Women who are ≥60 years of age and those at high risk for cardiovascular disease or breast cancer, or both, should not take HRT. When prescribing HRT for patients without these contraindications, there are things you can do to minimize the risk:
- Limit the duration of HRT to the shortest treatment required.9
- Use a transdermal delivery system. Compared with oral administration, the patch appears to lower the risk of thromboembolism.10
- Prescribe a low-dose HRT regimen. The lower dose may reduce the risk of cardiovascular disease, but it will take longer to achieve symptom relief—typically, 8 to 12 weeks vs 4 weeks for women on a standard dose.11 A low-dose regimen is particularly important for women who are obese. Because of the higher serum estradiol levels found in this patient population, they need a smaller quantity of estrogen and progesterone to achieve symptom relief.12
- Taper slowly—over as long as 6 to 12 months—which may minimize hot flash severity and frequency.13
Compounded hormones. Some women prefer compounded hormones, which are often individualized based on the results of blood or saliva testing, in hopes of avoiding the risks associated with HRT. While compounds are typically marketed as a safer and more effective means of alleviating menopausal symptoms, however, there is limited evidence of their efficacy. What’s more, the lack of standardization, resulting in variations in formulations and dosages from one product to another, raises questions about the safety of compounded hormones.14-16
Antidepressants alleviate hot flashes
Both selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), which target neurotransmitters involved in the hypothalamic thermoregulation center, have been found to reduce both the severity and frequency of hot flashes.4,17,18 Women who have hot flashes have a 2-fold increase in risk for depression, and antidepressant therapy may help alleviate mood disturbances in addition to providing vasomotor symptom relief,19,20 even in women who do not meet the criteria for clinical depression.21
Which antidepressants are most effective? Venlafaxine, desvenlafaxine, and paroxetine have been shown to provide the best vasomotor symptom relief, with symptom reduction of 67% vs 15% with placebo.15,22 It is important to note, however, that studies of individual agents have had different inclusion criteria and different means of randomization. TABLE 217,21-30 summarizes the evidence, recommended dosing, expected onset of symptom relief, and common adverse effects of antidepressants used to treat hot flashes.
Other agents have more adverse effects. Certain antihypertensives (clonidine and methyldopa) and the antiepileptic gabapentin may alleviate hot flashes, but none is an optimal treatment. Clonidine has been shown to be effective in both oral and transdermal forms, but the drug is associated with hypotension, among other adverse effects. Methyldopa has not been well studied and is not viewed as a first-line agent.5 And, although gabapentin at doses ≥900 mg/d reduces the frequency of hot flashes, many women cannot tolerate the nausea, headache, dizziness, and confusion that are common adverse effects.31-33
Table 2
Antidepressants for hot flashes? Here's what to consider
| Medication (usual dose) | Symptom relief | Adverse effects |
|---|---|---|
| SNRIs | ||
| Desvenlafaxine (100 mg/d)24 | Hot flash reduction in 1-2 wk; peak effect at 4 wk | Increased BP, decreased appetite, dry mouth, nausea |
| Duloxetine*23 | Limited data on onset of action or adverse effects | |
| Venlafaxine (75 mg/d)22 | Hot flash reduction in 1-2 wk | Constipation, decreased appetite, dry mouth, increased anxiety, nausea |
| SSRIs | ||
| Citalopram (10 mg/d)*21,25 | Hot flash reduction in 1-2 wk; peak effect at 4-8 wk | Dry mouth, nausea, palpitations, somnolence (may be useful for concomitant insomnia), sweating |
| Escitalopram (10-20 mg/d)26 | Limited data on dosing, onset of action, or adverse effects | |
| Fluoxetine (20 mg/d)21,27 | Hot flash reduction within 3 wk; peak effect at 6 mo | Appetite loss, constipation, dizziness, dry mouth, fatigue, mood changes, nausea, nervousness, sleep disturbances, sweating |
| Fluvoxamine (50 mg/d) | Limited data on onset of action or adverse effects | |
| Paroxetine (10-12.5 mg/d; may be increased to 25 mg/d after 2 wk if no relief)*28,29 | Hot flash reduction in 1-2 wk | Dry mouth, headache, insomnia, nausea, somnolence; reduces the plasma concentration of active metabolite of tamoxifen, and should not be used concurrently |
| Sertraline (50 mg/d)†17,30 | Hot flash reduction in 1-2 wk; peak effect at 3 wk | Anxiety, diarrhea, dry mouth, fatigue, nausea |
| BP, blood pressure; SNRIs, serotonin-norepinephrine reuptake inhibitors; SSRIs, selective serotonin reuptake inhibitors. *Can be given with HRT. †Mixed efficacy data; use as second-line treatment only. | ||
Exercise: Little help for hot flashes, but it may boost mood
Data on physical activity’s effect on hot flashes are rather limited. Overall, exercise has not been found to improve or worsen hot flashes,5 but it does improve mood swings associated with menopause.34 Any type of exercise may be beneficial.
Small studies have found that specific activities, such as paced respiration and yoga, improve hot flashes, but larger studies are needed to clarify effect size.5 Other lifestyle interventions, such as limiting alcohol consumption, decreasing spicy food intake, avoiding hot drinks, and eliminating caffeine, may alleviate hot flashes, as well.