Estrogenic Therapy by Implantation of Stilbestrol Pellets

Abstract

The new synthetic estrogen, diethylstilbestrol (4:4-dihydroxy-alpha:beta-diethyl stilbene), announced by Dodds and coworkers, 1 has been found capable of producing in animals all the effects previously obtained with naturally occurring estrogens. Early reports indicated that it would be clinically useful when we began studies upon patients in March, 1939. We found in 41 patients (14 complete castrates, 7 partial castrates, 5 patients with primary eunuch-oidism and amenorrhea, and 15 patients with severe symptoms of the spontaneous menopause), that relief of the nervous and vasomotor symptoms, estrous changes in the vaginal smears, proliferative endo-metrial changes and breast growth could be produced by oral or subcutaneous administration of 1 mg to 5 mg daily of diethylstilbestrol dipropionate. An analysis of these studies is to be published elsewhere.

To determine whether subcutaneous pellet implantation would be effective, hard pellets of diethylstilbestrol dipropionate weighing approximately 100 mg each were implanted in 6 women who had had both ovaries removed. The sterile pellets were inserted through a small subcutaneous incision in the lumbar region and the wound closed with a stitch. Within 2 days the castrate type vaginal smears showed estrous changes and within 7 to 10 days this response was marked. Endometrial biopsies showed active proliferation within 7 days. The menopausal symptoms, both psychic and vasomotor, were greatly relieved. These changes persisted as long as the pellets remained in place. Symptoms recurred within about 2 weeks in 3 cases when pellets were removed and not replaced.

The pellets were extracted and weighed at intervals and the average daily absorption calculated by the weight loss. Pellets have been removed after periods varying from 27 to 53 days. Average daily absorption per pellet has ranged from 0.127 to 0.250 mg, corresponding to a dose of 2,540 to 5,000 international (estrone) units daily.