Menopause

Menopause is a normal biological event that marks the end of a woman's reproductive years. It is the point when menstruation stops permanently. On average, menopause occurs at age 51, but like the beginning of menstruation in adolescence, timing varies from person to person. Today, an estimated 50 million women in the United States have reached menopause and most women will spend at least one-third of their lives in or beyond menopause.

Menopause is the last stage of a gradual biological process in which the ovaries reduce their production of female sex hormones. Estrogen production in the body diminishes slowly over a period of years, commonly resulting in hot flashes, night sweats, mood swings, and memory loss. This gradual phase before the permanent cessation of menstrual periods is sometimes called perimenopause. The process of menopause is considered complete when a woman has not menstruated for an entire year. Another type of menopause, known as surgical menopause, occurs if both ovaries are removed for medical reasons. This may be done at the time of a hysterectomy (removal of the uterus).

Living without the protective effects of estrogen increases a woman's risk for developing serious medical conditions, including osteoporosis and cardiovascular disease. There are a variety of treatments available, however, to help ease the symptoms of and reduce health risks associated with menopause.

Signs and Symptoms

Each woman experiences her own variation of the typical symptoms of menopause. Some studies even suggest that the signs and symptoms of menopause may vary between cultural groups. For example, up to 80% of American women experience hot flashes during menopause while only 10% of Japanese women experience that symptom. Some researchers speculate that these differences may be due to differences in diet, lifestyle, and/or cultural attitudes toward aging.

In general, however, the loss of estrogen that occurs during menopause causes the following symptoms: Over time, depleted estrogen levels can contribute to the development of more serious medical conditions, including the following:

Causes

Menopause is caused by a gradual reduction in the amount of estrogen produced in the ovaries. Estrogen, a female hormone produced primarily by the ovaries, is essential for the reproductive process and influences menstrual cycles, pregnancy, some aspects of mood, and the aging process. In the years leading up to menopause, the ovaries become less functional and produce lower amounts of estrogen and progesterone (another female hormone). Studies indicate that women who smoke may reach menopause at a younger age than those who do not smoke. Some researchers speculate that the timing of menopause onset may be hereditary, but the evidence to support this claim is limited.

Although menopause usually occurs naturally, it can be artificially induced through surgical removal of the ovaries (this is called surgical menopause). Menopause can also be caused by ovarian failure from cancer therapy, such as chemotherapy or radiation treatments.

Risk Factors

Menopause is part of the natural aging process in all women, unless it is caused by surgical removal of both ovaries. (This operation, known as a bilateral oopherectomy, may be performed at the time of a hysterectomy). Surgical menopause tends to cause a more abrupt onset of symptoms. The following risk factors may also hasten the onset of menopausal symptoms:

Diagnosis

In general, menopause is considered complete when a woman has not menstruated for at least 1 year. A healthcare provider will perform an examination that includes a Pap smear, blood tests looking at hormone and cholesterol levels, and, possibly, a bone density measurement. It is important to have a thorough discussion with the healthcare provider regarding the benefits and risks of different options for reducing symptoms and health risks. If vaginal bleeding resumes unexpectedly once menopause has occurred, your doctor may consider a test called an endometrial biopsy. In this test (performed in the office), a gynecologist takes a sample of the uterine lining (the endometrium) and examines them under the microscope for abnormal changes.

Preventive Care

The following preventive measures may help diminish symptoms and reduce the risk of serious complications (such as osteoporosis and cardiovascular disease) associated with menopause:

Treatment Approach

The goal in treating menopause is to alleviate symptoms and reduce the risk for long-term medical conditions, such as heart disease, breast cancer, and osteoporosis. There are a variety of treatment options available to menopausal women. To help determine the most appropriate treatment, it is important for each woman to discuss personal risks and benefits with her healthcare provider.

To combat symptoms and prevent the development of osteoporosis associated with diminished estrogen levels, hormone replacement therapy (HRT) may be considered. HRT involves the administration of the female sex hormones, estrogen and progesterone. Estrogen replacement therapy (ERT) refers to the administration of estrogen alone. ERT has proven to be very effective in relieving many of the symptoms of menopause, and is also thought to help prevent osteoporosis.

Hormone treatment for menopause is quite controversial, however. Preliminary research suggested that HRT might help prevent heart disease. But, the latest and largest studies report that that is not the case. In fact, HRT may increase your risk for both heart disease and stroke. Also, of particular concern is that taking ERT can put you at increased risk for breast cancer. Based on these concerns and scientific evidence to date, physicians are unable to recommend long term use of HRT. For some women, taking HRT for a short period of time (like 1 to 2 years) to relieve symptoms of menopause may be fine.

