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Perimenopause - An Integrative Approach by Dr. Tori Hudson More than ever before, women are entering menopause, educating themselves, asking their doctors questions, and requesting information about options for treatment. No two women's menopause transition is alike and women themselves, educators, and health care practitioners are experiencing the challenge of evaluating and managing each woman individually to achieve optimal results and optimal health. Many women begin to experience an array of physical and mental emotional symptoms long before they meet the definition of menopause. These changes that occur over as much as several years usually from around age 40 to 51 are a transition period called "perimenopause". A narrower definition is the transition period from regular to irregular menses. On average, the onset of perimenopause occurs around age 47 and the average duration is 4 to 5 years. The symptoms of decreased hormone levels and perimenopause symptoms are varied, unpredictable and often go unrecognized as a perimenopause symptom. Due to not recognizing a problem as a perimenopause symptom, lack of precision in FSH testing , inadequate understanding of menopause on the part of both patient and health care practitioner, many women become dissatisfied with their health care. The signs and symptoms of perimenopause include menstrual irregularities and changes in the amount of blood loss, hot flashes, night sweats, vaginal dryness and thinning, skin changes, fatigue, decreased libido, decrease in arousal and orgasmic response, mood swings, weight gain, joint paints, depression, anxiety, changes in memory and cognition, sleep disturbance, hair loss on head, hair growth and acne of face, heart palpitations, nausea, headaches, urinary tract infections, urinary incontinence, and the beginning stages of osteoporosis and heart disease. The symptoms initially will vary from subtle and infrequent to overt and daily. Symptoms can be mild, moderate, or severe. Some women will have no significant menopausal symptoms except in the menstrual cycle and others will have symptoms that are progressive and problematic for years to come. Perimenopause is a time of instability and unpredictability. Many things are changing other than estrogen and progesterone levels. Women's hormone levels are changing not only in their total serum levels, but they are also changing in relationship to each other. Women are also aging which contributes to many of the changes like weight gain, changes in metabolic rate, and outlook on life. Factors such as age, stress, and body weight also begin to play a larger role in estrone production. The two most significant changes associated with the perimenopause and continuing into the postmenopausal years are decreases in bone mineral content and changes in lipid profiles. Perimenopausal women should be screened to determine those who are at risk for osteoporosis and those who are at risk for premature cardiovascular disease. Adequate advice about diet, exercise, nutritional supplementation should be fundamental for all women. Individual assessments and recommendations about the use of either phytoestrogens, natural hormones, and/or conventional hormone replacement therapy, bisphosphonates, lipid lowering and antihypertensive medications need to be made for each woman based on her risk factors and needs and preferences. Natural therapies are very well suited for the perimenopause patient. Conventional HRT is not the only option. Women who should not or do not want to take hormones may turn to herbal and nutritional therapies for managing their menopausal symptoms and risk factors. These natural therapies are increasingly popular and have a growing body of scientific evidence to support their efficacy. A 1998 report indicates that 42% of adults have tried alternative medicines. According to a survey in 1993 of 1,539 adults, one in three said they used at least one alternative therapy in the past year. Phytoestrogens Plants manufacture thousands of chemical compounds vital to the health and function of the plant. Those chemical compounds, generally known as micro-nutrients, are consumed in the diet by humans whenever the plants are eaten. One of these class of chemical compounds manufactured by plants are known as phytoestrogens. Over 300 plants contain phytoestrogen compounds. They comprise a large part of our diet, and our found in medicinal plants as well. There are several sub classifications of phytoestrogens; the following partial list may be helpful:
For the purposes of this paper, we will concentrate on the isoflavones. Isoflavones have a similar structure to endogenous steroidal sex hormones. They have the ability to bind to estrogen receptors on human cells, and in women, they have a preference for binding to the beta form of the estrogen receptor. As a result of this, they preferentially express estrogenic effects in the central nervous system, blood vessels, bone and skin, and they do so without causing stimulation of the breast or uterus. It is estimated that soy isoflavones are 1/400th to 1/1000th the potency of estradiol. However, in that they are structurally related to endogenous estrogens, they are able to mimic some of the effects of estrogen, but to a significantly less degree. Uniquely, isoflavones may also act as anti-estrogens, much like "Selective Estrogen Receptor Modulators" (SERMs). Isoflavones can be thought of as one of natures' SERMs. Therapeutically, isoflavones may alleviate menopause symptoms, and lower the incidence of osteoporosis, coronary artery disease, breast and uterine cancer. Soy Isoflavones Several studies have now been done on the effect of soy isoflavones on vasomotor symptoms. Most show a benefit, but others do not. Numerous soy isoflavone studies have reported improvement in vasomotor symptoms in menopausal women. Six published studies report improvements with soy protein rich in isoflavones. , , , , , Four used soy protein or