Every year, approximately 2 million women in the United States enter menopause. Most of these women will experience a wide variety of symptoms related to fluctuating or declining levels of estrogen, progesterone, follicle-stimulating hormone, and luteinizing hormone. For instance, approximately 80% of these women will experience vasomotor symptoms (VMS) at some point during perimenopause to postmenopause. Research has shown that VMS can cause substantial emotional and physical distress, and that approximately 60% of women will seek help from a healthcare practitioner to alleviate these symptoms. By tradition, hormone therapy (HT) has been widely and effectively used to treat VMS. However, some women may prefer not to use HT or they may not be good candidates for its use. The purpose of this article is to provide nurse practitioners with an overview of alternative (non-HT) methods discussed in the literature for the treatment of VMS. NPs can then provide VMS sufferers with information, education, guidance, and referrals regarding alternative treatment modalities so that these women can aim to achieve adequate symptom relief.

Perimenopause to Postmenopause

In 2008, approximately 43 million US women were between the ages of 40 and 65 years.¹ Most women in this age group are in the perimenopausal to postmenopausal stage of life, and will stop menstruating at some point between the ages of 40 and 58 (mean age, 51 years).^2,3 Each year, about 2 million US women enter menopause.²

During perimenopause, the ovaries may produce widely fluctuating amounts of estrogen and progesterone, resulting in menstrual cycles that may vary in length and frequency until cessation of menses occurs. This period of variability may last 4-8 years.² Of note, a small proportion of women may have normal cycles until their final menstrual period. From a clinical standpoint, a woman has reached menopause when she has had no menstrual bleeding due to natural causes for 12 months.^2,3

Vasomotor Symptoms

Some women experience VMS as the changes in their menstrual cycle start to occur, others have VMS without any noticeable changes in their period, and still others experience VMS as a result of surgically- or pharmacologically-induced menopause related to treatment for breast or gynecologic cancer.^2,4,5 The variability and ultimate decline in serum estrogen levels in women experiencing natural menopause, or the abrupt cessation of estrogen secretion in women experiencing surgical or chemical menopause, usually causes VMS—hot flashes and night sweats—as well as other signs and symptoms listed in Table 1.^2,5-12

 

Vasomotor symptoms are the most frequently reported symptoms by women who are (1) in the menopausal transition, (2) postmenopausal, or (3) receiving systemic therapy such as tamoxifen for breast cancer.^13,14 Moreover, VMS, as compared with other menopause-related symptoms, are associated with the greatest amount of emotional and physical distress.^5,15 Fourteen percent to 51% of premenopausal women, 79% of perimenopausal women, and 65% of postmenopausal women experience VMS.^12,16,17 VMS may also affect some women into their 70s.¹³ 

Because VMS can last for many years, interfere with sleep and daily activities, and affect quality of life (QoL),^15,17,18 60% of women seek advice and/or intervention from a clinician to provide relief.¹² A 2002 Gallup poll showed that women who sought clinical attention for VMS relief did so because of hot flashes (70%), night sweats (68%), mood disturbances (50%), and/or sleep disturbances (49%).¹² Most women experience these symptoms for 6 months to 2 years, but as many as 10% may experience them for ≥10 years.¹² To meet these women’s needs, NPs must be able to educate, advise, and, if indicated, refer patients so that they can implement appropriate lifestyle modifications, interventions, and/or treatments.

Hot flashes are described as a symptom complex that begins with a sudden sense of redness, flushing, warmth, or intense heat; hot flashes typically start at the chest and then spread to the neck and face, and may be accompanied by sweating, palpitations, and anxiety.^15,17 Hot flashes, which may last just a few seconds or for as long as 10 minutes, have an average duration of 4 minutes.¹⁰ For some women, they occur only a few times a week; others experience hot flashes hourly.¹⁰

Women who experience hot flashes, compared with those who do not, have an increased core temperature and a reduced thermoneutral zone (the zone between shivering and sweating).¹¹ Although the exact neuroendocrine mechanism responsible for VMS is not completely understood, one hypothesis ascribes these symptoms to fluctuating estrogen and progesterone levels and estrogen withdrawal, which leads to a series of changes in levels of neurotransmitters and other hormones.^5,11,17 This phenomenon, in turn, results in an increase in a woman’s core temperature and a narrowing of the thermoneutral zone, which leads to skin vasodilation and a feeling of warmth.^10,11,17 As levels of estrogen decline during menopause, there is an increased release of norepinephrine and serotonin from the hypothalamus.15,19 This activity lowers the set point of the thermoregulatory nucleus, allowing subtle changes in core body temperatures to trigger inappropriate heat-loss mechanisms.¹⁵

