Patient education: Menopausal hormone therapy (Beyond the Basics)

INTRODUCTION — Menopause is defined as the time in a female's life, usually between age 45 and 55 years, when the ovaries stop producing follicles that contain eggs (ovulating) and menstrual periods end. After menopause, a female can no longer get pregnant.

Menopause does not happen suddenly; most females experience several years of changes in their menstrual periods before they stop completely. During this time (also called the menopausal transition or "perimenopause"), many females start to have menopausal symptoms. These result from intervals of declining levels of estrogen in the body and can include hot flashes, night sweats, mood changes, sleep problems, and vaginal dryness. During the menopause transition intervals of low estrogen levels often alternate with intervals of normal estrogen levels, leading to oscillating symptom patterns. A female is said to have completed menopause once she has gone a full year without having a period. The average age for a female to stop having periods is 51 years. (See "Patient education: Menopause (Beyond the Basics)".)

During the transition to menopause, the ovarian production of estrogen decreases by more than 90 percent. The decrease in ovarian estrogen production is what leads to the typical symptoms of hot flashes, night sweats, and eventually vaginal dryness. Some females also notice dry eyes. Some females experience an increase in anxiety and depression during this transition, especially those who have previously experienced these symptoms. Sleep problems are also common at this time. There are a number of options available to ease the symptoms of menopause, including estrogen and nonhormonal options. This article explains how estrogen works and discusses the risks and benefits of menopausal hormone therapy. Information about non-estrogen treatment options is available separately as well. (See "Patient education: Non-estrogen treatments for menopausal symptoms (Beyond the Basics)".)

WHAT IS MENOPAUSAL HORMONE THERAPY? — Menopausal hormone therapy is the term used to describe the two hormones, estrogen and progestin, that are given to relieve bothersome symptoms of menopause. Estrogen is the hormone that relieves the symptoms. Females with a uterus must also take progestin (a progesterone-like hormone) to prevent uterine cancer. This is because estrogen alone can cause the lining of the uterus to overgrow (potentially leading to uterine cancer).

Females who have had a hysterectomy do not have a uterus and cannot develop uterine cancer. These females are treated with estrogen alone.

Types of estrogen — Estrogen is available in many different forms. For hot flashes, it can be taken as a transdermal patch (worn on the skin), an oral pill, or a "ring" or tablet that is inserted into the vagina. There are also creams and sprays that can be put on the skin.

The preferred estrogen is estradiol. The standard dose of oral estradiol is 1 mg daily by mouth. Lower doses such as 0.5 mg seem to have fewer side effects. Estradiol is the estrogen that is identical to the one the ovary makes throughout reproductive life. Estradiol can be given by mouth, skin patch, vaginal ring, spray, or gel.

Estrogen patch — Many experts now prefer treating females with the estradiol patch rather than estrogen pills (because it is associated with a lower risk of blood clots than estrogen pills). A combination estrogen and progestin patch is also available. Some patches need to be replaced every few days, while others are only replaced once a week.

Estrogen patches work as well as estrogen pills to increase bone density and treat menopausal symptoms. Females with a uterus who use an estrogen patch must also take a progestin to decrease the risk of uterine cancer. (See 'Types of progestin' below.)

Estrogen pill — Although estradiol is the preferred type of estrogen, there are other types that are sometimes used. All types of estrogen can help to relieve menopausal symptoms.

Combination pills that include both estrogen and progestin are available. (See 'Types of progestin' below.)

Low-dose birth control pill — Very low-dose birth control pills are a good option for females in their 40s who have bothersome hot flashes, irregular bleeding, and who still need a reliable form of birth control. Caution should be used for females over 40 years who are also obese because of the higher risk of blood clots. Females over 40 years who have hypertension are at increased risk of stroke if they take birth control pills. Birth control pills are generally not recommended for postmenopausal females, because the dose of estrogen is higher than needed to relieve hot flashes. (See "Patient education: Hormonal methods of birth control (Beyond the Basics)" and "Patient education: Menopause (Beyond the Basics)", section on 'Menopause and birth control'.)

Vaginal estrogen — Females with vaginal dryness can also be treated with very low doses of estrogen that treat the dryness but not hot flashes (because the dose is too low to get into the bloodstream). Vaginal estrogen comes in a cream, vaginal ring, or vaginal estrogen tablets. The low-dose vaginal estrogens do not require the use of a progestin pill. Vaginal estrogen used to treat dryness is discussed in a separate article. (See "Patient education: Vaginal dryness (Beyond the Basics)".)

