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Hormone Replacement Therapy

Definition

Hormone replacement therapy (HRT) is the use of synthetic or natural female hormones to make up for the decline or lack of natural hormones produced in a woman's body. HRT is sometimes referred to as estrogen replacement therapy (ERT), because the first medications that were used in the 1960s for female hormone replacement were estrogen compounds.

Estrogens

In order to understand how HRT works and the controversies surrounding it, women should know that there are different types of estrogen medications commonly prescribed in the United States and Europe. These drugs are given in a variety of prescription strengths and methods of administration. There are at present three estrogen compounds used in Western countries. Only the first two are readily available in the United States.

Estrone. Estrone is the form of estrogen present in women after menopause. It is available as tablets under the brand name Ogen. The most commonly prescribed estrogen in the United States, Premarin, is a so-called conjugated estrogen that is a mixture of estrone and other estrogens.
Estradiol. This is the form of estrogen naturally present in perimenopausal women. It is available as tablets (Estrace), skin patches (Estraderm), or vaginal creams (Estrace).
Estriol. Estriol is a weaker form of estrogen produced by the breakdown of other forms of estrogen in the body. This is the form of estrogen most commonly given in Europe, under the brand name Estriol. It is the only form that is thought not to cause cancer.

In addition to pills taken by mouth, skin patches, and vaginal creams, estrogen preparations can be given by injection or by pellets implanted under the skin. Estrogen implants, however, are used less and less frequently.

Progestins

Most HRT programs include progestin treatment with estrogen compounds. Progestins—sometimes called progestogens—are synthetic forms of progesterone that are given to reduce the possibility that estrogen by itself will cause cancer of the uterus. Progestins are commonly prescribed under the brand names Provera and Depo-Provera. Other common brand names are Norlutate, Norlutin, and Aygestin.

Estrogen/testosterone combinations

Women's ovaries secrete small amounts of a male sex hormone (testosterone) throughout their lives. Women who have had both ovaries removed by surgery are sometimes given testosterone along with estrogen as part of HRT. Combinations of these hormones are available as tablets under the brand name Estratest or as vaginal creams. Women who cannot take estrogens can use 1% testosterone cream alone for problems with vaginal soreness.

Estrogen/tranquilizer combinations

There are several medications that combine estrogen with a tranquilizer like chlordiazepoxide (sold under the trade name Menrium) or meprobamate (sold under the trade name PMB). Many doctors warn against these combination drugs because the tranquilizers can be habit-forming.

Purpose

Hormone replacement therapy has been prescribed for two primary purposes: preventive treatment against osteoporosis and heart disease; and relief of physical symptoms associated with menopause.

Menopausal symptoms

Women in midlife enter a stage of development called menopause, when their menstrual periods become irregular and finally stop. The early phase of this transition is called the perimenopause. In the United States, the average age at menopause is presently 50 or 51, but some women begin menopause as early as 40 and others as late as 55. It can take as long as 10 years for a woman to complete the process. Women who have had their ovaries removed surgically are said to have undergone surgical menopause.

Doctors have not always agreed on definitions of menopause. Some use age as the baseline. Others define menopause as the point when a woman has had no menstrual periods for a full calendar year. Still others define menopause as the end of ovulation. It is not always clear, however, when a woman has had her last period or when she has stopped ovulating. In addition, women who take oral contraceptives can have breakthrough bleeding long after they have stopped ovulating. As a result, some doctors now measure the level of follicle-stimulating hormone (FSH) in a woman's blood to estimate whether the woman has entered menopause. During perimenopause, the FSH levels in a woman's blood rise as her body attempts to stimulate the release of ripe ova. An FSH level over 40 is considered an indicator of menopause.

During the menopausal transition, the levels of estrogen in the woman's body drop. The lowered estrogen level is responsible for a group of symptoms that include hot flashes (or flushes), weight gain, changes in skin texture, mood swings, heart palpitations, sleep disturbances, a need to urinate more frequently, and loss of sexual desire. The estrogen that is given in HRT has been shown to eliminate hot flashes, night sweats, lack of vaginal lubrication, and urinary tract problems. HRT will not prevent weight gain or wrinkles. It also does not cure depression in most women.

Preventive care

HRT has been recommended by some doctors to protect women against two serious midlife health problems, including osteoporosis and heart disease. While clinical trials have continued to demonstrate HRT's effectiveness in preventing osteoporosis, women must weigh the risk of the therapy with the benefits. The trials also showed that HRT actually increased rather than decreased risk of heart disease.