Factors associated with an increased risk for experiencing VMS include age (40-58 years), higher body mass index (BMI), smoking, baseline anxiety and/or depression, and having less than a college education.^6,12 Ethnicity also plays a role: African Americans have the highest prevalence of VMS, followed by Hispanic Americans, Caucasians, Chinese Americans, and Japanese Americans.^3,10,12 Postmenopausal Caucasians, more than postmenopausal women of other racial groups, report more difficulty sleeping.³ In addition, women who undergo surgically- or chemically-induced menopause, as opposed to natural menopause, are thought to have a higher incidence, more abrupt onset, longer duration, and increased severity of VMS.^5,10,19,20

Traditional Hormonal Management

Traditional HT has been shown to be the most effective treatment for VMS,^{5,7,10,16,17,21-23} reducing symptoms by up to 90%.¹⁷ However, following the early discontinuation of the estrogen/progestin arm of the Women’s Health Initiative (WHI) in 2002,²⁴ major concerns arose regarding HT use. This arm of the WHI was terminated early because the test statistic for invasive breast cancer exceeded the stopping boundary for this adverse effect and the global index statistic supported risks (eg, coronary heart disease, stroke, pulmonary embolism) exceeding benefits (eg, colorectal cancer, hip fracture).^17,24,25 Concern about an increased risk for breast cancer recurrence led to early termination of the HABITS (Hormonal Replacement Therapy After Breast Cancer—Is It Safe?) trial.¹⁵ As a consequence of these trials and reports about them in the media, some women and their clinicians have sought alternative methods for VMS management.^11,15 These alternatives are discussed in the next sections.

Dietary and Lifestyle Modifications

Weight Loss—Obese women, versus women with a normal BMI, have reported higher VMS scores and lower health-related QoL scores.⁶ A longitudinal study showed that a weight increase exceeding 11 pounds correlated with a significant increase in somatic symptoms.⁶ By contrast, weight loss has been found to reduce VMS risk.^6,12

Because women with higher adiposity have higher estrogen concentrations, they were first thought to have fewer VMS than their thinner counterparts (androstenedione is aromatized into estrone in adipose tissue and is therefore a supplemental source of estrogen).¹⁷ However, current findings have suggested that increased adiposity is a potent insulator that inhibits heat loss and requires more events to achieve heat loss, thereby increasing the level of VMS.¹⁷ Body fat has been shown to have the strongest insulating capacity of any body tissue; therefore, obese persons have a decreased ability to efficiently dissipate heat.¹⁷ A greater percentage of body fat correlates with a higher frequency and duration of VMS—more so during the menopausal transition period than during the postmenopausal period.¹⁷ Having a BMI >27 kg/m² has been found to directly correlate with more frequent hot flashes and night sweats.³ Weight loss, with attention to loss of fat mass, is a relevant recommendation for women with a high BMI during the menopause transition, especially when they are seeking alternative methods for VMS management.^17,26

Diet. NPs should advise VMS sufferers to avoid hot and/or spicy foods and beverages and consume cool or cold foods and drinks to reduce core body temperature.^3,12,27 Sugar- and caffeine-containing foods and beverages have been linked to increased frequency and severity of VMS.³ Sipping on a cool beverage, especially water, during a hot flash may reduce its severity and provide relief. Drinking the recommended 6-8 glasses a day can help replace fluids lost by increased sweating and has been found to reduce VMS.³ 

