Figure. Illustration (C) Nancy Goodman Lawrence, nancygoodmanlawrence.com.

VASOMOTOR SYMPTOMS

It's believed that hot flashes originate in the hypothalamus, where estrogen withdrawal causes a dysfunction in the central thermoregulatory center. The trigger is thought to be changing levels of estrogen in the circulation, not lowered levels. Neurotransmitters, primarily norepinephrine and serotonin, also play a role in hot flashes. Shanafelt and colleagues describe the pathway as starting with estrogen withdrawal, which leads to a decrease in the release of endorphin and catecholestrogen, causing an increased hypothalamic release of norepinephrine and serotonin, which lowers the thermoregulatory set point.1 As a result, subtle changes in core body temperature will set off heat-loss mechanisms such as sweating and sending blood to the peripheral circulation, close to the surface, where it can get cooled.

Studies indicate that 55% to 79% of women experience vasomotor symptoms to some degree during and after the menopausal transition.2, 3 The average duration of these symptoms ranges from five to 10 years, regardless of treatment,4 with the severity and frequency of symptoms peaking during late perimenopause and early postmenopause.5, 6 A meta-analysis found that for most women vasomotor symptoms didn't return to baseline until eight years after menopause, and in 10% of women it took as long as 12 years.7

Who will have hot flashes? The answer to that question isn't known. But there's strong evidence that race and ethnicity are factors. African Americans report the highest incidence of hot flashes and Asians report the lowest.8-10 The reason is unclear, but it may be related to cultural influences or genetic factors.11

There appears to be an association between body mass index (BMI) and hot flashes-the underlying mechanism is believed to be the conversion of androgens to estrogen in body fat, resulting in endogenous estrogen at levels that vary according to a woman's body size-but study findings are conflicting. Some suggest that increased BMI lowers the risk of hot flashes while others indicate the opposite.10 Recent studies that find increased hot flashes in women with higher BMIs, especially those with abdominal fat, challenge the prevailing belief that thin women have less endogenous estrogen and thus suffer more from hot flashes.12, 13 The association could also be explained by an increased core body temperature in heavier women, whose body fat provides insulation.14

There's mixed evidence of the effects of physical activity on hot flash risk.15 In a study of 1,427 women ages 45 to 64 years, sedentary subjects reported more vasomotor symptoms than physically active subjects did.16 But a review of the literature on lifestyle factors and hot flashes found no relationship between physical activity and risk of hot flashes, although the authors note that small sample sizes and low incidence of hot flashes could have affected their findings.17

Genetics also likely plays a role. A study of a subsample of 174 women from the Seattle Midlife Women's Heath Study found that polymorphisms in the cytochrome P-450 (CYP) isoenzyme CYP19 11r allele were associated with more frequent and severe hot flashes.18 A study of a multiracial and multiethnic group of women (N = 1,467) from the Study of Women's Health Across the Nation compared the prevalence of vasomotor symptoms to results of genotyping for single nucleotide polymorphisms in sex steroid-metabolizing genes and estrogen receptors.19 The researchers found associations between certain polymorphisms and the prevalence of vasomotor symptoms that were specific to race and ethnicity and assert that more study is needed.

There's strong evidence that smoking increases the risk of hot flashes10, 17 and some evidence that low socioeconomic level and stress are risk factors.8, 14 Vasomotor symptoms are associated with increases in depression, anxiety, sleep disturbances, and somatic symptoms such as fatigue, pain, or dizziness.20-22 Women with vasomotor symptoms are significantly more likely to suffer from depression, and that likelihood increases as symptoms increase in severity.20, 23

Managing vasomotor symptoms. Estrogen therapy is the most effective treatment for menopause-related hot flashes.24 But its well-known risks related to cardiovascular disease and breast cancer limit its use; many women prefer nonhormonal strategies. (See the first article in this series, "Menopausal Hormone Therapy: What We Know Now," June 2011). Other available treatments include nonhormonal pharmaceutical agents, complementary therapies, and exercise.

Nonhormonal pharmaceutical agents include selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and gabapentin (Neurontin). All three are effective in treating hot flashes, but efficacy varies among the SSRIs and SNRIs. In a pooled analysis of 12 studies the SSRI paroxetine (Paxil) and the SNRI venlafaxine (Effexor) decreased hot flash scores by 41% and 33%, respectively, compared with 18% for placebo, 13% for fluoxetine (Prozac), and 3% for sertraline (Zoloft).25 The same analysis found that gabapentin decreased scores by 35% to 38%. The SSRI escitalopram (Lexapro) is also effective in decreasing the frequency and severity of hot flashes.26

The SSRIs and SNRIs are generally well tolerated, with discontinuation rates ranging from 5% to 21% in primary care.27, 28 The most common adverse effects are sexual dysfunction, nausea, and weight gain; others include sleep disturbances, dry mouth, temporary nausea, fatigue, and constipation. Gabapentin is also well tolerated; in clinical trials, drop-out rates of 10% to 13% due to adverse effects, usually dizziness, have been reported.29, 30 Adverse effects tend to be greater early in treatment and diminish after two to three weeks with both gabapentin and the SSRIs and SNRIs.

