Hormone Replacement Therapy (HRT)
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:
- Estrogen alone (known as estrogen therapy [ET])
- Estrogen in combination with progestogen (known as estrogen-progestogen therapy [EPT]).
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:
- Women who have a uterus (have not had a hysterectomy) receive estrogen plus progesterone or a progestin (EPT).
- Women who do not have a uterus (have had a hysterectomy) receive estrogen alone (ET).
General Recommendations for HRT
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:
- 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.
- EPT should not be used for more than 3 - 5 years because of increased risk for breast cancer. ET has less risk for breast cancer and appears to be safe for use for up to at least 7 years.
- Women should not take HRT (either EPT or ET) unless they have a low risk for stroke, heart disease, blood clots, and breast cancer.
- In general, doctors recommend that patients who choose HRT take the lowest possible dose for relief of symptoms for the shortest amount of time.
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:
- Current, past, or suspected breast cancer
- History of endometrial cancer
- Vaginal bleeding of unknown cause
- Current or past history of blood clots
- High blood pressure that is untreated or poorly managed
- History of angina, heart attack, or other heart or circulation problems
HRT Forms and Regimens
HRT comes in several forms:
- Oral tablets or pills
- Skin patches
- Vaginal cream or tablet
- Vaginal ring
- Topical gel or spray
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.)
Benefits of HRT
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.
Risks of HRT
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).
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.
Other Drugs Used for Menopausal Symptoms
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.