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Menopause

Highlights

Menopause

Menopause is a natural process that occurs as a woman’s ovaries stop producing eggs and the production of female hormones (estrogen and progesterone) declines. Menopause can also occur if a woman’s ovaries are damaged by certain diseases or cancer treatments, or if they are surgically removed. Natural menopause usually develops gradually between the ages of 45 - 55. During this transition time, called “perimenopause,” menstrual periods become more irregular and begin to taper off. After menstrual periods have stopped for 12 months, a woman is considered to have reached menopause. On average, American women reach menopause around the age of 51, but menopause can occur at younger or older ages.

Perimenopausal Symptoms

During perimenopause, women may have various symptoms. Symptoms differ among women, and may range from mild to severe. Hot flashes, an intense sudden build-up of body heat, are the most common symptom. Some women have no symptoms.

Treatment

Menopause is a natural condition. It is not a disease that needs medical treatment. However, some women seek treatment for the relief of perimenopausal symptoms. Hormone replacement therapy (HRT) is the most effective drug treatment for hot flashes, but long-term use can increase the risks of   heart attack, stroke, blood clots in the lungs, breast cancer, and cancer of the uterus (endometrial cancer). Therefore, doctors recommend that women who use HRT should take the lowest possible dose for the shortest possible time.

Women who have a uterus are prescribed estrogen- progestogen therapy (EPT). Women who do not have a uterus take estrogen alone (ET). HRT comes in different forms including pills, patches, creams, sprays, and vaginal suppository rings.

Updated Hormone Replacement Therapy Guidelines

Several medical associations have released updated guidelines and recommendations for HRT. Some key points:

Calcium and Vitamin D Supplements

Healthy postmenopausal women with good diets do not need to take calcium and vitamin D supplements, according to a 2013 recommendation from the U.S. Preventive Services Task Force (USPSTF). According to the USPSTF, daily low-dose amounts of vitamin D and calcium supplements do not prevent fractures and can increase the risk of kidney stones. Talk with your doctor about whether or not you need these supplements. Additional research is needed to evaluate possible benefits of higher dose vitamin D.

New Drug Approvals

In 2013, the FDA approved two non-hormonal drugs for treatment of menopausal symptoms:

Introduction

Menopause is a natural process that occurs as a woman’s ovaries stop producing eggs, and the production of hormones such as estrogen and progesterone declines. Menopause can also occur if a woman’s ovaries are surgically removed or if they are damaged by certain diseases or cancer treatments.

Menopause does not occur suddenly. A period called perimenopause usually begins a few years before the last menstrual cycle. There are two stages in the transition:

Menopause is considered to have occurred after a woman has gone a full 12 months without a period. Menopause marks the end of menstruation and a women’s fertility. American women reach menopause at an average age of 51 years, although it can occur as early as age 40 to as late as the early 60s. Women now have a life expectancy of more than 80 years. Currently, women can expect to live some 30 or 40 years of their lives in the postmenopausal state.

Menopause is not a disease. However, many conditions are associated with estrogen depletion, including heart disease, osteoporosis, and other complications. Fortunately, effective treatments are available for these conditions.

In a number of studies, most women have reported menopause as a positive experience and have welcomed it as a sign of a new stage in life.

Causes

Menopause is a normal part of the aging process. It occurs naturally after a woman's ovaries stop producing eggs and releasing hormones necessary for fertility.

The ovaries are two small, almond-shaped organs located on either side of the uterus. They are key components of a woman's reproductive system. The ovaries contain 200,000 - 400,000 follicles, tiny sacks that contain the materials needed to produce mature eggs, or ova. Each month during the menstrual cycle, the ovaries release an egg, which travels through the Fallopian tube to the uterus. As a woman ages, her ovarian supply of eggs decreases. Eventually, the ovaries stop releasing eggs and her monthly menstrual periods cease. The word menopause comes from the Greek words “mens” for month and “pausis” for cessation.