Complementary and alternative medicine (CAM). Many women turn to CAM for relief from hot flashes, despite scant evidence to support many of the most common strategies. Phytoestrogens, or plant-based estrogens, are among the most popular products, particularly isoflavones, one type of phytoestrogen often derived from soy. It's believed that the high soy content of many Asian diets accounts for the lower rates of hot flashes among Asian women. But little scientific evidence supports the use of phytoestrogens to reduce hot flashes. A 2007 Cochrane review found no evidence that phytoestrogens relieve hot flashes,31 while a more recent meta-analysis found inconclusive evidence, with a significant positive trend.32 Red clover, another source of isoflavones, hasn't been found effective against hot flashes.33, 34

Black cohosh, a plant in the buttercup family, is also popular, but evidence of its effectiveness is mixed. A 2008 systematic review found the evidence for efficacy to be inconclusive,35 while a 2010 meta-analysis found some effectiveness (although the researchers noted a high degree of heterogeneity in the included studies).36 Additionally, a National Institutes of Health randomized clinical trial found that black cohosh was less effective than placebo at reducing hot flashes (34% versus 63%, respectively).33

Acupuncture, a form of traditional Chinese medicine, has produced mixed findings but with a positive trend for effectiveness. A systematic review conducted in 2008 found no significant difference between true acupuncture and sham acupuncture-the placement of needles in placebo sites.37 There's some debate, however, over whether sham acupuncture itself constitutes a treatment; needling regardless of site has produced known physiologic effects.38 A recent study found that both sham and true acupuncture improved hot flashes and that women couldn't distinguish between the two.39 Recent studies have also shown positive results when sham acupuncture isn't used as the control. The 2009 large multicenter Acupuncture on Hot Flushes Among Menopausal Women trial found that women who received 10 acupuncture sessions and advice on self-care had significantly fewer and less intense hot flashes after 12 weeks than women who received only self-care advice.40 The benefits were only short-term, though; no differences were found at six and 12 months. A 2010 multicenter study also found significantly greater improvement with the use of acupuncture.41

Exercise is often recommended as a way to minimize hot flashes, but the evidence supporting it is weak. A 2009 Cochrane review concluded that evidence was insufficient to determine its effectiveness, although the researchers noted "a weak trend for exercise to be more effective than no intervention."42 The researchers updated their review in 2011 and concluded that, although evidence continued to be weak, results of some newer trials showed the benefits of exercise among menopausal women, both those who did and did not suffer from hot flashes.43

INSOMNIA

Sleep disturbances are common during and after the menopausal transition. Overall, 40% to 48% of peri- and postmenopausal women report having difficulty sleeping.44 A study by Tom and colleagues found that women in the menopausal transition were two-to-three-and-a-half times more likely than premenopausal women to report severe sleep difficulty.45 There's a significant drop in sleep time in women after the age of 50,46 and sleep quality and efficiency decrease as well.47, 48

Insomnia, defined as difficulty falling asleep or staying asleep that results in daytime impairment or distress,49 significantly affects women's lives. It can cause daytime sleepiness, decreased concentration, mood disorders, decreased productivity, decreased quality of life, and job-related and motor vehicle accidents.50, 51 A study of 5,781 postmenopausal women found that women experiencing night awakenings (n = 141) at least twice weekly had greater activity impairment (including presenteeism) and poorer health-related quality of life than women who didn't have insomnia and the general population.50

Causes of insomnia. Women reporting sleep disturbances should be assessed for the presence of a primary sleep disorder, particularly sleep-disordered breathing (SDB) and periodic limb movement.52 The prevalence of both of these disorders has been shown to increase during and after menopause. Assessment for SDB is especially important: studies show its serious health implications, including the risk of hypertension, cardiovascular disease, stroke, and death from any cause.53, 54

