Endocrine consequences of continuous antiestrogen therapy with tamoxifen in premenopausal women.

ABSTRACT

Daily administration of estrogen antagonists to premenopausal women has been incorporated into the adjuvant treatment of breast cancer. We have studied the changes in reproductive hormones, pituitary responses to hypothalamic-releasing hormones, and endometrial histology during treatment with the antiestrogen tamoxifen in five healthy, premenopausal women. These studies were carried out during one menstrual cycle before and during two cycles of antiestrogen treatment. All subjects continued to have regular menses with biphasic basal body temperature records. During treatment, estradiol (E2) levels were increased but followed the usual pattern reflecting follicular maturation and corpus luteum formation. The mean E2 concentration at the midcycle peak and during the luteal phase was twice that observed during the non-treatment cycle. By contrast, the concentrations and secretory patterns of luteinizing hormone and follicle-stimulating hormone were not greatly changed, and the gonadotropin responses to gonadotropin-releasing hormone were not suppressed. Endometrial biopsies obtained during the follicular phase of control and tamoxifen treatment cycles showed no differences whereas biopsies obtained during the luteal phase of tamoxifen cycles uniformly showed a lack of changes attributed to progesterone action with no progression of histologic changes beyond those expected on day 7-8 of the luteal phase. These observations are consistent with maturation of multiple ovarian follicles, a surprising finding considering the normal gonadotropin concentrations. The retarded development of the endometrium in the presence of supranormal serum E2 and progesterone concentrations is a morphologic demonstration of the antiprogestational effect of antiestrogens. The lack of gonadotropin suppression in the presence of hyperestrogenemia suggests a major antiestrogen action on the hypothalmus and pituitary gland.

ABSTRACT

PIP Administration of antiestrogen has recently been incorporated into the management of breast cancer. To explore the endocrine consequences of this therapy 5 healthy premenopausal volunteers were observed and treated with daily administration of the antiestrogen Tamoxifen. During the treatment period all subjects continued to have regular menses and basal body temperature; estradiol (E2) levels increased but followed a regular pattern, and its concentration at midcycle and during the luteal phase were twice as high as during nontreatment. On the other hand, concentrations of LH and of ESH were not greatly changed. In the presence of higher concentrations of E2 and of progesterone the endometrium showed a retarded development, thus demonstrating the antiprogestational effect of Tamoxifen. The lack of gonadotropin suppression also suggests a major antiestrogen action on the hypotalamus and pituitary glands.