Exercise. Regular physical activity and exercise are encouraged. Even though a significant correlation has not been found between exercise and either a reduction or an increase in VMS,⁶ a strong correlation has been found between improvement in health-related QoL outcomes and a reduction in symptoms, especially psychological and psychosomatic symptoms, that can affect women in menopause.⁶ Studies on the effects of exercise have focused primarily on physiologic outcomes such as body composition and bone density changes.⁶ Only a few studies have reported on the effect of exercise on VMS and mood-status changes. Some studies have shown that more physically active women have fewer menopausal symptoms, less nervousness, and a reduction in depression.^6,7 Observational studies have indicated that women who are more active report fewer and less severe symptoms, but the evidence is inconclusive.^7,27 The mechanism of action with regard to exercise’s presumed beneficial effect on VMS is unknown.⁷ Also, only a few studies have investigated the impact of physical activity on QoL during menopause.⁷ Perhaps exercise affects endogenous opioid production, specifically the neurotransmitter beta-endorphin, which is known to affect thermoregulation. With exercise, levels of these endorphins rise—counteracting a drop in endorphin levels related to declining estrogen levels during menopause.^7,27 

Women who are physically active on a regular basis are reported to have a higher level of self-esteem.⁷ And women who have a higher level of self-esteem report fewer menopausal symptoms and distress than do those who report low self-esteem.⁷ These findings support the correlation between regular physical activity and improvements in psychological well-being and physical self-worth and a diminution in reported menopausal symptoms, regardless of the stage of menopause.⁷ Also, women who participate in regular physical exercise are more likely to have lower adiposity and lower BMI, which have been correlated with decreased VMS.

Relaxation Techniques—Paced respirations that include slow, controlled diaphragmatic breathing have been shown to reduce VMS.^12,22,23 A 12-session program of applied relaxation techniques, wherein women are taught specific ways to rapidly calm down and gain control at VMS onset, has been shown to be highly effective.²⁸ If applied relaxation is initiated at the first sign of a hot flash, women can calm themselves through their breathing, reducing norepinephrine activity and enhancing beta-endorphin activity, and thereby improve their sense of well-being and minimize the hot flash.²⁸ Women who utilize these techniques have experienced a decrease in VMS and improved psychological well-being.^12,22,23,28

Yoga. Two separate pilot studies involving women who experienced at least 4 hot flashes a day and who attended an average of 7-8 yoga classes over 3 months showed that these women experienced fewer hot flashes per week and a reduction in hot flash severity.^22,23 In one study, women also reported fewer sleep disturbances and improved sleep quality.²² It is uncertain whether yoga, in and of itself, reduces hot flashes, but perhaps the controlled breathing, paced respirations, relaxation techniques, postures, and meditation used in yoga may improve psychological well-being and, ultimately, a woman’s ability to cope with VMS.^22,23

Acupuncture. Studies have shown that hot flash frequency has diminished in women after receiving acupuncture. Deng et al¹⁴ evaluated the immediate and long-term effects of true acupuncture versus sham acupuncture on hot flash frequency in women with breast cancer. The mean number of hot flashes per day was reduced from 8.7 to 6.2 in the true acupuncture group and from 10.0 to 7.6 in the sham group. True acupuncture was associated with 0.8 fewer hot flashes per day than sham acupuncture at 6 weeks, but the difference did not reach statistical significance (P = .3). Of interest, when participants in the sham acupuncture group were crossed over to true acupuncture, a further reduction in the frequency of hot flashes occurred. This reduction in hot flash frequency persisted for up to 6 months after the completion of treatment. 

Nedstrand et al²⁸ compared the effects of applied relaxation versus electro-acupuncture on psychological well-being in breast cancer-treated women with VMS. In both groups, hot flashes diminished by >50%, climacteric symptoms significantly decreased during treatment and for 6 months post-treatment, and psychological well-being improved significantly during treatment and at follow-up visits. Mood improved significantly in the electro-acupuncture group.

Acupuncture may activate beta-endorphins in the brain (similar to exercise) and help stabilize thermoregulation and increase psychological well-being.^14,28 Researchers recommend larger, longer, more intense programs of acupuncture to produce a greater reduction in symptoms and evaluate the effectiveness of this modality in reducing VMS.^3,14,28

Lifestyle modifications. NPs should encourage women to avoid, or at least limit, alcohol consumption, and they should advise smokers to begin a smoking-cessation program, not only to improve overall health, but also to reduce the existence, frequency, and/or duration of VMS.^3,12  Smoking is associated with an earlier onset of menopause, an increase in most menopause-related symptoms, and increased bone loss.³ In some studies, the level of alcohol consumption has been found to bear a significant correlation with the number of hot flashes experienced; however, other studies have found no such correlation.²⁶ NPs should encourage women to assess the effects of alcohol consumption in relation to the number, intensity, and duration of their VMS.