A 2001 sleep study by Bixler and colleagues included a one-night sleep laboratory evaluation of 1,000 men and women.55 The prevalence of sleep apnea was 2.7% in postmenopausal women not taking hormone therapy and 0.5% in premenopausal women. A later examination of menopausal status and SDB in 589 women enrolled in the Wisconsin Sleep Cohort Study found that menopause was significantly associated with an increased risk of SDB (defined as repeated episodes of apnea-hypopnea during sleep) even after adjusting for age, smoking, and weight.56 Postmenopausal women were two-and-a-half times more likely than premenopausal women to have five or more apnea-hypopnea episodes a night and three-and-a-half times more likely to have 15 or more episodes. A recent study of 93 women found that postmenopausal women were one-and-a-half times more likely than premenopausal women to have more than five apnea-hypopnea episodes an hour during sleep.47

Periodic limb movement, a parasomnia characterized by bilateral repetitive movements of the extremities (usually the legs but sometimes also the arms), disrupts sleep, and there's some evidence that it's more prevalent in postmenopausal women.47, 57 This may be owing to estrogen's effect on dopamine.

Vasomotor symptoms can also disturb sleep in peri- and postmenopausal women. Studies consistently find significant associations between sleep difficulty, particularly nighttime and early morning awakening, and hot flashes or night sweats.44, 58, 59

Sedentarism has been found to be associated with sleep difficulties in menopausal women. In their study of 149 Ecuadorean women, Chedraui and colleagues found that sedentary women had more than three times the risk of daytime sleepiness than more active women did.59 And in a study of 340 women, Arakane and colleagues found that sedentarism (15 minutes or less of twice-weekly activity) correlated positively with elevated scores on the Insomnia Severity Index.58

Cognitive behavioral therapy(CBT) is the primary nonpharmacologic treatment and should be considered the first-line treatment for sleep problems during menopause. CBT aims at developing thoughts and behaviors that promote sleep and eliminating those that contribute to insomnia (see Table 1). There's strong support for CBT's effectiveness in treating insomnia when it's conducted by a behavioral specialist, such as a licensed therapist or psychologist.60-62 Although I found no studies that looked at the effectiveness of CBT in improving sleep in otherwise healthy menopausal women, a meta-analysis that looked at its use in men and women ages 55 and older found moderate-to-large positive effects.61 Sleep-hygiene behaviors, such as maintaining a quiet sleeping environment and avoiding caffeine, are sometimes considered CBT, but on their own they haven't been correlated with sleep improvement in people with sleep disturbances.63

Table 1. Cognitive Behavioral Therapy Strategies for Insomnia

Women who don't have access to CBT may find self-help methods useful. A meta-analysis found small-to-moderate improvements in sleep outcomes after use of self-help cognitive-behavioral methods such as audiotapes, online programs, and sleep diaries.64 But the authors write of the strong possibility of publication bias in the studies reviewed, which may have led to an overestimation of the effect of these interventions.

Pharmacologic agents should be used only when nonpharmacologic strategies don't work. Those used most often are benzodiazepines, nonbenzodiazepines, antidepressants, and melatonin receptor agonists. A meta-analysis of 105 studies found that benzodiazepines and nonbenzodiazepines were effective treatments for insomnia, producing shorter delays in sleep-onset times (known as sleep-onset latency) and improvements in sleep as recorded in sleep diaries.65 It also found that some of the older antidepressants, particularly doxepin (Sinequan) and trazodone (Desyrel and others), may help as well. But all of these drug classes were associated with significant risk of adverse effects: headache, dizziness, nausea, fatigue, and somnolence, among others.

In a relatively recent class of sleep medications, the melatonin receptor agonists, there's only one drug available, ramelteon (Rozerem). It has been shown to decrease sleep-onset latency and increase total sleep time.49 But the improvement is small; sleep onset was less than 10 minutes sooner with ramelteon than with placebo and total sleep time was only 11 to 14 minutes longer, depending on the dose. It's usually well tolerated; the most common adverse effects, headache and somnolence, are similar to those associated with other sleep medications. Rare neuropsychiatric reactions have been reported with use of zolpidem (Ambien), more often in women than in men. These include driving, walking, and eating while asleep, usually without any memory of the event.

CAM. There's little scientific evidence to support the use of most CAM approaches in managing insomnia. Results of a recent meta-analysis were weakly positive for yoga, t'ai chi, and acupressure and mixed for acupuncture.66 The results did not support the use of herbal medicines, while studies examining homeopathy, massage, and aromatherapy did not meet the inclusion criteria. An earlier systematic review also found no evidence that the use of homeopathy medicines or treatment by a homeopath were effective in treating insomnia.67

The evidence for the effectiveness of isoflavones is weak as well. Hachul and colleagues found a positive effect for isoflavones in their study; the percentage of women who reported moderate-to-severe insomnia decreased from 94% to 63% in women in the placebo group and from 90% to 37% in the group using isoflavones.68 The sample of 38 women was too small, however, to place confidence in the results.

