Abstract

PIP: Studies of the physiology of gonadotropin-releasing hormone (GnRH), undertaken at the Reproductive Unit, Vincent Research Laboratories, Massachusetts General Hospital, have involved a careful examination of normal subjects to establish a range of frequencies and amplitudes of gonadotropin secretion which would appropriately define the normal. From this normative data base, clinically identifiable reproductive disorders have been examined in a similar fashion, and a biochemical definition of these disorders as an end result of aberrant GnRH secretion has been realized in some instances. Use also has been made of individuals who appear to lack any measurable evidence of pulsatile GnRH secretion as an ablation replacement "experiment of nature." The data of studies of male physiology investigated in 20 normal men agreed with previous reports of pulsatile gonadotropin secretion in normal men except for the large range of variability which was found in this population. The range of frequencies of luteinizing hormone (LH) pulsations/24 hours study varied from as low as 7 to as high as 17 pulses in these subjects with normal gonads. This lower limit of frequency abuts upon the abnormal population of hypogonadotrophic males. Additional subjects were observed who displayed consistently low amplitudes of their LH pulsations which were evident on repeat study, yet all of these subjects continued to meet the entrance requirements and were normally virilized. This observation has expanded understanding of the range of normal gonadotropin secretion in men. 40 men with idiopathic hypogonadotrophic hypogonadism (IHH) were examined. Exogenous replacement of GnRH in these deficient individuals was accomplished by means of a portable infusion pump. The IHH subjects appeared to undergo a normal puberty while on exogenous GnRH replacement. Studies of female physiology were begun by observing 39 menstrual cycles in 62 women identified at 6 stages of the normal menstrual cycle. The patterns of gonadotropin secretion varied considerably across the normal menstrual cycle. The nature of GnRH secretion was examined in women with both primary (IHH) and secondary "hypothalamic" amenorrhea. 51 studies have been performed thus far on 40 women. All but 1 of the women with IHH displayed an apulsatile pattern of gonadotropin secretion. Several subjects with secondary amenorrhea also exhibited an apulsatile pattern of gonadotropin secretion. The female gonad was responsive to a precise program of GnRH stimulation which may deviate only minimally without loss of reproduction function. Such disordered patterns of GnRH secretion serve to define the limits of normal and abnormal function.