Vasomotor symptoms

Aromatase inhibitors are relatively well tolerated however have a number of distinct side effects are observed that stem from the state of estrogen deprivation induced by aromatase inhibitors. Side effects include hot flashes, joint and muscle aches, vasomotor symptoms and vaginal dryness. Variable effects of aromatase inhibitors on lipid levels have been observed. Trials comparing third generation aromatase inhibitors to tamoxifen have also repotted an increased risk of cardiovascular events in the group receiving aromatase inhibitors. 

UPMALIS D H, LOBO R, BRADLEY L, WARREN M, CONE F L, LAMIA C A (2000) VaSOmotor symptom relief by soy isoflavone extract tablets in postmenopausal women a multicenter, double-blind, randomized, placebo-controlled study. Menopause. 1 236-42. 

Hormone-replacement therapy remains the most effective treatment for vasomotor symptoms and vulvovaginal atrophy and should be considered for women experiencing these symptoms. 

Oral or transdermal estrogen products should be prescribed at the lowest effective dose for the relief of vasomotor symptoms. Topical products in the form of creams, tablets, or rings should be prescribed for women exclusively experiencing vulvovaginal atrophy. 

Hormone-replacement therapy improves overall well-being and mood in women with vasomotor symptoms but has not demonstrated an improvement in quality of life in women without vasomotor symptoms. 

This series of trials, and many more, has led to the dramatic change in how HRT is currently prescribed and greater understanding of the associated risks. HRT, once thought of as a cure-all for menopausal symptoms, is now a therapy that should be used only to reduce the frequency and severity of vasomotor symptoms associated with menopause in women without risk factors for CHD or breast cancer. The changes that have occurred over the years in the use of HRT further support the importance of evidence-based practice and judicious medication use. 

Vasomotor symptoms, as well as other menopausal symptoms, occur in over 50% of perimenopausal women and over 80% of menopausal women.5 Menopausal symptoms tend to be more severe in women who undergo surgical menopause compared with natural menopause because of the more rapid decline in estrogen concentrations. Women who seek medical treatment should undergo laboratory evaluation to rule out other conditions that may present with similar symptoms, such as abnormal thyroid function or pituitary adenoma. Once other conditions have been excluded, HRT should be considered. 

Hormone-replacement therapy remains the most effective treatment for vasomotor symptoms and vulvovaginal atrophy and should be considered for women experiencing these symptoms. The goals of treatment are to alleviate or reduce menopausal symptoms and to improve the patient s quality of life while minimizing adverse effects of therapy. The appropriate route of administration should be chosen based on individual patient symptoms and should be continued at the lowest dose for the shortest duration consistent with treatment goals for each patient. 

Nonpharmacologic therapies for menopause-related symptoms have not been studied in large randomized trials, and evidence of benefit is not well documented. Owing to minimal adverse effects with these types of interventions, it maybe prudent for patients to try lifestyle or behavioral modifications before and in addition to pharmacologic therapy. The most common nonpharmacologic interventions for vasomotor symptoms include4,7,8... 

Exercise demonstrated an improvement in quality of life but did not improve vasomotor symptoms. Paced respiration, a form of deep, slow breathing, improved vasomotor symptoms in a small group of patients. 

HRT is indicated primarily for the relief of moderate to severe vasomotor symptoms. It remains the most effective treatment for vasomotor symptoms and should be considered only in women experiencing those symptoms. Women with mild vasomotor symptoms may benefit from nonpharmacologic therapy alone however, many women will seek medical treatment for these symptoms. The benefits of HRT outweigh the risks in women who do not have CHD or CHD and breast cancer risk factors however, careful consideration should be given to alternative therapies for the relief of menopausal symptoms in women with these risks. Women should be involved in the decision and may choose to use HRT despite having some risk factors owing to the severity of their symptoms. Regardless of the situation, HRT should be prescribed at the lowest dose that relieves or reduces menopausal symptoms and should be recommended only for short-term use. Women should be reassessed every 6 to 12 months, and discontinuation of therapy should be considered. 