Melatonin may be an effective option for women who have difficulty falling asleep. A recent meta-analysis found that melatonin decreased sleep-onset latency by more than 23 minutes in both children and adults, although it didn't change the total sleep time or the awakening time.69 The authors write that melatonin should be taken so that it works with the biologic clock, optimally three to six hours before the onset of endogenous melatonin, which usually occurs as natural light dims. Small doses help to prevent morning sleepiness.

PSYCHOLOGICAL SYMPTOMS

Most women will go through the menopausal years without significant mood changes. But a number of large studies have found that the menopausal transition is associated with increased rates of depression and anxiety.70-74 The increased risk is highest in women with a history of mood disorders, but menopause raises the risk of depression and anxiety even in women without such a history. Symptoms tend to be worse in the perimenopausal period, when hormones are in the most flux and hot flashes are at their peak.73 Studies have consistently found a strong association between vasomotor symptoms and both depression and anxiety.20, 21 According to a retrospective chart review of 487 women, anxiety was more likely during perimenopause than postmenopause, and women with the most bothersome vasomotor symptoms were most likely to report anxiety.23

Women's vulnerability to depression and anxiety during menopause is thought to arise from the effect of erratic levels of estrogens on neurotransmitters, particularly serotonin and norepinephrine, and their brain receptors.75 During perimenopause the cyclical response patterns developed during the reproductive years no longer maintain hormonal homeostasis. As women reach postmenopause, the hormones stabilize at lower levels.

Some women also report changes in cognitive functioning, particularly affecting memory, during menopause. Two large longitudinal studies found a small, transient cognitive decrement during perimenopause that's unrelated to sleep deprivation or depression, and that in postmenopause cognitive function returns to premenopausal levels.11, 76

A body of evidence suggests that there's a domino effect: changing estrogen levels trigger hot flashes, which then disrupt sleep, which leads to mood disturbances. The domino hypothesis was first posited by Campbell and Whitehead in their 1977 study of estrogen and menopausal symptoms, where they found that relief of symptoms led to improved psychological well-being.77 This hypothesis has been supported by other studies that found strong associations between vasomotor symptoms, insomnia, and mood disorders.78, 79 Results of other studies haven't been as clear-cut.80, 81 For example, Joffe and colleagues found that sleep quality was worse in depressed women, not because of being awakened by vasomotor symptoms, but rather because of going to bed later, spending less time sleeping, and having problems falling asleep.81 Burleson and colleagues did find some support for the domino hypothesis but concluded that it doesn't fully account for disordered mood in menopause.80 Although both vasomotor symptoms and sleep problems caused same-day or next-day worsened mood, "Trouble sleeping is not the only, or perhaps even the most important, link between vasomotor symptoms and mood," the researchers write.

Managing depression and anxiety during menopause. The first step is to rule out an organic cause, particularly thyroid disease, which is common in older women,82, 83 as well as factors unrelated to menopause, such as preexisting mental illness, significant loss, or family history of mood disorders.74

Interventions include exercise, CBT, and medication. A comparative study found an 18% to 22% improvement in depressed mood in postmenopausal women who engaged in a supervised program of moderate exercise for six months; those in the control group had no improvement.84 There's also evidence that low-intensity aerobic activities such as yoga have a positive effect on mood in menopausal women.42 CBT is considered first-line treatment for anxiety disorders. Group CBT has been found to be effective in menopausal women.85

Medication is the primary treatment for severe depression or anxiety or for moderate depression or anxiety that doesn't respond to nonpharmacologic strategies; the SSRIs and SNRIs are the agents of choice. The use of estrogen or estrogen combined with progestin hasn't been found to have any effect on major depression in menopausal women.86, 87 There's no difference in the severity of depression in women taking estrogen and in those not taking it, nor does estrogen improve mood when given to postmenopausal women with mild-to-moderate depression. But it's been beneficial when given in combination with an SSRI, probably because of effects on vasomotor symptoms.88

Some CAM therapies may be helpful. A 2007 systematic review found that St. John's wort and black cohosh appeared to be effective in relieving depression and anxiety, and kava was effective in relieving anxiety, although there's a risk of liver damage with kava use.33 Ginseng was shown to have a positive effect as well, but the authors note that results were based on only two observational studies. A 2010 study found that red clover also alleviated depression and anxiety in postmenopausal women.89

NURSING IMPLICATIONS

Unless physical activity is contraindicated, all women should be encouraged to engage in exercise; it has many benefits for menopause symptoms and for overall health. The safety and efficacy of pharmacologic therapies should be reviewed. CAM therapies are very popular, but the research on these therapies for menopausal symptoms is weak and most studies have only short-term follow-up times.90 There's a vast amount of information on CAM products on the Internet, and nurses should teach women how to distinguish the reliable from the questionable. Remind women to let their providers know about any CAM products they're using. Explain that botanical products and other supplements aren't always benign. Some, such as kava, have the potential to cause serious adverse effects or may interact with other medications they're taking. Providing women with up-to-date information allows them to make informed choices.