The ovaries produce two major female hormones: estrogen and progesterone. As a woman enters menopause, the ovarian production of these hormones declines and fluctuates until it eventually stops.

Estrogen. Estrogen has different forms. The strongest form is estradiol. Other important, but less powerful estrogens are estrone and estriol. Most of the estrogens in the body are produced by the ovaries, but they can also be formed by other tissues, such as body fat, skin, and muscle. Estrogens are essential for the reproductive process. They also affect and help regulate function in other parts of the body including the brain and central nervous system, the bones, the liver, and the urinary tract.

Progesterone. Progesterone, the other major female hormone, is necessary for thickening and preparing the uterine lining for the fertilized egg.

Hormonal Changes in Menopause. Menopause is marked by the following hormonal changes:

Premature (early) menopause is menopause that occurs before age 40. Women who have a family history of premature menopause are genetically more susceptible to starting menopause early. Premature menopause can also result from:

Symptoms

The most prominent symptoms of the transition to menopause include:

Although forgetfulness is often mentioned as a symptom, evidence indicates that menopause does not affect memory or other cognitive functions. It is normal for both men and women to experience some memory lapses as part of the natural aging process.

Complications

The decline in estrogen after menopause can increase the risk for a number of health problems for women.

Coronary artery disease is the number one killer of women. Although young women have a much lower risk for coronary artery disease  than young men, after menopause women catch up. After age 60, women’s risk of dying from heart disease is very close to that of men. Estrogen loss is believed to play a major role in this increased risk. Woman who reach menopause before the age of 35 have a significant increase in risk for heart disease as they age. This increase is primarily due to a rise in levels of LDL (“bad” cholesterol) and triglycerides, and a decrease in levels of HDL (“good”) cholesterol).

Thrombus

Osteoporosis is a disease of the skeleton in which bones become "thin" and prone to fracture. In other words, the bone loses calcium and density. At age 65, about 30% of women have osteoporosis, and nearly all of them are unaware of their condition. After age 80, up to 70% of women develop osteoporosis. Osteoporosis is a major risk factor for fracture in the spine and hip. The decrease in bone density can also lead to bone loss in the jaw and subsequent tooth decay.

Osteoporosis

The drop in estrogen levels brought on by menopause can thin the linings of the urethra and bladder, which may contribute to both stress and urge (overactive bladder) types of urinary incontinence.

Because of vaginal drying, women are at increased risk for recurrent urinary tract infections after menopause.

Weight gain is common during a woman’s middle-aged years, especially between the ages of 50 - 59. The hormonal changes associated with menopause contribute to these body changes. Gaining weight around the abdomen (the so-called apple shape) is a specific risk factor for heart disease, diabetes, and many other health problems. Higher body mass index (BMI) may also be associated with increased risk for more frequent or severe hot flashes.

Different types of weight gain

Estrogen loss can contribute to slackness and dryness in the skin and wrinkles. Many women experience thinning of their hair and some have temporary hair loss.

Lifestyle Changes

Simple changes in lifestyle and diet can help control menopausal symptoms such as hot flashes. Avoid hot flash triggers like spicy foods, hot beverages, caffeine, and alcohol. Dress in layers so that clothes can be removed when a hot flash occurs. For vaginal dryness, there are non-estrogen lubricants such as KY Jelly, Replens, and Astroglide.

When women reach menopause, they are at increased risk for heart disease. A heart-healthy diet and other lifestyle changes are important ways to control cholesterol and blood pressure levels.

Heart-healthy recommendations include:

A combination of calcium and vitamin D can reduce the risk of osteoporosis, the bone loss associated with menopause. The best sources are from calcium-rich and vitamin D-fortified foods.

Doctors are currently reconsidering the use of calcium and vitamin D supplements. The U.S. Preventive Services Task Force (USPSTF) advises that healthy postmenopausal women don’t need to take these supplements. According to the USPSTF, taking daily low-dose amounts of vitamin D supplements (less than 400 IU), with or without calcium supplements (less than 1,000 mg), does not prevent fractures. For higher doses, the USPSTF says there is not enough evidence to make a recommendation. In addition to possible lack of benefit, these supplements are associated (even at lower doses) with certain risks, like kidney stones.

