What should I know about Menopause?

Menopause is a very natural part of a woman’s life cycle. While it marks the end of a woman’s reproductive cycle, it can be the beginning of an exciting and rewarding time of life. Our culture has come a long way from viewing menopause with dread and associating it with a perceived decrease in a woman’s value. Understanding the natural progression of age in a woman’s body and becoming acquainted with the therapies available, allows women today to effectively manage their symptoms and to be proactive in maintaining their health for their later years.

By definition, menopause is the transition period between the reproductive years of a woman's life and the cessation of ovarian function. Unless brought about by surgery or other causes, natural changes in a woman's body generally occur between the ages of 35 and 50. Menopausal symptoms are unique to each individual, both in duration and in intensity.

Many women associate the years of menopausal symptoms with the term itself. However, menopause marks the permanent fall in production of estrogen and cessation of the menstrual cycle. It is during perimenopause that most of the symptoms associated with the term menopause are experienced. During the three to five year period before the cessation of menstrual cycles, there is a decrease in the production of estrogen. This period of perimenopause brings on a variety of symptoms that are often very inconsistent. Hot flashes may occur at times and then disappear for months. The normal menstrual cycle becomes irregular only to become regular again. It is also during perimenopause that some mood changes and brief bouts of insomnia may be evident. The inconsistency of the symptoms and the manner in which they affect the individual woman are characteristics of perimenopause itself.

During menopause, it is important for a woman to recognize the health risks that are associated with a decline in estrogen. It is at this time that there is an increased risk for cardiovascular disease and for osteoporosis. Awareness of these risk factors gives a woman the opportunity to manage her health effectively by choosing lifestyle patterns that promote and maintain health. Menopause is not a time to be dreaded, nor a time to think that an active and full life will be compromised. It is a time to celebrate the natural cycles of a woman’s life, and a time develop lifestyle habits that will provide support for the years to come.

In younger women who are having menopausal symptoms, and in women who have had a hysterectomy but still have one or both of their ovaries, a blood test called an FSH level, or follicle stimulating hormone level may be useful to confirm menopause. If you have your ovaries removed or undergo some cancer treatments, you may experience rapid onset of menopause, and may need special management of your symptoms.

A natural process that unfolds as the ovaries cease to function, menopause generally starts around age fifty. (Early menopause can be initiated by surgery and other causes.) As ovarian function gradually declines, dramatic shifts occur in four hormones that regulate the menstrual cycle: estrogen, progesterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH). The term "climacteric" is often applied to these profound changes in hormone levels.


International Menopause Society, 2004.

  • One half of all women over 50 will at some time have a fracture caused by osteoporosis.
  • Menopausal women are up to three times more likely than men to have Alzheimer's disease, and research suggests menopause may play a significant role.
  • Recent surveys have found that more than half of all women don’t know that menopause is associated with an increased risk of heart disease.
  • By the year 2025, the World Health Organization estimates that 1.1 billion women will be age 50 or over.

North American Menopause Society, 2000.

    The median age for onset of perimenopause is 47.5 years. In the US, there are an estimated 41.75 million women over the age of 50. Most women spend 1/3 to 1/2 of their life in post menopause. Smoking has been identified as a cause of early menopause.
  • Spontaneous menopause occurs at the average age of 51.4 years in Western women.
  • The menopause transition lasts an average of 4 years.
  • In 2000, there were 45.6 million postmenopausal American women, 39.9 million of these women are over the age of 51.

Signs and Symptoms

[span class=alert]The following list does not insure the presence of this health condition. Please see the text and your healthcare professional for more information.[/span]

Menopausal complaints: Around the ages of 48-52, many changes begin to occur in a woman’s body. Unwanted symptoms of hormone imbalances include:

    Hot flashes, usually presented as flushing of the face, neck, chest, and back Insomnia Mild to moderate depression Joint pain and muscle pain Water retention (edema) Heart palpitations Headaches Vaginal dryness Increased sweating

Some Physical Changes During Menopause: A woman’s body undergoes a number of changes as she passes through menopause. These changes may need to be supported with medications and/or dietary supplements as well as lifestyle/dietary adjustments.

    Some body structures (sphincter muscles of the bladder and rectum) may lose muscle tone. Breast size, shape, and firmness may change. Skin wrinkling and loss of skin tone may occur due to a loss of collagen, a key protein that keeps skin firm and young looking. Body fat may accumulate in areas such as thighs and hips. Bone mass and strength may decrease. Metabolism may slow down, increasing chances of weight gain. Nervous system changes such as emotional swings, tiredness, insomnia, forgetfulness, headaches, anxiety, irritability, and depression may occur. The risk of heart disease may go up. Atherosclerosis (hardening of the arteries), may be more likely to develop as a result of low estrogen. A woman may experience chest pains and high blood pressure. Frequent hot flashes may occur, with as increase in sweating, heart palpitations, redness and flushing, and dizziness. Genitourinary tract - vaginal dryness and irritation may occur, making sexual intercourse painful. There may be a loss of sex drive, an increased formation of urinary cysts, and an increase in bladder and urinary tract infections. Musculoskeletal changes - osteoporosis is a major consequence of menopause and declining estrogen levels. Reduced calcium absorption may result in bone thinning; joint, bone, and muscle aches; bone fractures; and an eventual decrease in height.

Immediate Changes

  • Hot flashes, causing flushing in the face, neck, chest, and back
  • Insomnia
  • Mild to moderate depression
  • Bone, joint and muscle aches/pains
  • Swelling
  • Heart beat fluctuations
  • Headaches
  • Vaginal dryness
  • Increased sweating

Physical Changes

  • Decreased control over urination and bowel movements
  • Breast size, shape, and firmness may be altered
  • Skin wrinkling and loss of tone may occur
  • Body fat may redistributed to thighs and hips
  • Decrease in metabolism which may increase weight

Treatment Options


Role of Estrogen: Estrogens are hormones that prepare the endometrial cells of the uterus for pregnancy. Estrogens (estradiol and estrone) have many functions in the body, including:

    Cause ovulation, helping to rebuild the lining of the uterus following menstruation. Assist in the development of secondary sex characteristics, including breast development and distribution of body hair. Promote cholesterol balance and nourish the blood and circulatory system. Improve bone density and strength by increasing calcium and phosphate absorption. Increase the softness, smoothness, thickness, and elasticity of the skin.