OSTEOPOROSIS. Osteoporosis is a disorder in which the bones become more brittle and more easily fractured. It is a particular problem for postmenopausal women because the lower levels of estrogen in the blood lead to weakening of the bone. About 25% of Caucasian women will develop severe osteoporosis; Asian women have a slightly lower risk level; Latino and African American women are least at risk.

In addition to race, there are other factors that put some women at higher risk of developing osteoporosis. Women in any of the following groups should take bone loss into account when considering HRT:

family history of osteoporosis
menopause before age 40
kidney disease and dialysis
thin body build or being underweight
history of colitis, Crohn's disease, or chronic diarrhea
thyroid medications
childlessness
chronic use of antacids
lack of exercise
poor food choices, including high salt intake, lack of vitamin D, high caffeine consumption, and low calcium intake
smoking and alcohol abuse
cortisone therapy

HEART DISEASE. Heart disease is a major health concern of women in midlife. It is the leading cause of death in women over 60. The primary disorders of the circulatory system in postmenopausal women are stroke, hypertension, and coronary artery disease. While doctors once believed that HRT helped decrease heart disease and stroke among postmenopausal women, a major clinical trial discovered the opposite to be true. In 2002, the Women's Health Initiative (WHI) stopped giving HRT to the women enrolled in the study because of adverse effects. Among these effects was a 29% increase in coronary heart disease and 41% increase in stroke in postmenopausal women taking HRT.

Other major factors that are known to increase the risk of heart disease include:

Estrogen replacement patches adhere to a patient's skin and slowly administer estrogen to the body.

(Illustration by Argosy Inc.)

history of smoking
being overweight
high-fat diets
alcohol abuse
family history of heart disease
high blood pressure
high blood cholesterol levels
diabetes.

Less important risk factors include being African American, having a sedentary lifestyle, undergoing menopause before age 45, and having high levels of family- or job-related stress.

Precautions

Medical conditions

The findings of the WHI presented new problems for the women relying on hormones to ease their transition to menopause and postmenopausal years and for doctors prescribing HRT. The combination of estrogen and progesterone also was found to increase risk of invasive breast cancer by 26%, which was the reason researchers halted the study. In addition, while some clinicians have thought that HRT helped delay dementia (a disorder of the mind that affects memory and perception), the WHI also found that combined estrogen/progesterone increased the risk of probable dementia in women age 65 and older. Physicians and women were advised not to panic about HRT, however. Short-term use of the therapy may not produce these risks. Women have been advised to meet with their physicians and weigh the benefits against the risks on an individual basis.

Certain groups of women should not use HRT. They include women with:

breast cancer
cancer of the uterus
heart disease
abnormal vaginal bleeding that has not been diagnosed
high blood pressure that rises when HRT is used
liver disease
gallstones or diseases of the gallbladder

Drug interactions

HRT can interact with other prescription medications that a woman may be taking. Women who are taking corticosteroids, drugs to slow the clotting of blood (anticoagulants), and rifampin should ask their doctor about possible interactions.

Combining estrogens with certain other medicines can cause liver damage. Among the drugs that may cause liver damage when taken with estrogens are:

acetaminophen (Tylenol), when used in high doses over long periods
anabolic steroids such as nandrolone (Anabolin) or oxymetholone (Anadrol)
medicine for infections
antiseizure medicines such as divalproex (Depakote), valproic acid (Depakene), or phenytoin (Dilantin)
antianxiety drugs, including chlorpromazine (Thorazine), prochlorperazine (Compazine), and thioridazine (Mellaril).

In addition, estrogens may interfere with the effects of bromocriptine (Parlodel), used to treat Parkinson's disease and other conditions; they may also increase the chance of toxic side effects when taken with cyclosporine (Sandimmune), a drug that helps prevent organ transplant rejection.

Description

HRT medications come in several different forms, including tablets, stick-on patches, injections, and creams that are worn inside the vagina. The form prescribed depends on the purpose of the hormone replacement therapy. Women who want relief from vaginal dryness, for example, would be given a cream or vaginal ring. Women using HRT to relieve hot flashes or to prevent osteoporosis and heart disease often prefer oral medications or patches. All HRT medications used in the United States are available only with a doctor's prescription.

Hrt treatment regimens

One of the complications of HRT is the number of treatment options, including combinations of types of estrogen; dosage levels; forms of administration; and whether or not progestins are used with the estrogen to offset the risk of uterine cancer. This variety, however, means that a woman who wants to use HRT while minimizing side effects can try different forms of medication or dosage schedules when she consults her doctor. It is vital, however, for women to follow their doctor's directions exactly and not change dosages themselves.

