Designer Estrogens - Are They for Me?

Frederick R. Jelovsek MD

New categories of drugs have recently become available for the prevention of osteoporosis without all of the uterine and breast tissue stimulation effects of normal postmenopausal estrogen replacement therapy (ERT). These new drugs, selective estrogen receptor modulators (SERMs), are important for women because a woman's lifetime relative risk of hip fracture is equal to the development of breast, uterine and ovarian cancer combined. Also, only 20 to 30% of women who are prescribed ERT remain on it for over a year. The biggest reason they stop it is because of irregular uterine bleeding and because of the side effects from the progestin therapy needed to counteract the endometrial effect of estrogen alone. The biggest reason women never start on ERT or never fill their prescriptions is fear of breast cancer.

A recent review article, Goldstein SR: Selective estrogen receptor modulators: A new category of therapeutic agents for extending the health of postmenopausal women. Am J Obstet Gynecol 1998;179:1479- 84. has given us the material to answer some questions that women have about ERT.

If I need estrogen for the control of hot flashes and vaginal dryness, will any of the new medications help that without increasing my risk for breast cancer?

No. In general these specialized estrogens either make hot flashes worse (tamoxifen) or no real improvement (raloxifene). Neither of them help with vaginal dryness either, so lubrication or topical estrogens may be needed for this problem.

If I have a family history of heart disease, which medications are best for me?

Right now, only estrogen (conjugated estrogens, estradiol) has been studied and shown to decrease the new occurrence of heart disease. If you already have heart disease, estrogens may be associated with more adverse events when treatment is first started. Tamoxifen and raloxifene (Evista®) both lower total cholesterol and low density lipoproteins, but they do not increase the good cholesterol, high density lipoproteins. We do not know yet if they will prevent the new occurrence of heart disease. It is unlikely, however, they will cause heart disease.

Can I prevent osteoporosis and heart problems without increasing my risk for breast cancer or uterine cancer?

Raloxifene (Evista®) does not cause tissue proliferation in either the breast or the uterus as opposed to tamoxifen which seems to prevent breast cancer but causes endometrial cancer in up to 4% of women on long term use. They both help prevent osteoporosis.

If I already have osteoporosis can I use these new drugs?

These compounds prevent osteoporosis but the data is not yet in on treatment of osteoporosis. Right now either estrogens or the bisphosphonate, Fosamax® are recommended for osteoporosis treatment. If the side effects of the Fosamax® (stomach upset) are too great or estrogens are contraindicated, raloxifene (Evista®) should be a good substitute.

What are the side effects I can expect from the new selective estrogens?

Raloxifene may cause some leg cramps, but it also has a lower incidence of breast pain and abnormal uterine bleeding compared to estrogen and progestin hormone replacement therapy. If a woman is on tamoxifen for breast cancer, besides endometrial cancer, hot flashes get worse and polyps and hyperplasia of the endometrium can cause abnormal bleeding.

Which osteoporosis preventatives affect what?

Effects of osteoporosis preventatives