In addition, there are non-hormonal medications and non-drug therapies that can help reduce your risk for long-term medical conditions associated with menopause: Other remedies that may help alleviate the symptoms of menopause include magnesium, black cohosh, acupuncture, and relaxation techniques.

Lifestyle

Exercise
The benefits of exercise include: Diet
The right diet can help a woman battle many of the risks and discomforts associated with menopause. A low-fat, low-cholesterol diet, for example, may diminish the risk of heart disease in menopausal women by providing the following benefits: In addition, soy-based foods like tofu have been shown to help minimize certain symptoms of menopause, including hot flashes. Adding plenty of calcium to the diet can also help a menopausal women avoid bone loss. (Foods rich in calcium include dairy products, leafy green vegetables, almonds, and dried beans). High fiber meals may also help lower a woman's risk of high cholesterol and heart disease.

Medications

There are many medications available in the form of natural and synthetic hormones (estrogen and progesterone) to treat symptoms of menopause. Commonly referred to as hormone replacement therapy (HRT), these medications are usually administered in pill form, although skin patches and vaginal creams may also be used.

The following information represents a summary of the most commonly used hormone medications. A woman and her healthcare provider can discuss the pros and cons of all treatment options to determine which approach is most appropriate.

Estrogen
Estrogen replacement therapy (ERT) refers to the administration of the female sex hormone, estrogen. In addition to reducing the symptoms of menopause, ERT is thought to help prevent the devastating effects of osteoporosis. Most studies showing long-term beneficial effects for ERT have examined this hormone alone.

The decision regarding whether to take estrogen depends on several factors including the severity of your menopausal symptoms as well as your risk for osteoporosis and breast cancer.

Studies indicate that estrogen helps to reduce hot flashes and vaginal dryness. It can also slow bone loss thereby minimizing fractures associated with osteoporosis, and improve cholesterol levels. Women who take estrogen may be at lower risk for Alzheimer's disease, colon cancer, and macular degeneration.

Despite these potential advantages, studies indicate that estrogen increases the risk of developing breast cancer and, possibly, gallbladder disease, asthma, liver disease, blood clots, stroke, and, if used without progesterone, uterine cancer. Side effects of estrogen use include bloating, nausea, and breast tenderness.

Estrogen is available in a variety of forms—estradiol is considered the strongest form and estropipate the weakest. Mixtures of estrogens (also known as conjugated estrogens) are also often prescribed.

Estrogens (or estrogen derivatives) Progesterone
Estrogen stimulates the growth of the inner lining of the uterus (endometrium); it is the endometrium that sheds during menstruation. ERT used after menopause can also stimulate endometrium growth, but this growth may occur uncontrollably and even result in cancer. Progesterone counteracts this dangerous effect on the uterus and reduces the risk of developing uterine cancer by causing monthly shedding of the endometrium. Therefore, when a menopausal woman has not had a hysterectomy (has an intact uterus), progesterone is used in combination with estrogen.

In rare instances, progesterone may be used without estrogen to treat hot flashes and other symptoms of menopause. Generally, however, most physicians recommend that women who have a uterus use a combination of estrogen and progesterone to combat symptoms of menopause and reduce the risk of uterine cancer. Progesterone is available in synthetic forms (progestins) and natural forms. Natural progesterones appear to cause fewer side effects than synthetic progesterones.

Progesterones frequently prescribed include: Combination Therapy
Combinations of estrogen and progesterone in a single pill may be prescribed to make the daily treatment regimen easier.

Common combination prescriptions include: Testosterone
Although generally considered a male hormone, testosterone may be prescribed to a woman in small amounts in combination with estrogen. Testosterone appears to improve bone mass, sexual drive, and mental alertness. Side effects of this therapy include increased body hair, acne, fluid retention, anxiety, and depression. The long-term risks of testosterone are not well known at this time.

Common prescriptions with testosterone include: Selective Estrogen-Receptor Modulators (SERMs)
A woman who either cannot or who chooses not to take estrogen may be advised to try a class of drugs called selective estrogen-receptor modulators (SERMs). Raloxifene, the main drug in this category used for menopause, helps to prevent osteoporosis without increasing a woman's risk of developing breast or uterine cancer. These medications do not improve symptoms of menopause, however, and may even make those symptoms worse.

Bisphosphonates
Another class of medications, the biphosphonates, is used primarily for women with early signs of bone loss or osteoporosis, and cannot take hormones. Alendronate, one type of biphosphonate, helps to build bone mass, particularly once osteoporosis has set in.

