Clinical Management
The treatment of menopause-associated vasomotor symptoms is a common clinical challenge. Before treatment begins, a detailed patient history of hot flashes is needed, including frequency and severity as well as the effect they have on activities of daily living. Women differ in their attitude toward hot flashes. No treatment is needed unless the hot flashes are bothersome to the woman. Some women seek only to reduce their symptoms slightly while others request more complete amelioration.
The decision to undertake treatment should be based on the severity of the symptoms, an assessment of treatment-related risks, and the woman's personal attitudes about menopause and medication. The clinical goal is to tailor therapy to each individual woman's needs using the various options. Clinicians are advised to enlist women's participation in decision making when weighing the benefits, harms, and scientific uncertainties of options.
In most women, hot flashes will abate over time without any intervention. When therapy is desired, various nonpharmacologic and pharmacologic options are available. The recommended clinical management approach includes lifestyle modification followed by nonprescription and/or prescription therapies, when needed.
Lifestyle Changes
In women who need relief from mild menopause-related hot flashes, The North American Menopause Society (NAMS) recommends first considering lifestyle changes, which include environmental manipulations and behavioral changes, such as keeping the core body temperature as cool as possible, participating in regular exercise, and avoiding hot flash triggers. Use of paced respiration is another option to consider, based on its effectiveness in studies, ease of use, and lack of side effects. Because both obesity and a sedentary lifestyle are linked to increased hot flashes, a strategy to maintain a healthy weight and to exercise regularly may be helpful.
Nonprescription Remedies
When lifestyle changes are not adequate to achieve the desired level of relief from mild hot flashes, adding a nonprescription remedy may be considered. A trial of dietary isoflavones or supplements containing black cohosh or vitamin E may be an option, primarily because these remedies are not associated with serious side effects. However, because of inconclusive efficacy data, this is not a consensus recommendation.
Soy foods and Isoflavone supplements
Efficacy in clinical trials of both soy foods and isoflavone supplements (from either soy or red clover) has been mixed, possibly because it is limited to the subset of women who are equol producers. Nevertheless, for women with frequent hot flashes, clinicians may consider recommending soy foods or soy isoflavone supplements. Most hot flash studies used isoflavone amounts of 40 to 80 mg/day. Whole foods may be a better choice than isoflavone supplements or fortified foods, based on lack of potential isoflavone "overdose" with soy foods. Effects, if any, may take several weeks. Isoflavones exhibit a low incidence of side effects, although caution is advised when estrogenicity is a concern. Whether these foods or supplements can treat hot flashes effectively and safely in women who have had or are at risk for breast cancer is unknown.
Additional studies are needed to determine whether there are differences among whole food, soy protein, and isoflavone extracts. Whole soy foods have been consumed for thousands of years and are presumed safe, but supplements and fortified foods may contain high levels of isolated isoflavones, the long-term effects of which are unknown.
Black cohosh
In the most recent trials of black cohosh, the results have been negative. However, some older and smaller trials from Germany have shown some efficacy for hot flashes. With its low incidence of side effects, a black cohosh supplement (two 20-mg tablets daily of a 27-deoxyactein standardized preparation) taken for less than 6 months is likely to do no harm and may provide relief of mild hot flashes.
Vitamin E
Vitamin E, 800 IU/day, is another nonprescription option to try for hot flash relief, although clinical evidence is mixed. A statistically significant but not clinically significant decrease in hot flashes among breast cancer survivors was noted in one clinical trial, although older trials found no benefit for vitamin E over placebo. Because vitamin E seems to be nontoxic at low doses, inexpensive, and available without a prescription, it is a reasonable option for a trial. Effects, if any, may take weeks.
Topical progesterone creams
Scientific data are lacking regarding the efficacy and safety of topical progesterone creams for relief of hot flashes. Contents and concentrations vary widely in different brands of nonprescription progesterone creams. Additionally, safety concerns regarding systemic progestogen preparations may also apply to topical progesterone preparations. Therefore, NAMS does not recommend use of progesterone creams for hot flash relief.
Other treatments
Given the lack of efficacy data, NAMS also does not recommend dong quai, evening primrose oil, ginseng, licorice, Chinese herb mixtures, acupuncture, or magnet therapy for hot flash relief.
