What is hormone therapy? |

Indications and Procedures

During a woman’s reproductive years, a complex feedback loop among the hypothalamus, pituitary gland, and ovaries causes the ovaries to produce various sex hormones, the major ones being estrogens and progesterone. These hormones are responsible for developing the secondary sexual characteristics such as breasts and pubic hair, for governing the menstrual cycle, and for maintaining a pregnancy should one occur. They also have profound effects on a woman’s skin, heart, blood vessels, lipids (blood fats such as cholesterol), bones, blood, and other systems.

As women approach menopause, changes begin to occur in the hormone feedback loop. The menstrual cycle typically becomes shorter and more irregular, and then menses cease altogether. As hormone levels decline and the ratio between the estrogens and progesterone changes, the woman’s body undergoes other changes such as thinning of the mucous membranes in the reproductive and urinary tract, drying of the skin, thinning of the bones, and alterations in cholesterol levels. Perimenopausal women may also experience hot flashes, night sweats, insomnia, mood swings, and other uncomfortable symptoms. Postmenopausal women do continue to produce sex hormones, although in smaller amounts. The adrenal glands are responsible for much of the postmenopausal hormone production, and some production occurs by conversion of other hormones in the body tissues.

Menopause normally occurs between the ages of forty-five and fifty-five, with an average age of about fifty-one. Menopause before the age of forty is called "premature menopause." A woman who stops menstruating because of a total hysterectomy, in which not only the uterus but also the Fallopian tubes and ovaries are removed, undergoes what is called a "surgical menopause." Women who undergo radiation of the ovaries also experience an artificial menopause. The discomforts associated with menopause may be exaggerated in these women.

Health care providers have used hormone therapy, formerly called "hormone replacement therapy (HRT)," to treat uncomfortable perimenopausal symptoms and to prevent or treat a number of conditions associated with the postmenopausal state. Hormone therapy may include estrogen alone or a combination of estrogen and progesterone. At times, other hormones such as testosterone may be used to treat symptoms, but it is the estrogen-progesterone combination that constitutes what is commonly thought of as hormone therapy. Estrogen therapy is the use of estrogen alone and was formerly known as "estrogen replacement therapy (ERT)."

Hormone therapy may also be prescribed to manage conditions that cause menorrhagia (heavy menstrual bleeding), such as uterine fibroids (noncancerous growths in the uterus), endometriosis (monthly growth of the uterine lining tissue outside the uterus), and ovarian cysts. The long-term risks and contraindications are similar to those for perimenopausal and menopausal women.

Uses and Complications

A variety of estrogens and progestogens are available for the treatment of menopausal symptoms. They include oral estrogens and progestin, transdermal estrogens, injectable estrogens and progestins, and topical estrogens. Oral estrogens for hormone therapy include conjugated estrogens, micronized estradiol, piperazine estrone sulfate, ethinyl estradiol, and quinestrol. Of these, the conjugated equine estrogens have been most extensively studied over a long period of time. They are usually well tolerated by patients. Various estrogens are also available as transdermal patches, inhalable sprays, or vaginal creams or rings. Various combination products are available to administer estrogen with a progestin, including oral and transdermal formulations. Progesterone may be supplied by oral progestins, oral progesterone, topical vaginal preparations, subdermal implants, and levonorgestrel-containing IUDs.

In the 1990s, clinicians provided hormone therapy (then called "hormone replacement therapy") to prevent osteoporosis and heart attacks; the hormone therapy relieved vaginal dryness and hot flashes as well. It was thought that hormone therapy would also provide a number of other benefits for conditions ranging from mood swings to insomnia to prevention of Alzheimer’s disease. At various times throughout the twentieth century, health care providers and researchers recommended that all women in perimenopause begin hormone therapy.

In 1998, results from a large clinical trial, the HERS study (Heart and Estrogen/Progestin Replacement Study), which enrolled women with existing heart disease, demonstrated an unanticipated increase in heart attacks for women in the first year of medication; furthermore, there was no cardiac benefit in the years to follow. In 2002, the Women’s Health Initiative (WHI) published groundbreaking results of a large study of women on estrogen and progestin; the trial was ended early because of safety concerns. Findings included blood clots and an increased risk for breast cancer, but a decrease in colon
cancer and osteoporotic fractures. Researchers concluded that the risks of taking the medications were not worth the benefits.

A subsequent study of estrogen alone was stopped early because of a small increase in stroke risk. Research has also shown that women using estrogen-only treatments are at higher risk of developing coronary heart disease. Major medical organizations now recommend that hormone therapy should be used only in the smallest effective dose, for the shortest effective period of time, and only for relief of severe symptoms, primarily hot flashes. Hormone therapy should not be used only to prevent osteoporosis.