Estrogen deficient women usually start menopause early and have the most severe symptoms. A deficiency in estrogen can be a major cause of infertility, menopausal symptoms, osteoporosis, and increased risk of heart disease.

Role of Progesterone: Progesterone prepares the lining of the womb for pregnancy and implantation and decreases uterine contractions. Progesterone normally maintains fluid balance, acting as a natural diuretic, by increasing sodium and water elimination from the body. Progesterone deficiency may cause various mild to severe symptoms. This deficiency may be largely responsible for causing premenstrual syndrome (PMS). The adrenal glands produce progesterone throughout the entire menstrual cycle, whereas the ovaries only produce it in significant amounts during the premenstrual phase of the cycle. Progestins (progesterone and medroxyprogesterone) have a balancing effect on estrogen. When progesterone levels drop to near zero, estrogen dominance occurs with side effects including:

    Water retention, swelling (edema) Fatigue, lack of energy Breast swelling Premenstrual mood swings Loss of sex drive Uterine fibroids Cravings for sweets Weight gain, fatty deposits in thighs and hips Cold hands, cold feet (low thyroid)

The addition of medroxyprogesterone to estrogen was reported to potentially negate some of the beneficial changes of estrogen, most notably the increase in HDL cholesterol levels. (1) However, progestin therapy has been reported to offset the increase in triglycerides seen with unopposed estrogen replacement. Estrogen dominance may not mean that a woman has too much estrogen - it may simply be that the progesterone component is out of balance.

Hormonal Replacement Therapy (HRT): Hormonal replacement is supplemental hormonal therapy with synthetic estrogen and usually includes a progestin. HRT influences many aspects of health, and as studies continue and conclude we are learning that these influences can be negative. Climacteric symptoms (the symptoms of hormonal changes such as flushing, insomnia and sweating), osteoporosis, cardiovascular disease, breast and endometrial cancer, blood clots and Alzheimer's disease (2) are just a few of the areas that may be altered with HRT. A decision to use HRT may depend on a woman's individual views of the menopausal transition, the postmenopausal phase, and its consequences. Health providers and patients should be thoroughly informed about the symptoms associated with hormonal deprivation, the associated risks of osteoporosis and cardiovascular disease, and the potential risks of HRT when used in these conditions.

In exchange for benefits, women on synthetic estrogens may suffer from irregular vaginal bleeding and may have an increased chance of breast cancer and/or endometrial cancer. (3) , (4) Progestin use combined with estrogen has been shown to decrease the incidence of uterine cancer. (5) For many women, synthetic estrogens may be undesirable, or their doctor may not recommend synthetic estrogens due to a pre-existing condition. Synthetic estrogens have also been reported to cause fluid retention and may increase the severity of asthma and migraines. (6) , (7) Contraindications to taking synthetic HRT should be discussed with a doctor, but include the following:

Contraindications to the Use of Hormonal Replacement Therapy (HRT)

Cancer Cardiovascular disease
Diabetes Hypertension
Smoking High cholesterol levels
Tendency to gain weight Fluid retention
Liver disease Breast cancer
Fibrocystic breast disease Thrombophlebitis or thromboembolism
Unexplained vaginal bleeding Uterine fibroids
Endometriosis Gall bladder disease
Mental disorders Anxiety and depression
Irritable bowel syndrome

Concerns Regarding the use of Hormone Replacement Therapy (HRT): In July of 2002 a study was published greatly questioning not only the benefits of HRT but also the now confirmed risk of using HRT. (8) The concern arose from the results of one of the trials being conducted by The Women's Health Initiative (WHI). Since 1993 the WHI has enrolled over 160,000 postmenopausal women between the ages of 50 and 79 in one of several trials evaluating strategies designed to promote health and well-being as women age. In one of the trials, 16,608 of these women who were randomly placed in one of two groups; a placebo (sugar pill) group or a group taking estrogen and progestin. Specifically the women in the treatment group were taking a combination prescription tablet containing 0.625mg of conjugated estrogens and 2.5mg of medroxyprogesterone acetate.

The design was to follow the women enrolled in the trial for 8.5 years. However, after just 5 years, the trail was stopped because a routine review of the data found that the women on the hormone combination had an increased risk of breast cancer. Other large trials have raised similar concerns as the WHI trial, (9) , (10) but the WHI was the first to confirm this increase breast cancer risk in healthy women who still had their uterus.

Other concerns were found as well. From the data of the WHI trial, if you had 10,000 women taking estrogen and progestin and compared that group to a similar group taking placebo, over a 1-year period the group of women using the hormone combination would experience the following;

    7 more events related to coronary heart disease 8 more strokes 8 more blood clots in the lungs, known as pulmonary embolisms 8 more cases of invasive breast cancer
However, the study did show some benefit to using the hormone combination because this same group of 10,000 women would have;
    6 fewer cases of colorectal cancer 5 fewer hip fractures

It is important to note that though this trial raises great concern about the use of HRT, these results only pertain to the use of this combination and dose of estrogen and progestin. At this point we do not know whether other combinations, doses or the use of estrogen alone provides a greater benefit or a greater risk. In fact, the WHI has decided to continue all other trials in progress including one evaluating diet, calcium and vitamin D supplementation and even one evaluating the use of estrogen alone in women who no longer have a uterus. The decision to use HRT has become even more difficult. (11)

