A positive effect of GH treatment on CVD and fracture risk could be concluded , but study design limitations have to be considered .
Stroke and secondary brain tumours remained more prevalent .
Regrowth and recurrences of (peri)pituitary tumours were not increased in patients with GH treatment compared to similar patients without GH treatment .
All fatal and nonfatal malignancies were not more prevalent in  GH-treated adults compared to the general population .
Due to the positive effects demonstrated in r and omized clinical trials on cardiovascular surrogate markers and bone metabolism , a positive effect of growth hormone ( GH ) treatment on clinical ly relevant end-points seems feasible .
In this review , we discuss the long-term efficacy and safety of GH treatment in adult patients with growth hormone deficiency ( GHD ) with emphasis on morbidity : fatal and nonfatal cardiovascular disease ( CVD ) and stroke , fractures , fatal and nonfatal malignancies and recurrences , and diabetes mellitus .
Fifteen years of GH replacement increases bone mineral density in hypopituitary patients with adult-onset GH deficiency
Objective Few studies have determined the effects of more than 5–10 years of GH replacement  in adults on bone mineral content ( BMC ) and bone mineral density ( BMD ) . Design / patients In this prospect i ve , single-centre , open-label study , the effects of 15 years of GH replacement on BMC and BMD , measured using dual-energy X-ray absorptiometry , were determined in 126 hypopituitary adults ( 72 men ) with adult-onset GH deficiency ( GHD ) . Mean age was 49.4 ( range 22–74 ) years at the initiation of the study . Results The mean initial GH dose of 0.63 ( s.e.m . 0.03 ) mg/day was gradually lowered to 0.41 ( 0.01 ) mg/day after 15 years . The mean serum IGF1 SDS increased from −1.69 ( 0.11 ) at baseline to 0.63 ( 0.16 ) at the study end ( P<0.001 vs baseline ) . The 15 years of GH replacement induced a sustained increase in total body BMC ( + 5 % , P<0.001 ) and BMD ( + 2 % , P<0.001 ) . Lumbar ( L2–L4 ) spine BMC increased by 9 % ( P<0.001 ) and BMD by 5 % ( P<0.001 ) . In femur neck , a peak increase in BMC and BMD of 7 and 3 % , respectively , was observed after 7 years ( both P<0.001 ) . After 15 years , femur neck BMC was 5 % above the baseline value ( P<0.01 ) , whereas femur neck BMD had returned to the baseline level . In most variables , men had a more marked response to GH replacement than women . Conclusions Fifteen-year GH replacement in GHD adults induced a sustained increase in total body and lumbar ( L2–L4 ) spine BMC and BMD . In femur neck , BMC and BMD peaked at 7 years and then decreased towards baseline values
A positive effect of GH treatment on CVD and fracture risk could be concluded , but study design limitations have to be considered .
Stroke and secondary brain tumours remained more prevalent .
Regrowth and recurrences of (peri)pituitary tumours were not increased in patients with GH treatment compared to similar patients without GH treatment .
All fatal and nonfatal malignancies were not more prevalent in  GH-treated adults compared to the general population .
Due to the positive effects demonstrated in r and omized clinical trials on cardiovascular surrogate markers and bone metabolism , a positive effect of growth hormone ( GH ) treatment on clinical ly relevant end-points seems feasible .
In this review , we discuss the long-term efficacy and safety of GH treatment in adult patients with growth hormone deficiency ( GHD ) with emphasis on morbidity : fatal and nonfatal cardiovascular disease ( CVD ) and stroke , fractures , fatal and nonfatal malignancies and recurrences , and diabetes mellitus .