REPRODUCTIVE ENDOCRINE AND ENDOMETRIAL EFFECTS OF RALOXIFENE HYDROCHLORIDE, A SELECTIVE ESTROGEN-RECEPTOR MODULATOR, IN WOMEN WITH REGULAR MENSTRUAL CYCLES

Previous studies of raloxifene conducted in animal models and postmeno pausal women have demonstrated antiestrogenic action on the endometriu m. The purpose of this first study of raloxifene in women with normal menstrual cycles was to determine its reproductive endocrine and endom etrial effects. In part I, raloxifene (400 mg) was administered for 5 days in the follicular, periovulatory, or luteal phase of the menstrua l cycle (n = 12). In part II, women were randomized to receive raloxif ene (100 or 200 mg) for 28 days beginning on day 3 of the cycle (n = 1 9). All women ovulated in both parts of the study. Raloxifene did not alter the length of the menstrual cycle or the day of the LH surge. A 5-day course of raloxifene administered in any phase of the cycle elev ated FSK area under the curve (AUC) for the entire cycle and estradiol AUC for the second half of the cycle compared with those in control c ycles. In part II, raloxifene also appeared to increase the FSH AUC an d estradiol AUC. Raloxifene decreased the number of gland mitoses in f ollicular phase endometrial biopsies. Subtle effects suggestive of gla nd-stromal dysynchrony were noted in a limited number of the secretory phase endometrial biopsies. This study has demonstrated that 1) ralox ifene does not prevent ovulation in women with normal menstrual cycles ; 2) ovarian estrogen production will continue, and in some cases incr ease, in response to raloxifene; and 3) antiestrogenic effects of ralo xifene on the endometrium are subtle in the endocrine milieu of normal to high circulating estradiol concentrations.