Nutritional Suplementation


Calcium is a number-one consideration for women before, during, and after menopause. Calcium's importance for maintaining strong, healthy bones and slowing bone loss cannot be overstated. Studies have suggested that during perimenopause, calcium absorption decreases. (12) Calcium supplements are a prudent dietary measure, especially during menopause. Various types and dosage forms of calcium including calcium-fortified milk, high calcium milk powder, and chicken egg shell powder have been shown to delay bone loss in postmenopausal women. (13) , (14) , (15)

Microcrystalline calcium hydroxyapatite (MCHC) is a well-absorbed calcium supplement that has been studied and found effective for slowing bone loss. MCHC comes from specially-processed bone meal that is free of lead and other contaminants sometimes found in bone meal. Preliminary studies suggest that supplementing with MCHC relieves back pain associated with osteoporosis. (16) MCHC also may prevent or even restore bone loss. (17)


While calcium gets the most attention when it comes to mineral nutrition for bones, magnesium is also vitally important. Supplementing with magnesium can improve menopausal symptoms and risk factors, especially the risk of osteoporosis. Magnesium is required for calcium to work properly: magnesium helps bone absorb calcium. Studies link decreased bone density with low levels of dietary magnesium. (18) , (19) Magnesium also aids in the muscle relaxation of skeletal muscles and has a mild tranquilizing effect. (20) One study demonstrated that induced magnesium depletion in postmenopausal women could result in poor cardiovascular functioning during exercise. These symptoms included a greater need for oxygen and energy and an increased heart rate. (21) Experts recommend taking calcium and magnesium in a two-to-one ratio, meaning that you take half as much magnesium as calcium. Magnesium aspartate or magnesium citrate are recommended for optimum absorption.

Gamma Oryzanol

A small Japanese study involving 40 women evaluated the use of gamma-oryzanol on menopausal symptoms. Thirty-six women reported some symptom improvement including hot flashes, weakness, joint pain, muscle pain, headaches, insomnia, nervousness. (22)

Soy Isoflavones

In cultures where soy products are consumed in abundance, women’s health problems, certain cancers, and cardiovascular disease are reported to be less prevalent. (23) Consuming more soy products in the diet increases the amount of phytoestrogens that you get, which act similar to the natural estrogens found in the body only weaker. Soy isoflavones, such as genistein and daidzein are rich in phytoestrogens and are thought to reduce the symptoms of menopause, support healthy bone structure and decrease the risk of certain cancers. (24) , (25) , (26) , (27)

There has been recent interest in the reported use of soy isoflavones in women for decreasing bone loss caused by estrogen deficiency. (28) , (29) Ipriflavone is a synthetic isoflavone. Numerous studies have evaluated ipriflavone and its impact on maintaining bone density. Various studies have supported the use of this isoflavone for the maintenance of bone density. (30) , (31) , (32) , (33) However, opposite results have been noted when ipriflavone was evaluated in postmenopausal women with osteoporosis. An extensive placebo-controlled study involving 474 women lasted 4 years. Two hundred milligrams of ipriflavone three times a day was compared to placebo, with both groups receiving a calcium supplement. This study demonstrated that ipriflavone did not prevent bone loss. (34)

Large studies of particular groups of people have noted that diets with a lot of soy is associated with a lowered risk of cancers, including breast cancer. (35) Evidence in support for these claims has come from animal studies and laboratory studies of breast cancer cells from humans. (36) , (37) , (38) Researchers concluded that in order to reduce the risk of breast cancer, the beneficial effects occur from soy and soy isoflavones in the diet prior to and during puberty. (39)

Another consideration important to menopausal health is that soy intake is associated with a reduction in cardiovascular risk due to cholesterol regulating effects. Researchers have concluded in a study on the effects of soy protein on cardiovascular health that soy supplementation use results in significant improvements in lipid and lipoprotein levels, blood pressure, and the perceived severity of certain symptoms of menopause. (40) It has also been reported in an animal study that the isoflavones in soy protein improve cardiovascular risk factors without negative effects on the reproductive system. (41) In October 1999, the FDA authorized the use of a health claim that foods containing soy protein included in a diet low in saturated fat and cholesterol may reduce the risk of coronary heart disease (CHD) by lowering blood cholesterol levels. Scientific studies indicate that 25 grams of soy protein daily in the diet is needed to show a significant cholesterol lowering effect.

The soy isoflavone genistein has been shown to stimulate the growth of a particular type of breast cancer in women that is dependent on estrogen. (42) , (43) Genistein has also been shown to cancel out the beneficial effects of tamoxifen in women with certain estrogen positive breast tumors. (44) Therefore, women with estrogen positive breast cancer or who are on tamoxifen should discuss the use of isoflavones with their healthcare professional.

Dehydroepiandrosterone (DHEA)

DHEA has exhibited some promise in easing the symptoms of menopause. As women get older and approach menopause, their DHEA levels begin to decrease. One study showed that among the group of women studied, the older women with lower DHEA levels had more symptoms of depression. (45) Other studies have linked low DHEA levels to depression. (46) A study evaluating depression and DHEA levels in the elderly showed that scores on depression tests improved with DHEA supplementation. (47) Other studies have confirmed that overall mental health is not as good in peri- and postmenopausal women when DHEA levels are low. (48)

In postmenopausal women, DHEA supplementation has improved sexual arousal. (49) A study involving 120 postmenopausal women between the ages of 51 and 99 has noted that good DHEA-sulfate levels are directly related to good bone mineral density. (50) One study suggests that long-term use of DHEA may decrease certain cardiovascular risks in postmenopausal women. (51) Also, in postmenopausal women, DHEA has shown similar hormonal effects as estrogen-progestin replacement therapy. (52)


Melatonin levels decrease as we age with a distinct difference noted between premenopausal women and postmenopausal women. (53) Most hormone levels change with age as well. One study evaluating the relationship between hormones, melatonin and menopause noted that menopausal women with the lowest levels of melatonin were able to appropriately influence these hormones while taking a melatonin supplement in the evening. These women also reported a better mood and less signs of depression. (54)