American Association of Clinical Endocrinologistshttp://www.aace.com

Centers for Disease Control and Preventionhttp://www.cdc.gov/reproductivehealth/WomensRH/Menopause.htm

North American Menopause Societyhttp://www.menopause.org

womenshealth.govhttp://www.womenshealth.gov

American Academy of Sleep Medicinehttp://www.aasmnet.org

MedlinePlus: Sleep Disordershttp://www.nlm.nih.gov/medlineplus/sleepdisorders.html

Restless Legs Syndrome Foundationhttp://www.rls.org

American Sleep Apnea Associationhttp://www.sleepapnea.org

National Center for Complementary and Alternative Medicine at the National Institutes of Healthhttp://nccam.nih.gov

American Psychological Associationhttp://www.apa.org

MedlinePlus: Mental Healthhttp://www.nlm.nih.gov/medlineplus/mentalhealth.html

Substance Abuse and Mental Health Services Administrationhttp://www.samhsa.gov

1. Shanafelt TD, et al. Pathophysiology and treatment of hot flashes Mayo Clin Proc. 2002;77(11):1207-18 [Context Link]

2. Blumel JE, et al. A large multinational study of vasomotor symptom prevalence, duration, and impact on quality of life in middle-aged women Menopause. 2011;18(7):778-85 [Context Link]

3. Williams RE, et al. Frequency and severity of vasomotor symptoms among peri- and postmenopausal women in the United States Climacteric. 2008;11(1):32-43 [Context Link]

4. Col NF, et al. Duration of vasomotor symptoms in middle-aged women: a longitudinal study Menopause. 2009;16(3):453-7 [Context Link]

5. Guthrie JR, et al. The menopausal transition: a 9-year prospective population-based study. The Melbourne Women's Midlife Health Project Climacteric. 2004;7(4):375-89 [Context Link]

6. Woods NF, Mitchell ES. Symptoms during the perimenopause: prevalence, severity, trajectory, and significance in women's lives Am J Med. 2005;118(Suppl 12B):14-24 [Context Link]

7. Politi MC, et al. Revisiting the duration of vasomotor symptoms of menopause: a meta-analysis J Gen Intern Med. 2008;23(9):1507-13 [Context Link]

8. Freeman EW, et al. Hot flashes in the late reproductive years: risk factors for African American and Caucasian women J Womens Health Gend Based Med. 2001;10(1):67-76 [Context Link]

9. Gold EB, et al. Longitudinal analysis of the association between vasomotor symptoms and race/ethnicity across the menopausal transition: Study of Women's Health Across the Nation Am J Public Health. 2006;96(7):1226-35 [Context Link]

10. Whiteman MK, et al. Risk factors for hot flashes in midlife women J Womens Health (Larchmt). 2003;12(5):459-72 [Context Link]

11. Green R, Santoro N. Menopausal symptoms and ethnicity: the Study of Women's Health Across the Nation Womens Health (Lond Engl). 2009;5(2):127-33 [Context Link]

12. Thurston RC, et al. Adiposity and reporting of vasomotor symptoms among midlife women: the Study of Women's Health Across the Nation Am J Epidemiol. 2008;167(1):78-85 [Context Link]

13. Thurston RC, et al. Abdominal adiposity and hot flashes among midlife women Menopause. 2008;15(3):429-34 [Context Link]

14. Gold EB, et al. Lifestyle and demographic factors in relation to vasomotor symptoms: baseline results from the Study of Women's Health Across the Nation Am J Epidemiol. 2004;159(12):1189-99 [Context Link]

15. Ziv-Gal A, Flaws JA. Factors that may influence the experience of hot flushes by healthy middle-aged women J Womens Health (Larchmt). 2010;19(10):1905-14 [Context Link]

16. Moilanen J, et al. Prevalence of menopause symptoms and their association with lifestyle among Finnish middle-aged women Maturitas. 2010;67(4):368-74 [Context Link]