At present, women who are taking a combination of estrogens and progestins are placed on one of three dosage schedules:

Estrogen pills taken daily from the first through the 25th day of each month, with a progestin pill taken daily during the last 10-14 days of the cycle. Both drugs are then stopped for the next five to six days to allow the uterus to shed its lining.
Estrogen pills taken on a daily basis with low-dose progestin pills, also on a daily basis. Both medications are taken continuously with no days off.
Estrogen pills and low-dose progestins taken on a daily basis for five days each week, with both medications stopped on the last two days of each week.

TIMING AND LENGTH OF TREATMENT. One of the disagreements about HRT concerns the best time to begin using it. Some doctors think that women should begin using HRT while they are still in perimenopause. Others think that there is no harm in a woman's waiting to decide. Either way, the question of timing means that a woman should keep track of changes in her periods and other signs of perimenopause so that her doctor can evaluate her readiness for HRT.

The other question of timing concerns length of treatment. Some women use HRT only as long as they need it to relieve the symptoms of menopause. Others regard it as a lifetime commitment because of concerns about osteoporosis. One study found that the average length of time that women stay on HRT is 23 months. Information from the WHI released in 2002 and 2003 would indicate that long-term HRT use produced too many risks for the expected benefits.

UNWANTED SIDE EFFECTS. In addition to the identified health risks mentioned above, much of the disagreement about unwanted side effects from HRT concerns the role of progestins in the estrogen/progestin combinations that are commonly prescribed. Many women who find that estrogen relieves hot flashes and other symptoms of menopause have the opposite experience with progestin. Progestin frequently causes moodiness, depression, sore breasts, weight gain, and severe headaches.

Other treatment approaches

Women who are uncertain about HRT, or who should not take estrogens, should know about other treatment options, such as natural progesterone. Progestins, which are synthetic hormones, were developed because natural progesterone cannot be absorbed in the body when taken in pill form. A new technique called micronization has made it possible for women to take natural progesterone by mouth. Many women prefer this form of hormone because it lacks the side effects of the synthetic progestins even though it is somewhat more expensive. The most common form of natural progesterone is called Prometrium. which is available by prescription only. Another form of natural progesterone consists of the hormone suspended in vitamin E oil. It is absorbed through the skin and is available without a prescription.

Alternative therapies also are available. Many mainstream as well as alternative practitioners recommend changes in diet and nutrition as helpful during menopause. Women who limit their intake of fats and salts, increase their use of fresh fruits and vegetables, quit smoking, and drink only in moderation often find that these dietary changes help them feel better. Naturopaths typically recommend vitamin and mineral supplements for general well-being as well as for relief from hot flashes and leg cramps. In addition, herbal teas and tonics are helpful to some women in treating water retention, insomnia, constipation, or moodiness.

Women who find menopause emotionally stressful because of negative social attitudes toward older women are often helped by meditation, biofeedback, therapeutic massage, and other relaxation techniques. Yoga and tai chi provide physical exercise as well as stress reduction. Exercise is an important safeguard against osteoporosis.

Preparation

Women who are considering HRT should visit their doctor for a series of tests to make sure that they do not have any serious health disorders. They should have a Pap smear and breast examination to rule out cancer. They also should have a urinalysis, a bone density test, and blood tests to measure their red blood cell level, blood sugar level, cholesterol level, and liver and thyroid function.

In addition to these tests, most doctors will also give a progesterone challenge test. It consists of doses of progesterone given over a 10-day period to see if the woman is still producing her own estrogen. If she bleeds at the end of the test, she is still producing estrogen.

Aftercare

Aftercare is a very important part of HRT. Women who are taking HRT will need to see their doctor more frequently. At a minimum, they should be checked twice a year with a blood pressure test and breast examination. They should have a complete physical on a yearly basis. Any abnormal bleeding must be reported to the doctor as soon as it occurs. The doctor will need to order a tissue biopsy or dilation and curettage (D & C) in order to rule out cancer of the uterus.

Women who are taking HRT and decide to stop should taper their dosage over a period of several months rather than discontinuing abruptly. A gradual reduction minimizes the possibility of hot flashes and other side effects.

Key terms

Dilation and curettage (D & C) — A surgical procedure in which the patient's cervix is widened (dilated) and the endometrium is scraped with a scoop-shaped instrument (curette).

Estrogen — The primary sex hormone that controls normal sexual development in females. During the menstrual cycle, estrogen helps prepare the body for possible pregnancy.

Follicle-stimulating hormone (FSH) — A hormone produced by the pituitary gland that stimulates the follicles in the ovaries to swell and release ripe ova. Doctors sometimes use its levels in a woman's blood to evaluate whether she is in menopause.