soy foods and two used soy extracts. Criticisms of these studies have been that relatively small numbers of women were studied, most were short term (not more than 12 weeks), the benefit only up to about a 45% reduction, and not all were double-blind clinical trials. In the year 2,000, we began to see publication of studies that were not so promising. A soy product studied in breast cancer patients with hot flashes concluded that the soy did not alleviate hot flashes. Some were on Tamoxifen some were not; (twice as many were on Tamoxifen). Although there was no clear difference in the effect of soy on hot flashes in either group. Patients ranged in age from 18 to over 50. Perhaps the most glaring fault of the study was lack of information about who was postmenopausal versus premenopausal and who had natural menopause, chemotherapy induced menopause, or surgical menopause. A study of breast cancer survivors with hot flashes The most current study on soy isoflavones and vasomotor symptoms reported disappointing results. The most significant difference between the previous studies and this current study is that those six studies were over 12 weeks time or less. This study continued for 24 weeks and symptoms generally declined in all three treatment groups during the first 12 weeks but either increased or showed no change during the last 12 weeks. The important thing to consider here is whether the earlier studies with a seemingly positive outcome in the soy groups were encouraging merely due to a short period of time in the study period. Based on these results, soy isoflavones in the treatment of vasomotor symptoms may not provide the relief we hav e come to hope for. Future studies may need to develop new methods or tools for collecting symptom data that are either more accurate, or extend all studies over at least the 24 weeks. Other soy studies demonstrate that increasing the soy foods in the diet regulate the menstrual cycle, stabilize bone density, , , and reduce cholesterol. Red Clover Isoflavones Red clover is a member of the legume family and has been used world wide as a source of hay for cattle, horses and sheep and used by humans historically as a source of protein in the leaves and young sprouts. Historically, it has also been recognized as a medicinal plant to humans and more recently as a menopausal herb. The principal substances of red clover include the flavonoid glycosides, coumestans, volatile oils, L-Dopacaffeic acid conjugates, polysaccharides, and some miscellaneous resins, fatty acids, hydrocarbons, alcohols, chlorophylls, minerals and vitamins. At least four clinical trials have been conducted on the effect of red clover isoflavones on vasomotor symptoms. Two show benefit and two do not. The first two published studies on red clover and vasomotor symptoms showed no statistically significant difference between the red clover standardized extract and the placebo during a 3 month period, although both groups did improve. , It was suggested that the negative results of these studies were due to inadequate controls and that women in the control group were in fact getting meaningful amounts of phytoestrogens in their diet. Two other studies of 40 mg standardized extract of red clover produced a 75% reduction in hot flushes after 16 weeks in 30 women. The difference between placebo and red clover isoflavones was statistically significant (p < 0.001). A similar study evaluated 40 mg of red clover standardized isoflavones for two months. 23 post menopausal women found that red clover users had a 54% reduction in hot flushes versus 30% in the placebo group. Other intriguing results of red clover were found as a result of these 4studies: no endometrial thickening, increase in HDL, and no abnormalities in liver function tests, CBC, or estradiol. Lastly, a published study showed that red clover isoflavones may reduce coronary vascular disease by increasing arterial elasticity by 23%. Additional botanicals Black cohosh has emerged as the single most important herb for the treatment of menopausal symptoms. Although the bulk of the research has been uncontrolled studies, there have been six well-publicized studies. In one of the largest studies, 629 women with menopausal complaints were given a liquid standardized extract of black cohosh twice per day for six to eight weeks. As early as four weeks, clear improvements in the menopausal ailments was seen in 80 percent of the women. Complete disappearance of symptoms occurred in approximately 50 percent. Symptoms included hot flashes, night sweats, headaches, insomnia and mood swings. The other studies reported improvements in fatigue, irritability, hot flashes and vaginal dryness. The most recent study on black cohosh was of eighty-five women diagnosed with breast cancer who were experiencing hot flashes. Fifty-nine of them (70%) were taking tamoxifen during the trial. Participants took either black cohosh standardized extract of 40 mg twice daily or placebo. Both the black cohosh and placebo groups had a decline in the number and intensity of hot flashes during the first month of about 27%. Women in the black cohosh group did report a greater reduction in sweating. Although the results of this study are not consistent with other studies showing benefit from black cohosh for menopausal symptoms, it is important to acknowledge that the results should take into account that black cohosh may not work in the presence of an anti-estrogen, such as tamoxifen. Other weaknesses in the study that could be pointed out is that the duration was only two months and there was a high dropout rate with most of the women who remained in the black cohosh group taking the tamoxifen. Ginseng Panax ginseng, also known as Korean or Chinese ginseng, contains at least 13 different triterpenoid saponins, collectively known as ginsenosides. Whether it involves reducing mental or physical fatigue, , , , enhancing the ability to cope with various physical and mental stressors by supporting the adrenal glands, or