Chilling Out Hot Flashes: Tips for Patient-Centered Management of Menopausal Symptoms

Charles P. Vega, MD; Anna L. Altshuler, MD, MPH


February 05, 2016

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Perspectives on Managing Symptoms of Menopause

Charles P. Vega, MD: Hello. I'm Chuck Vega, clinical professor of family medicine at the University of California, Irvine. Welcome to another segment of Critical Issues in Women's Health. I'm joined by Anna Altshuler, an obstetrician/gynecologist at California Pacific Medical Center in San Francisco, California. Anna, welcome.

Anna L. Altshuler, MD, MPH: Thank you, Chuck.

Benefits and Risks of Hormone Therapy

Dr Vega: We have talked about contraception and family planning, but now let's move to the other end of the childbearing spectrum, to perimenopause and menopause.

There is always some controversy about the management of symptoms of menopause. Many women do not experience moderate or severe symptoms associated with menopause. Among women with hot flashes, which is one of the most common symptoms, about one third experience more than 10 hot flashes a day—interfering with daily life and functioning—and they can suffer some very disabling symptoms.

Hormone therapy (HT) is effective for treating hot flashes. In a Cochrane review,[1] HT reduced hot flashes by 75%, so highly effective treatment is available. We should be using the lowest effective dose of HT available for the shortest duration of time required to manage symptoms.

The risks associated with HT have been well described. The most significant of these, which I always counsel patients about, is the risk for venous thromboembolism (VTE). The patient should be screened for their risk for VTE before prescribing HT. My patients are particularly attuned to the potential risk for breast cancer associated with the use of HT. This risk is associated with a high number needed to harm, so a great many women have to receive a prescription for HT to incur one additional case of breast cancer.

Another major safety concern is the risk for cardiovascular disease (CVD) associated with HT. More recent research[2] indicates that the risk for CVD is probably not significantly increased for women between the ages of 50 and 60 years who use HT for a brief amount of time—between 1 and 3 years. This is different from the Women's Health Initiative,[3] in which an older cohort used the drug over a longer period of time.

Stepwise Approach to Prescribing HT

Dr Vega: We want to be patient-centered; we want to respect patients' wishes and beliefs. Many women have heard about the potential dangers of HT and may not be interested in it for many reasons, including safety. In general, how do you approach a patient in thinking about prescribing HT?

Dr Altshuler: It's a common conversation, and we take a stepwise approach that is similar to other areas of medicine. If a woman is experiencing hot flashes that are interfering with her life, I want to make sure that it's truly related to being perimenopausal. We want to rule out such things as thyroid disease, and assess whether the patient may be taking any other medications that are contributing to the vasomotor symptoms. Once those are ruled out, we start with lifestyle changes.

For example, if a woman is obese, she is at higher risk of having severe hot flashes, so weight loss is a recommendation. Stopping smoking and reducing caffeine and alcohol intake are other modifiable factors.[4] Carrying around a fan or staying in cool environments—turning on the air conditioning when necessary—and dressing in layers are very easy things to do.

Another thing that has been shown to help is paced respiration, in which a woman takes deep breaths six to eight times a minute.[5] Sometimes that can reduce the degree of hot flashes. It has been proven to work.

For night sweats (another common symptom that women experience in the perimenopausal years), sleeping in a cool environment, improving sleep hygiene, or using sedating medications to help them sleep may be options.

If someone tries these things and still continues to have hot flashes, we go to pharmacologic therapy. This should be individualized to each patient as you had discussed.

The most effective medication we have available is systemic HT containing estrogen.[6] Women should be screened to make sure that they are appropriate candidates—those who are less than age 60 (who had their last menstrual period within the past 10 years) with moderate to severe symptoms. We believe that HT is safest in this population, according to the Women's Health Initiative and other studies.[1,3]

You discussed the risk factors that we screen for, and the mantra is "smallest dose necessary for the shortest duration." The latest recommendation is to use HT for up to 5 years, but there is no clear cutoff point. If a woman reaches age 65 and continues to have severe symptoms and benefits from therapy, she may continue therapy and this decision should continue to be individualized. Also, there is a recommendation to reduce the estrogen dose over the years, so reduce the dose at least on a yearly basis.

Dr Vega: That's an excellent point. More recent research suggests that the average duration of menopausal symptoms can be, for many women, up to a decade. We certainly counsel women about trying to wean off HT—and for my practice an attempt to wean off HT is made every 6 months at least—because many women find that they want to try to stop the HT. If weaning doesn't work, then they go back on. We try again, and measure exactly how bad the symptoms became when they were off treatment.

Certain patients advance past age 70 years [and] simply cannot tolerate life without HT. For them, shared decision-making is very important, and we should document that they understand the risk. Do what you can for prevention by reducing CVD risk factors as much as possible. Those risks are modifiable through lifestyle, but also through drug therapy. Pay attention to annual mammography and breast cancer screening for these patients. It seems to work, but it takes diligence on the part of both patient and physician.

Dr Altshuler: There are many different formulations for estrogen-based HT: pills, patches, and vaginal formulations. Some evidence suggests, on the basis of observational studies, that transdermal estrogen may be associated with a lower risk for VTE compared with oral regimens.[7] That is another consideration as you are reducing the amount of estrogen that a woman is exposed to. Remember also to prescribe a progestin along with estrogen for women who have a uterus.