Another study was completed evaluating premenopausal and menopausal women who were also experiencing either insomnia, depression, obesity or hyperprolactinemia. Overnight urine levels of melantonin were found to be low in women with insomnia and obesity. The study was unable to determine the role of melatonin in obesity, however it was suggested that women experiencing sleep disorders could possibly benefit from melatonin supplementation. (55) Reviews of medical literature have also suggested a beneficial role of melatonin in menopausal women experiencing insomnia. (56)

Vitamin C, Vitamin D

Bone loss and decreases in bone mineral density is inevitable as we age. It is important to slow this process, maintain strong healthy bones and thus decrease the risk of bone fractures. According to the National Osteoporosis Foundation, over half of Americans older than 50 have low bone mineral density and 80% of them are women. (57) Especially when used with other therapies, numerous studies have supported the use of vitamin C to help support bone mineral density. (58) , (59) , (60) , (61)

Vitamin D is one of the primary regulators of calcium absorption. Deficiencies are frequently found in postmenopausal women with or at risk for osteoporosis. (62) , (63) , (64) , (65) Considering this relationship, vitamin D insufficiency may have an effect on bone strength. (66)


Flaxseed oil is one of the greatest sources of essential fatty acids. These fatty acids have several important functions and may potentially have a valuable role in protecting against cardiovascular risks in postmenopausal women. Studies have shown that flaxseed oil supplementation may possibly lower total cholesterol including LDL cholesterol, HDL cholesterol and triglycerides in postmenopausal women. (67) In addition, flaxseed along with a consistent diet may influence hormone metabolism within postmenopausal women by decreasing the concentrations of serum 17 beta-estradiol and estrone sulfate and increasing the concentration of serum prolactin concentrations. (68)

Herbal Suplementation

Black Cohosh

A tall perennial plant, black cohosh was valued by Native Americans as an herbal remedy for female problems. The herb became known in colonial days for relieving menstrual cramps. Its usage then spread to Europe, where it still remains popular today.

Research has shown that black cohosh root contains substances called "phytoestrogens" that partially mimic estrogen’s effect on the body. (69) One of these ingredients, "formononetin" has shown an estrogen-like activity in rat studies. (70) Formonontein is an" isoflavone." Soybeans also contain isoflavones, which may explain why women in countries where soy is a staple, Japan, for example, seem to have fewer problems with menopause.

Clinical studies have reported positive effects on menopausal and postmenopausal complaints with standardized extracts of black cohosh. (71) , (72) , (73) Most of the clinical research for black cohosh has been completed using a specific product, Remifemin®. Remifemin® is a standardized preparation of 1mg triterpene glycosides calculated as 27-deoxyacetin. This standardized extract of black cohosh has been reported to have a low occurrence of side effects as well as low toxicity levels. In addition, this extract has been prescribed as an alternative to hormone replacement therapy in European phytotherapy. (74) In one study, black cohosh improved the symptoms in peri- and post-menopausal women, although there was no indication of estrogen-like effects. (75)

Scientists are not completely sure how phytoestrogens work, but the current thinking is that they attach themselves to estrogen receptors in the uterus. When the real estrogen arrives, the seat is taken, so to speak, preventing the estrogen from acting on the target tissues. In the case of low estrogen, phytoestrogens may help make up for the estrogen’s absence. In the case of too much estrogen, it may prevent estrogen from overacting on the body. In this way, phytoestrogens seem to have a balancing influence that improves female function. But, compared to real hormones, phytoestrogens are rather weak. They do not alter bodily processes as powerfully as real hormones do. In the case of black cohosh, while it lowered luteinizing hormone (LH) levels, no change was noted in follicle stimulating hormone (FSH), showing that its effects are not the same as estrogen itself. (76)


Chasteberry has a long folk history of use in women’s health. Chasteberry has been recommended for use in mild to moderate symptoms in endometriosis, menopause and PMS. (77) , (78) , (79) The actual activity of chasteberry is not fully established, though studies point to a progesterone-like effect (80) , (81) , (82) as well as stimulation of luteinizing hormone (LH) and inhibition of follicle stimulating hormone (FSH). (83) , (84)

Red Clover

There has been a great deal of research and reviews on the effects of phytoestrogens as they relate to menopausal symptoms. (85) Research has focused on the red clover extract, which contains four principle phytoestrogens (biochanin A, fomonontein, genistein, and daidzein), all with reported estrogen-like activity. (86) A commercial extract of red clover (Promensil™), standardized to contain a certain amount of phytoestrogens, has gained a great deal of attention in the management of menopause and related symptoms. Studies involving this extract have demonstrated a range of response from no advantage over placebo to a notable improvement in certain symptoms of menopause. (87) , (88)

Dong Quai

Dong quai is generally considered when evaluating options for relieving the symptoms of menopause. However, numerous studies evaluating the use of dong quai for that purpose have not had promising results. One indicated that dong quai showed only weak estrogen-like activity (89) whereas another stated it was no more helpful than placebo in treating menopausal symptoms. (90) Reviews of the medical literature question the benefit of dong quai in treating menopausal symptoms as well. (91) , (92) , (93) One study noted that dong quai stimulated cell growth of a specific type of breast cancer. (94)

American Ginseng

A study involving 384 postmenopausal women compared the use of ginseng to placebo for relief of related symptoms. Benefit was seen for depression and general well-being and health. However, no advantage was seen for hot flashes and physical changes that occur to the vagina and surrounding area. This study seems to indicate that the beneficial effects seen may not be related to hormonal-like effects anticipated. (95)

Since ginseng is commonly used to treat menopausal symptoms, studies have evaluated not only the estrogen-like activity but also the potential of ginseng to stimulate the growth of certain types of breast cancer cells. Though no activity on estrogen receptors was noted in a laboratory study, ginseng stimulated cell growth of a specific type of breast cancer. (96) A second laboratory study evaluating the same type of breast cancer cells had opposite results. Compared to estradiol, American ginseng did not increase cell growth. In fact, when tested with certain drugs designed to fight breast cancer, cell growth was actually decreased. (97)