Nutrition and Dietary Supplements

Soy
Soy foods contain plant-based estrogens (phytoestrogens) called isoflavones that appear to reduce hot flashes, improve cholesterol, and may decrease bone loss. The North American Menopause Society (NAMS) recommends including soy foods in the diet, rather than soy supplements or other substances with phytoestrogens, to help reduce menopausal symptoms. However, researchers are still working to determine whether soy increases or decreases a woman's risk of developing either breast or uterine cancer.

Flaxseed
Flaxseed contains omega-3 fatty acids and plant-based estrogens (phytoestrogens) called lignans that may help reduce symptoms of menopause, protect against breast cancer, and prevent heart disease. More research is needed to determine the connection between the use of flaxseed and breast cancer in particular.

Calcium
The National Institutes of Health (NIH) and NAMS recommends that postmenopausal women consume between 1,000 and 1,500 milligrams of calcium per day to boost bone mass. Some studies suggest that calcium may be particularly effective when combined with ERT. Foods rich in calcium include dairy, green leafy vegetables, black strap molasses, almonds, and dried beans. If adequate amounts of calcium are not being obtained through the diet, calcium supplements may be necessary. Calcium is available in many forms, but one in particular—calcium citrate—appears to be more easily absorbed from the intestinal tract than other forms.

Vitamin D
Vitamin D, along with calcium, is essential for building and maintaining healthy bones throughout life. In fact, calcium can be absorbed into the body only when vitamin D is present. As levels of vitamin D diminish with age, calcium deficiencies can arise, increasing the risk for osteoporosis and bone fractures. The recommended dietary intake for vitamin D is currently 400 IU per day for women between the ages of 50 and 70 years and 600 IU for those older than age 70. Sources of this vitamin include sunlight, fatty fish, dairy fortified with vitamin D, and supplements. Most women can meet their vitamin D needs with moderate exposure to the sun and with supplements.

Magnesium
Magnesium helps the body absorb calcium. These two nutrients should be taken together in a 2:1 ratio, calcium: magnesium (for example, 1,000 to 1,500 milligrams of calcium and 500 to 750 milligrams of magnesium per day). In addition, as estrogen levels drop during menopause, magnesium levels seem to diminish as well. For this reason, magnesium may also help to relieve some menopausal symptoms such as hot flashes. More research is needed. Rich sources of magnesium include tofu, nuts (particularly Brazil nuts, almonds, cashews, black walnuts, and pine nuts), pumpkin and squash seeds, peanuts and other legumes, green leafy vegetables, wheat germ, soy bean flour, and black strap molasses.

Boron
Boron assists in the proper metabolism (processing by the body) of magnesium. Studies suggest that 1 to 3 milligrams of boron per day is needed to maintain normal levels of magnesium. If normal levels of magnesium are not present, the body is less able to absorb calcium. Menopausal women who take boron supplements, therefore, can boost levels of calcium in their blood, which helps prevent bone loss. Generally, however, adequate amounts of boron can be obtained through foods such as vegetables, nuts, and legumes.

Vitamin K
Studies suggest that 45 milligrams of vitamin K per day may help prevent bone loss. Vitamin K can be found in green tea, turnip greens, broccoli, spinach, cabbage, asparagus, and dark green lettuce. Because this vitamin, in both supplement and dietary forms, helps blood to clot, it must not be consumed by those taking blood-thinning medications, such as warfarin.

Omega-3 Fatty Acids
Preliminary studies indicate that omega-3 fatty acids (in the form of fish oil or flaxseed) help to improve cholesterol levels and decrease the risk of heart disease.

Antioxidants
Antioxidants, such as vitamins C and E, may help women avoid serious medical conditions associated with menopause. For example, studies have shown that over the long term (10 years or more), 250 to 500 milligrams of vitamin C taken one to two times per day decreases the risk of heart disease and increases bone mass. In addition, 400 to 800 IU of vitamin E per day lowers the risk of heart disease and, possibly, other age-related illnesses such as Alzheimer's disease and macular degeneration. Large population studies also strongly suggest that intake of food sources of vitamin E (such as wheat germ, nuts [particularly walnuts, almonds, and hazelnuts], vegetable oil [including canola, corn, soybean, and safflower], spinach, kale, sweet potatoes, and yams) also decreases the risk of a stroke after menopause.

Herbs

The information available to date suggests that menopausal symptoms may be alleviated for some women by using herbs, particularly black cohosh. Symptom improvement is different for each woman, however—some women have a noticeable improvement in symptoms such as hot flashes, mood swings, and insomnia, while others notice no change or only experience relief for a short period of time.

