Physiologic estradiol replacement following oophorectomy: failure to maintain precastration gonadotropin levels

To determine whether regularly menstruating women retain an intact pituitary sensitivity to estrogen negative feedback following bilateral salpingo-oophorectomy, 6 parous women, aged 31 to 47, reporting regular menstrual cycles were studied following total abdominal hysterectomy and bilateral salpingo-oophorectomy for non-endocrine-related indications. During closure of the incision, a 12.5-mg continuous-release crystalline 17 beta-estradiol pellet was implanted in the subcutaneous tissue. Antecubital venous blood was sampled preoperatively and at 1, 4, and 8 weeks postoperatively and stored frozen (-15C) until assayed for follicle-stimulating hormone (FSH), luteinizing hormone (LH), and 17 beta-estradiol by radioimmunoassay. Despite maintenance of serum estradiol levels in the mid-follicular phase range (40 to 80 pg/ml), the serum concentration of both FSH and LH progressively increased. By the fourth postoperative week, both FSH and LH concentrations had increased significantly (P less than .05). This trend continued and, by 8 weeks after surgery, both gonadotropin levels were in the postmenopausal range. The authors conclude that even when replacement begins immediately following castration, physiologic estradiol at concentrations characteristic of the normal midfollicular phase is not sufficient to maintain suppression of gonadotropins. Whether these observations reflect a change in pituitary sensitivity to 17 beta-estradiol feedback, the removal of nonsteroidal inhibitory substances of gonadal origin, or the lack of an appropriate composite steroidal milieu remains unanswered.