Evening Primrose

A study evaluated the use of gamolenic acid for the relief of menopause associated flushing and sweating. Gamolenic acid is better known as gamma-linolenic acid, an omega-6 fatty acid. The treatment group received evening primrose oil as the source of gamolenic acid and vitamin E. This group was compared to a placebo group. Although there was a reduction in the maximum number of night time hot flashes, the study concluded that overall, gamolenic acid was no better than placebo in treating menopausal flushing. (98)

Diet & Lifestyle

    Eat a healthy diet low in animal fats, consisting of plenty of fresh vegetables and fruits (organic where possible). Eat whole, unprocessed foods, no preservatives. Drink plenty of quality water (either reverse osmosis, bottled, or filtered). Limit meats and increase soy products, legumes, and whole grains. Limit refined sugars. No carbonated beverages – high phosphate content may bind calcium. Eat olive oil in foods to replace other oils (extra virgin, cold pressed) and eat cold water fishes (salmon, cod) at least two times a week for essential fatty acids. Limit carbohydrates and eat on a regular schedule to limit blood sugar fluctuations. Limit alcohol and caffeine consumption. Exercise regularly.


  1. View Abstract: Os I, et al. The EWA (Estrogen in Women With Atherosclerosis) Study: A Randomized Study of the Use of Hormone Replacement Therapy in Women With Angiographically Verified Coronary Artery Disease. Characteristics of the Study Population. Effects On Lipids and Lipoproteins. J Intern Med. Apr2000;247(4):433-41.
  2. View Abstract: Rapp SR, Espeland MA, Shumaker SA, et al. Effect of Estrogen Plus Progestin on Global Cognitive Function in Postmenopausal Women: The Women's Health Initiative Memory Study: A Randomized Controlled Trial. JAMA. May2003;289(20):2663-72.
  3. View Abstract: Koukoulis GN. Hormone Replacement Therapy and Breast Cancer Risk. Ann N Y Acad Sci. 2000;900:422-8.
  4. Follingstad AH. Estriol, The Forgotten Estrogen? JAMA. 1978;239(1):29-30.
  5. View Abstract: Fujimoto J, et al. Progestins Suppress Estrogen-induced Expression of Vascular Endothelial Growth Factor (VEGF) Subtypes in Uterine Endometrial Cancer Cells. Cancer Lett. Jul1999;141(1-2):63-71.
  6. View Abstract: De Campos DA, et al. Hormone Replacement Therapy and Cancer of the Breast. 1. Does Replacement Therapy Increase the Risk of Cancer of the Breast? Acta Med Port. Oct1997;10(10):697-703.
  7. View Abstract: Breckwoldt M, et al. Benefits and Risks of Hormone Replacement Therapy (HRT). J Steroid Biochem Mol Biol. Jun1995;53(1-6):205-08.
  8. View Abstract: Writing Group for the Women's Health Initiative Investigators. Women's Health Initiative. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial. JAMA. Jul2002;288(3):321-33.
  9. View Abstract: The Writing Group for the PEPI Trial. Effects of hormone replacement therapy on endometrial histology in postmenopausal women. The Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial. JAMA. Feb1996;275(5):370-5.
  10. View Abstract: Grady D, Herrington D, Bittner V, Blumenthal R, Davidson M, Hlatky M, et al, HERS Research Group. Cardiovascular disease outcomes during 6.8 years of hormone therapy: Heart and Estrogen/progestin Replacement Study follow-up (HERS II). JAMA. Jul2002;288(1):49-57.
  11. View Abstract: Writing Group for the Women's Health Initiative Investigators. Women's Health Initiative. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial. JAMA. Jul2002;288(3):321-33.
  12. View Abstract: Wishart JM, Clifton PM, Nordin BE. Effect of perimenopause on calcium absorption: a longitudinal study. Climacteric. Jun2000;3(2):102-8.
  13. View Abstract: Cleghorn DB, et al. An open, crossover trial of calcium-fortified milk in prevention of early postmenopausal bone loss. Med J Aust. Sep2001;175(5):242-5.
  14. View Abstract: Lau EM, Woo J, Lam V, Hong A. Milk supplementation of the diet of postmenopausal Chinese women on a low calcium intake retards bone loss. J Bone Miner Res. Sep2001;16(9):1704-9.
  15. View Abstract: Schaafsma A, Pakan I, van der Veer E. Positive effects of a chicken eggshell powder-enriched vitamin-mineral supplement on femoral neck bone mineral density in healthy late post-menopausal Dutch women. Br J Nutr. Mar2002;87(3):267-75.
  16. View Abstract: Pines A, et al. Clinical trial of microcrystalline hydroxyapatite compound (‘Ossopan’) in the prevention of osteoporosis due to corticosteroid therapy. Curr Med Res Opin. 1984;8:734-742.
  17. View Abstract: Stellon A, et al. Microcrystalline hydroxyapatite compound in prevention of bone loss in corticosteroid-treated patients with chronic active hepatitis. Postgrad Med J. 1985;61:791-796.
  18. View Abstract: Sojka JE, et al. Magnesium Supplementation and Osteoporosis. Nutr Rev. 1995;53(3):71-74.
  19. View Abstract: Tranquilli AL, et al. Calcium, Phosphorus, and Magnesium Intakes Correlate with Bone Mineral Content in Postmenopausal Women. Gynecol Endrocrinol. 1994;8(1):55-58.