Some new products are available, such as the new combination product containing a conjugated estrogen with a selective estrogen receptor modulator called bazedoxifene, which is an alternative to the progestin component in combined HT. It is going to be on the market shortly.

Dr Vega: What is the projected benefit, compared with a product that contains a progestin?

Dr Altshuler: It reduces the risk for breast cancer.

Dr Vega: That certainly can be an option, and we should pay attention to the trials that might demonstrate a difference. Given the relatively small number of events, it's not going to be easy to demonstrate a significant difference. Certainly it makes sense in terms of the pharmacology and the physiology.

Nonhormonal Therapies for Menopausal Symptoms

Dr Vega: What about women who do not want to use a prescription that contains estrogen and are instead interested in complementary and alternative medicine (CAM)? You mentioned deep breathing, which certainly can be effective and is relatively easy to use, but what about patients who want to take something? A variety of different CAM products physiologically affect the estrogen receptor.

Dr Altshuler: That's right. Unfortunately, there has not been a single complementary or alternative method that is superior to placebo. Some examples are phytoestrogens (soybeans, soy products), red clover, black cohosh, vitamin E (which has some marginal benefits, perhaps), and acupuncture.[8] Many of these methods are very safe and may offer benefits to individual women. As long as there is no contraindication to their use, it's reasonable to try them, although they will not be as effective as replacing the hormones.

Women who are not eligible for HT can consider other medications. A new one has been approved [Brisdelle®], which contains paroxetine, a selective serotonin reuptake inhibitor also contained in the antidepressant Paxil®. A new low dose has recently entered the market— 7.5 mg, which is less than the 20 mg used for depression. This product may also reduce the severity and frequency of daily hot flashes. It also is not as effective as using estrogen-based products but still may offer some relief.

Dr Vega: Absolutely. Other options, such as gabapentin and venlafaxine, can be effective for hot flashes specifically—that is really what we are treating here.

Bioidentical Hormone Therapy

Dr Vega: Taking another look at HT, we have the issue of compounded hormones. Compounded therapy is something patients can really believe in. Certain clinicians have staked a claim that this therapy, which is made in a proprietary compounding pharmacy, is superior to what we traditionally use as HT. Do you have any thoughts? What is the party line, and how should we manage requests for compounded HT?

Dr Altshuler: There seems to be a lot of confusion about compounded hormones, because they use bioidentical hormones in the compounding process. Some bioidentical hormones are US Food and Drug Administration (FDA) approved. For example, estradiol, which is in most HT formulations, and micronized progesterone are both bioidentical. What we mean by that is that these hormones are derived from soy and yam products that are chemically altered to have the same molecular structure as the hormones in our bodies. These products already exist. Common hormones used in the custom compounding process include testosterone, progesterone, estriol, estrone, estradiol, and dehydroepiandrosterone (DHEA) in various amounts. They are usually administered to the body through nonstandard routes, such as implants or suppositories.

The challenge is that the doses of these products are adjusted on the basis of serial hormone testing. However, a lot of these tests (such as saliva tests) have not been shown to match the bioavailability or the bioactivity of these hormones. It's very hard to determine the appropriate therapeutic dose or to titrate the level accurately. Also, each batch of compounded hormone may be different, so it's very difficult to know when someone is changing or needs a higher or lower dose, or whether that person is even receiving what we are prescribing.

You also can imagine a scenario where a woman feels better after receiving a compounded bioidentical hormone, but you don't know whether the dose is supratherapeutic or appropriate for her. It's important for women who have a uterus to receive an appropriate amount of progesterone for uterine protection, and with these compounded hormones, it's hard to know whether the dose is correct. There is no good way to test for it, either.

Overall, compounded hormones are not advised because of the limited quality control and oversight, the untested purity, and lack of batch-to-batch consistency. Women are better off using the FDA-approved hormonal treatments, which have the same hormones but have been tested to improve symptoms.

Dr Vega: That's absolutely right. That's why the American College of Obstetricians and Gynecologists recommends against the routine use of compounded bioidentical hormones for women.[9] The FDA has done testing, and they found that when tested for potency, these compounded hormones had error rates of 34% compared with < 2% for the FDA-approved hormones.

There are nonpharmacologic approaches to treatment, particularly for hot flashes, that can be a good first-line approach. Having a discussion with patients and assessing the potential risks and benefits of HT before prescribing it and then looking to some newer modes of delivery—such as transdermal and the combination pills that are coming out now that do not use a progestin—may offer a different level of safety for patients. Sticking to that mantra of "smallest dose for the shortest duration possible" serves most women very well, but it's important to understand that it is not going to work for every single patient. A minority of women will need longer-term treatment just to maintain some quality of life, because these symptoms can be quite debilitating.

Anna, it's been a great discussion. Do you have anything to add?

Dr Altshuler: When women are deciding to use compounded hormones, it's important to ask them why. There is a lot of misconception related to motivation. Premarin®—the conjugated equine estrogen that was used in the Women's Health Initiative, and one of the older products that we have available—is made from urine from horses. That is a big turnoff for a lot of women for ethical reasons.

Products are available that do not use those kind of formulations. There are alternatives that are FDA-approved if a woman's reason to use the compounded hormone is to avoid Premarin products. It's important to point out that plant-derived products are available if they are hoping for alternatives.

Dr Vega: Absolutely. That is a great point, and it's a nice one to close on in a patient-centered way.

Thank you very much for your participation, and hopefully we will see you again on Critical Issues.

Dr Altshuler: Thank you for having me.


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