Faculty Bibliography

Tamoxifen was approved for breast cancer prevention in October 1998. Thus, for the first time, we as gynecologists are being asked to prescribe this drug to healthy women. In the past each one of us has cared for women with breast cancer who have been treated with tamoxifen by oncologists or breast surgeons for the malignancy. Effects of tamoxifen on the uterus resulting in carcinomas, hyperplasia, and polyps are well known. Furthermore, tamoxifen has estrogenic properties in the venous system, increasing the incidence of deep vein thrombosis and pulmonary emboli. A new SERM (selective estrogen receptor modulator), raloxifene, has been approved for prevention and treatment of osteoporosis in postmenopausal women. It does not have stimulatory effects on the endometrium; however, it is estrogenic in the venous system. Preclinical data, as well as the breast cancer incidence reported in studies of the skeleton, seem to indicate that its effects in the breast are similar to those of tamoxifen. This article reviews tamoxifen and the new SERM, raloxifene, in an attempt to help gynecologists better understand each compound and what data are currently known, what we hope to learn from future studies, and what currently makes sense for clinical practice

OBJECTIVE: To determine the effects of a selective estrogen receptor modulator, raloxifene, on postmenopausal endometrium. METHODS: Healthy postmenopausal women (n = 415) were randomly assigned to one of the following four groups: 60 or 150 mg/day raloxifene hydrochloride, 0.625 mg/day conjugated equine estrogens, or placebo, and treated for 1 year. Endometrial biopsies were obtained in a blinded fashion at baseline and every 6 months after the ultrasound studies. Transvaginal ultrasound, with uterine size measurements, was done at baseline and at 3-month intervals. Saline-infusion sonohysterography was done at baseline and every 6 months. RESULTS: There were no statistically significant differences in baseline characteristics. Mean endometrial thickness, measured by transvaginal ultrasound, was unchanged from baseline to end point in the placebo and raloxifene groups, whereas in the estrogen group it was significantly thicker by 5.5 mm (P < .001). Mean uterine volume, calculated from transvaginal ultrasound measurements, was higher in the estrogen group only (22 cm3, P < .001). Of the 358 women with paired biopsies, endometrial hyperplasia was present in 2.1%, 0%, and 26.1% of the end-point biopsies in the placebo, raloxifene, and estrogen groups, respectively (P < .001). Proliferative endometrium was present in 2.1% of the end-point biopsies in the placebo group, 1.7% in the combined raloxifene groups, and 39.8% in the estrogen group (P < .001). CONCLUSION: Raloxifene, at 60 or 150 mg/day for 1 year, did not stimulate the postmenopausal endometrium. End-point endometrial thickness, morphology, and uterine volume in the raloxifene groups were similar to those observed at baseline and in the placebo group

Selective estrogen receptor modulators (SERMs) are a new category of therapeutic agents, which bind with high affinity to estrogen receptors and mimic the effect of estrogens in some tissues but act as estrogen antagonists in others. Tamoxifen, a triphenylethylene derivative, was the first clinically available SERM. It is a potent anti-estrogen in the breast, and its use in breast cancer patients has made it the most widely prescribed antineoplastic drug worldwide. It has estrogen-like activity on bone metabolism, as well as cholesterol reduction. However, its ability to produce proliferation, and polyp formation, and even carcinomas, in the endometrium is well known. A new SERM, raloxifene, a benzothiopene derivative, has a clinical profile similar to tamoxifen's. However, preclinical as well as clinical studies reveal that unlike tamoxifen it is a pure anti-estrogen in the uterus. It has recently been FDA approved for prevention of osteoporosis in postmenopausal women. This report reviews pertinent preclinical and currently available clinical studies about this new SERM and discusses clinical applicability

Selective estrogen receptor modulators are a new category of therapeutic agents that bind with high affinity to estrogen receptors and mimic the effect of estrogens in some tissues but act as estrogen antagonists in others. Tamoxifen, a triphenylethylene derivative, was the first clinically available selective estrogen receptor modulator. It is a potent antiestrogen in the breast, and its use in breast cancer patients has made it the most prescribed antineoplastic drug worldwide. It has estrogen-like activity on bone metabolism, and it also reduces cholesterol. However, its ability to produce proliferation, polyp formation, and even carcinomas in the endometrium is well known. A new selective estrogen receptor modulator, raloxifene, a benzothiopene derivative, has a clinical profile similar to that of tamoxifen. However, both preclinical and clinical studies reveal that, unlike tamoxifen, it is a pure antiestrogen in the uterus. It has recently been approved by the Food and Drug Administration for prevention of osteoporosis in postmenopausal women. This report reviews pertinent preclinical and currently available clinical studies about this new selective estrogen receptor modulator and discusses clinical applicability