To assist in regulation of core body temperature, NPs can encourage women to dress in layers of lightweight, moisture-wicking fabrics (eg, cotton, linen) and to use fans or air conditioning to keep room temperatures cool.^3,12,27 NPs can advise women to avoid wearing silk or synthetic fabrics that do not absorb sweat, as well as turtlenecks, slips, and full-length stockings.³

Non-hormonal Pharmacologic Interventions

Although HT has been found to be the most effective treatment for the reduction of VMS, some women may prefer not to use HT or they may not be good candidates for its use (Table 2).²⁹ Non-hormonal pharmacologic interventions are alternatives that women may inquire about (see the right side of page for Table 3). The following sections provide a brief overview of the current literature regarding pharmacologic approaches to the treatment of VMS, including their associated risks and benefits.

Antidepressants—Antidepressants have been found to effectuate a modest reduction in hot flashes and improve mood in women suffering from mood disorders.^11,12 The mechanism whereby antidepressants reduce VMS is unknown.¹² Some experts postulate that the fluctuations and the eventual reduction in estrogen levels result in changes in the levels of neurotransmitters, specifically serotonin and norepinephrine, increasing core temperature and narrowing a woman’s thermoneutral zone.^11,12,16 Because serotonin and norepinephrine are neurotransmitters in the thermoregulatory nuclei of the hypothalamus, they are thought to play a role in normal thermoregulatory function.¹⁶ 

The American College of Obstetricians and Gynecologists (ACOG), the American Association of Clinical Endocrinologists (AACE), and The North American Menopause Society (NAMS) consider antidepressants to be the most effective non-hormonal pharmacologic treatment for VMS.¹² Although antidepressants have been used for VMS relief, they have not been approved by the US Food and Drug Administration for this indication.¹² When prescribing antidepressants for this purpose, NPs must be aware that individual agents (1) have variable efficacy;12 (2) can be associated with nausea, decreased appetite, mouth dryness, sleeplessness, and sexual dysfunction; and (3) should be tapered slowly to prevent discontinuation syndrome.¹¹

Fluoxetine. The recommended dosage of this selective serotonin reuptake inhibitor (SSRI) is 20 mg/day.¹² NPs must use caution when prescribing fluoxetine to women who are using tamoxifen because fluoxetine inhibits cytochrome P450 (CYP450) 26D and can alter tamoxifen’s metabolism and affect its efficacy.¹¹

Paroxetine. The mechanism of action of this SSRI is thought to be related to an increase in serotonin levels and a decrease in luteinizing hormone levels, resulting in reduced VMS severity.²⁵ The recommended dosage is 12.5-25 mg/day.¹² A randomized, double-blind, placebo-controlled study of 165 menopausal women showed that those who received paroxetine CR had a 50% reduction in hot flash scores.³⁰ Although the duration of the effects was unknown, treatment was well tolerated, especially at the lower dose. NPs must use caution in prescribing paroxetine for women who are using tamoxifen because the SSRI inhibits CYP450 26D and can alter tamoxifen’s metabolism and affect its efficacy.¹¹

Venlafaxine, a serotonin-norepinephrine reuptake inhibitor (SNRI), has been found to reduce hot flash frequency by up to 55%.¹¹ This agent is a reasonable first-line therapy in breast cancer survivors.⁵ The recommended dosage is 75 mg/day.¹²

Desvenlafaxine succinate, the succinate salt form of the major active metabolite of venlafaxine, is highly selective for serotonin and norepinephrine transporters, well absorbed with good bioavailability, and well tolerated with few adverse effects.¹⁶ Desvenlafaxine exhibits minimal effects on CYP450 pathways and can be used to treat moderate to severe VMS. Studies have shown a 50% reduction from baseline in the number of hot flashes after 1 week of treatment. A 100-mg daily dose has been shown to reduce moderate to severe VMS by 64% by week 12 and significantly improve night-time sleep. Dose-related side effects include asthenia, constipation, dry mouth, nausea, dizziness, headache, insomnia and somnolence, decreased libido, and abnormal thinking, with nausea, dizziness, and difficulty sleeping being the most common. To reduce adverse effects, NPs start patients on a dosage of 50 mg/day, with the dosage titrated up to 100 mg/day as tolerated. As with all SSRIs and SNRIs, the dosage is gradually tapered when patients are taken off the drug.¹⁶ Although low-dose desvenlafaxine is not known to have cardiovascular side effects, NPs need to monitor patients’ blood pressure at treatment initiation and throughout treatment because of reports of treatment-related hypertension with high doses of desvenlafaxine.¹⁶