17. Greendale GA, Gold EB. Lifestyle factors: are they related to vasomotor symptoms and do they modify the effectiveness or side effects of hormone therapy? Am J Med. 2005;118(Suppl 12B):148-54 [Context Link]

18. Woods NF, et al. Polymorphisms in the estrogen synthesis and metabolism pathways and symptoms during the menopausal transition: observations from the Seattle Midlife Women's Health Study Menopause. 2006;13(6):902-10 [Context Link]

19. Crandall CJ, et al. Vasomotor symptom prevalence is associated with polymorphisms in sex steroid-metabolizing enzymes and receptors Am J Med. 2006;119(9 Suppl 1):S52-S60 [Context Link]

20. Joffe H, et al. Vasomotor symptoms are associated with depression in perimenopausal women seeking primary care Menopause. 2002;9(6):392-8 [Context Link]

21. Lermer MA, et al. Somatic and affective anxiety symptoms and menopausal hot flashes Menopause. 2011;18(2):129-32 [Context Link]

22. Lu SY, et al. Factors related to depression during menopause: a study in southern Taiwan J Nurs Res. 2009;17(2):128-35 [Context Link]

23. Seritan AL, et al. Self-reported anxiety, depressive, and vasomotor symptoms: a study of perimenopausal women presenting to a specialized midlife assessment center Menopause. 2010;17(2):410-5 [Context Link]

24. North American Menopause Society. . Estrogen and progestogen use in postmenopausal women: 2010 position statement of the North American Menopause Society Menopause. 2010;17(2):242-55 [Context Link]

25. Loprinzi CL, et al. Newer antidepressants and gabapentin for hot flashes: an individual patient pooled analysis J Clin Oncol. 2009;27(17):2831-7 [Context Link]

26. Freeman EW, et al. Efficacy of escitalopram for hot flashes in healthy menopausal women: a randomized controlled trial JAMA. 2011;305(3):267-74 [Context Link]

27. Arroll B, et al. Efficacy and tolerability of tricyclic antidepressants and SSRIs compared with placebo for treatment of depression in primary care: a meta-analysis Ann Fam Med. 2005;3(5):449-56 [Context Link]

28. MacGillivray S, et al. Efficacy and tolerability of selective serotonin reuptake inhibitors compared with tricyclic antidepressants in depression treated in primary care: systematic review and meta-analysis BMJ. 2003;326(7397):1014 [Context Link]

29. Butt DA, et al. Gabapentin for the treatment of menopausal hot flashes: a randomized controlled trial Menopause. 2008;15(2):310-8 [Context Link]

30. Guttuso T Jr., et al. Gabapentin's effects on hot flashes in postmenopausal women: a randomized controlled trial Obstet Gynecol. 2003;101(2):337-45 [Context Link]

31. Lethaby AE, et al. Phytoestrogens for vasomotor menopausal symptoms Cochrane Database Syst Rev. 2007(4):CD001395 [Context Link]

32. Bolanos R, et al. Soy isoflavones versus placebo in the treatment of climacteric vasomotor symptoms: systematic review and meta-analysis Menopause. 2010;17(3):660-6 [Context Link]

33. Geller SE, et al. Safety and efficacy of black cohosh and red clover for the management of vasomotor symptoms: a randomized controlled trial Menopause. 2009;16(6):1156-66 [Context Link]

34. Nelson HD, et al. Nonhormonal therapies for menopausal hot flashes: systematic review and meta-analysis JAMA. 2006;295(17):2057-71 [Context Link]

35. Borrelli F, Ernst E. Black cohosh (Cimicifuga racemosa) for menopausal symptoms: a systematic review of its efficacy Pharmacol Res. 2008;58(1):8-14 [Context Link]

36. Shams T, et al. Efficacy of black cohosh-containing preparations on menopausal symptoms: a meta-analysis Altern Ther Health Med. 2010;16(1):36-44 [Context Link]

37. Cho SH, Whang WW. Acupuncture for vasomotor menopausal symptoms: a systematic review Menopause. 2009;16(5):1065-73 [Context Link]

38. Birch S. Controlling for non-specific effects of acupuncture in clinical trials Clinical acupuncture and oriental medicine. 2003;4(2-3):59-70 [Context Link]

39. Venzke L, et al. A randomized trial of acupuncture for vasomotor symptoms in post-menopausal women Complement Ther Med. 2010;18(2):59-66 [Context Link]

40. Borud EK, et al. The Acupuncture on Hot Flushes Among Menopausal Women (ACUFLASH) study, a randomized controlled trial Menopause. 2009;16(3):484-93 [Context Link]

