Hormone Therapy (HT)
Hormone therapy (HT), also known as menopausal hormone therapy (MHT) or hormone replacement therapy (HRT), uses medications that contain the female hormones that the body has stopped producing after menopause. The primary reasons that women use HT are for the relief of hot flashes and night sweats (vasomotor symptoms), and vaginal dryness.
Hormone therapy uses either:
- Estrogen alone (known as estrogen therapy [ET]).
- Estrogen in combination with progestogen (known as estrogen-progestogen therapy [EPT]).
Different types of estrogen are used in hormone therapy products. They include estradiol and conjugated estrogens.
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 HT
Current guidelines support the use of HT for the treatment of severe hot flashes that do not respond to non-hormonal therapies. General recommendations include:
- HT may be started in women who have recently entered menopause.
- HT should not be used in women who have started menopause many years ago.
- Women should not take HT (either EPT or ET) if they have risks for stroke, heart disease, blood clots, and breast cancer.
- Currently, there is no consensus on how long HT should be used or at what age it should be discontinued. Treatment should be individualized for a woman's specific health profile.
- HT should be used only for menopause symptom management, not for chronic disease prevention.
Before starting HT, your doctor should give you a comprehensive physical exam and take your medical history to evaluate your risks for:
- Heart disease
- Blood clots
- Breast cancer
While taking HT, you should have regular mammograms and pelvic exams and Pap smears. Current guidelines recommend that if HT 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 HT while in their 50s. Women who start HT past the age of 60 appear to have a higher risk for side effects such as heart attack, stroke, blood clots, or breast cancer. HT should be used with care in this age group.
Women who experience premature menopause are usually prescribed HT 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.
When a woman stops taking HT, perimenopausal symptoms may recur. There is about a 50% chance of hot flashes recurring regardless of whether HT is suddenly stopped or gradually tapered off. When a woman reaches full menopause, symptoms will eventually go away.
Because HT offers protection against osteoporosis, when women stop taking HT their risks for bone thinning and fractures increases. For women who have used HT for several years, doctors should monitor their bone mineral density and prescribe bone-preserving medications if necessary.
Until 2002, doctors used to routinely prescribe HT 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 HT.
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 therapy. As new data are released and analyzed, there have been a number of changes in the way HT is prescribed and a better understanding of its risks.
Women who should not take hormone 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
HT Forms and Regimens
HT comes in several forms:
- Oral tablets or pills
- Skin patches
- Vaginal cream or tablet
- Vaginal ring
- Topical gel or spray
HT pills and skin patches are considered "systemic" therapy because the medication delivered affects the entire body. The risk for blood clots, heart attacks, and certain types of cancers is higher with hormone pills than with skin patches or other transdermal forms.
Vaginal forms of HT are called "local" therapy. 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.
"Bioidentical" hormone 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 HT
Perimenopausal and Menopausal Symptoms
Systemic HT is mainly recommended for relieving menopausal symptoms such as hot flashes, night sweats, and sleep problems, as well as vaginal dryness. Local HT (delivered vaginally) is used specifically for treating vaginal dryness and atrophy; and accompanying pain during sexual intercourse. HT does not prevent certain other problems associated with menopausal changes, such as thinning hair or weight gain. It is unclear whether HT helps improve mood.
Estrogen increases and helps maintain bone density. HT 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. Duavee is a drug that contains a combination of conjugated equine estrogen and the selective estrogen receptor modulator (SERM) bazedoxifene. It is approved to treat hot flashes and prevent osteoporosis in women with a uterus.
Although HT may have some benefits in addition to menopausal symptoms, results from the Women's Health Initiative (WHI) studies strongly indicate that HT should be used only for relief of menopausal symptoms, not for prevention of chronic disease.
Risks of HRT
Heart Disease, Heart Attack, and Stroke
HT may increase the risk of heart disease and heart attack in older women, or in women who began estrogen use more than 10 years after their last period. HT is probably safest in healthy women under age 60 who begin taking it within 10 years after the start of menopause. Taking HT in order to prevent heart disease is not recommended. Women who have a history of heart disease or heart attack should not take HT. HT may increase the risk of stroke.
HT increases the risk for formation of blood clots in the veins (deep venous thrombosis) or in the lungs (pulmonary embolism). The risk for blood clots is higher with oral forms of HT than with transdermal forms (skin patches, creams). There appears to be little, if any, increase in the risk of blood clots when transdermal forms of HT are used.
Estrogen- progestogen therapy (EPT) increases the risk for breast cancer if used for more than 3 to 5 years. This risk appears to decline within 3 years of stopping combination HT.
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 HT increase breast cancer density, making mammograms more difficult to read. This can cause cancer to be diagnosed at a later stage. Women who take HT 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.
Long-term use (more than 5 to 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).
Endometrial (Uterine) Cancers
Taking estrogen-only therapy (ET) for more than 3 years significantly increases the risk of endometrial cancer. If taken for 10 years, the risk is even greater. Adding progesterone 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 therapy is recommended for women with a history of endometrial cancer.
It is not clear if HT use is associated with an increased risk of lung cancer, women who smoke and who are past or current users of HT should be aware that that EPT may possibly promote the growth of lung cancers.
HT increases the risk of developing gallbladder disease.
The Women's Health Initiative Memory Study and other studies suggest that combined HT does not reduce the risk of cognitive impairment or dementia and may actually increase the risk of cognitive decline. Researchers are continuing to study the effects of HT on Alzheimer disease risk.
Other Drugs Used for Menopausal Symptoms
Despite its risks, hormone therapy appears to be the most effective treatment for hot flashes. There are, however, nonhormonal treatments for hot flashes and other menopausal symptoms.
The antidepressants known as selective serotonin-reuptake inhibitors (SSRIs) are sometimes used for managing mood changes and hot flashes. A low-dose formulation of paroxetine (Brisdelle) is approved to treat moderate-to-severe hot flashes associated with menopause. Other SSRIs and similar antidepressant medicines are used "off-label" and may have some benefit too. They include fluoxetine (Prozac, generic), sertraline (Zoloft, generic), venlafaxine (Effexor), desvenlafaxine (Pristiq), paroxetine (Paxil, generic), and escitalopram (Lexapro, generic).
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 decided against approving gabapentin for this indication because the drug demonstrated only modest benefit. Gabapentin may cause:
- Swelling of the hands and feet
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.
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
- Fluid retention
Testosterone also adversely affects cholesterol and lipid levels, and combined estrogen and testosterone may increase the risk of breast cancer. Many experts do not consider testosterone safe or effective for treatment of menopausal symptoms.
Non-Hormonal Treatments for Vaginal Dryness and Atrophy
Vaginal lubricants (such as KY Jelly and Astroglide) and moisturizers (such as Replens) can be purchased without a prescription and are safe and helpful for treating vaginal dryness and dyspareunia (painful sexual intercourse). Dyspareunia is a result of thinning vaginal tissues (vaginal atrophy) due to low estrogen levels.
The North American Menopause Society recommends lubricants and long-acting moisturizers as first-line treatments for vaginal atrophy. For women who still experience discomfort, low-dose vaginal (local) estrogen is the next option.
Ospemifene (Osphena) is approved as a non-hormonal prescription drug for treating menopausal-associated vaginal dryness and 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.