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Hormonal Therapy
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Hormonal Therapy

Hormone replacement therapy (HRT) refers to the use of estrogen plus progestin for the treatment of perimenopausal symptoms. It is also commonly referred to as "opposed estrogen therapy."

Estrogen and progestin combinations (pills or tablets)

conjugated estrogens/medroxyprogesterone Premphase Prempro estradiol/norethindrone acetate Activella

Transdermal combination preparations (a patch placed on the skin that continuously releases estrogen and progestin)

estradiol/norethindrone acetate CombiPatch

Oral progestin (pills or tablets; used along with an estrogen-only preparation)

medroxyprogesterone Provera micronized progesterone Prometrium norethindrone Micronor Norlutin Nor-QD norethindrone acetate Aygestin

Progestin intrauterine device (IUD; used along with an estrogen-only preparation)
levonorgestrel Mirena

Estrogen-progestin hormone therapy, or HRT, is recommended for all women with a uterus who choose to take estrogen. Using estrogen without progestin greatly increases your risk of endometrial cancer. Taking progestin with estrogen eliminates this increased risk.1

How It Works
HRT increases the estrogen and progestin levels in your body. There are several standard hormone replacement therapy schedules, including continuous and cyclic along with higher-dose and low-dose.

Combining progestin with estrogen:

  • Protects against endometrial cancer (which can develop with estrogen-only therapy).
  • Is not needed for women who have no uterus.
  • May trigger monthly withdrawal bleeding when progestin is used periodically (such as in cyclic HRT).

Patch warning. Direct sunlight or high heat can increase, then lower, the amount of hormone released from a patch. This can give you a big dose at the time and leave less hormone for the patch to release later in the week. Avoid direct sunlight on the hormone patch. Also avoid using a tanning bed, heating pad, electric blanket, hot tub, or sauna while you are using a hormone patch.

Why It Is Used
The estrogen in hormone therapy is used by some postmenopausal women to increase estrogen levels. This helps prevent osteoporosis and perimenopausal symptoms, such as hot flashes and sleep problems. HRT is known to cause a small increase in the risk of breast cancer, blood clots, cardiovascular disease, or dementia. These risks may be different for women in their 50s. Research is ongoing.
The FDA recommends HRT only for:

  • Short-term treatment of menopausal symptoms, at the lowest effective dose for as short a time as possible.
  • Osteoporosis prevention and treatment, in select cases. Most experts recommend that HRT only be considered for women with significant risk of osteoporosis that may outweigh their risks of taking HRT.3 Women are now encouraged to consider all possible osteoporosis treatments and to compare their risks and benefits.4 For more information, see the topic Osteoporosis.

Who should not use HRT
You should not use HRT if you:

  • Could be pregnant.
  • Have a personal history of breast cancer.5
  • Have a personal history of certain endometrial cancers.
  • Have a personal history of pulmonary embolism, deep vein thrombosis, heart attack, or stroke.1
  • Have vaginal bleeding from an unknown cause.
  • Have active liver disease. You may be able to use an alternative to oral estrogen that bypasses the liver, such as estrogen delivered from a skin patch (transdermal) or vaginal cream.

How Well It Works
HRT increases estrogen levels, which:6, 7

  • Helps prevent postmenopausal osteoporosis by slowing bone loss and promoting some increase in bone density.7
  • Reduces hot flashes, depression, and sleep problems in most, but not all, women.7, 8
  • Maintains the lining of the vagina, reducing irritation.
  • Increases skin collagen levels, which drop as estrogen levels naturally decrease. Collagen is responsible for the stretch in skin and muscle.
  • Reduces the risk of dental problems, such as tooth loss and gum disease.
  • May slightly lower the risk of colon cancer.6 (This is based on one study.)

Side Effects
Risks of hormone replacement therapy
Hormone replacement therapy was part of a large set of clinical trials called the Women's Health Initiative (WHI). The HRT portion of these trials showed a small increase in the rate of breast cancer among the women taking a combination of 0.625 mg of estrogen plus 2.5 mg of progestin daily. WHI data has also shown an increased rate of cardiovascular disease and dementia with HRT use.

  • Within the first 2 years, HRT use slightly increased the number of women with blood clots in the lungs (pulmonary embolism) and legs (deep vein thrombosis). This risk increased in all healthy postmenopausal women, regardless of risk factors.9
  • During the second year, HRT use began to slightly increase heart attack and stroke risk in all healthy postmenopausal women, regardless of risk factors. Early signs of heart disease first became apparent during the first year of use.9, 10 Heart disease risk may differ for younger menopausal women.11, 12
  • After 1 year, HRT use increased the number of abnormal mammograms by approximately 4% per year. Daily estrogen-progestin increased breast density compared with estrogen alone or placebo. Although the abnormal mammograms required additional medical evaluation, they were not linked to an early increase in breast cancer. Studies are ongoing to learn more about breast density change from HRT.13
  • After 4 years of use, HRT-related breast cancers first became apparent. The number of HRT-related breast cancers increased with each additional year of HRT use. Women taking HRT generally had larger, more advanced tumors than women who developed breast cancer while taking placebo treatment.6 (Some of these cancers, however, may respond more favorably to treatment.)14
  • After 4 years, HRT use slightly increased the incidence of Alzheimer’s disease and other dementias in women ages 65 and older. HRT does not provide protection from dementia or cognitive impairment, as was previously believed.15 (Most of the women in this study started HRT several years after menopause, when Alzheimer's risk naturally increases. Therefore, experts do not yet know whether Alzheimer's risk is the same for younger women who use short-term HRT starting at menopause.)