41. Kim KH, et al. Effects of acupuncture on hot flashes in perimenopausal and postmenopausal women-a multicenter randomized clinical trial Menopause. 2010;17(2):269-80 [Context Link]

42. Daley AJ, et al. Exercise to reduce vasomotor and other menopausal symptoms: a review Maturitas. 2009;63(3):176-80 [Context Link]

43. Daley A, et al. Exercise for vasomotor menopausal symptoms Cochrane Database Syst Rev. 2011(5):CD006108 [Context Link]

44. Kravitz HM, et al. Sleep difficulty in women at midlife: a community survey of sleep and the menopausal transition Menopause. 2003;10(1):19-28 [Context Link]

45. Tom SE, et al. Self-reported sleep difficulty during the menopausal transition: results from a prospective cohort study Menopause. 2010;17(6):1128-35 [Context Link]

46. Bixler EO, et al. Women sleep objectively better than men and the sleep of young women is more resilient to external stressors: effects of age and menopause J Sleep Res. 2009;18(2):221-8 [Context Link]

47. Hachul H, et al. Does the reproductive cycle influence sleep patterns in women with sleep complaints? Climacteric. 2010;13(6):594-603 [Context Link]

48. Xu M, et al. Comparison of subjective and objective sleep quality in menopausal and non-menopausal women with insomnia Sleep Med. 2011;12(1):65-9 [Context Link]

49. Roth T, et al. Ramelteon (TAK-375), a selective MT1/MT2-receptor agonist, reduces latency to persistent sleep in a model of transient insomnia related to a novel sleep environment Sleep. 2005;28(3):303-7 [Context Link]

50. Bolge SC, et al. Burden associated with chronic sleep maintenance insomnia characterized by nighttime awakenings among women with menopausal symptoms Menopause. 2010;17(1):80-6 [Context Link]

51. LeBlanc M, et al. Psychological and health-related quality of life factors associated with insomnia in a population-based sample J Psychosom Res. 2007;63(2):157-66 [Context Link]

52. Freedman RR, Roehrs TA. Sleep disturbance in menopause Menopause. 2007;14(5):826-9 [Context Link]

53. O'Connor GT, et al. Prospective study of sleep-disordered breathing and hypertension: the Sleep Heart Health Study Am J Respir Crit Care Med. 2009;179(12):1159-64 [Context Link]

54. Young T, et al. Sleep disordered breathing and mortality: eighteen-year follow-up of the Wisconsin sleep cohort Sleep. 2008;31(8):1071-8 [Context Link]

55. Bixler EO, et al. Prevalence of sleep-disordered breathing in women: effects of gender Am J Respir Crit Care Med. 2001;163(3 Pt 1):608-13 [Context Link]

56. Young T, et al. Menopausal status and sleep-disordered breathing in the Wisconsin Sleep Cohort Study Am J Respir Crit Care Med. 2003;167(9):1181-5 [Context Link]

57. Polo-Kantola P, et al. Estrogen replacement therapy and nocturnal periodic limb movements: a randomized controlled trial Obstet Gynecol. 2001;97(4):548-54 [Context Link]

58. Arakane M, et al. Factors relating to insomnia during the menopausal transition as evaluated by the Insomnia Severity Index Maturitas. 2011;69(2):157-61 [Context Link]

59. Chedraui P, et al. Factors related to increased daytime sleepiness during the menopausal transition as evaluated by the Epworth sleepiness scale Maturitas. 2010;65(1):75-80 [Context Link]

60. Edinger JD, et al. Cognitive behavioral therapy for patients with primary insomnia or insomnia associated predominantly with mixed psychiatric disorders: a randomized clinical trial Sleep. 2009;32(4):499-510 [Context Link]

61. Irwin MR, et al. Comparative meta-analysis of behavioral interventions for insomnia and their efficacy in middle-aged adults and in older adults 55+ years of age Health Psychol. 2006;25(1):3-14 [Context Link]

62. Morin CM, et al. Psychological and behavioral treatment of insomnia: update of the recent evidence (1998-2004) Sleep. 2006;29(11):1398-414 [Context Link]

63. Yang CM, et al. Maladaptive sleep hygiene practices in good sleepers and patients with insomnia J Health Psychol. 2010;15(1):147-55 [Context Link]

64. van Straten A, Cuijpers P. Self-help therapy for insomnia: a meta-analysis Sleep Med Rev. 2009;13(1):61-71 [Context Link]

65. Buscemi N, et al. The efficacy and safety of drug treatments for chronic insomnia in adults: a meta-analysis of RCTs J Gen Intern Med. 2007;22(9):1335-50 [Context Link]