However, calcium and vitamin D are important nutrients. Supplements may be appropriate for certain people including those who do not get enough vitamin D through sunlight exposure and those who do not consume enough calcium in their diet. They are also helpful for people who have been diagnosed with osteoporosis. Talk with your doctor about whether or not you should take supplements.

Calcium. Women should consume low-fat dairy products and other foods rich in calcium (dark green vegetables, sardines), or calcium-fortified foods and beverages (orange juice, cereal), to get enough calcium in their diet. Calcium supplements may be an option for women who do not consume adequate amounts of calcium in their diets. Calcium supplements include calcium carbonate (such as Caltrate, Os-Cal, and Tums), calcium citrate (Citracal), calcium gluconate, and calcium lactate. Although each kind provides calcium, they all have different calcium concentrations, absorption capabilities, and other actions.

Calcium benefit

The standard recommended calcium dose for women age 50 years and older is at least 1,200 mg per day. High doses (over 2,500 mg per day) of calcium supplements may increase the risk for kidney stones and may possibly increase the risk for heart attack. Adults who consume adequate amounts of calcium in their diets do not need to take a calcium supplement. Taking more calcium than recommended is not helpful and may cause harmful side effects.

Calcium source

Vitamin D. Vitamin D is necessary for the absorption of calcium in the stomach and gastrointestinal tract and is the essential companion to calcium in maintaining strong bones.

Vitamin D is made in the skin using energy from the ultraviolet rays in sunlight. As people age, their vitamin D levels decline. Levels also fall during winter months and when people have inadequate exposure to sunlight.

Vitamin D source

The recommended daily intake of vitamin D is 800 - 1,000 IU a day after age 50. Dietary sources of vitamin D include fatty fish (salmon, mackerel, tuna), egg yolks, liver, and vitamin D-fortified foods and beverages (milk, orange juice, soy milk, cereals). Older women who do not get enough vitamin D solely from diet or sunlight may need to take a supplement. Vitamin D supplements are available either as D2 (ergocalciferol) or D3 (cholecalciferol). They work equally well for bone health. Like calcium supplements, vitamin D supplements may increase the risks for kidney stones.

Calcium and vitamin D supplements can be taken as separate supplements or as a combination supplement. If separate preparations are used, they do not need to be taken at the same time. Given the controversies over the benefits and safety of these supplements, be sure to discuss with your doctor whether supplements are a good choice for you. As an alternative to supplements, many doctors recommend making dietary changes to increase calcium and vitamin D intake, and getting 15 minutes a day of sun exposure.

Effect on the Heart. One drink a day in women who are not at risk for alcohol abuse may be beneficial for the heart. However, the American Heart Association recommends that women have no more than one drink per day.

Effect on Bones. Excessive alcohol consumption increases the risk for brittle bones and osteoporosis.

Effect on Breast Cancer. Alcohol increases the risk for breast cancer. Any woman who is at high risk should consider not drinking at all or drinking very sparingly.

Many women need to increase physical activity and reduce caloric intake in the years before and after menopause. Weight gain is common during these years, and it can be sudden and distressing, particularly when habitual exercise and eating patterns are no longer effective in controlling weight. In addition to reducing risk factors for heart disease, weight loss may help lessen frequency and severity of hot flashes.

Women should pursue a lifestyle that includes a balanced aerobic and weight resistance exercise program appropriate to their age and medical conditions. Brisk walking, stair climbing, hiking, dancing, weight lifting, and tai chi are all helpful. Some studies report that exercise may help reduce hot flashes. A healthy diet plus regular, consistent exercise can also help ward off the weight gain associated with menopause. Weight-bearing exercises are specifically helpful for protecting against bone loss.