The results of these trials demonstrate that ERT or HRT should not be prescribed for the prevention of CHD or in patients with preexisting CHD. For women suffering from vasomotor symptoms with a history of CHD, including CHD risk factors, alternative therapies should be considered. Additionally, lifestyle modifications should be implemented, and therapies to treat risk factors such as hypertension and hyperlipidemia should be prescribed. It is important to note that the average age of women included in the HERS and the WHI trials was 67 and 63 years, respectively. Therefore, these trials were unable to assess the true risk in younger, potentially healthier women with fewer cardiovascular risk factors. 

Because the WHI is the best evidence to date linking HRT with breast cancer, women with a personal history of breast cancer and possibly even a strong family history of breast cancer should avoid the use of HRT and consider non-hormonal alternatives for the treatment of vasomotor symptoms. 

Observational and prospective data have consistently demonstrated an increased risk in thromboembolic events with the use of HRT.2,3,19,20 Women taking HRT have approximately doubled the risk of those not taking HRT. Therefore, these risks need to be weighed carefully when considering the use of HRT for the treatment of vasomotor symptoms. 

A number of non-hormonal therapies have been studied for symptomatic management of vasomotor symptoms, including antidepressants [e.g., selective serotonin reuptake inhibitors (SSRIs) and venlafaxine], herbal products (e.g., soy, black cohosh, and dong quai), and a group of miscellaneous agents (e.g., gabapentin, clonidine, and megestrol). The choice of therapy depends on the patient s concomitant disease states, such as depression and hypertension, and the risk for potential adverse effects. 

Black cohosh has been one of the most studied herbal remedies for vasomotor symptoms, and it has not demonstrated a substantial benefit over placebo. The mechanism of action, safety profile, drug-drug interactions, and adverse effects of black cohosh remain unknown. In non-placebo-controlled trials conducted for 6 months or less, black cohosh demonstrated a small reduction in vasomotor symptoms. It has not been shown to be effective for vasomotor symptoms in women with breast cancer.33 There have been case reports of hepatotoxicity with the use of black cohosh.36 Caution should be exercised when considering the use of this product, especially in patients with liver dysfunction. 

Dong quai and several other herbal products, including evening primrose oil, passion flowers, sage, valerian root, flaxseed, and wild yam, have not demonstrated efficacy with regard to the relief of vasomotor symptoms, and the safety of these products is also questionable.4,33,35 Therefore, these products should not be recommended for the relief of vasomotor symptoms in postmenopausal women. 

Overall, non-hormonal therapies are less effective in treating vasomotor symptoms than HRT but do offer an important option for women experiencing menopausal symptoms who cannot or are unwilling to take HRT. The antidepressants gabapentin and clonidine have the best evidence for efficacy of all the non-hormonal options and should be considered first as an alternative to HRT. The most important considerations in choosing an alternative therapy are the patient s comorbidities and the efficacy and safety of the medication. 

Assess the patient for use of HRT by evaluating for the presence of vasomotor symptoms. If the patient is experiencing bothersome vasomotor symptoms, consider the use of HRT only after assessing for risk factors for heart disease and breast cancer. If vasomotor symptoms are tolerable and/or the patient has risk factors for heart disease and/or breast cancer, consider alternative, non-hormonal treatments for vasomotor symptoms. 

Educate the patient on lifestyle or behavioral interventions that may help to alleviate vasomotor symptoms. 

Monitor the patient for a reduction in vasomotor symptoms, vaginal dryness, and improvement in sleep. Also monitor for breakthrough bleeding and spotting, adverse effects of HRT, and improvement in QOL. 

Fugate SE, Church CO. Nonestrogen treatment modalities for vasomotor symptoms associated with menopause. Ann Pharmacother 2004 38 1482-1499. 

Utian WH, Shoupe D, Backmann G, et al. Relief of vasomotor symptoms and vaginal atrophy with lower doses of conjugated equine estrogens and medroxyprogesterone acetate. Fertil Steril 2001 75 1065-1079. 

---