Prescription Therapies: Hormonal Options
When lifestyle changes and nonprescription approaches do not provide the desired relief, prescription options are available. Hormonal approaches, primarily systemic estrogen therapy/estrogen-progestogen therapy (ET/EPT), are most often prescribed and are the only government-approved therapies in the United States and Canada for treating moderate to severe hot flashes. During perimenopause, follicle-stimulating hormone and estradiol levels fluctuate. Dosing estrogen at this time provides uncertain results. After menopause is reached and ovarian activity ceases, response to estrogen therapy will be more predictable.
Systemic estrogen therapy and estrogen-progestogen therapy
NAMS considers treatment for moderate to severe menopause-related hot flashes to be a primary indication for systemic ET and EPT. Use of ET and EPT should be limited to the shortest duration consistent with treatment goals, benefits, and risks for the individual woman.
NAMS recommends considering lower-than-standard doses of ET and EPT (i.e., daily doses of 0.3 mg conjugated estrogens tablet, 0.25-0.5 mg 17beta-estradiol tablet, 0.025 mg 17beta-estradiol patch, or the equivalent). Many studies have demonstrated that these doses provide similar vasomotor symptom relief. Lower EPT doses are better tolerated and may or may not have a more positive safety profile than standard doses; however, lower doses have not been tested for outcomes (including endometrial safety) in long-term trials.
For all women with an intact uterus who are using estrogen therapy, NAMS recommends that they receive adequate progestogen, either in a continuous combined or continuous sequential EPT regimen. However, there is insufficient evidence regarding long-term endometrial safety to recommend use of long-cycle progestogen (i.e., progestogen every 3-6 months for 12-14 days), a progestin-containing intrauterine device (IUD), or low-dose estrogen without progestogen as an alternative to standard EPT regimens. If utilizing any of these approaches, close surveillance of the endometrium is recommended, pending more definitive research. Some women with an intact uterus who choose EPT may experience undesirable side effects from the progestogen component.
If the initial ET/EPT dose is not effective, it may be increased. For women who are not obtaining symptom relief with once-daily dosing of oral ET due to the possibility of their metabolizing the hormone more rapidly, twice-daily dosing with half doses may be advised or they may be switched to transdermal ET. There is often no need to increase the total daily oral dose in women suspected of having rapid or irregular metabolism of exogenous estrogen. In such women, stability of the circulating estrogen level may be more important than attainment of an absolute level. The route of administration can also be switched. Transdermal ET may provide more stable levels of circulating estrogen than oral therapies. Another option is the vaginal estrogen ring (Femring) that is FDA-approved for treating hot flashes.
There are few clinical trial data on custom hormone preparations. For most women, NAMS does not recommend these preparations for hot flash relief, due to lack of efficacy and safety data on the specific compounded prescriptions.
With cyclic ET regimens (i.e., estrogen only for 3 weeks followed by 1 week off therapy), hot flashes may return by the end of the hormone-free week. This is especially true with 17beta-estradiol, due to its rapid clearance from the body. Thus, NAMS recommends using continuous ET regimens before cyclic regimens when treating hot flashes.
If hot flashes persist after an adequate trial (i.e., 2-3 months) of hormone therapy (HT), other conditions associated with hot flashes should be considered in the differential diagnosis.
When ET/EPT is discontinued abruptly, hot flashes often return within several days, depending on the type and route of estrogen therapy. No specific protocols can be recommended for discontinuing therapy to avoid rebound hot flashes. Some clinicians gradually decrease the dose, whereas others lengthen the time between doses. There are no data to suggest that one method is better than the other. If hot flashes recur, ET/EPT may be reinstituted then discontinued at a later time.
Prescription progestogen
Prescription progestogen alone can be used to treat hot flashes of varying severity. In clinical trials, DMPA, MPA, and megestrol acetate have demonstrated efficacy. Short-term use of these drugs seems reasonable in women without contraindications who do not wish to try estrogen but who are not opposed to trying another hormone, although progestogens have been linked to breast cancer risk in some studies.