treating the atrophic vaginal changes due to lack of estrogen, ginseng is a valuable tool for many menopausal women. Combination products Most of the herbal combination products available contain either 5 or more plants, some that contain phytoestrogens and some that have some other therapeutic benefit specific to menopause. Other combination products contain a mixture of plans and nutrients such as soy or vitamin E. Most all of these combination products have not been researched, even though an individual ingredient has been. One herbal combination product that has been the subject of a clinical trial contains dong quai, motherwort, licorice root, burdock root and wild yam root. Women were randomly assigned to the herbal combination 2 caps 3 times daily or a placebo for three months. After three months, one hundred percent of the women taking the botanical formula had a reduction in their symptom severity, while only 6 percent of women receiving placebo showed a decrease. Seventy-one percent of women taking the herbal formula reported a reduction in the total number of symptoms, while only 17 percent of the women taking placebo reported a decrease in the total number of their symptoms. The botanical formula was most effective in treating hot flashes, mood changes, and insomnia. There were no clear effects of blood levels of estradiol or total estrogens, although there was actually a trend for a decrease in the treatment group. Serum progesterone levels also appeared to decrease in the herbal group. No clear effects of the botanical formula were apparent in HDL cholesterol, triglycerides, or total cholesterol. Numerous other botanicals have been used historically in the practice of traditional herbal medicine for the treatment of menopausal symptoms. Some either have no research, no confirming research, or only a small study showing some efficacy. They include wild yam, dong quai, licorice, chaste tree, kava, sage, hops and more. For other individual symptoms, other considerations include St. John's wort can treat mild to moderate depression, , Kava can treat anxiety and hot flashes, and ginkgo to improve memory. Selected nutrients Individual nutrients have been used for specific perimenopausal symptoms. Supplements such as vitamin E to decrease hot flashes , bioflavonoids and vitamin C have been shown to treat hot flashes, melatonin, L-tryptophan and 5-hydroxytryptophan for insomnia, vitamins B6, folic acid and B12 for depression, and glucosamine sulfate, borage oil and chondroitin sulfate for joint pains. Natural Hormones Natural hormones are by definition, defined as a plant derived compound that has been converted in the manufacturing laboratory to a hormone and the end product hormone that is made is biochemically identical to endogenous hormones. Estradiol, estriol, estrone, progesterone, and testosterone are sex steroid hormones that can be made as natural hormones. Non natural hormones include plant derived compounds that are then made into non bio-identical hormones such as esterified estrogens or estinyl estradiol, animal hormones such as conjugated equine estrogens and synthetics such as medroxyprogesterone acetate (MPA) and methyl testosterone. The natural hormones estriol and estradiol tend to be combined in a formula called a bi-estrogen formula along with progesterone and sometimes testosterone. Doses can be compounded that are equivalent to conventional hormone doses, but one of the true advantages of natural hormones is that many different formulations can be compounded to individually address each persons unique menopause situation or individually titrated up or down as the need arises. Natural hormones have a shorter half life, tend to be better tolerated than other hormones, and can be combined to achieve the suggested anti-estrogen effects of estriol in the breast , , with the anti-resorptive stronger symptom relieving effects of estradiol. Natural progesterone is significantly better tolerated than MPA, and has a better effect on lipids and on dilating coronary arteries. Natural progesterone by itself, can also be used very effectively in the perimenopause. Problems that can be addressed include regulating the menstrual cycle, hot flashes, night sweats, mood swings, sleep disruption, and premenstrual symptoms. A transdermal progesterone cream was studied for its ability to control vasomotor symptoms (hot flashes )and to evaluate its ability to prevent bone loss. 102 healthy women within 5 years of menopause were randomly assigned to receive either transdermal progesterone cream of a placebo. Subjects were instructed to apply a quarter teaspoon of cream (1/4 tsp contained 20 mg progesterone or placebo) to the skin daily. Each also received a multivitamin and 1200 mg of calcium. Measurements included medical history, physical examination, bone mineral density testing of the hip and spine (DEXA), thyroid (TSH), hormone (FSH), lipids profile (cholesterol, etc), and regular chemistry profile. The women kept weekly symptom diaries and were seen every 4 months for one year. Bone density and chemistry profile were repeated at the end of one year. Prior to the initiation of the study, 30 of the 43 (69%) in the treatment group and 26 of the 47 (55%) had hot flashes. Twenty five of 30 (83%) women in the treatment group experienced improvement or resolution of their hot flashes and five of 26 (19%) placebo subjects showed improvement or resolution. The number of women who showed a gain in bone mineral density did not differ between the treatment group and the placebo group. Conclusion Women in the perimenopause transition years who are beginning to experience various and episodic perimenopause symptoms are in a good position to try botanical and nutritional therapies to relieve their symptoms. In the perimenopause and postmenopausal years, choices about nutritional supplements and herbal therapies versus natural hormones versus conventional HRT can be made on an individual basis. 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