Anticonvulsant—Gabapentin, a gamma aminobutyric acid analog, may have a direct effect on the hypothalamic thermoregulatory center located in the ventromedial hypothalamus.²⁵ At a dosage of 900 mg/day, gabapentin was found to reduce the severity and frequency of hot flashes by approximately 50% in postmenopausal women and in women with breast cancer.²⁵ One study showed that gabapentin users experienced a mean reduction of 2.05 hot flashes/day.^11,12 A randomized, double-blind, placebo-controlled study of 420 women with breast cancer showed a 44% reduction in frequency, a 9% reduction in duration, and a 46% reduction in severity of hot flashes after 8 weeks of therapy with gabapentin 900 mg/day.¹⁵ Gabapentin, given alone or with an antidepressant, has been associated with a similar reduction in hot flash frequency.¹¹ This finding supports the discontinuation of one agent when starting another in order to reduce unnecessary polypharmacy.¹¹ 

Side effects associated with gabapentin include lightheadedness, dizziness, peripheral edema, decreased serum albumin, and somnolence/fatigue.^11,15 Dizziness, unsteadiness, and drowsiness reported by some women after 1 week of treatment appeared to improve by week 2 and return to baseline by week 4.³¹ Recommended dosing for gabapentin is 300 mg 3 times daily (total daily dose, 900 mg).^12,31

Alpha-adrenergic Agonist—Use of clonidine, an agent used to treat hypertension, has been associated with a modest improvement in VMS related to duration of treatment.^11,25 Clonidine reduces peripheral and central vascular reactivity, thereby reducing VMS severity, and it has been shown to significantly reduce VMS frequency.²⁵ Clonidine was found to reduce the mean number of daily hot flashes by 1.63 after 8 weeks when given orally at a daily dose of 0.1 mg or as a transdermal patch weekly (0.1 mg daily equivalent).¹²

Herbal Remedies and Dietary Supplements

The mechanism of action whereby herbal remedies reduce VMS frequency is unknown.¹² The effects may be sensitive to dose, methods of extraction, type of plant, and whether or not these agents are taken singly or in combination.²¹ NAMS states that women with mild VMS symptoms not controlled by lifestyle modifications may consider herbal remedies.¹² The NAMS statement is based on the fact that these remedies have not been associated with serious side effects when used for a short duration of ≤6 months; however, because of inconclusive efficacy data, use of herbal remedies is not a consensus recommendation.¹² AACE does not advocate for or against the use of herbal remedies but cautions about the lack of regulations and standardizations and the potential for interaction with other medications and health conditions.¹² ACOG does not recommend the use of herbal remedies, citing a lack of significant effects on VMS and a lack of clinical efficacy.¹² 

Black Cohosh (Cimicifuga racemosa)—This herbal product contains glycosides and terpenes. Many smaller studies have shown black cohosh to be more effective than placebo in reducing the severity of mild to moderate VMS, sweating, anxiety, depression, and mood and sleep disturbances.^25,32 Recent evidence has suggested that black cohosh acts as a selective estrogen receptor modulator (SERM) with mild estrogenic effects. Purported estrogenic effects have resulted in a recommendation that black cohosh not be used in women with a history of breast cancer or estrogen-dependent tumors.^12,25 Of note, a 1-year randomized, double-blind, placebo-controlled trial conducted from May 2001 to September 2004 on 351 women—known as the HALT (Herbal Alternatives for Menopause) study—showed that black cohosh, used alone or in combination with dietary soy, multibotanicals, counseling, or placebo, did not affect reproductive hormones, the endometrium, the vaginal epithelium, the menstrual cycle, vaginal dryness, VMS intensity, or the number of VMS episodes per day.^21,32 The authors of the study recommended that clinicians educate women about the lack of evidence with regard to clinical efficacy.³²

For the record, the recommended daily dose of black cohosh is 40 mg.¹² Because most studies have not investigated the effectiveness or safety of black cohosh use for >6 months, ACOG advises that its use be limited to ≤6 months.³³ According to ACOG,³³ although black cohosh is a botanical treatment widely used in Europe for menopausal symptoms, its benefits have been evaluated primarily in small short-term studies using since-invalidated measures. The few randomized, controlled trials on black cohosh showed no significant reduction in hot flashes.