Black cohosh (Cimicifuga racemosa)
Black cohosh is used to relieve symptoms of menopause including hot flashes, irritability, mood swings, and feelings of depression. This herb is considered a safe and effective alternative to estrogen when hormones cannot be used.

Dong quai (Angelica sinensis)
Dong quai, in combination with other herbs, has been used for thousands of years in Traditional Chinese Medicine to relieve symptoms of menopause. While there continue to be reports of improvement in symptoms using this herb, the effect of using dong quai by itself varies from woman to woman. Clinical studies comparing dong quai only to a placebo do not confirm a specific benefit of this herb. In general, however, dong quai is thought to be safe for relief of menopausal symptoms, particularly if hormones cannot be used.

Red clover (Trifolium pratense)
Red clover contains high quantities of plant-based estrogens called isoflavones that may improve menopausal symptoms, reduce the risk of bone loss, and lower the risk of heart disease by improving blood pressure and possibly by increasing HDL cholesterol (the "good" kind of cholesterol).

Asian ginseng (Panax ginseng)
Asian ginseng may be used by menopausal women to reduce stress, improve general well-being, decrease feelings of depression, and enhance memory. This herb is thought to have estrogen-like activities, although not all studies support this assertion.

Wild yam (Dioscorea villosa)
Many women claim that wild yam (when used as a cream) improves menopausal symptoms, particularly vaginal dryness. While this extract has been converted to progesterone in laboratory test tubes, the value of wild yam for menopausal symptoms has not yet been fully evaluated in people or even in animals.

Evening primrose (Oenothera biennis)
Some women report that evening primrose oil diminishes the frequency and intensity of their hot flashes, but these claims have not been proven by scientific studies.

Although the following herbs have not been investigated in clinical studies, a professional herbalist will carefully evaluate an individual woman and may consider prescribing one or more of the following to alleviate symptoms of menopause:

Acupuncture

Acupuncture enhances the release of endorphins (opiate-like hormones), and preliminary studies suggest that it may improve mood, including feelings of sadness and fear, in menopausal women. It may also help to balance hormones and relieve hot flashes.

Massage and Physical Therapy

Stress reduction is an important aspect of living with menopause. Massage may reduce stress and promote healthy circulation and general relaxation.

Homeopathy

Although homeopathic remedies have not been studied for menopause, a licensed and certified homeopath might consider one or more of the following remedies to help ease symptoms: A homeopathic doctor considers many different aspects of an individual before a particular prescription is chosen. Women considering using a homeopathic remedy should be evaluated and treated by a well-trained homeopath.

Mind/Body Medicine

Some studies suggest that learning to relax the body (through paced respiration, or slow, deep breathing) may reduce the intensity of hot flashes.

Traditional Chinese Medicine

In Traditional Chinese Medicine, or TCM, a woman is not generally referred to as "menopausal." Rather, a practitioner of TCM might say that she exhibits "kidney yin deficiency." TCM is based, in part, on a belief in yin and yang—defined as opposing energies, such as earth and heaven, winter and summer, and happiness and sadness. The focus of TCM, like many other alternative therapies, is to maintain balance and prevent illness. Therefore, a TCM practitioner would attempt to restore balance in the case of a "kidney yin deficiency" by boosting kidney energy. This is done with a combination of acupuncture, herbs, and other methods of treatment (specific diagnoses and treatments vary from woman to woman). Menopausal women in China report improvement in mood swings, irritability, anxiety, tension, and depression from TCM remedies, particularly acupuncture.

Other Considerations

Prognosis and Complications

As estrogen levels diminish during menopause, a woman's risk of developing the following medical conditions may increase: Menopause is part of the natural aging process for all women. There are many therapies available, however, to help ease the symptoms of and reduce health risks associated with menopause. Selecting the appropriate treatment, whether medications, TCM, herbal remedies, or lifestyle changes, can minimize discomfort and maximize the opportunities for a vital, healthy, satisfying life during and after menopause.

References

Albertazzi P, Pansini F, Bonaccorsi G, et al. The effect of dietary soy supplementation on hot flushes. Obstet Gynecol. 1998;91:6-11.

Alekel DL, St. Germain A, Peterson CT, et al. Isoflavone-rich soy protein isolate attentuates bone loss in the lumbar spine of perimenopausal women. Am J Clin Nutr 2000;72:844-852.

Alexandersen P, Toussaint A, Christiansen C, et al. Ipriflavone in the treatment of postmenopausal osteoporosis: A randomized controlled trial. JAMA. 2001;285(11):1482-1488.