Women should get at least 30 minutes of exercise each day (for weight loss, 60 - 90 minutes is preferred). While more exercise is better, any amount of exercise is helpful.

There are many unproven methods for relieving menopausal symptoms, some more effective than others. Acupuncture, meditation, and relaxation techniques are all harmless ways to reduce the stress of menopause. Some women report great benefit from these practices, but there is no scientific proof of effectiveness.

Acupuncture
Acupuncture, hypnosis, and biofeedback are all alternative ways to control pain. Acupuncture involves the insertion of tiny sterile needles, slightly thicker than a human hair, at specific points on the body.

Women often try herbal or so-called natural remedies to treat menopausal symptoms. There have been numerous studies conducted on various herbal products and other complementary and alternative therapies. These studies have not found that these approaches are beneficial. Some herbs and supplements can have adverse side effects.

Phytoestrogens and Isoflavones. Many studies have researched plant estrogens (phytoestrogens), which are generally categorized as isoflavones (found in soy and red clover) and lignans (found in whole wheat and flaxseed). No evidence to date indicates that phytoestrogen foods or supplements provide any benefit for hot flashes, night sweats, or other menopausal symptoms. They also do not appear to help lower cholesterol or prevent heart disease. Nevertheless, soy is a healthy food choice. The best sources of soy protein are soy food products (such as tofu, soy milk, and soybeans), not supplements.

Soy isoflavones contain genistein and daidzein, which are estrogen-like compounds. While some studies have suggested that soy food consumption may protect against estrogen-responsive cancers such as breast and endometrial cancer, other studies have indicated that high intakes of soy may increase the risks of these cancers. The American Cancer Society recommends that women with breast cancer eat only moderate amounts of soy food and avoid taking dietary supplements that contain high amounts of isoflavones.

Other Herbs and Supplements. The following herbs and dietary supplements are sometimes used for menopausal symptoms and have certain risks:

Generally, manufacturers of herbal remedies and dietary supplements do not need approval from the Food and Drug Administration (FDA) to sell their products. Just like with drugs, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been a number of reported cases of serious and even lethal side effects from herbal products. Patients should check with their doctors before using any herbal remedies or dietary supplements.

Medications

Hormone replacement therapy, also known as menopausal hormone therapy (MHT) or hormone therapy (HT), uses medications that contain the female hormones that the body has stopped producing after menopause. The primary reasons that women use HRT are for the relief of hot flashes, night sweats, and vaginal dryness.

Hormone replacement therapy uses either:

The term “progestogen” encompasses both progesterone and progestin. Progesterone is the name for the natural hormone that the body produces. Progestin refers to a synthetic hormone that has progesterone effects. Because estrogen alone can increase the risk for uterine (endometrial) cancer, progestogen is added to estrogen to protect the uterine lining (endometrium) and reduce this risk.

Women receive either ET or EPT depending on whether they have a uterus:

Current guidelines support the use of HRT for the treatment of severe hot flashes that do not respond to non-hormonal therapies. Specific recommendations include:

Initiating Therapy. Before starting HRT, your doctor should give you a comprehensive physical exam and take your medical history to evaluate your risks for heart disease, stroke, blood clots, osteoporosis, and breast cancer. While taking HRT, you should have regular mammograms and pelvic exams and Pap smears. Current guidelines recommend that if HRT is needed, it should be initiated around the time of menopause. Studies indicate that the risk of serious side effects is lower for women who use HRT while in their 50s. Recent research suggests that women who start HRT past the age of 60 have a higher risk for side effects such as heart attack, stroke, blood clots, or breast cancer.

Women who experience premature menopause are usually prescribed HRT or oral contraceptives to help prevent bone loss. These women should be reevaluated when they reach the age of natural menopause (around age 51) to determine whether they should continue to take hormones.

Discontinuing Therapy. When a woman stops taking HRT, perimenopausal symptoms may recur. There is about a 50% chance of hot flashes recurring regardless of whether HRT is suddenly stopped or gradually tapered off. When a woman reaches full menopause, symptoms will eventually go away.

