Hot flashes—a review of the literature on alternative and complementary treatment approaches

Alternative Medicine Review, August, 2003 by Hazel A. Philp

Pathophysiology of Hot Flashes

Despite multiple theories, the exact pathophysiology of hot flashes remains unknown. (23,24) Even though hot flashes are most likely multifactorial in origin, dysfunction of the central thermoregulatory centers due to decreased levels of estrogen has long been thought to be the primary cause. (25) Figure 1 illustrates potential physiological triggers of hot flashes. In addition, it may be that estrogen withdrawal, rather than low circulating estrogen levels, leads to hot flashes. (26) Changes in levels or function of the neurotransmitters norepinephrine (which lowers the thermoregulatory set point, triggering a heat loss mechanism) (26,27) and serotonin, (28,29) changes in gonadotropin release through the hypothalamus, (30) and interactions among prostaglandins, catecholamines, endorphins and other neuropeptides (25) have all been implicated.

Conventional Pharmacological Treatment Options

Conventional hormonal treatment options for hot flashes include estrogen with our without progestins or selective estrogen receptor modulators (SERMs--e.g., raloxifene, tamoxifen). Nonhormonal pharmacological treatments include serotonin reuptake inhibitors (SSRIs--e.g., venlafaxine) or antihypertensives (e.g., clonidine).

While hormone replacement therapy has historically been prescribed for hot flashes, partly because of purported protection from long-term chronic degenerative disease, studies are currently calling this practice into question. Randomized trials of conjugated estrogens plus progestins (HRT) have found no benefit from these compounds for either primary or secondary prevention of heart disease. (31) In fact, HRT appears to be associated with increased risk of heart attacks, stroke, deep venous thrombosis (DVT), pulmonary embolism (PE), and gallbladder disease. (32) A 26-percent increase in breast cancer was noted in women who took HRT, resulting in discontinuation of that arm of the 8.5 year study after five years. (32,33) Progestins alone may produce vaginal bleeding, thromboembolic events, bloating, weight gain, (24) and increased risk of primary or recurring breast cancer. (34,35)

Other adverse effects of HRT include headache, nausea, water retention, phlebitis, breast tenderness, irritability, (36) and withdrawal vaginal bleeding, which is the main reason women stop taking HRT. (37,38)

Botanical Medicine in the Treatment of Hot Flashes

Due to the side effects and risks associated with conventional approaches to hot flashes, many women are turning to alternatives. Botanical medicine offers some of the most-thoroughly researched options.

Phytoestrogens

Phytoestrogens are plant substances functionally similar to 17[beta]-estradiol or that produce estrogenic effects. (39) They have a structure similar to estrogen (Figure 2), which enables them to bind to estrogen receptors (ER), but are 100-1,000 times weaker than estradiol. (40) The three main classes of phytoestrogens are isoflavones, lignans, and coumestans. Isoflavones are the most widely studied class of phytoestrogens, with genistein (4'5,7-trihydroxyisoflavone) and daidzein (4,7-dihydroisoflavone) and their respective [beta]-glycosides, genistin and daidzin, providing the most data to date. (40,41)