Baeksgaard L, Andersen KP, and Hyldstrup L. Calcium and vitamin D supplementation increases spinal BMD in healthy, postmenopausal women. Osteoporos Int. 1998;8:255-260.

Barnabei VM, Phillips, TM, Hsia J. Plasma homocysteine in women taking hormone replacement therapy: the Postemenopausal Estrogen/Progestin Interventions (PEPI) Trial. J Womens Health Gend Based Med. 1999;8(9):1167-1172.

Barnhart KT, Freeman E, Grisso JA. The effect of dehydroepiandrosterone supplementation to symptomatic perimenopausal women on serum endocrine profiles, lipid parameters, and health-related quality of life. J Clin Endocrinol Metab 1999;84:3896-3902.

Bittner V. Hormone replacement therapy in clinical cardiology. Cardiol Rev. 2000;8(1):57-64.

Blake JM, Collins JA, Reid RL, et al. The SOGC statement on the WHI report on estrogen and progestin use in postmenopausal women. J Obstet Gynaecol Can. 2002;24(10):783-790, 793-802.

Brincat MP. Hormone replacement therapy and the skin. Maturitas. 2000;35(2):107-117.

Brzezinski A. "Melatonin replacement therapy" for postmenopausal women: is it justified? Menopause. 1998;5:60-64.

Bush TL. Preserving cardiovascular benefits of hormone replacement therapy. J Reprod Med. 2000;45(3Suppl):259-273.

Carr BR, Bradshaw KD. Disorders of the ovary and female reproductive tract. In: Fauci A, Braunwald E, Isselbacher KJ, et al, eds. Harrison's Principles of Internal Medicine. New York: McGraw Hill.;1998:2102-2106.

Chenoy R, Hussain S, Tayob Y, et al. Effect of oral gamolenic acid from evening primrose oil on menopausal flushing. BMJ. 1994;308:501-503.

Contreras I, Parra D. Estrogen replacement therapy and the prevention of coronary heart disease in postmenopausal women. Am J Health Syst Pharm. 2000;57(21):1963-1971.

Cyr MG. Postmenopausal hormone therapy in the aftermath of the WHI. What patients need to know. Postgrad Med. 2003;113(3):15-18, 20.

Duker E-M, Kopanski L, Jarry H, et al. Effects of extracts from Cimcifuga racemosa on gonadotropin release in menopausal women and ovariectomized rats. Planta Med. 1991; 57:420-424.

Fardellone P, Brazier M, Kamel S, et al. Biochemical effects of calcium supplementation in postmenopausal women: influence of dietary calcium intake. Am J Clin Nutr. 1998;67:1273-1278.

Fillit HM. The role of hormone replacement therapy in the prevention of Alzheimer's disease [Review]. Arch Intern Med. 2002;162:1934-1942.

Freedman RR, Woodward S. Behavioral treatment of menopausal hot flushes: evaluation by ambulatory monitoring Am J Obstet Gynecol. 1992;167:436-439.

Gabapentin. NMIHI. Accessed at http://www.nmihi.com/f/gabapentin.html on September 9, 2018.

Gandy S, Duff K. Post-menopausal estrogen deprivation and Alzheimer's disease. Exp Gerontol. 2000;35(4):503-511.

Gardner C. Ease through menopause with homeopathic and herbal medicine. J Perianesth Nurs. 1999;14(3):139-143.

Giardina EG. Heart disease in women. Int J Fertil Womens Med. 2000;45(6):350-357.

Glazier MG, Bowman MA. A review of the evidence for the use of phytoestrogens as a replacement for traditional estrogen replacement therapy. Arch Intern Med. 2001;161(9):1161-1172.

Grady D, Herringon D, Bittner V, et al. Cardiovascular disease outcomes during 6.8 years of hormone therapy: Heart and Estrogen/progestin Replacement Study follow-up (HERS II). JAMA. 2002;288(1):49-57.

Greene RA. Estrogen and cerebral blood flow: a mechanism to explain the influence of estrogen on the incidence and treatment of Alzheimer's disease. Int J Fertil Womens Med. 2000;45(4):253-257.

Grimes DA, Lobo RA. Perspectives on the Women's Health Initiative trial of hormone replacement therapy. Obstet Gynecol. 2002;100(6):1344-1353.

Grodstein F, Newcomb PA, Stampfer MJ. Postmenopausal hormone therapy and the risk of colorectal cancer: a review a meta-analysis.Am J Med. 1999;106(5):574-582.