Women who take estrogen supplementation without a progestogen are at increased risk for developing excessive thickening of the lining of the uterus. This situation can ultimately result in carcinoma (cancer) of the uterus. The development of ovarian cancer is also possible. For this reason, women who have not had a hysterectomy are advised to take only estrogen with concomitant provision of progestogens. If the combination is given on a cyclical basis, however, the woman will most likely experience monthly withdrawal bleeding. This is not always acceptable to postmenopausal women. Most women who take a continuous dose of a lower-dose progestogen will not bleed at all after a year of its continuous use; the remainder will bleed occasionally.

Women who take oral estrogen supplements have an increased tendency to develop blood clots. This risk is greatly decreased with transdermal formulations. Estrogen therapy is also associated with an increased risk of gallbladder disease.

Women who should not take estrogen-containing hormones at all include those with unexplained vaginal bleeding, a history of uterine or breast cancer, liver disease, or a history of blood clots in the veins. Hormone therapy should be used with caution in women with seizure disorders, high blood pressure, diabetes mellitus, migraines, gallbladder disease, and certain other conditions. Minor adverse effects of hormone treatment include swelling, breast tenderness, bloating, headaches, and increased cervical mucus.

As the supply of estrogen decreases, women experience thinning and drying of the vaginal tissues. The cervix, uterus, and ovaries become smaller in size, and the cervix stops producing mucus. In addition, the ligaments that support the reproductive organs become more relaxed. These changes may lead to painful sexual intercourse, bleeding with minor trauma, itching, vaginal discharge, and prolapse of the uterus. Topical vaginal formulations, rather than oral, systemic medications, are recommended if only vaginal thinning and dryness are indicated, .

The tissues of the bladder and urethra also become thinner, which may lead to urinary urgency, painful urination, or increased frequency. Some women even become incontinent. The evidence is not entirely clear about the usefulness of estrogen in this setting.

Vasomotor instability refers to the changes that lead to hot flashes and increased sweating. These flashes may be accompanied by heart palpitations, weakness, fatigue, dizziness, or lightheadedness. The episodes may cause nighttime awakening or insomnia, which in turn may lead to memory problems or irritability. The major treatment for vasomotor instability is the administration of estrogen, although progestogens have been used in women who cannot take estrogen. Some women find relief from a different type of drug called clonidine. Other treatments, which have not been studied as thoroughly as estrogen and progesterone, include various vitamin and mineral supplements, tranquilizers, and antidepressants.

All people gradually lose bone mass as they age, but in the years following menopause, this process accelerates in women, particularly in the type of bone known as "trabecular bone." Postmenopausal women’s risk for hip fracture becomes two to three times that of men. For this reason, estrogen has been recommended in the past for prevention of osteoporosis, particularly in women who are thin, who smoke cigarettes, who have a strong family history of osteoporosis, who drink large amounts of alcohol, or who have some other risk factor. With concerns about the safety of estrogens, however, other drugs are increasingly used to prevent or treat osteoporosis, including drugs from the classes known as bisphosphonates and selective estrogen receptor modulators (SERMs). Calcitonin and progestogens may also be used, but they do not seem to be as effective as the estrogens, bisphosphonates, or SERMs. All menopausal women should probably take supplemental calcium and vitamin D, exercise regularly, stop smoking if needed, and limit alcohol, caffeine, salt, and animal proteins to minimize their risk of developing osteoporosis.

Before menopause, very few women have heart attacks. This state changes rapidly after menopause, and by age seventy, women have the same risk of heart attack as men. However, major medical organizations have recommended that combination therapy not be used for the prevention of cardiac disease.

As people age, they experience changes in the skin and hair.
The skin becomes thinner and less elastic, particularly in sun-exposed areas. There is some loss of pubic hair and hair in the armpits. Some women experience balding, and some develop coarse facial hair. Body hair may either increase or decrease. The skin has estrogen receptors, so those changes are thought to be caused by decreased estrogen. Hair changes are more likely to result from a change in the ratio of estrogen to testosterone in the body after menopause. Testosterone levels remain nearly the same before and after menopause, while estrogen levels drop drastically. Topical hormones have been used to ameliorate or prevent skin changes, especially vaginal atrophy and dryness; however, use of systemic hormones is not supported for these indications.

Some studies have found that women in early menopause experience more irritability, depression, and feelings of anxiety. It is not clear if these changes are attributable to some change in brain chemistry as a result of decreased estrogen, to societal expectations about aging, or to some other factor. Some researchers have suggested that the lack of sleep caused by hot flashes and night sweats, rather than menopause itself, is the source of mood changes. Furthermore, many perimenopausal women have multiple stressors, such as caring for aging parents, which may contribute to depression and anxiety. In contrast to past practice, current evidence does not support the use of hormone therapy for depression or prevention of Alzheimer’s disease and other dementias.

In summary, the only indication for systemic hormone administration is for severe menopausal symptoms at the lowest possible dose for the shortest period of time; those with abnormal bleeding conditions should discuss the long-term risks of hormone therapy with their clinicians. Topical preparations may be used for indications such as vaginal dryness or discomfort.

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