Medications:

Hormone Replacement Therapy (HRT)

Doctors used to believe that HRT could help reduce the risk of heart disease and other health risks in addition to treating menopausal symptoms. 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, enrolled 161,809 women ages 50 - 79 in 40 different medical centers. Part of the study was intended to examine the health benefits and risks of hormone replacement therapy, including the risks of breast cancer, heart attacks, strokes, and blood clots. Analysis of the data from this ongoing study and other studies have raised concerns about an increased risk of developing breast cancer, heart attacks, strokes, and blood clots.

As a result, there have been a number of changes in the way hormone therapy is prescribed. Current guidelines support the use of HRT for the treatment of hot flashes. Specific recommendations:

• HRT may be started in women who have recently entered menopause.
• HRT should not be used in women who have started menopause many years ago.
• HRT should not be used for longer than 5 to 7 years.
• Women who take HRT should have a low risk for stroke, heart disease, blood clots, or breast cancer.

To reduce the risks of estrogen replacement therapy and still gain the benefits of the treatment, your doctor may recommend:

• Using a lower dose of estrogen or a different estrogen preparation (for instance, a vaginal cream rather than a pill)
• Frequent and regular pelvic exams and Pap smears to detect problems as early as possible
• Frequent and regular physical exams, including breast exams and mammograms

Beginning estrogen replacement therapy years after menopause has occurred is generally not recommended.

In general, doctors recommend that patients who choose HRT take the lowest possible dose for relief of symptoms for the shortest amount of time.

When a woman stops taking HRT, perimenopausal symptoms may recur. There is some debate about whether it is better to abruptly stop the medication or to taper it off gradually. Gradual discontinuation of HRT may delay -- but not prevent -- the reappearance of symptoms. However, when a woman reaches full menopause, symptoms will eventually go away.

Hormones Used in HRT. Hormone replacement therapy uses either estrogen alone (known as ET or unopposed estrogen) or in combination with forms of progesterone (known as combined hormone therapy or EPT). Women who have a uterus (have not had a hysterectomy) receive estrogen plus progesterone or a progestin. Women who do not have a uterus (have had a hysterectomy) receive estrogen alone.

For women who have a uterus, progesterone or a progestin is added to estrogen to protect the uterine lining (endometrium) and reduce the risk of endometrial cancer. (Progesterone is the name for the natural hormone that the body produces. Progestin, also called progestogen, refers to a synthetic hormone that has progesterone effects.)

The primary reason for using HRT is the relief of hot flashes, night sweats, and vaginal dryness. HRT comes in several forms:

• Oral tablets or pills
• Skin patches
• Vaginal cream or tablet
• Vaginal ring
• Nasal spray
• Topical gel

When estrogen and progesterone are prescribed together, recommended schedules include:

• Cyclic hormone therapy is often recommended when a woman is starting menopause. With this therapy, estrogen is taken in pill or patch form for 25 days, with progestin added somewhere between days 10 - 14. The estrogen and progestin are used together for the remainder of the 25 days. Then, no hormones are taken for 3 - 5 days. There may be monthly bleeding with cyclic therapy.
• Continuous, combined therapy involves taking estrogen and progestin together every day. Irregular bleeding may occur when starting or switching to this therapy. Most women stop bleeding within 1 year.

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

• Current, past, or suspected breast cancer
• Vaginal bleeding of unknown cause
• Current or past history of blood clots
• High blood pressure that is untreated or poorly managed
• Angina that is currently symptomatic or heart attack that occurred recently
• Active liver problems

"Biodentical" Hormones. Bioidentical” hormone replacement therapy is promoted as a supposedly 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.)

Benefits of HRT

Periomenopausal and Menopausal Symptoms. HRT is mainly recommended for relieving menopausal symptoms, including hot flashes, night sweats, vaginal dryness, sleep problems, and mild depression. HRT does not prevent certain other problems associated with menopausal changes, such as thinning hair.

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. HRT increases and helps maintain bone density.. Estrogen must be taken for life for maximum protection against osteoporosis, therefore increasing the risk of side effects. [For more information, see In-Depth Report #18: Osteoporosis.]

Colorectal Cancer. Estrogen plus progestin HRT may reduce the risk of colorectal cancer. Again, for most women the risks of longterm HRT do not outweigh the benefits.

Heart Disease. Younger women with a natural or surgically induced menopause are at increased risk for heart disease and may benefit from estrogen replacement therapy. This recommendation does not apply to older women.

Adverse Effects of HRT

Heart Disease. HRT does not prevent heart disease except in women with premature menopause and may increase the risk for heart disease and heart attack, especially in older women. Results from the Women� ' s Health Initiative study found that women who began HRT within 10 years of menopause had less risk of heart disease than women who begin HRT later on. This suggests that HRT may be safest for women younger than age 60, and should be avoided by women older than age 60. Any woman who is considering HRT should be sure to have her blood pressure and cholesterol levels evaluated. Estrogen can increase the risk for heart attack in women who have advanced heart disease.

Stroke. HRT may increase the risk of stroke, regardless of years since menopause. It is certainly no longer recommended as a strategy to prevent stroke. In addition, HRT appears to worsen the outlook for women who are at increased risk for stroke and women who have had a stroke.

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.

Breast Cancer. Many studies have reported a higher risk for breast cancer in postmenopausal women who take combination estrogen-progesterone hormone replacement therapy. According to the most recent studies, long-term use (5 years or more) of combination HRT increases the risk of developing and dying from breast cancer. This risk decreases within 5 years of stopping combination HRT.

Estrogen-only HRT does not significantly increase the risk of developing breast cancer if it is used for less than 10 years. If used for more than 10 years, it may increase the risk of breast (and ovarian) cancers, especially for women already at higher risk for breast cancer.

HRT increases 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. Recent studies have noted that breast cancer rates have fallen as HRT use has declined.

Endometrial (Uterine) Cancers. Estrogen overstimulates the tissue lining the uterus (the endometrium) and causes uncontrolled cell growth, a condition known as hyperplasia, which is a strong risk factor for cancer. Taking estrogen-only replacement therapy (ERT) increases the risk of endometrial cancer at least five-fold. Adding progesterone or a progestin to estrogen helps to reduce this risk. Women who take ERT should anticipate uterine bleeding, especially if they are obese, and may need endometrial biopsies and other gynecologic tests.

Ovarian Cancer. Long-term use (more than 5 - 10 years) of HRT may increase the risk of developing and dying from ovarian cancer. The risk appears to be particularly significant for women who take estrogen-only HRT . The risk is less clear for combination HRT.

Other Drugs Used for Menopausal Symptoms

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

Antidepressants. The antidepressants known as selective serotonin-reuptake inhibitors (SSRIs) are sometimes used for managing mood changes and hot flashes. They include fluoxetine (Prozac), sertraline (Zoloft), venlafaxine (Effexor), desvenlafaxine (Pristiq), and paroxetine (Paxil,). However, these drugs can cause side effects, such as sexual problems.

Gabapentin. Several small studies suggest that gabapentin (Neurontin), a drug used for seizures and nerve pain, may relieve hot flashes. Gabapentin may cause drowsiness, dizziness, fatigue, and swelling of the hands and feet.

Clonidine. Clonidine (Catapres) 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 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.