Hormone — A substance secreted by an endocrine gland that is carried by blood or other body fluids to its target tissues or organs.

Hot flash — A warm or hot sensation on the face, neck and upper body, sometimes accompanied by flushing and sweating. Some women refer to hot flashes as hot flushes.

Osteoporosis — A bone disorder in which the bones become brittle, porous, and easily broken. It is a major health concern for postmenopausal women.

Ovary — The female sex gland that produces eggs and female reproductive hormones.

Ovulation — The cyclical process of egg maturation and release from the ovary.

Progesterone — A female hormone produced by the ovary. It functions to prepare the lining of the uterus to receive a fertilized ovum.

Progesterone challenge test — A test that is given to see if a woman is still secreting estrogen. It consists of doses of progesterone given over a 10-day period.

Progestin — Synthetic progesterone available as an oral medication.

Testosterone — A male sex hormone that is sometimes given as part of HRT to women whose ovaries have been removed. Testosterone helps with problems of sexual desire.

Uterus — The hollow organ in women in which fertilized eggs develop during pregnancy. The uterus is sometimes called the womb.

Risks

The short-term risks associated with HRT include a range of physical side effects. Common side effects include fluid retention, bloating, weight gain, sore breasts, leg cramps, vaginal discharges, migraine headaches, hair loss, nausea and vomiting, acne, depression, shortness of breath, and dizziness. Potentially serious side effects include tissue growths in the uterus (fibroids), gallstones, thrombophlebitis, hypoglycemia, abnormal growth (hyperplasia) of uterine tissue, thyroid disorders, high blood pressure, and cancer.

Long-term risks should be discussed with a woman's physicians before considering hormone replacement therapy. Identified risks for combined (estrogen plus progestin) HRT use include increased incidence of invasive breast cancer, stroke, heart disease, and pulmonary embolism.

Normal results

Normal results of HRT include relief of hot flashes, night sweats, vaginal dryness, and urinary symptoms associated with menopause.

Resources

Books

Goldman, Lee, et al, editors. Cecil Textbook of Medicine. 21st ed. W. B. Saunders, 2000.

Goroll, Alan H. Primary Care Medicine. 4th ed. Lippincott Williams & Wilkins, 2000.

Periodicals

Doering, Paul L. "Treatment of Menopause Post-WHI: What Now?" Drug Topics April 21, 2003: 85.

Elliott, William T. "HRT, Estrogen, and Postmenopausal Women: Year-old WHI Study Continues to Raise Questions." Critical Care Alert July 2003: 1.

Other

Menopausal Hormone Replacement Therapy. Fact sheet. National Cancer Institute. http://rex.nci.nih.gov.

therapy /ther·a·py/ (-pe) the treatment of disease; see also treatment.

ablation therapy the destruction of small areas of myocardial tissue, usually by application of electrical or chemical energy, in the treatment of some tachyarrhythmias.

adjuvant therapy the use of chemotherapy or radiotherapy in addition to surgical resection in the treatment of cancer.

antiplatelet therapy the use of platelet-modifying agents to inhibit platelet adhesion or aggregation and so prevent thrombosis, alter the course of atherosclerosis, or prolong vascular graft patency.

art therapy the use of art, the creative process, and patient response to the products created for the treatment of psychiatric and psychologic conditions and for rehabilitation.

aversion therapy , aversive therapy that using aversive conditioning to reduce or eliminate undesirable behavior or symptoms; sometimes used synonymously with aversive conditioning.

behavior therapy a therapeutic approach that focuses on modifying the patient's observable behavior, rather than on the conflicts and unconscious processes presumed to underlie the behavior.

biological therapy treatment of disease by injection of substances that produce a biological reaction in the organism.

chelation therapy the use of a chelating agent to remove toxic metals from the body, used in the treatment of heavy metal poisoning. In complementary medicine, also used for the treatment of atherosclerosis and other disorders.

cognitive therapy , cognitive-behavioral therapy that based on the theory that emotional problems result from distorted attitudes and ways of thinking that can be corrected, the therapist guiding the patient to do so.

convulsive therapy treatment of mental disorders, primarily depression, by induction of convulsions; now it is virtually always by electric shock (electroconvulsive t.) .

couples therapy marital t.

dance therapy the therapeutic use of movement to further the emotional, social, cognitive, and physical integration of the individual in the treatment of a variety of social, emotional, cognitive, and physical disorders.

electroconvulsive therapy (ECT) a treatment for mental disorders, primarily depression, in which convulsions and loss of consciousness are induced by application of brief pulses of low-voltage alternating current to the brain via scalp electrodes.

