The effects of treatment and the individual responsiveness to growth hormone (GH) replacement therapy in 665 GH-deficient adults

Data from 665 adults with GH deficiency (GHD; 332 women; 169 childhood-onse t GHD; mean age, 44 yr) were analyzed to determine the efficacy of and indi vidual responsiveness to GH replacement therapy. GH replacement was started at enrolment into KIMS (Pharmacia & Upjohn, Inc. International Metabolic D atabase). Mean maintenance doses of GH after 6 and 12 months were 0.43 and 0.53 mg/day (1.3 and 1.6 IU/day) for men and women, respectively. Serum ins ulin-like growth factor I (IGF-I) sn score increased from -2.2 and -4.2 in men and women, respectively, to 1.8 and -0.9 at 6 months and 0.8 and -0.7 a t 12 months. The waist/hip ratio decreased after 6 and 12 months, with the changes more pronounced in men. The waist/hip ratio was not influenced by a ge of onset of GHD, severity of hypopituitarism, or gonadal status. Total c holesterol decreased significantly in men, and high density lipoprotein cho lesterol increased in women. Systolic blood pressure was unchanged during G H therapy, but diastolic blood pressure decreased in women. Quality of life , determined by a specific questionnaire for assessment of GHD in adults, i mproved after 6 and 12 months of GH therapy; this was more pronounced in ad ult-onset than in childhood-onset GHD, but was not influenced by gender, se verity of hypopituitarism, or gonadal status. In 80% of patients, the start ing dose of GH was 0.27 mg/day or less. This and the absence of a correlati on between body weight and change in IGF-I were consistent with a dose-titr ation approach, which would tend to obscure individual variations in respon ses (determined by IGF-I levels). Nonetheless, the increase in IGF-I was si gnificantly higher in men than in women on similar mean GH doses. Weak corr elations were observed between the maintenance dose of GH and the change in IGF-I in men and women receiving sex steroid replacement, but not in patie nts with untreated hypogonadism or an intact gonadotropin reserve. Similarl y, the increment in IGF-I was not related to the severity of GHD, as determ ined by the number of additional pituitary hormone deficiencies. Difference s in IGF-I generation may partly explain the gender differences in reductio n of central adiposity. These data highlight the value of large longitudina l surveillance databases in defining the optimum dose regimen for GH replac ement and indicate that women may need a higher replacement dose of GH than men.