokinin-receptor antagonists.

SSRI/SNRIS

Several SSRIs, including paroxetine, fluoxetine, sertraline and citalopram, have been shown to be more effective than placebo in reducing hot flashes. 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.

Oxybutynin

Oxybutynin is medication typically used for overactive bladder symptoms and urge incontinence. Oxybutynin (2.5-5 mg immediate release twice daily up to 15 mg extended release daily) has shown to be effective for vasomotor symptom management. Common side effects include dry mouth, urinary retention, drowsiness, constipation and vision changes. Caution should be taken in prescribing oxybutynin in patients ages 65 and older due to an association with cognitive impairment and risk of delirium.

Neurokinin receptor antagonists

Neurokinin (NK) receptor antagonists are a novel treatment for vasomotor symptoms. This nonhormone approach directly targets the neural mechanism underlying the symptoms. Fezolinetant (Veozah), a NK-3 receptor antagonist, was found to be safe and efficacious for the treatment of moderate to severe vasomotor symptoms. This medication has been approved by the FDA at a dose of 45 mg daily. The most common side effects of fezolinetant in clinical studies included headache, abdominal pain, diarrhea, and nausea. Elinzanetant is another medication in this class and is a NK-1 and NK-3 receptor antagonist. Elinzanetant has been studied in clinical trials for vasomotor symptoms and is currently undergoing FDA approval.

Supplements and other drugs: 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.

Clonidine, a treatment for high blood pressure, has also been studied and appears to have a moderate effect in the treatment of hot flashes. However, it has been associated with several side effects. Due to the high risk of adverse effects and other more effective therapies with available, clonidine is not recommended as an initial strategy to treat vasomotor symptoms.

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 treatments

The first-line treatments for AIMSS include exercise, acupuncture and nonsteroidal anti-inflammatory drugs (NSAIDS). 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. NSAIDS may be used for short-term pain relief but chronic use is not recommended.

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 gynaecologic cancer patients.

[Side note from the LGSOC Initiative: Some people with low-grade serous ovarian cancer also comment that an antihistamine 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 of deficient levels.

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.

References

• Bell SG, Dalton L, McNeish BL, Fang F, Henry NL, Kidwell KM, McLean K. Aromatase inhibitor use, side effects and discontinuation rates in gynecologic oncology patients. Gynecol Oncol. 2020 Nov;159(2):509-514. doi: 10.1016/j.ygyno.2020.08.015. Epub 2020 Aug 23. PMID: 32847676; PMCID: PMC8036903.
• Sinno AK, Pinkerton J, Febbraro T, Jones N, Khanna N, Temkin S, Iglesias D, Pothuri B. Hormone therapy (HT) in women with gynecologic cancers and in women at high risk for developing a gynecologic cancer: A Society of Gynecologic Oncology (SGO) clinical practice statement: This practice statement has been endorsed by The North American Menopause Society. Gynecol Oncol. 2020 May;157(2):303-306. doi: 10.1016/j.ygyno.2020.01.035. Epub 2020 Feb 15. PMID: 32067815.
• The 2023 Nonhormone Therapy Position Statement of The North American Menopause Society Advisory Panel. The 2023 nonhormone therapy position statement of The North American Menopause Society. Menopause. 2023;30(6):573-590. doi:10.1097/GME.0000000000002200
• Cardoso F, Parke S, Brennan DJ, et al. Elinzanetant for Vasomotor Symptoms from Endocrine Therapy for Breast Cancer. N Engl J Med. Published online June 2, 2025. doi:10.1056/NEJMoa2415566
• Bobo JA, Lubrano B, Rosario-Concepcion R, et al. Treatment Modalities for Aromatase Inhibitor-Associated Musculoskeletal Syndrome (AIMSS): A Scoping Review of Prospective Treatment Studies. J Pain Res. 2025;18:1853-1889. Published 2025 Apr 7. doi:10.2147/JPR.S492891
• Gupta A, Henry NL, Loprinzi CL. Management of Aromatase Inhibitor-Induced Musculoskeletal Symptoms. JCO Oncol Pract. 2020;16(11):733-739. doi:10.1200/OP.20.00113
• Hyder T, Marino CC, Ahmad S, Nasrazadani A, Brufsky AM. Aromatase Inhibitor-Associated Musculoskeletal Syndrome: Understanding Mechanisms and Management. Front Endocrinol (Lausanne). 2021 Jul 27;12:713700. doi: 10.3389/fendo.2021.713700. PMID: 34385978; PMCID: PMC8353230.

First published: July 20, 2022 Last updated: August 17, 2025