electroshock therapy (EST) electroconvulsive t.

endocrine therapy treatment of disease by the use of hormones.

estrogen replacement therapy administration of an estrogen to treat estrogen deficiency, as that following menopause; in women with a uterus, a progestational agent is usually included to prevent endometrial hyperplasia.

enzyme therapy in complementary medicine, the oral administration of proteolytic enzymes to improve immune system function; used for a wide variety of disorders and as adjunctive therapy in cancer treatment.

family therapy group therapy of the members of a family, exploring and improving family relationships and processes and thus the mental health of the collective unit and of individual members.

fibrinolytic therapy the use of fibrinolytic agents (e.g., prourokinase) to lyse thrombi in patients with acute peripheral arterial occlusion, deep venous thrombosis, pulmonary embolism, or acute myocardial infarction.

gene therapy manipulation of the genome of an individual to prevent, mask, or lessen the effects of a genetic disorder.

group therapy psychotherapy carried out regularly with a group of patients under the guidance of a group leader, usually a therapist.

highly active antiretroviral therapy (HAART) the aggressive use of extremely potent antiretroviral agents in the treatment of human immunodeficiency virus infection.

hormonal therapy , hormone therapy endocrine t.

hormone replacement therapy the administration of hormones to correct a deficiency, such as postmenopausal estrogen replacement ttherapy.

immunosuppressive therapy treatment with agents, such as x-rays, corticosteroids, or cytotoxic chemicals, that suppress the immune response to antigen(s); used in conditions such as organ transplantation, autoimmune disease, allergy, multiple myeloma, and chronic nephritis.

inhalation therapy former name for respiratory care (2).

light therapy

1. phototherapy (def. 1).

2. photodynamic t.

marital therapy a type of family therapy aimed at understanding and treating one or both members of a couple in the context of a distressed relationship, but not necessarily addressing the discordant relationship itself; sometimes used more restrictively as a synonym of marriage therapy .

marriage therapy a subset of marital therapy (q.v.) that focuses specifically on the bond of marriage between two people, enhancing and preserving it.

massage therapy the manipulation of the soft tissues of the body for the purpose of normalizing them, thereby enhancing health and healing.

milieu therapy treatment, usually in a psychiatric hospital, that emphasizes the provision of an environment and activities appropriate to the patient's emotional and interpersonal needs.

music therapy the use of music to effect positive changes in the psychological, physical, cognitive, or social functioning of individuals with health or educational problems.

occupational therapy the therapeutic use of self-care, work, and play activities to increase function, enhance development, and prevent disabilities.

oral rehydration therapy (ORT) oral administration of a solution of electrolytes and carbohydrates in the treatment of dehydration.

orthomolecular therapy treatment of disease based on the theory that restoration of optimal concentrations of substances normally present in the body, such as vitamins, trace elements, and amino acids, will effect a cure.

photodynamic therapy intravenous administration of hematoporphyrin derivative, which concentrates selectively in metabolically active tumor tissue, followed by exposure of the tumor tissue to red laser light to produce cytotoxic free radicals that destroy hematoporphyrin-containing tissue.

physical therapy

1. treatment by physical means.

2. the health profession concerned with the promotion of health, the prevention of disability, and the evaluation and rehabilitation of patients disabled by pain, disease, or injury, and with treatment by physical therapeutic measures as opposed to medical, surgical, or radiologic measures.

poetry therapy a form of bibliotherapy in which a selected poem, which may be created by the patient, is used to evoke feelings and responses for discussion in a therapeutic setting.

PUVA therapy a form of photochemotherapy for skin disorders such as psoriasis and vitiligo; oral psoralen administration is followed two hours later by exposure to ultraviolet light.

radiation therapy radiotherapy.

relaxation therapy any of a number of techniques for inducing the relaxation response, used for the reduction of stress; useful in the management of a wide variety of chronic illnesses caused or exacerbated by stress.

replacement therapy

1. treatment to replace deficiencies in body products by administration of natural or synthetic substitutes.

2. treatment that replaces or compensates for a nonfunctioning organ, e.g., hemodialysis.

respiratory therapy see under care.

substitution therapy the administration of a hormone to compensate for glandular deficiency.

thrombolytic therapy fibrinolytic t.

thyroid replacement therapy treatment with a preparation of a thyroid hormone.

hormone replacement therapy

n. Abbr. HRT

The therapeutic administration of estrogen and progesterone, especially to postmenopausal women, to reduce symptoms and signs of estrogen deficiency such as hot flashes and osteoporosis.