Experts do not yet know whether lower-dose, shorter-term HRT reduces or eliminates these risks.

Serious health events caused or prevented by HRT, per 1,000 women (estrogen 0.625 mg plus progestin 2.5 mg)
Health event After 2 years of HRT use After 5.2 years of HRT use
Blood clots (venous thromboembolism)
6 more*
9 more
Coronary artery disease
3 more **
4 more
Breast cancer
No change***
4 more
1 more****
4 more
Colorectal cancer
No change
3 fewer#
Hip fractures
1 fewer
2 fewer
No change
No change

* Risk is greatest during the first 2 years of use.
** Signs develop as early as the first year of use.
*** First noted after 4 years of use.
**** First noted after 1 year of use.
# Benefit noted after 3 years of use.

These average increased risks are relatively low in the general population of postmenopausal women. Your personal risk that hormone therapy may stimulate breast cancer, cardiovascular problems, blood clots, or neurological changes may be significantly lower or higher, depending on your risk factors. Not all possible risk factors are known.

Estrogen side effects

Side effects that can occur with all forms of estrogen but are more frequent with oral estrogen include:

  • Irregular vaginal bleeding.
  • Headaches.
  • Nausea.
  • Vaginal discharge.
  • Fluid retention.
  • Weight gain.
  • Breast tenderness.
  • Spotting or darkening of the skin, particularly on the face.
  • Asthma. Newly diagnosed asthma appears to be more common among women taking HRT or estrogen-alone (ERT) than women who are not. (Estrogen is thought to be a factor that causes or worsens asthma across the life span.)
  • Gallstones. Women who use estrogen replacement therapy are more likely to have gallstones that cause symptoms than women who do not use ERT. (High estrogen levels are linked to gallbladder disease.)
  • Rarely, an increased growth of preexisting uterine fibroids or a worsening of endometriosis.

In addition, the estrogen patch (transdermal estrogen) may cause skin irritation.
Some of these side effects, such as headaches, nausea, fluid retention, weight gain, and breast tenderness, may go away after a few weeks of use.

Progestin side effects
The side effects of progestin often cause women to stop using hormone replacement therapy (HRT). Adjusting the progestin dose, changing the dosing schedule, or changing the type of progestin may reduce side effects. The progestin intrauterine device (IUD) reduces or eliminates side effects that are common with oral progestin.

Progestin side effects include:

  • Mood changes, such as anxiety, irritability, or depression.
  • Headache.
  • Breast pain or tenderness.
  • Abdominal pain or bloating (distention).
  • Dizziness or drowsiness.
  • Diarrhea.
  • Vaginal discharge.
    Cyclic progestin (taken 10 to 14 days per month) is more likely to cause:
  • Premenstrual-like symptoms, such as bloating, cramping, breast tenderness, nausea, and depression.
  • Monthly withdrawal bleeding.

The combination transdermal patch may cause skin irritation.
See Drug Reference for a full list of side effects. (Drug Reference is not available in all systems.)

What To Think About
If you have been taking HRT, talk with your health professional about your reasons for taking it. Are you taking it to help with perimenopausal symptoms or for long-term health reasons? Consider changing to another treatment, depending on the problem you are using HRT to treat. If HRT seems like the best choice for you, plan to use the lowest possible effective dose.

If you are unable to tolerate the side effects of progestin in hormone replacement therapy and you have not had a hysterectomy, try nonhormonal treatment options.

Some women use estrogen-only therapy (ERT) if testing does not show abnormalities of the lining of the uterus (endometrium). However, because this greatly increases your risk of uterine cancer, health professionals don't recommend taking estrogen alone. If you do take estrogen without progestin, you must have regular checks for precancerous changes of the endometrium. This means an annual pelvic exam along with an annual endometrial biopsy or transvaginal ultrasound.

The British Million Women Study has confirmed the Women's Health Initiative findings and has provided more information about estrogen, progestin, and breast and endometrial cancers.18 This is important information for women deciding whether to take estrogen without progestin, as described above.

When given with a skin patch, estrogen-progestin enters the bloodstream directly, without passing through the liver. The estrogen and progestin in pills must be processed by the liver before entering the bloodstream. This is why women with liver or gallbladder disease can usually use a patch form of HRT.

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