  20. View Abstract: Altura BM, et al. Role of Magnesium in Patho-physiological Processes and the Clinical Utility of Magnesium Ion Selective Electrodes. Scand J Clin Lab Invest. 1996;224S: 211-34.
  21. View Abstract: Lukaski HC, Nielsen FH. Dietary magnesium depletion affects metabolic responses during submaximal exercise in postmenopausal women. J Nutr. May2002;132(5):930-5.
  22. View Abstract: Ishihara M, et al. Clinical effect of gamma-oryzanol on climacteric disturbance -on serum lipid peroxides. Nippon Sanka Fujinka Gakkai Zasshi. Feb1982;34(2):243-51.
  23. View Abstract: Barnes S. Evolution of the health benefits of soy isoflavones. Proc Soc Exp Biol Med. 1998;217:386-398.
  24. View Abstract: Kritz-Silverstein D, Goodman-Gruen DL. Usual dietary isoflavone intake, bone mineral density, and bone metabolism in postmenopausal women. J Womens Health Gend Based Med. Jan2002;11(1):69-78.
  25. View Abstract: Adlercreutz H. Phytoestrogens: Epidemiology and a possible role in cancer protection. Environ Health Perspect. 1995;103S:103-112.
  26. View Abstract: Cotroneo MS, Wang J, Fritz WA, Eltoum IE, Lamartiniere CA. Genistein action in the prepubertal mammary gland in a chemoprevention model. Carcinogenesis. Sep2002;23(9):1467-1474.
  27. View Abstract: Wu AH, Wan P, Hankin J, Tseng CC, Yu MC, Pike MC. Adolescent and adult soy intake and risk of breast cancer in Asian-Americans. Carcinogenesis. Sep2002;23(9):1491-6.
  28. View Abstract: Ishimi Y, et al. Selective effects of genistein, a soybean isoflavone, on B-lymphopoiesis and bone loss caused by estrogen deficiency. Endocrinology. 1999;140:1893-1900.
  29. View Abstract: Setchell KD, et al. Dietary isoflavones: biological effects and relevance to human health. J Nutr. 1999;129:758S-767S.
  30. View Abstract: Halpner AD, Kellermann G, Ahlgrimm MJ, Arndt CL, Shaikh NA, Hargrave JJ, Tallas PG. The effect of an ipriflavone-containing supplement on urinary N-linked telopeptide levels in postmenopausal women. J Womens Health Gend Based Med. Nov2000;9(9):995-8.
  31. View Abstract: Ohta H, Komukai S, Makita K, Masuzawa T, Nozawa S. Effects of 1-year ipriflavone treatment on lumbar bone mineral density and bone metabolic markers in postmenopausal women with low bone mass. Horm Res. 1999;51(4):178-83.
  32. View Abstract: Agnusdei D, Bufalino L. Efficacy of ipriflavone in established osteoporosis and long-term safety. Calcif Tissue Int. 1997;61(Suppl 1):S23-7.
  33. View Abstract: Gennari C, Adami S, Agnusdei D, Bufalino L, Cervetti R, Crepaldi G, et al. Effect of chronic treatment with ipriflavone in postmenopausal women with low bone mass. Calcif Tissue Int. 1997;61(Suppl 1):S19-22.
  34. View Abstract: Alexandersen P, Toussaint A, Christiansen C, et al. Ipriflavone in the Treatment of Postmenopausal Osteoporosis, A Randomized Controlled Trial. JAMA. 2001;285:1482-1488.
  35. View Abstract: Messina MJ, Persky V, Setchell KDR. Soy Intake and Cancer Risk: A Review of the in Vitro and in Vivo Data. Nutr Cancer. 1994;21:113.
  36. View Abstract: Peterson TG, et al. Metabolism of the isoflavones genistein and biochanin A in human breast cancer cell lines. Am J Clin Nutr. 1998;68(6 Suppl):1505S-1511S.
  37. View Abstract: Barnes S. Effect of genistein on in vitro and in vivo models of cancer. J Nutr. 1995;125(3 Suppl):777S-783S.
  38. View Abstract: Barnes S. The chemopreventive properties of soy isoflavonoids in animal models of breast cancer. Breast Cancer Res Treat. 1997;46:169-170.
  39. View Abstract: Brown NM, et al. Xenoestrogens alter mammary gland differentiation and cell proliferation in the rat. Environ Health Perspect. 1995;103:708-713.
  40. View Abstract: Washburn S, Burke GL, Morgan T, et al. Effect of soy protein supplementation on serum lipoproteins, blood pressure, and menopausal symptoms in perimenopausal women. Menopause. 1999;6:7-13.
  41. View Abstract: Anthony MS, Clarkson TB, Hughes CL Jr, et al. Soybean isoflavones improve cardiovascular risk factors without affecting the reproductive system of peripubertal rhesus monkeys. J Nutr. 1996;126:43-50.
  42. View Abstract: Allred CD, Allred KF, Ju YH, et al. Soy diets containing varying amounts of genistein stimulate growth of estrogen-dependent (MCF-7) tumors in a dose-dependent manner. Cancer Res. Jul2001;61(13):5045-50.
  43. View Abstract: Hsieh CY, Santell RC, Haslam SZ, Helferich WG. Estrogenic effects of genistein on the growth of estrogen receptor-positive human breast cancer (MCF-7) cells in vitro and in vivo. Cancer Res. Sep1998;58(17):3833-8.
  44. View Abstract: Ju YH, Doerge DR, Allred KF, Allred CD, Helferich WG. Dietary Genistein Negates the Inhibitory Effect of Tamoxifen on Growth of Estrogen-dependent Human Breast Cancer (MCF-7) Cells Implanted in Athymic Mice. Cancer Res. May2002;62(9):2474-7.
  45. View Abstract: Morrison MF, et al. DHEA-S levels and depressive symptoms in a cohort of African American and Caucasian women in the late reproductive years. Biol Psychiatry. Nov2001;50(9):705-11.