Hammar M, Berg G, Lindgren R. Does physical exercise influence the frequency of postmenopausal hot flushes? Acta Obstet Gynecol Scand. 1990;69(5):409-412.

Haggans CJ, Hutchins AM, Olson BM, et al. Effect of flaxseed consumption on urinary estrogen metabolites in postmenopausal women. Nutr Cancer. 1999;33(2):188-195.

Heller HJ, Stewart A, Haynes S, et al. Pharmacokinetics of calcium absorption from two commercial calcium supplements. J Clin Pharmacol. 1999;39:1151-1154.

Herrington DM, Klein KP. Randomized clinical trials of hormone replacement therapy for treatment or prevention of cardiovascular disease: a review of the findings. Atherosclerosis. 2003;166(20:203-212.

Hirata JD, Swiersz LM, Zell B, et al. Does dong quai have estrogenic effects in postmenopausal women? a double-blind, placebo controlled trial. Fertil Steril. 1997;68(6):981-986.

Hormone replacement therapy (HRT). NMIHI. Accessed at http://drugs.nmihi.com/hormone-replacement.htm on September 9, 2018.

Howes JB, Sullivan D, Lai N. The effects of dietary supplementation with isoflavones from red clover on the lipoprotein profiles of post menopausal women with mild to moderate hypercholesterolaemia. Atherosclerosis. 2000;152:143-147.

Hulley S, Furberg C, Barrett-Connor E, et al. Noncardiovascular disease outcomes during 6.8 years of hormone therapy: Heart and Estrogen/progestin Replacement Study follow-up (HERS II). JAMA. 2002;288(1):58-66.

Humphries KH, Gill S. Risks and benefits of hormone replacement therapy: the evidence speaks. CMAJ. 2003;168(8):1001-1010.

Irvin JH, Domar AD, Clark C, et. al. The effects of relaxation response training on menopausal symptoms. J Psychosom Obstet Gynecol. 1996;17:202-207.

Iwamoto I, Kosha S, Noguchi S, et al. A longitudinal study of the effect of vitamin K2 on bone mineral density in postmenopausal women a comparative study with vitamin D3 and estrogen-progestin therapy. Maturitas. 1999;31:161-164.

Jeri AR. The effect of isoflavones phytoestrogens in relieving hot flushes in Peruvian postmenopausal women. Paper presented at: 9th International Menopause Society World Congress on the Menopause; October 20, 1999; Yokahama, Japan.

Kass-Annese B. Alternative therapies for menopause. Clin Obstet Gynecol. 2000;43(1):162-183.

Kelley GA. Exercise and regional bone mineral density in postmenopausal women. Am J Phys Med Rehabil. 1998;77:76-87.

Kronenberg F, Fugh-Berman A. Complementary and alternative medicine for menopausal symptoms: a review of randomized, controlled trials. Ann Intern Med. 2002;137:805-813.

Kuller LH, Simkin-Silverman LR, Wing RR, et al. Women's healthy lifestyle project: a randomized clinical trial. Circulation. 2001;103:32.

LeBoff MS, Kohlmeier L, Hurwitz S, et al. Occult vitamin D deficiency in postmenopausal US women with acute hip fracture. JAMA. 1999;281:1505-1511.

Lemaitre RN, Heckbert SR, Psaty BM, Smith NL, Kaplan RC, Longstreth WT. Hormone replacement therapy and associated risk of stroke in postmenopausal women. Arch Intern Med. 2002;162:1954-1960.

Leveille SG, LaCroix AZ, Koepsell TD, et. al. Dietary vitamin C and bone mineral density in postmenopausal

Li CI, Malone KE, Porter PL, et al. Relationship between long durations and different regimens of hormone therapy and risk of breast cancer. JAMA. 2003;289(24):3254-3263.

Lianzhong W, Xiu Z. 300 cases of menopausal syndrome treated by acupuncture. J Trad Chin Med. 1998;18(4):259-262.

Lieberman S. A review of the effectiveness of Cimicifuga racemosa (black cohosh) for the symptoms of menopause. J Womens Health. 1998;7(5):525-529.

Liske E. Therapeutic efficacy and safety of Cimicifuga racemosa for gynecologic disorders. Advances in Natural Therapy. 1998;75:45-53.

Lokkegaard E, Pedersen AT, Heitmann BL, et al. Relation between hormone replacement therapy and ischaemic heart disease in women: prospective observational study. BMJ. 2003;326(7386):426.

Loprinzi CL, Barton DL, Rhodes D. Management of hot flashes in breast-cancer survivors. Lancet. 2001;2:199-204.

