Growth hormone administration normalizes the ovarian responsiveness to follicle-stimulating-hormone in the early stages of the follicular maturation in women with Down Syndrome

To investigate the sensitivity of ovary to follicle-stimulating hormone (FSH) during the early follicular phase of the human menstrual cycle in patients with Down Syndrome (DS) six postmenarchal patients with Down Syndrome and twelve normoovulatory women were studied. Randomly, DS patients were submitted in two consecutive cycles to a treatment with GH (0.1 IU/Kg i.m.) or saline for 3 days. Pure FSH (75 IU) was given i.v. at day 3 and plasma levels of LH, FSH, E2, Testosterone, DHEAS, Androstenedione, GH and IGF-I were assayed in samples collected for a period of 26 h after the injection. Data were compared with those obtained from controls receiving pure FSH or saline. In control patients FSH injection increased E2 stimulated area under curve (AUC). This value was significantly greater than that found in DS patients, who exhibited an E2-stimulated AUC superimposable to saline treated controls. In DS GH plasma concentrations were significantly lower than in control group (p < 0.05). The treatment with GH is able to normalize the ovarian response to FSH in DS patients at levels similar to those found in FSH treated controls. Moreover in GH treated cycles, both GH and IGF-I plasma concentrations were higher at time of FSH injection with respect to those found in the cycles where saline was given. These results indicate that the ovarian sensitivity to FSH in patients with DS is blunted. Lower GH plasma levels found in this group may in part account for this biological feature, since GH treatment is able to restore the ovarian response, probably via an increase of IGF-I plasma concentrations.