Oral contraceptives
Perimenopausal women who need both hot flash relief and contraception may achieve both goals with low-dose, combined estrogen-progestin oral contraceptives (OCs). NAMS supports this use for otherwise healthy women who do not smoke or have other contraindications. The potential side effects of nausea, mood swings, and headaches can usually be decreased or eliminated by altering the regimen or dose. Relief of hot flashes should be achieved within 2 to 3 months of starting therapy. If hot flashes occur during the placebo week, adding a low dose of supplemental estrogen or shortening or eliminating the placebo interval may provide relief. DMPA offers another option for hot flash relief and contraception, although adverse effects are greater than with OCs. Standard menopausal doses of ET/EPT have not been well studied with respect to protection from an unwanted pregnancy and, thus, should not be relied on for contraception.
If EPT is needed postmenopause, transitioning from a combination OC to EPT should be done as soon as appropriate. Even OCs with very low hormone doses still provide significantly more hormone than in standard EPT, which may increase exposure to unnecessary risks from long-term use.
Prescription Therapies: Nonhormonal Options
In women with hot flashes for whom hormones are not an option, nonhormonal prescription drugs have shown some effectiveness in relieving hot flashes. However, there are no comparative trials in similar patient populations to guide clinicians in selecting a particular option.
Antidepressants
If there are no contraindications, NAMS recommends the antidepressants venlafaxine (at dosages of 37.5-75 mg/day), paroxetine (12.5-25 mg/day), or fluoxetine (20 mg/day) as options for women with hot flashes who are not candidates for hormone therapy, including breast cancer survivors. The additional antidepressant effect may benefit some women who suffer from mood disorders.
Hot flash relief, if any, is almost immediate with these therapies, whereas for depression, effects often are not observed for 6 to 8 weeks. This rapid onset of action can be a powerful reinforcement for women who do not find relief from other, simpler methods. A brief trial of 1 week may determine if these agents are going to be effective.
Side effects, especially nausea and sexual dysfunction, should be monitored. Women who experience drowsiness should take the drug at night. Venlafaxine is the most likely in its class to promote weight loss (by causing anorexia), and may be preferred by overweight women. Paroxetine has similar side effects, although less nausea and anorexia. It can also cause blurred vision, although this is rare. Fluoxetine is less likely to cause acute withdrawal side effects because of its longer half-life.
To minimize side effects, very low doses of these antidepressants can be used when starting therapy. If not effective, the dose can be increased after 1 week. Higher doses than those used in trials do not seem appropriate, given the lack of additional efficacy and the potential for increased toxicity. Taking the drugs with food may lessen nausea.
These antidepressant medications should not be stopped abruptly, as sudden withdrawal has been associated with headaches and anxiety. Women who have been using an antidepressant for at least 1 week should taper off the drug. Tapering may require up to 2 weeks, depending on the initial dosage.
Gabapentin
Gabapentin is another nonhormonal option recommended by NAMS for treating hot flashes. Therapy can be initiated at a daily dose of 300 mg (although starting at 100 mg/day may be advisable in women older than age 65). Bedtime administration is advised, given the initial side effect of dizziness. In women who continue to have hot flashes, the dose can be increased to 300 mg twice daily and then to three times daily, at 3- to 4-day intervals. Increased efficacy may be seen at even higher doses, although this has not been well studied. Antacids may reduce the bioavailability of gabapentin; the drug should be taken at least 2 hours after antacid use.
Clonidine
Clonidine is sometimes used to treat mild hot flashes, although it is less effective than the newer antidepressants or gabapentin. In addition, clonidine has a side effect profile that limits its use in many women. The initial oral dose for hot flash treatment is 0.05 mg twice daily, but women may require at least 0.1 mg twice daily. The clonidine patch, delivering 0.1 mg/day, can also be considered. When discontinuing higher-dose therapy, the dose should be gradually tapered to avoid adverse side effects.
Methyldopa/Bellergal
Given their toxicity, NAMS does not recommend methyldopa or Bellergal as hot flash treatments for most women.
Any hot flash treatment may need to change over time because of gradually lowering levels of ovarian hormones through perimenopause and the possible appearance of medical conditions unrelated to menopause or menopause treatments. New research and changing ideas about treatments may have an impact on health decisions. Before switching from one therapy to another, a washout period may be required.
