Q&A on Menopause
Expert Answers to Frequently Asked and Compelling Questions on Menopause Care

Released: May 08, 2024

Expiration: May 07, 2025

Lila E. Nachtigall
Lila E. Nachtigall, MD, NCMP

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Key Takeaways
  • Vasomotor symptoms (VMS) such as hot flashes are associated with significant health- and quality of life‒related burdens and can last for more than 15 years in 10% to 15% of patients.
  • Several therapies are now available to manage VMS safely, with more emerging, including hormonal and nonhormonal options.

In this commentary adapted from a live satellite symposium question and answer session, Lila E. Nachtigall, MD, NCMP, answers frequently asked clinical questions about using hormonal therapy (HT) and nonhormonal therapy in the management of vasomotor symptoms (VMS) associated with menopause.

If a patient who has been doing well on HT started before 60 years of age and within 10 years of the onset of menopause, are you able to continue the agent, or should you discontinue it?
If patients start HT younger and are doing fine on it, they definitely can continue treatment. In my practice, I have a lot of 80-year-old patients who have been taking HT for 20-30 years and are doing well. I think healthcare professionals (HCPs) should reevaluate whether therapy is still needed at least once per year. If it is still needed, they can continue. I often lower the dose during this reevaluation period, but if hot flashes return, I restart the old dose. If they do not return, patients continue at the lower dose.

The initial results of the Women’s Health Initiative study demonstrated that some previous recommendations are now no longer valid. HCPs used to universally recommend using HT for the shortest period of time possible (eg, 5 or 10 years). Although long-term use of HT certainly comes with risks, we know now based on the reanalysis of data that the duration of therapy really depends on the symptoms of the individual patient, as long as there are no contraindications.

Can bazedoxifene be used for life?
The duration of use for each medication will be unique to the situation and patient, but I do not write prescriptions for VMS with the intention of continuing them indefinitely. I reevaluate any medication at least once per year for a change in risks, benefits, or other considerations for each patient. However, I do believe that a combination of estrogen and bazedoxifene is very safe. Personally, I have many patients who have been taking it for many years without any issues, but continuation of this therapy is certainly still something HCPs should reevaluate regularly, even if it is well-tolerated.

Do you recommend tapering or stopping estrogen therapy in a patient who develops venous thromboembolism?
If patients experience deep vein thrombosis on estrogen, I stop the agent immediately because it is likely the primary cause or a major contributing factor. In these patients, there are other ways of treating their hot flashes. I would recommend a nonhormonal therapy.

Do you prescribe or recommend HT in patients with a history of estrogen receptor‒negative breast cancer post bilateral mastectomy?
Yes, if the tumor was estrogen receptor negative, estrogens actually are indicated for those patients, especially after bilateral mastectomy. There may be a few breast cancer cells remaining after mastectomy, but if the tumor was estrogen receptor negative, I think it is safe to assume that any cells left behind would be estrogen receptor negative, as well.

Were women older than 60 years of age and more than 10 years post menopause included in fezolinetant studies?
Yes, to some degree. Fezolinetant studies included patients 40-65 years of age and did not exclude patients with a long duration of menopause. However, there have not been enough women older than 65 years of age evaluated to determine if their response would differ from younger patients. Although the majority of patients on the studies performed thus far had an average time since onset of hot flashes of 6-7 years, we have no clinical trial flags raising a concern about those using therapy beyond 10 years.

Are there any benefits to cardiovascular disease or osteoporosis with the neurokinin receptor antagonists?
Whether neurokinin receptor antagonists will provide any benefits to cardiovascular disease is not known yet and will not be known until data are available from long-term studies. However, physiologically, hot flashes are associated with cardiovascular disease due to vasomotor instability. Therefore, we expect that if hot flashes are decreased or eliminated, cardiovascular disease may be decreased or eliminated, as well. This suggests a potential benefit, but there is no way to know for sure without long-term data. Regarding osteoporosis, HCPs are not aware of any neurokinin receptors in the bone, so other strategies are used to prevent osteoporosis.

If neurokinin receptor antagonists are discontinued, do VMS return?
Yes, this could occur as it does when patients discontinue treatment with estrogen. HCPs should reevaluate the need for therapy periodically (eg, annually) by holding therapy. This will provide an indication of whether the hot flashes are still occurring for that patient and if therapy is still needed. I have patients who continued to require therapy for VMS for several decades, so it is very likely some patients will need to restart therapy.

Aside from cautions related to liver enzyme elevations, are there other safety concerns when using fezolinetant?
Fezolinetant had a very safe profile in clinical studies. Study participants receiving fezolinetant experienced rates of adverse events similar to participants receiving placebo. In addition, in the phase III clinical trials where there were elevations of liver function tests, the drugs were not stopped, and levels returned to normal.

The prescribing information recommends checking liver function tests before starting therapy. If they are 2 times the upper limit of normal or higher, patients should not start therapy. After initiating fezolinetant, HCPs should check liver function levels at 3, 6, and 9 months post initiation. If there are no changes in liver function tests, there is no need to continue testing regularly if the patient continues medication. Use of fezolinetant should be avoided in those with documented cirrhosis and in combination with medications that inhibit CYP1A2. In addition, fezolinetant is primarily excreted by the kidneys, and use is contraindicated in those with severe or end-stage renal disease.

Your Thoughts?
Which therapies do you prescribe to help patients improve VMS associated with menopause? Leave a comment to join the discussion!

Poll

1.

What are the most common barriers to treating menopause-associated VMS in your patients? (Choose all that apply)

2.

Which of the following nonhormonal therapies would you consider to help patients manage menopause-associated VMS? (Choose all that apply) 

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