  46. View Abstract: Goodyer IM, et al. Adrenal Secretion during Major Depression in 8- to 16-year-olds, I. Altered Diurnal Rhythms in Salivary Cortisol and Dehydroepiandrosterone (DHEA) at Presentation. Psychol Med. Mar1996;26(2):245-56.
  47. View Abstract: Wolkowitz OM, et al. Dehydroepiandrosterone (DHEA) Treatment of Depression. Biol Psychiatry. Feb1997;41(3):311-18.
  48. View Abstract: Nagata C, et al. Serum concentrations of estradiol and dehydroepiandrosterone sulfate and soy product intake in relation to psychologic well-being in peri- and postmenopausal Japanese women. Metabolism. Dec2000;49(12):1561-4.
  49. View Abstract: Hackbert L, Heiman JR. Acute dehydroepiandrosterone (DHEA) effects on sexual arousal in postmenopausal women. J Womens Health Gend Based Med. Mar2002;11(2):155-62.
  50. View Abstract: Takayanagi R, et al. Dehydroepiandrosterone (DHEA) as a possible source for estrogen formation in bone cells: correlation between bone mineral density and serum DHEA-sulfate concentration in postmenopausal women, and the presence of aromatase to be enhanced by 1,25-dihydroxyvitamin D3 in human osteoblasts. Mech Ageing Dev. Apr2002;123(8):1107-14.
  51. View Abstract: Lasco A, Frisina N, Morabito N, et al. Metabolic effects of dehydroepiandrosterone replacement therapy in postmenopausal women. Eur J Endocrinol. Oct2001;145(4):457-61.
  52. View Abstract: Genazzani AD, et al. Oral dehydroepiandrosterone supplementation modulates spontaneous and growth hormone-releasing hormone-induced growth hormone and insulin-like growth factor-1 secretion in early and late postmenopausal women. Fertil Steril. Aug2001;76(2):241-8.
  53. View Abstract: Okatani Y, Morioka N, Wakatsuki A. Changes in nocturnal melatonin secretion in perimenopausal women: correlation with endogenous estrogen concentrations. J Pineal Res. Mar2000;28(2):111-8.
  54. View Abstract: Bellipanni G, Bianchi P, Pierpaoli W, Bulian D, Ilyia E. Effects of melatonin in perimenopausal and menopausal women: a randomized and placebo controlled study. Exp Gerontol. Feb2001;36(2):297-310.
  55. View Abstract: Blaicher W, Speck E, Imhof MH, et al. Melatonin in postmenopausal females. Arch Gynecol Obstet. Feb2000;263(3):116-8.
  56. View Abstract: Brzezinski A. Melatonin replacement therapy" for postmenopausal women: is it justified? Menopause. Mar1998;5(1):60-4.
  57. National Osteoporosis Foundation. Disease Statistics. Available at: Accessed Jul2002.
  58. View Abstract: Morton DJ, Barrett-Connor EL, Schneider DL. Vitamin C supplement use and bone mineral density in postmenopausal women. J Bone Miner Res. Jan2001;16(1):135-40.
  59. View Abstract: Hall SL, Greendale GA. The relation of dietary vitamin C intake to bone mineral density: results from the PEPI study. Calcif Tissue Int. Sep1998;63(3):183-9.
  60. View Abstract: Wang MC, Luz Villa M, Marcus R, Kelsey JL. Associations of vitamin C, calcium and protein with bone mass in postmenopausal Mexican American women. Osteoporos Int. 1997;7(6):533-8.
  61. View Abstract: Leveille SG, LaCroix AZ, Koepsell TD, Beresford SA, Van Belle G, Buchner DM. Dietary vitamin C and bone mineral density in postmenopausal women in Washington State, USA. J Epidemiol Community Health. Oct1997;51(5):479-85.
  62. View Abstract: Villareal DT, et al. Subclinical Vitamin D Deficiency in Postmenopausal Women with Low Vertebral Bone Mass. Journal of Clinical Endocrinology and Metabolism. 1991;72(3):628-34.
  63. View Abstract: Rassouli A, Milanian I, Moslemi-Zadeh M. Determination of serum 25-hydroxyvitamin D(3) levels in early postmenopausal Iranian women: relationship with bone mineral density. Bone. Nov2001;29(5):428-30.
  64. View Abstract: Mezquita-Raya P, Munoz-Torres M, Luna JD, et al. Relation between vitamin D insufficiency, bone density, and bone metabolism in healthy postmenopausal women. J Bone Miner Res. Aug2001;16(8):1408-15.
  65. View Abstract: Brot C, Vestergaard P, Kolthoff N, Gram J, Hermann AP, Sorensen OH. Vitamin D status and its adequacy in healthy Danish perimenopausal women: relationships to dietary intake, sun exposure and serum parathyroid hormone. Br J Nutr. Aug2001;86(Suppl 1):S97-103.
  66. View Abstract: Mezquita Raya P, Munoz Torres M, Lopez Rodriguez F, et al. Prevalence of vitamin D deficiency in populations at risk for osteoporosis: impact on bone integrity. Med Clin (Barc). Jun2002;119(3):85-9.
  67. View Abstract: Lucas EA, Wild RD, Hammond LJ, Khalil DA, Juma S, Daggy BP, et al. Flaxseed improves lipid profile without altering biomarkers of bone metabolism in postmenopausal women. J Clin Endocrinol Metab. Apr2002;87(4):1527-32.
  68. View Abstract: Hutchins AM, Martini MC, Olson BA, Thomas W, Slavin JL. Flaxseed consumption influences endogenous hormone concentrations in postmenopausal women. Nutr Cancer. 2001;39(1):58-65.
  69. Jarry H, et al. The Endocrine Effects of Constituents of Cimicifuga racemosa. 2. In Vitro Binding of Constituents to Estrogen Receptors. Planta Med. Aug1985;4:316-19.
  70. Jarry H, et al. Endocrine Effects of Constituents of Cimicifuga racemosa. 1. The Effect on Serum Levels of Pituitary Hormones in Ovariectomized Rats. Planta Med. Feb1985;1:46-49.
