Quality of life in menopause encompasses more than just absence of symptoms. It includes enjoyment of life, participation in meaningful relationships, work, and play (Matthews and Bromberger, 2005). Although most women in Western societies report hot flashes and night sweats, for most of these women such symptoms do not affect quality of life. In fact, data from the Melbourne Women's Mid-life Project show that well-being increases across the menopause transition (Dennerstein et al., 2003). Lifestyle changes are recommended first for vasomotor symptoms. These include weight reduction for women who are significantly overweight; it has long been considered that women who were obese had fewer vasomotor symptoms because of elevated estrone levels from aromatization of adipose tissue to androgens than to estrone. However, new evidence shows that the occurrence of VMS in obese perimenopausal women may be due to the increased heat insulation afforded by greater adiposity, leading to more hot flashes (Freedman, 2002; Glickman-Weiss et al., 1999). Smoking is associated with hot flashes, so the patient is encouraged to quit or reduce smoking to decrease the incidence of hot flashes (Whiteman et al., 2003). The data on alcohol use and hot flashes is mixed (Gold et al., 2004). Observational studies of physical activity and VMS do not show a relationship with hot flashes (Li et al., 2003; Li et al., 1999; Sternfeld et al., 1999).
Menopause hormone therapy (MHT), however, is very effective for treatment of hot flashes and night sweats and by secondary gain can be useful for treating sleep disturbances that result from waking related to hot flashes. Prior to 2002 when the Women's Health Initiative (WHI) was halted because of increased risk for women taking estrogen and progestin therapy for breast cancer (anticipated) and for increased risk for heart disease, stroke, and other thromboembolic events (unanticipated), MHT was recommended for all postmenopausal women to protect against osteoporosis and heart disease as well as for treatment of symptoms including hot flashes, vaginal dryness, mood changes, sleep disturbances, and sexual dysfunction. Subsequently, the estrogen-only arm of the WHI was discontinued as well, because of the increased risk of stroke (RR 1.4 for women on estrogen alone). In addition, data from the WHI demonstrated increased risk of dementia and urinary incontinence with use of MHT (Hendrix et al., 2005; Shumaker et al., 2004).
Presently, the Federal Drug Administration (FDA) indicates use of MHT for moderate (with sweating) to severe (limits activities) hot flashes with a frequency of 80 to 100 per week. The FDA recommends use of the smallest dose MHT to alleviate symptoms for the shortest amount of time possible. Prior to 2002, the oral dose of conjugated equine estrogen (CEE) recommended to protect from heart disease and osteoporosis and to alleviate all symptoms was 0.625 mg daily. There was aggressive marketing to women's health professionals that this or an equivalent dose in another preparation was the standard of care to control symptoms. The side effects usually encountered at this dose included breast tenderness and breakthrough bleeding. In the recent past there has been development of lower dose products that are half to one-quarter the CEE 0.625 mg dose in patch and oral forms and to use of local therapy for vaginal symptoms has been recommended.
MHT is an excellent treatment for distressing hot flashes. The side effect profile has been extensively studied, in fact more so than nearly all other drugs on the market. If a woman chooses to use MHT, a starting dose of CEE 0.3 mg or a 25 mcg transdermal patch is recommended. If vaginal symptoms are problematic, then MHT options include vaginal estrogen creams (PremarinTM (CEE), EstraceTM (estradiol), rings (Estring™, Femring™), or tablets (Vagifem™). New products are coming on the market all the time. Menostar is a 14 mcg transdermal patch that came on the market in 2004. It has FDA approval for the treatment of osteopenia (prevention of osteoporosis). However, it can be used for treatment of hot flashes when choosing a low dose estrogen product.
One caveat to keep in mind is that for women with an intact uterus (one who has not had a hysterectomy), a prescription for a progestin must accompany the use of estrogen products. This protects the lining of the uterus from unopposed estrogen effect (over stimulation), which can lead to a proliferative endometrium, hyperplasia, or endometrial cancer.
Stopping use of MHT as soon as no longer necessary is a reasonable goal. It is not easy to identify when that time might be. Stopping when symptoms are no longer problematic is important because individual risk to a woman using MHT accumulates with length of time used. The recommendation by the FDA to use MHT for the shortest time possible, however, is not a clear or well-defined concept. Grady recommends stopping MHT every 6 to 12 months to establish whether the MHT is still needed (Grady, 2005). The woman can expect a return of hot flashes for a period of time when stopping the hormones, and these usually peak at about four weeks. Seventy percent of women reported mild hot flashes upon stopping MHT, with 30% reporting troubling flashes (Ettinger, Grady, Tosteson, Pressman, and Macer, 2003). Of the latter group, 25% resumed treatment in six months. It is recommended to taper the MHT by day in order to avoid writing multiple prescriptions for varying doses. This means use of MHT every other day for two weeks, to three times a week, to twice weekly, and so on, taking longer than a month to finish with the goal of reducing discomfort from hot flashes.