66. Sarris J, Byrne GJ. A systematic review of insomnia and complementary medicine Sleep Med Rev. 2011;15(2):99-106 [Context Link]

67. Cooper KL, Relton C. Homeopathy for insomnia: a systematic review of research evidence Sleep Med Rev. 2010;14(5):329-37 [Context Link]

68. Hachul H, et al. Isoflavones decrease insomnia in postmenopause Menopause. 2011;18(2):178-84 [Context Link]

69. Van Geijlswijk IM, et al. The use of exogenous melatonin in delayed sleep phase disorder: a meta-analysis Sleep. 2010;33(12):1605-14 [Context Link]

70. Bromberger JT, et al. Depressive symptoms during the menopausal transition: the Study of Women's Health Across the Nation (SWAN) J Affect Disord. 2007;103(1-3):267-72 [Context Link]

71. Cohen LS, et al. Risk for new onset of depression during the menopausal transition: the Harvard study of moods and cycles Arch Gen Psychiatry. 2006;63(4):385-90 [Context Link]

72. Freeman EW, et al. Associations of hormones and menopausal status with depressed mood in women with no history of depression Arch Gen Psychiatry. 2006;63(4):375-82 [Context Link]

73. Tangen T, Mykletun A. Depression and anxiety through the climacteric period: an epidemiological study (HUNT-II) J Psychosom Obstet Gynaecol. 2008;29(2):125-31 [Context Link]

74. Woods NF, et al. Depressed mood during the menopausal transition and early postmenopause: observations from the Seattle Midlife Women's Health Study Menopause. 2008;15(2):223-32 [Context Link]

75. Deecher D, et al. From menarche to menopause: exploring the underlying biology of depression in women experiencing hormonal changes Psychoneuroendocrinology. 2008;33(1):3-17 [Context Link]

76. Greendale GA, et al. Menopause-associated symptoms and cognitive performance: results from the Study of Women's Health Across the Nation Am J Epidemiol. 2010;171(11):1214-24 [Context Link]

77. Campbell S, Whitehead M. Oestrogen therapy and the menopausal syndrome Clin Obstet Gynaecol. 1977;4(1):31-47 [Context Link]

78. Avis NE, et al. Longitudinal study of hormone levels and depression among women transitioning through menopause Climacteric. 2001;4(3):243-9 [Context Link]

79. Zervas IM, et al. Additive effect of depressed mood and vasomotor symptoms on postmenopausal insomnia Menopause. 2009;16(4):837-42 [Context Link]

80. Burleson MH, et al. Daily vasomotor symptoms, sleep problems, and mood: using daily data to evaluate the domino hypothesis in middle-aged women Menopause. 2010;17(1):87-95 [Context Link]

81. Joffe H, et al. Depression is associated with worse objectively and subjectively measured sleep, but not more frequent awakenings, in women with vasomotor symptoms Menopause. 2009;16(4):671-9 [Context Link]

82. Hickey M, et al. Evaluation and management of depressive and anxiety symptoms in midlife Climacteric. 2012;15(1):3-9 [Context Link]

83. Joffe RT, et al. Subclinical hypothyroidism, mood, and cognition in older adults: a review Int J Geriatr Psychiatry. 2012 [Context Link]

84. Villaverde Gutierrez C, et al. Influence of exercise on mood in postmenopausal women J Clin Nurs. 2012;21(7-8):923-8 [Context Link]

85. Khoshbooii R, et al. Effectiveness of group cognitive behavioral therapy on depression among Iranian women around menopause Aust J Basic Appl Sci. 2011;5(11):991-5 [Context Link]

86. Kornstein SG, et al. The influence of menopause status and postmenopausal use of hormone therapy on presentation of major depression in women Menopause. 2010;17(4):828-39 [Context Link]

87. Morrison MF, et al. Lack of efficacy of estradiol for depression in postmenopausal women: a randomized, controlled trial Biol Psychiatry. 2004;55(4):406-12 [Context Link]

88. Parry BL. Optimal management of perimenopausal depression Int J Womens Health. 2010;2:143-51 [Context Link]

89. Lipovac M, et al. Improvement of postmenopausal depressive and anxiety symptoms after treatment with isoflavones derived from red clover extracts Maturitas. 2010;65(3):258-61 [Context Link]

90. Wong VC, et al. Current alternative and complementary therapies used in menopause Gynecol Endocrinol. 2009;25(3):166-74 [Context Link]

For 27 additional continuing nursing education articles on women's health topics, go to http://www.nursingcenter.com/ce.