Because HRT offers protection against osteoporosis, when women stop taking HRT their risks for bone thinning and fractures increases. For women who have used HRT for several years, doctors should monitor their bone mineral density and prescribe bone-preserving medications if necessary.

Safety Concerns. Until 2002, doctors used to routinely prescribe HRT to reduce the risk of heart disease and other health risks in addition to treating menopausal symptoms. That year, the results of an important study, called the Women's Health Initiative (WHI), led doctors to revise their recommendations regarding HRT.

The WHI, started in 1991, is an on-going health study of nearly 162,000 postmenopausal women. Part of the study focuses on the benefits and risks of hormone replacement therapy. As new data are released and analyzed, there have been a number of changes in the way hormone therapy is prescribed and a better understanding of its risks.

Woman who should not take hormone replacement therapy include those with the following conditions:

HRT comes in several forms:

Vaginal forms of HRT are called “local” therapy. Pills and skin patches are considered “systemic” therapy because the medication delivered affects the entire body. The risk for blood clots is higher with hormone replacement pills than with skin patches or other transdermal forms. Doctors generally prescribe vaginal applications of low-dose estrogen therapy to specifically treat menopausal symptoms such as vaginal dryness and pain during sex. This type of ET is available in a cream, tablet, or ring that is inserted into the vagina.

"Biodentical" Hormones. Bioidentical” hormone replacement therapy is promoted as a supposedly more natural and safer alternative to commercial prescription hormones. Bioidentical hormones are typically compounded in a pharmacy. Some compounding pharmacies claim that they can customize these formulations based on saliva tests that show a woman’s individual hormone levels.

The FDA and many professional medical associations warn patients that “bioidentical” is a marketing term that has no scientific validity. Formulations sold in these pharmacies have not undergone FDA regulatory scrutiny. Some of these compounds contain estriol, a weak form of estrogen, which has not been approved by the FDA for use in any drug. In addition, saliva tests do not give accurate or realistic results, as a woman’s hormone levels fluctuate throughout the day.

FDA-approved hormones available by prescription come from different synthetic and natural sources, including plant-based. (For example, Prometrium is a progesterone derived from yam plants.)

Periomenopausal and Menopausal Symptoms. HRT is mainly recommended for relieving menopausal symptoms, including hot flashes, night sweats, vaginal dryness and accompanying pain during sexual intercourse, and sleep problems. Evidence is mixed as to whether HRT helps improve mood; the progestogens in EPT may worsen mood in some women. HRT does not prevent certain other problems associated with menopausal changes, such as thinning hair or weight gain.

Osteoporosis. Estrogen increases and helps maintain bone density. HRT may be useful for some women at high risk for osteoporosis, but for most women the risks do not outweigh the benefits. Other drugs, such as bisphosphonates, should be considered first-line treatment for osteoporosis.

Colon Cancer. Combination estrogen-progesterone HRT may provide some protection against colon cancer.

Heart Disease and Heart Attack. Taking HRT in order to prevent heart disease is not recommended. However, using HRT for a short period of time in younger women (below age 60 years) within 10 years after menopause does not appear to raise the risk for heart disease. Some recent research suggests that taking HRT early after menopause reduces cardiac disease risk without raising cancer risk.

Stroke. HRT may increase the risk of stroke in some age groups.

Mental Decline. Reviews of the Women’s Health Initiative Memory Study, as well as other more recent studies, have found that combined HRT does not reduce the risk of cognitive impairment, and may actually increase the risk of cognitive decline.

Thromboembolism. HRT is associated with a higher risk for thromboembolism, in which blood clots form in deep veins. This places women at risk for pulmonary embolism, in which the blood clot travels to the lungs. The risk for blood clots is higher with oral forms of HRT than with transdermal forms (skin patches, creams).