Nurse practitioners are alerted to the fact that some women may confuse black cohosh with blue cohosh. Blue cohosh has been found to have effects similar to those of black cohosh, but its safety has not been fully tested. Blue cohosh may exhibit estrogenic activity and, because of its ability to induce strong uterine muscle contractions, it may be a potential abortifacient.³⁴ Blue cohosh has been found to increase blood sugar levels and blood pressure, stimulate the small intestine, and encourage menstruation and increase menstrual flow.³⁴

Soy and Red Clover Isoflavones—Studies have shown little, if any, difference in the mean number of daily hot flashes in women who use soy or red clover isoflavones versus placebo.^11,12,21 Both herbal products are thought to act on estrogen receptors, and should not be used in women with a history of breast cancer or estrogen-dependent tumors.¹² Studies have not shown a reduction in hot flashes with the use of red clover, but some experts believe that isoflavones may relieve symptoms in postmenopausal women by acting like HT.³⁴ The recommended daily dose is 40-80 mg.¹² According to ACOG,³³ a few very limited studies have suggested that soy helps with VMS in the short-term (<2 years), whereas other studies have shown little difference between soy beverages or extracts and placebo. A study of two dietary phytoestrogen supplements derived from red clover showed no clinical effects on hot flashes or other symptoms.³³

Evening Primrose Oil—Active ingredients in evening primrose oil are alpha and gamma linolenic acid. The mechanism of action in the treatment of VMS is unknown.²⁵ A trial of 2000 mg/day of evening primrose oil, given with 10 mg/day of vitamin E, produced a reduction in daytime hot flashes, but there was a high dropout rate because of unrelieved symptoms, resulting in unreliable conclusions.²⁵ 

Naturopathic Approach—The approach used by naturopathic physicians when prescribing non-pharmacologic interventions or dietary supplements is known as the whole-person approach, which may affect response to therapy.²¹ Counseling menopausal women about diet, exercise, and emotional concerns; revising dosages; and adding other supplements are important aspects of the naturopathic approach.²¹ Of note, a small study showed that women treated by qualified herbal practitioners had a statistically significant reduction in menopausal symptoms, especially VMS.35 NPs working with women to reduce menopausal symptoms may consider adopting this approach in order to achieve higher satisfaction with treatment choices.

Conclusion

Despite the adverse findings regarding the use of HT in menopausal women in the WHI, and the evidence against its use in women with a history of breast cancer or estrogen-dependent tumors, there has been a lack of large, randomized controlled trials investigating alternative treatments for women who suffer from VMS. Some women experience VMS that are so severe that their QoL and activities of daily living are significantly affected. Clinicians may substantially underestimate their patients’ levels of concern about menopausal symptoms.¹⁹

The NP role in evaluating and treating women with VMS is to first assess their understanding of their menopausal symptoms and then to discuss the benefits, adverse effects, and scientific uncertainties related to each specific treatment option.¹¹ Working with each woman, NPs can develop an appropriate treatment plan based on her health history, lifestyle, and wishes; provide appropriate referrals; and, if necessary, work with her to encourage open communication. 

As with all new treatment plans, NPs need to schedule patients for follow-up visits in order to evaluate the plan’s effectiveness in reducing troublesome VMS, to minimize complications and side effects, and to assess for the need to change the treatment plan. Providing women with instructions and contact information to report or discuss adverse side effects or concerns will encourage them to maintain open communication throughout this transitional stage. With 79% of all women experiencing some degree of discomfort due to VMS and 60% of them seeking assistance in symptom management, NPs’ knowledge about treatment options must be as up-to-date as possible. NPs can then educate, collaborate with, and empower women to effectively manage their symptoms and improve their QoL.

Debra A. Walz is a recent graduate of the Women’s Health/Oncology Dual Nurse Practitioner Program and Mary-Jane McEneaney is Program Director of the Women’s Health Nurse Practitioner Program, both at Columbia University School of Nursing in New York City. The authors state that they do not have a financial interest in or other relationship with any commercial product named in this article.

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