Hormone therapy: An option in menopause

You've taken a detailed medical history and determined that hormone therapy is indicated either for short-term changes in the menopausal years or prevention of osteoporosis or heart disease later in life. What's your next move? Robert Rebar, MD, professor and chairman of the department of OB/GYN at the University of Cincinnati College of Medicine suggests the following:

· Give the lowest effective dose that causes the fewest side effects for any given patient.

· Choose a route of administration that is likely to be better for the patient, whether it is continuous combined estrogen/progestin, a transdermal estrogen patch, estrogen vaginal cream, or an estrogen-releasing ring.

· Prescribe the therapy for a limited amount of time, so the patient has to come back and see you. Talk with your patient about the therapy and understand how it affects her life.

· Most important, know that the decision to use hormone therapy is an ongoing process between patients and providers. The process is akin to finding the right birth control method for a woman - more than one or two visits often are required.

"It takes some time, and it takes some visits, and you can't expect to do it in the first visit for everybody," Rebar says of the hormone therapy process. "It's kind of like birth control pills. When we prescribe birth control pills, we ask patients to come back in four to six weeks, and they are told to come back if they have irregular bleeding or amenorrhea. Sometimes it takes two or three preparations before you find the right one for them."

A possible increased risk of breast cancer is one of the primary fears expressed by women who are considering hormone therapy, says Andrew Kaunitz, MD, professor and assistant chair of the department of OB/GYN at the University of Florida Health Sciences Center in Jacksonville.

The Nurses Health Study, One of the largest studies to date, showed that women who used both estrogen-only and combination estrogen/ progesterone therapies faced an increased risk of breast cancer.1 Contradictory results followed in a second, smaller study, which did not find a link between increased breast cancer and current or long-term hormone use.2

"There is a substantial amount of data on this subject, and if hormone therapy dramatically increased breast cancer risk, we would know that by now," Kaunitz says. "We cannot, however, exclude a modest increased risk of being diagnosed with breast cancer; however, there is no reason to believe there is an increased risk from dying of breast cancer. In fact, most of the existing studies show that there's a decreased risk, which probably reflects more surveillance of women on HRT [hormone replacement therapy] than other women."3

Consider these studies

Three studies published in 1997 offered further insights into the benefits of hormone therapy:

· Women who take estrogen for years after menopause appear to cut their risk of death from all causes by 37%. Partly due to breast cancer, however, the life-preserving benefits of estrogen appear to wane after a decade.4

· A decision-making model shows that even among women at risk for breast cancer, the presence of even one risk factor for coronary heart disease indicates HRT use.5

· Women who use hormone therapy reduce their risk for Alzheimer's dementia by 54%.6 (See the September 1997 Contraceptive Technology Update, p. 105, for a review of these studies.)

For women who have a uterus, combination hormone therapy delivers estrogen benefits, while progesterone/progestin protects against endometrial cancer. Wyeth-Ayerst of Philadelphia manufactures two estrogen/progestin combinations: Prempro and Premphase. The U.S. Food and Drug Administration recently approved an increased dosage of Prempro: 5 mg of medroxyprogesterone acetate with 0.625 mg conjugated estrogens.

Prescription oral estrogens include micronized estradiol (Estrace, Mead Johnson, Raritan, NJ), esterified estrogens (Estratab, Solvay, Marietta, GA), quinestrol (Estrovis, Parke-Davis, Morris Plains, NJ), estropipate (Ogen, Abbott, Abbott Park, IL), Ortho-EST (Ortho, Raritan, NJ), and conjugated equine estrogens (Premarin, Wyeth-Ayerst).

Transdermal patches deliver estradiol and can lessen moderate to severe vasomotor symptoms with a low estrogen dose. FemPatch from Parke-Davis is the most recent addition to this category, which includes Climara (Berlex, Wayne, NJ), Estra derm, and Vivelle (both Ciba-Geigy, Summit, NJ).

Vaginal preparations, such as creams and the Estring vaginal ring (introduced in 1997 by Pharmacia and Upjohn, Kalamazoo, MI) are indicated for specific treatment of urogenital atrophy. Since the effects are localized, vaginal estrogen therapy does not help with hot flashes or prevent osteoporosis or heart disease.7

Although one-dose combination hormone drugs offer a simple dosing regimen, clinicians may need to tailor a combination of estrogen and progesterone/progestin to best fit the individual patient's needs. Prescription progesterones/progestins include medroxyprogesterone acetate (Carnick, Cedar Knolls, NJ; Cycrin, Wyeth-Ayerst; Provera, Pharmacia and Upjohn), norethin drone acetate (Aygestin, Lederle), and megesterol (Megace, Bristol-Myers, New York City). Combination therapy can be administered cyclically, in which progestin is added for a period of time during the month, then removed, or both hormones can be given continuously, with a lower dose of progestin.

The status of current progesterone/progestin options in the United States poses a problem, observes Willa Brown, MD, director of personal health at Howard County Health Department in Columbia, MD.

"I don't know why pharmaceutical companies are not working to make different combinations of estrogens and progestins available in convenient packaging for hormone replacement therapy in this country," she says. "It requires persistence to find a regimen that a woman can stay on and have the many benefits of hormone therapy."

Two forms of progesterone, a progesterone vaginal cream and oral micronized progesterone, are under FDA consideration and may be in the marketplace soon, Rebar says. Both preparations may help clinicians manage the mood swings that come from the progesterone/progestin, he says.

References

1. Colditz GA, Hankinson SE, Hunter DJ, et al. The use of estrogens and progestins and the risk of breast cancer in postmenopausal women. NEJM 1995; 332:1,589-1,593.

2. Stanford JL, Weiss NS, Voigt LF, et al. Combined estrogen and progestin hormone replacement therapy in relation to risk of breast cancer in middle-aged women. JAMA 1995; 274:137-142.

3. Bergkvist L, Adami HO, Persson I, et al. Prognosis after breast cancer diagnosis in women exposed to estrogen and estrogen-progestogen replacement therapy. Am J Epidemiol 1989; 130:221-228.

4. Grodstein F, Stampfer MJ, Colditz, GA, et al. Postmenopausal Hormone Therapy and Mortality. NEJM 1997; 336:1,769-1,775.

5. Col NF, Eckman MH, Karas RH, et al. Patient-specific decisions about hormone replacement therapy in postmenopausal women. JAMA 1997; 277:1,140-1,147.

6. Kawas C, Resnick S, Morrison A, et al. A prospective study of estrogen replacement therapy and the risk of developing Alzheimer's disease: the Baltimore Longitudinal Study of Aging. Neurology 48:1,517-1,521.

7. North American Menopause Society. Menopause Basics. Cleveland: 1997.