Complementary and alternative therapies (CAM) are used by up to 50% of the population of the United States (Eisenberg et al., 1998), and menopause-aged women are targeted daily on television with products that are purported to help with all symptoms of menopause. Most CAM trials suffer serious design flaws, including most do not have a placebo arm, they are short duration, and they have few subjects. In addition, trials of dietary supplements often fail to adequately describe which part of the plant is used, how the herb is prepared, what solvents are used, and so on.
Black cohosh is probably the most extensively studied herb for hot flashes but findings vary across studies. The mechanism of action of this herb was long thought to be that of a weak phytoestrogen (plant estrogen) but research now suggests a nonhormonal effect (Low Dog, 2005). Black cohosh is available as a standardized extract in the commercial preparation RemifeminTM. Evening primrose oil has been studied, and though it is a rich source of gamma linolenic and linolenic acid, its efficacy for hot flashes is unproven. Ginseng is used in Asian cultures as a tonic and has no usefulness for hot flashes (Low Dog, 2005). Kava has been shown to be an effective anxiolytic in Cochrane reviews but concerns for hepatoxity need to be addressed (Pittler, 2000; Pittler et al., 2002).
Although there has been a great deal of interest in the use of soy for menopause symptoms, soy products are difficult to characterize because it makes a difference whether food products or extracts are being considered. Soy in food generally is considered safe when used as part of a balanced diet. Whether or not dietary soy conveys health benefits is unproven. Studies show conflicting results with regard to hot flashes (Faure et al., 2002; Han et al., 2002; Nikander et al., 2003; Penotti et al., 2003). Supplements of soy have unknown effects because most studies do not show percent of isoflavones (plant estrogen) included in the extract. Estroven is one herbal supplement that contains 55 mg of isoflavones from non-GMO soya, Japanese arrowroot, calcium, and vitamins E, B6, and folic acid.
Most clinical trials of red clover, Trifoloum pretense L. (PromensilTM), have failed to show any benefit over placebo (Baber et al., 1999; Knight et al., 1999; Tice et al., 2003). However, in a randomized, placebo control study of 30 women for 12 weeks, PromensilTM use resulted in a significant reduction in hot flashes from baseline (van de Weijer and R., 2002).
Other modalities have been investigated for relief of hot flashes in menopausal women, including acupuncture, magnetic therapy, reflexology, and homeopathy. An electronic search of relevant studies was reported at the NIH State-of-the-Science Consensus Conference on Management of Menopause-Related Symptoms found 11 intervention studies, including seven on acupuncture, one on magnets, one on reflexology and two on homeopathy (Carpenter and Neal, 2005). All the studies examined suffered from design flaws—most were uncontrolled, with small sample sizes making conclusions far from firm. And most have inconsistent results regarding improvement in hot flashes.
In the past, centrally active agents BellergalTM and ClonidineTM have been used to control hot flashes. BellergalTM was popular two decades ago and has limited efficacy for decreasing hot flash frequency or severity (Bergmans, Merkus, Corbey, Schellekens, and Ubachs, 1987; Lebherz and French, 1969). Clonidine™, an older hypertensive preparation, has been demonstrated to reduce hot flashes with only moderate efficacy, but toxicity limits its use (Loprinzi, 2005). In the 1990s selective serotonin reuptake inhibitors (SSRIs) were found to reduce hot flashes in women using them for other reasons. It appeared that the SSRIs were not only efficacious but also well tolerated (Stearns, 2000; Loprinzi, 1998). Subsequent placebo-controlled double blind studies of venlafaxine (EffexorTM) and paroxetine (PaxilTM) have shown reduction in hot flashes (Loprinzi 2000; Stearns, 2003). Pilot studies are ongoing for other, newer antidepressants, which also look promising. Gabapentin (NeurontinTM) has been anecdotally noted to decrease hot flashes, and ongoing trials promise new interest in its use. Gabapentin is relatively well tolerated by most women and may be one of the most efficacious and clinically appropriate agents for use along with the newer antidepressants (Loprinzi, 2005).
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