Pulmonary embolus

Breast Cancer. Estrogen- progestogen therapy (EPT) increases the risk for breast cancer if used for more than 3 – 5 years. This risk appears to decline within 3 years of stopping combination HRT.

Estrogen-only therapy (ET) does not significantly increase the risk of developing breast cancer if it is used for less than 7 years. If used for more than 7 years, it may increase the risk of breast (and ovarian) cancers, especially for women already at increased risk for breast cancer. The North American Menopause Society does not recommend ET use in breast cancer survivors as it has not been proven safe and may raise the risk of recurrence.

Both estrogen-only and combination HRT increase breast cancer density, making mammograms more difficult to read. This can cause cancer to be diagnosed at a later stage. Women who take HRT should be aware of the need for regular mammogram screenings.

The North American Menopause Society recommends that women who are at risk for breast cancer avoid hormone therapy and try other options to manage menopausal symptoms.

Endometrial (Uterine) Cancers. Taking estrogen-only replacement therapy (ET) for more than 3 years increases the risk of endometrial cancer at least five-fold. If taken for 10 years, the risk is ten-fold. Adding progesterone or a progestin to estrogen (EPT) helps to reduce this risk. Women who take ET should anticipate uterine bleeding, especially if they are obese, and may need endometrial biopsies and other gynecologic tests. No type of hormone replacement therapy is recommended for women with a history of endometrial cancer.

Ovarian Cancer. Long-term use (more than 5 - 10 years) of estrogen-only therapy (ET) may increase the risk of developing and dying from ovarian cancer. The risk is less clear for combination estrogen-progesterone therapy (EPT).

Lung Cancer. While it is not clear if HRT use is associated with increased risk of lung cancer, women who smoke and who are past or current users of HRT should be aware that some evidence indicates that EPT may promote the growth of lung cancers.

Gallbladder Disease. HRT can increase the risk of developing gallbladder disease.

Despite its risks, hormone replacement therapy appears to be the most effective treatment for hot flashes. There are, however, nonhormonal treatments for hot flashes and other menopausal symptoms.

Antidepressants.The antidepressants known as selective serotonin-reuptake inhibitors (SSRIs) are sometimes used “off-label” for managing mood changes and hot flashes. They include fluoxetine (Prozac, generic), sertraline (Zoloft, generic), venlafaxine (Effexor), desvenlafaxine (Pristiq), paroxetine (Paxil, generic), and escitalopram (Lexapro). In 2013, the FDA approved a low-dose formulation of paroxetine (Brisdelle) to treat moderate-to-severe hot flashes associated with menopause. Many experts were surprised by the FDA’s decision as an advisory panel had previously voted against approving the drug because studies showed it had limited benefit for menopausal hot flashes.

Gabapentin. Several small studies have suggested that gabapentin (Neurontin), a drug used for seizures and nerve pain, may relieve hot flashes. This drug is sometimes prescribed “off-label” for treating hot flash symptoms. However, in 2013 the FDA voted against approving gabapentin for this indication because the drug demonstrated only modest benefit. Gabapentin may cause drowsiness, dizziness, fatigue, and swelling of the hands and feet.

Clonidine. Clonidine (Catapres, generic) is a drug used to treat high blood pressure. Studies show it may help manage hot flashes. Side effects include dizziness, drowsiness, dry mouth, and constipation

Testosterone. Some doctors prescribe combinations of estrogen and small amounts of the male hormone testosterone to improve sexual function and increase bone density. Side effects of testosterone therapy include increased body hair, acne, fluid retention, anxiety, and depression. Testosterone also adversely affects cholesterol and lipid levels, and combined estrogen and testosterone may increase the risk of breast cancer. It is unclear whether testosterone is safe or effective for treatment of menopausal symptoms.

Non-Hormonal Treatments for Vaginal Dryness and Atrophy. Lubricants (such as KY Jelly, Replens, and Astroglide) can be purchased without a prescription and are safe and helpful for treating vaginal dryness and dyspareunia (painful sexual intercourse). Dysparenunia is a result of thinning vaginal tissues (vaginal atrophy).