Lloyd T, Johnson-Rollings N, Eggli DF, et al. Bone status among postmenopausal women with different habitual caffeine intakes: a longitudinal investigation. J Am Coll Nutr. 2000;19(2):256-261.

Martin MC, Block JE, Sanchez SD, Arnaud DC, Beyene Y. Menopause without symptoms: the endocrinology of menopause among rural Mayan Indians. Am J Obstet Gynecol. 1993;168(6 Pt 1):1839-1843.

Masaki KH, Losonczy KG, Izmirlian G. Association of vitamin E and C supplement use with cognitive function and dementia in elderly men. Neurology. 2000;54:1265-1272.

Menopause. NMIHI. Accessed at http://www.nmihi.com/m/menopause.htm on September 9, 2018.

Menopause Health Center. WebMD. Accessed at https://www.webmd.com/menopause/default.htm on September 9, 2018.

Menopause. MedlinePlus. Accessed at https://medlineplus.gov/menopause.html on September 9, 2018.

Menopause (For Consumers). NIH. Accessed at https://nccih.nih.gov/health/menopause on September 9, 2018.

Messina MJ. Soy foods and soybean isoflavones and menopausal health. Nutr Clin Care. 2002;5(6):272-282.

Miszko TA, Cress ME. A lifetime of fitness, exercise in the perimenopausal and postmenopausal woman. Clin Sports Med. 2000;19:215-231.

Mora S, Kershner DW, Vigilance CP, Blumenthal RS. Coronary artery disease in postmenopausal women. Curr Treat Options Cardiovasc Med. 2001;3(1):67-79.

Morris MC, Beckett LA, Scherr PA, et al. Vitamin E and vitamin C supplement use and risk of incident Alzheimer disease. Alzheimer Dis Assoc Disord. 1998;12:121-126.

Muneyyirci-Delale O, Nacharaju VL, Dalloul M, Altura BM, Altura BT. Serum ionized magnesium and calcium in women after menopause: Inverse relation of estrogen with ionized magnesium. Fertil Steril. 1999;71:869-872.

Murkies AL, Lombard C, Strauss BJG, et al. Dietary flour supplementation decreases post-menopausal hot flushes: effect of soy and wheat. Maturitas. 1995;21:189-195.

NAMS Consensus. Consensus Opinion: the role of isoflavones in menopausal health: consensus opinion of the North American Menopause Society. Menopause. 2000;7(4):215-229.

NAMS Consensus. Consensus Opinion: the role of calcium in peri-and postmenopausal women: consensus opinion of The North American Menopause Society. Menopause. 2001;8(20):84-95.

Nachtigall LE. Isoflavones in the management of menopause. J Br Meno Soc. 2001;suppl S1:8-12.

Nelson HD, Humphrey LL, Nygren P, Teutsch SM, Allan JD. Postmenopausal hormone replacement therapy: scientific review. JAMA. 2002. 288(7):872-881.

Nestel PJ, Pomeroy S, Kay S. Isoflavones from red clover improve systemic arterial compliance by not plasma lipids in menopausal women. J Clin Endocrinol Metab. 1999;84:895-898.

Nielson FH. Studies on the relationship between boron and magnesium which possibly affects the formation and maintenance of bones. Magnesium Trace Elem. 1990;9:61-69.

Nieves JW, Komar L, Cosman F, et al. Calcium potentiates the effect of estrogen and calcitonin on bone mass: review and analysis. Am J Clin Nutr. 1998;67:18-24.

Paroxetine. NMIHI. Accessed at http://www.nmihi.com/p/paroxetine.html on September 9, 2018.

Pepping J. Alternative therapies: black cohosh: Cimicifuga racemosa. Am J Health-Syst Pharm. 1999;56:1400-1402.

Potter SM, Baum JA, Teng H, et al. Soy protein and isoflavones: their effects on blood lipids and bone density in postmenopausal women. Am J Clin Nutr. 1998;68(s):1372s-1379s.

Qureshi IA. Ocular hypertensive effect of menopause with and without systemic hypertension. Acta Obstet Gynecol Scand. 1996;75(3):266-269.

Reaven GM, Abasi F, Bernhart S, et al. Insulin resistance, dietary cholesterol, and cholesterol concentration in postmenopausal women. Metabolism. 2001;50(5):594-597.

Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial. JAMA. 2002;288(3):321-333.

Ruml LA, Sakhaee K, Peterson R, et al. The effect of calcium citrate on bone density in the early and mid-postmenopausal period: a randomized placebo controlled study. Am J Ther. 1999;6:303-311.

Sano M, Ernesto C, Thomas RG, et al. A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer's disease. N Engl J Med. 1997;336:1216-1222.

