REPRODUCTIVE ENDOCRINE AND ENDOMETRIAL EFFECTS OF RALOXIFENE HYDROCHLORIDE, A SELECTIVE ESTROGEN-RECEPTOR MODULATOR, IN WOMEN WITH REGULAR MENSTRUAL CYCLES
Vl. Baker et al., REPRODUCTIVE ENDOCRINE AND ENDOMETRIAL EFFECTS OF RALOXIFENE HYDROCHLORIDE, A SELECTIVE ESTROGEN-RECEPTOR MODULATOR, IN WOMEN WITH REGULAR MENSTRUAL CYCLES, The Journal of clinical endocrinology and metabolism, 83(1), 1998, pp. 6-13
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.