In 2013, the FDA approved ospemifene (Osphena), the first non-hormonal prescription drug for treating menopausal-associated dyspareunia. Ospemifene is an oral drug (pill) that acts like an estrogen on vaginal tissues to make them thicker and less fragile. However, this drug may cause the lining of the uterus (endometrium) to thicken, which can increase the risk for uterine (endometrial) cancer. Because of this and other risks, ospemifene should only be taken for a short amount of time. Common side effects of ospemifene include hot flashes, vaginal discharge, and excessive sweating.

Resources

References

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LaCroix AZ, Chlebowski RT, Manson JE, Aragaki AK, Johnson KC, Martin L, et al. Health outcomes after stopping conjugated equine estrogens among postmenopausal women with prior hysterectomy: a randomized controlled trial. JAMA. 2011 Apr 6;305(13):1305-14.

Lethaby A, Hogervorst E, Richards M, Yesufu A, Yaffe K. Hormone replacement therapy for cognitive function in postmenopausal women. Cochrane Database Syst Rev. 2008 Jan 23;(1):CD003122.

MacBride MB, Rhodes DJ, Shuster LT. Vulvovaginal atrophy. Mayo Clin Proc. 2010 Jan;85(1):87-94.

Moyer VA; U.S. Preventive Services Task Force. Menopausal hormone therapy for the primary prevention of chronic conditions: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2013 Jan 1;158(1):47-54.

Moyer VA; U.S. Preventive Services Task Force. Vitamin D and calcium supplementation to prevent fractures in adults: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2013 May 7;158(9):691-6

[No authors listed]. Herbal medicines for menopausal symptoms. Drug Ther Bull. 2009 Jan;47(1):2-6.

[No authors listed] Management of osteoporosis in postmenopausal women: 2010 position statement of The North American Menopause Society. Menopause. 2010 Jan-Feb;17(1):25-54; quiz 55-6.

North American Menopause Society. The 2012 hormone therapy position statement of: The North American Menopause Society. Menopause. 2012 Mar;19(3):257-71.

North American Menopause Society. The role of local vaginal estrogen for treatment of vaginal atrophy in postmenopausal women: 2007 position statement of The North American Menopause Society. Menopause. 2007 May-Jun;14(3 Pt 1):355-69.

Prentice RL, Manson JE, Langer RD, Anderson GL, Pettinger M, Jackson RD, et al. Benefits and risks of postmenopausal hormone therapy when it is initiated soon after menopause. Am J Epidemiol. 2009 Jul 1;170(1):12-23. Epub 2009 May 25.

Reed SD, Newton KM, LaCroix AZ, Grothaus LC, Grieco VS, Ehrlich K. Vaginal, endometrial, and reproductive hormone findings: randomized, placebo-controlled trial of black cohosh, multibotanical herbs, and dietary soy for vasomotor symptoms: the Herbal Alternatives for Menopause (HALT) Study. Menopause. 2008 Jan-Feb;15(1):51-8.

Santen RJ, Allred DC, Ardoin SP, Archer DF, Boyd N, Braunstein GD, et al. Postmenopausal Hormone Therapy: An Endocrine Society Scientific Statement. J Clin Endocrinol Metab. 2010 Jun 21. [Epub ahead of print]

Schierbeck LL, Rejnmark L, Tofteng CL, Stilgren L, Eiken P, Mosekilde L, et al. Effect of hormone replacement therapy on cardiovascular events in recently postmenopausal women: randomised trial. BMJ. 2012 Oct 9;345:e6409.

Toh S, Hernández-Díaz S, Logan R, Rossouw JE, Hernán MA. Coronary heart disease in postmenopausal recipients of estrogen plus progestin therapy: does the increased risk ever disappear? A randomized trial. Ann Intern Med. 2010 Feb 16;152(4):211-7.



Review Date: 9/23/2013
Reviewed By: Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.
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