Types of progestin — Postmenopausal females with a uterus who are treated with estrogen alone have an increased risk of developing uterine cancer and hyperplasia (a precursor to uterine cancer). Taking a second hormone, progestin, minimizes this risk. (See "Patient education: Endometrial cancer diagnosis, staging, and surgical treatment (Beyond the Basics)".)

●Oral progestins – One commonly prescribed progestin pill is micronized natural progesterone. Other types of synthetic progestin pills (medroxyprogesterone acetate, norethindrone, norgestrel) are also available.

Natural progesterone has no negative effect on lipids and is a good choice for females with high cholesterol levels. In addition, natural progesterone might have other advantages when compared with medroxyprogesterone acetate.

●Intrauterine progestin – An intrauterine device (IUD) is a form of birth control; one type, the levonorgestrel IUD (brand names: Mirena, Liletta, Kyleena, Skyla), releases progestin to prevent pregnancy. In some countries, these types of IUDs (using a lower dose of levonorgestrel) are used in menopausal females taking estrogen to minimize the risk of developing uterine cancer. The IUD is not currently approved in the United States for use in menopausal females; however, if you already have one when you enter perimenopause, your doctor may suggest that you keep it in until after menopause is complete.

Compounded "Bioidentical" products — Many females have turned to compounded "bioidentical" hormone therapy as an alternative to conventional hormones for treating symptoms of menopause. "Bioidentical" means that the hormones used for therapy are identical in molecular structure to the hormones produced by the ovaries. "Compounded" means the preparation is mixed in a special compounding pharmacy in order to create a customized dose of hormones in the form of pills, creams, or vaginal suppositories.

The quality of these custom compounded products is not regulated by the US Food and Drug Administration (FDA), and the dose of hormones can vary from batch to batch. For these reasons, expert groups caution against using them. However, in 2019, an estrogen-progestin pill that is also bioidentical became available; this preparation is not compounded and is approved by the FDA, meaning that it has documented safety and efficacy. This might be a good option for females who prefer not to use more conventional hormone therapies. It has also not been found to cause undesirable side effects such as weight gain or high blood pressure.

RISKS AND BENEFITS OF HORMONE THERAPY — The Women's Health Initiative (WHI) was a large study designed to find out if hormone therapy would reduce the risk of heart attacks (coronary heart disease [CHD]) after menopause. The study found that taking estrogen-progestin in combination actually increases the risk of heart attacks, breast cancer, blood clots, and strokes in older postmenopausal females but not in younger postmenopausal females (females 50 to 59).

The results of the estrogen-only study were different. Females who took estrogen alone had a small increase in the risk of stroke and blood clots, but there was no increased risk of heart attacks. There was a decreased risk of breast cancer with estrogen alone.

Heart attacks — The risk of having a heart attack related to use of hormone therapy appears to depend on your age. There is no increased risk of heart attacks related to hormone therapy in females who:

●Became menopausal less than 10 years before starting hormones

or

●Were age 50 to 59 years when they took hormone therapy

Other studies since the WHI also report that hormone therapy does not increase heart attack risk in younger females; some suggest it might even lower the risk slightly. In the WHI, females who become menopausal more than 10 years ago or over age 60 years were at increased risk of having a heart attack related to hormone therapy.

Breast cancer — The Menopause Society concludes that typical use of menopausal hormone therapy does not appreciably increase the risk of breast cancer. In the WHI, the absolute excess risk was very low in young menopausal females taking combined therapy, and there was a reduction in risk in those on estrogen alone.

Osteoporotic fracture — The risk of breaking a bone at the hip or spine because of osteoporosis is lower in females who take estrogen-progestin or estrogen alone. However, hormone therapy is not recommended to prevent or treat osteoporosis, because there are bone medicines (called bisphosphonates or denosumab) that are very effective and have fewer serious risks. (See "Patient education: Osteoporosis prevention and treatment (Beyond the Basics)".)

Dementia — Among the older females studied in the WHI, there was no improvement in memory or thinking with either estrogen alone or with combined estrogen-progestin but there was an increase in the risk of developing dementia in older females who started hormones at a late age. No increase in dementia risk was seen in the younger menopausal females in the WHI or in other studies.

Some experts think that estrogen treatment might be helpful for preventing dementia if you take it in the earliest years after menopause (although this is not proven); taking it many years after menopause seems to be harmful.

Depression — Many females experience anxiety and/or depression during the transition to the menopause. Some studies show that estrogen treatment helps improve mood and decrease depression. However, some females need to be treated with both estrogen and an antidepressant to feel better. Once females reach their postmenopausal years and their hormones are stable, they usually begin to feel better. (See "Patient education: Depression in adults (Beyond the Basics)".)