  71. View Abstract: Lieberman S. A Review of the Effectiveness of Cimicifuga racemosa (black cohosh) for the Symptoms of Menopause. J Womens Health. Jun1998;7(5):525-29.
  72. Jarry H, et al. The Endocrine Effects of Constituents of Cimicifuga racemosa. 2. In Vitro Binding of Constituents to Estrogen Receptors. Planta Med. Aug1985;4:316-19.
  73. View Abstract: Dog TL, Powell KL, Weisman SM. Critical evaluation of the safety of Cimicifuga racemosa in menopause symptom relief. Menopause. Jul2003;10(4):299-313.
  74. View Abstract: McKenna DJ, et al. Black cohosh: efficacy, safety, and use in clinical and preclinical applications. Altern Ther Health Med. May2001;7(3):93-100.
  75. View Abstract: Liske E, et al. Physiological investigation of a unique extract of black cohosh (Cimicifugae racemosae rhizoma): a 6-month clinical study demonstrates no systemic estrogenic effect. J Womens Health Gend Based Med. Mar2002;11(2):163-74.
  76. View Abstract: Duker EM, et al. Effects of Extracts from Cimicifuga racemosa on Gonadotropin Release in Menopausal Women and Ovariectomized Rats. Planta Med. Oct1991;57(5):420-24.
  77. Hillebrand H. The Treatment of Premenstrual Aphthous Ulcerative Stomatitis with Agnolyt. Z Allgemeinmed. 1964;40(36):1577.
  78. McGibbon D. Premenstrual Syndrome. CMAJ. 1989;141(11):1124-25.
  79. View Abstract: Jarry H, et al. In Vitro Prolactin But Not LH and FSH Release Is Inhibited by Compounds in Extracts of Agnus castus: Direct Evidence for a Dopaminergic Principle by the Dopamine Receptor Assay. Exp Clin Endocrinol. 1994;102(6):448-54.
  80. Amann W. Elimination of Obstipation with Agnolyt. Ther Gegenew. 1965;104(9):1263-65.
  81. View Abstract: Makwana HG, et al. General Pharmacology of Vitex leucoxylon Linn Leaves. Indian J Physiol Pharmacol. 1994;38(2):95-100.
  82. View Abstract: Liu J, Burdette JE, Xu H, Gu C, van Breemen RB, Bhat KP, et al. Evaluation of estrogenic activity of plant extracts for the potential treatment of menopausal symptoms. J Agric Food Chem. May 2001;49(5):2472-9.
  83. View Abstract: Milewicz A, et al. Vitex Agnus castus Extract in the Treatment of Luteal Phase Defects Due to Latent Hyperprolactinemia. Results of a Randomized Placebo-controlled Double-blind Study. Arzneim Forsch/Drug Res. 1993;43(7):752-56.
  84. View Abstract: Bhargava SK. Antiandrogenic Effects of a Flavonoid-rich Fraction of Vitex Negundo Seeds: A Histological and Biochemical Study in Dogs. J Ethnopharmacol. 1989;27(3):327-39.
  85. View Abstract: Chiechi LM. Dietary Phytoestrogens in the Prevention of Long-term Postmenopausal Diseases. Int J Gynaecol Obstet. Oct1999;67(1):39-40.
  86. View Abstract: Knight DC. A review of the clinical effects of phytoestrogens. Obstet Gynecol. May1996;87(5 Pt 2):897-904.
  87. View Abstract: Knight DC, Howes JB, Eden JA. The effect of Promensil, an isoflavone extract, on menopausal symptoms. Climacteric. Jun1999;2(2):79-84.
  88. View Abstract: van de Weijer P, Barentsen R. Isoflavones from red clover (Promensil(R)) significantly reduce menopausal hot flush symptoms compared with placebo. Maturitas. Jul2002;42(3):187.
  89. View Abstract: Liu J, Burdette JE, Xu H, Gu C, van Breemen RB, Bhat KP, et al. Evaluation of estrogenic activity of plant extracts for the potential treatment of menopausal symptoms. J Agric Food Chem. May 2001;49(5):2472-9.
  90. View Abstract: Hirata JD, Swiersz LM, Zell B, Small R, Ettinger B. Does dong quai have estrogenic effects in postmenopausal women? A double-blind, placebo-controlled trial. Fertil Steril. Dec1997;68(6):981-6.
  91. View Abstract: Willhite LA, O'Connell MB. Urogenital atrophy: prevention and treatment. Pharmacotherapy. Apr2001;21(4):464-80.
  92. View Abstract: Hardy ML. Herbs of special interest to women. J Am Pharm Assoc (Wash). Mar2000;40(2):234-42.
  93. View Abstract: Shaw CR. The perimenopausal hot flash: epidemiology, physiology, and treatment. Nurse Pract. Mar1997;22(3):55-6, 61-6.
  94. View Abstract: Amato P, Christophe S, Mellon PL. Estrogenic activity of herbs commonly used as remedies for menopausal symptoms. Menopause. Mar2002;9(2):145-50.
  95. View Abstract: Wiklund IK, Mattsson LA, Lindgren R, Limoni C. Effects of a standardized ginseng extract on quality of life and physiological parameters in symptomatic postmenopausal women: a double-blind, placebo-controlled trial. Swedish Alternative Medicine Group. Int J Clin Pharmacol Res. 1999;19(3):89-99.
  96. View Abstract: Amato P, Christophe S, Mellon PL. Estrogenic activity of herbs commonly used as remedies for menopausal symptoms. Menopause. Mar2002;9(2):145-50.
  97. View Abstract: Duda RB, Zhong Y, Navas V, Li MZ, Toy BR, Alavarez JG. American ginseng and breast cancer therapeutic agents synergistically inhibit MCF-7 breast cancer cell growth. J Surg Oncol. Dec1999;72(4):230-9.
  98. View Abstract: Chenoy R, Hussain S, Tayob Y, O'Brien PM, Moss MY, Morse PF. Effect of oral gamolenic acid from evening primrose oil on menopausal flushing. BMJ. Feb1994;308(6927):501-3.