Sator MO, Akramian J, Joura EA, et al. Reduction of intraocular pressure in a glaucoma patient undergoing hormone replacement therapy. Maturitas. 1998;29(1):93-95.

Simkin-Silverman LR, Wing RR. Weight gain during menopause. Is it inevitable or can it be prevented? Postgrad Med. 2000;108(3):47-50, 53-56.

Simon JA, Hsia J, Cauley, JA, Richards C, Harris F, Fong J, et al. Postmenopausal hormone therapy and risk of stroke: The Heart and Estrogen-progestin Replacement Study (HERS). Circulation. 2001;103(5):638-642.

Slaven L, Lee C. Mood and symptom reporting among middle-aged women: the relationship between menopausal status, hormone replacement therapy, and exercise participation. Health Psychol. 1997;16(3):203-208.

Smith W, Mitchell P, Wang JJ. Gender, oestrogen, hormone replacement and age-related macular degeneration: results from the Blue Mountains Eye Study. Aust N Z J Opthalmol. 1997;25(Suppl 1):S13-S15.

Sertraline. NMIHI. Accessed at http://www.nmihi.com/s/sertraline.html on September 9, 2018.

Somekawa Y, Chiguchi M, Ishibashi T, et al. Soy intake related to menopausal symptoms, serum lipids, and bone mineral density in postmenopausal Japanese women. Obstet Gynecol. 2001;97:109-115.

Stark KD, Park EJ, Maines VA, et. al. Effect of a fish-oil concentrate on serum lipids in postmenopausal women receiving and not receiving hormone replacement therapy in a placebo-controlled, double-blind trial. Am J Clin Nutr. 2000;72:389-394.

Taylor M. Alternatives to conventional hormone replacement therapy. Compr Ther. 1997;23(8):514-532.

Teede HJ. The menopause and HRT. Hormone replacement therapy, cardiovascular and cerebrovascular disease. Best Pract Res Clin Endocrinol Metab. 2003;17(1):73-90.

Tode T, Kikuchi Y, Hirata J, et. al. Effect of Korean red ginseng on psychological functions in patients with severe climacteric syndromes. Int J Gynaecol Obstet. 1999;67:169-174.

Umland EM, Cauffield JS, Kirk JK, et al. Phytoestrogens as therapeutic alternatives to traditional hormone replacement in postmenopausal women. Pharmacotherapy. 2000; 20(8)981-990.

U.S. Preventive Services Task Force. Postmenopausal hormone replacement therapy for primary prevention of chronic conditions: recommendations and rationale. Ann Intern Med. 2002;137(10):834-839.

Venlafaxine. NMIHI. Accessed at http://www.nmihi.com/u/venlafaxine.html on September 9, 2018.

Vincent A, Fitzpatrick LA. Soy isoflavones: are they useful in menopause? Mayo Clin Proc. 2000;75:1174-1184.

Vingerling JR, Dielemans I, Witteman JCM, Hofman A, Grobbee DE, de Jong P. Macular degeneration and early menopause: a case-control study. BMJ.1995;310:1570-1571.

Vogel RA. The changing view of hormone replacement therapy. Rev Cardiovasc Med. 2003;4(2):68-71.

What is Menopause? Ada Health Accessed at https://ada.com/conditions/menopause/ on September 9, 2018.

Wiklund IK, Mattsson LA, Lindgren R, et. al. Effects of a standardized ginseng extract on quality of life and physiological parameters in symptomatic postmenopausal women: a double-blind, placebo-controlled trial. Int J Clin Pharm Res. 1999;XIX(3):89-99.

Wise P, Dubal D, Wilson M, Rau S, Bottner M. Minireview: Neuroprotective effects of estrogen—new insights into the mechanisms of action. Endocrinology. 2001;142(3):969-973.

Wyon Y, Lindgren R, Hammar M, Lundberg T. Acupuncture against climateric disorders? Lower number of symptoms after menopause. Lakartidningen. 1994;91(23):2318-2322.

Yochum LA, Folsom AR, Kushi LH. Intake of antioxidant vitamins and risk of death from stroke in postmenopausal women. Am J Clin Nutr. 2000;72:476-483.

Zell B, Hirata J, Marcus A, et al. Diagnosis of symptomatic postmenopausal women by Traditional Chinese Medicine practitioners. Menopause. 2000;7:129-134.

Zhang Y, Felson DT, Ellison RC, et al. Bone mass and the risk of colon cancer among postmenopausal women in the Framingham study. Am J Epidemiol. 2001;153(1):31-37.