Sleep problems — Many perimenopausal and postmenopausal females have sleep problems. Sometimes this is because they have hot flashes at night that interfere with sleep (night sweats). However, females can have trouble sleeping even if they don't have hot flashes. This can be due to disorders like restless leg syndrome and sleep apnea. Estrogen treatment is very effective for improving sleep in females with night sweats.

WHO SHOULD TAKE HORMONE THERAPY? — The most common reason for taking systemic hormone therapy is to treat bothersome menopausal symptoms, such as hot flashes or vaginal dryness. Most experts agree that hormone therapy is safe for healthy females who have menopausal symptoms and are within the first 10 years of the onset of menopause.

Some experts recommend that you taper and stop your systemic hormone therapy after four or five years to avoid any increased risk of breast cancer. However, this can be a challenge for many females because the average duration of hot flashes is approximately seven to eight years.

If you are using a patch, your doctor or nurse can give you a lower-dose patch to help you taper the dose. If you are taking pills, one way to do this is to skip one pill per week at first, then continue to gradually decrease the number of pills per week until you are no longer taking any.

If menopausal symptoms return as you lower your dose of hormones, you can try hormone therapy alternatives. Some females have to go back on hormone therapy for a while. (See "Patient education: Non-estrogen treatments for menopausal symptoms (Beyond the Basics)".)

Low-dose vaginal hormone therapy is used to treat vaginal dryness, vaginal burning, and frequent urinary tract infections caused by menopause. Low-dose vaginal therapy can be taken at any age because it is not associated with medical complications.

Who should avoid hormones? — Hormone therapy is not recommended for females with the following:

●Current or past history of breast cancer

●Coronary heart disease

●A previous blood clot, heart attack, or stroke

●Females at high risk for these complications

Females whose symptoms can be treated by nonmedication methods (cool bedroom, light and layered clothing, removing layers if hot flashes occur) or with mild symptoms may not need hormone therapy.

Females with breast cancer — Females with breast cancer often experience early menopause due to breast cancer treatments. In these females, estrogen or hormone therapy (by mouth or patch) is not recommended. The hormones could increase the chance of the cancer coming back.

Alternatives to hormone therapy are available and are often effective in relieving bothersome menopausal symptoms. These alternatives are discussed in detail in a separate article. (See "Patient education: Non-estrogen treatments for menopausal symptoms (Beyond the Basics)".)

WHERE TO GET MORE INFORMATION — Your health care provider is the best source of information for questions and concerns related to your medical problem.

This article will be updated as needed on our website (www.uptodate.com/patients). Related topics for patients, as well as selected articles written for health care professionals, are also available. Some of the most relevant are listed below.

Patient level information — UpToDate offers two types of patient education materials.

The Basics — The Basics patient education pieces answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials.

Patient education: Menopause (The Basics)
Patient education: Sex problems in females (The Basics)
Patient education: Vaginal dryness (The Basics)

Beyond the Basics — Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are best for patients who want in-depth information and are comfortable with some medical jargon.

Patient education: Menopause (Beyond the Basics)
Patient education: Non-estrogen treatments for menopausal symptoms (Beyond the Basics)
Patient education: Hormonal methods of birth control (Beyond the Basics)
Patient education: Vaginal dryness (Beyond the Basics)
Patient education: Endometrial cancer diagnosis, staging, and surgical treatment (Beyond the Basics)
Patient education: Gallstones (Beyond the Basics)
Patient education: Osteoporosis prevention and treatment (Beyond the Basics)
Patient education: Screening for colorectal cancer (Beyond the Basics)
Patient education: Depression in adults (Beyond the Basics)

Professional level information — Professional level articles are designed to keep doctors and other health professionals up-to-date on the latest medical findings. These articles are thorough, long, and complex, and they contain multiple references to the research on which they are based. Professional level articles are best for people who are comfortable with a lot of medical terminology and who want to read the same materials their doctors are reading.

Overview of androgen deficiency and therapy in females
Genitourinary syndrome of menopause (vulvovaginal atrophy): Clinical manifestations and diagnosis
Estrogen and cognitive function
Menopausal hot flashes
Menopausal hormone therapy and cardiovascular risk
Menopausal hormone therapy and the risk of breast cancer
Menopausal hormone therapy in the prevention and treatment of osteoporosis
Menopausal hormone therapy: Benefits and risks
Preparations for menopausal hormone therapy
Treatment of menopausal symptoms with hormone therapy
Genitourinary syndrome of menopause (vulvovaginal atrophy): Treatment