Impact of 5 years of growth hormone replacement therapy on cardiovascular risk factors in growth hormone–deficient adults

Background: The beneficial effects of recombinant human GH (rhGH) therapy in GH deficient (GHD) adults are well-established in the short term. However, data documenting the effects during prolonged follow-up are relatively scarce. Objective: To evaluate the reported effects of rhGH replacement (R5 years) in GHD adults on biochemical and anthropometric parameters, quality of life (QoL), bone metabolism, muscle strength, serious adverse events and mortality. Methods: We conducted a systematic literature search. Quality assessment of retrieved papers was performed using a quality assessment based on the modified STROBE statement. Results: We included 23 prospective studies with a rhGH treatment duration ranging from 5 to 15 years. Overall, beneficial effects were reported on QoL, body composition, lipid profile, carotid intima media thickness and bone mineral density. In contrast, the prevalence of the metabolic syndrome, glucose levels, BMI and muscle strength were not, or negatively, influenced. Most of the studies were uncontrolled, lacked the presence of a control group (of non-treated GHD patients), and reported no data on lipid-lowering and anti-diabetic medication. Overall mortality was not increased. Conclusion: rhGH treatment in adult GHD patients is well-tolerated and positively affects QoL in the long term. However, the metabolic and cardiovascular effects during long-term treatment are variable. The low numbers of long-term studies and studied patients and lack of control data hamper definite statements on the efficacy of prolonged treatment. Therefore continuous monitoring of the effects of rhGH replacement to enable an adequate risk-benefit analysis that may justify prolonged, potentially life-long, treatment is advisable.

Section: Endocrine Evaluationmentioning

confidence: 99%

“…Two studies scored intermediate (18,19), 15 studies were good quality (4,5,6,9,11,15,18,20,21,22,23,24,25,26,27) and six studies had an excellent methodological quality (7,10,13,15,16,28) (Table 1). Mean quality score was 7.3 (range 5.0-9.0), indicating that overall methodological quality was good.…”

Section: Quality Assessmentmentioning

confidence: 99%

Therapy of Endocrine disease: Long-term effects of recombinant human GH replacement in adults with GH deficiency: a systematic review

Appelman‐Dijkstra

Claessen

Roelfsema

et al. 2013

“…In addition, several studies have demonstrated that adult GHD patients have lower bone mass, increased fracture risk, and impaired quality of life (QoL) (3,4). Recombinant human growth hormone (rhGh) replacement therapy has shown to improve lipid profile, body composition, and QoL, to increase bone mass, and is available for adult patients with GHD for two decades now (5,6,7,8,9,10). Long-term follow-up studies, however, have shown that the prevalence of the metabolic syndrome does not ameliorate, and BMI even increases while on rhGh replacement.…”

Section: Introductionmentioning

confidence: 99%

Effects of discontinuation of growth hormone replacement in adult GH-deficient patients: a cohort study and a systematic review of the literature

Appelman‐Dijkstra

Rijndorp

Biermasz

et al. 2016

Background: Recombinant human growth hormone (rhGH) replacement is advocated in adult growth hormonedeficient (GHD) patients to increase bone mass and improve lipid profile, body composition, and quality of life. The long-term effects of discontinuation of rhGh replacement are unknown. Methods: This cohort study and systematic review aim to evaluate the long-term metabolic effects of discontinuation of rhGh replacement in adult GHD patients, with a subgroup analyses according to age (< or > 60 years). Data on anthropometry, lipids, glucose, and bone mass density (BMD) were assessed for 3 years after discontinuation. Results: Cohort study included 64 patients who had discontinued rhGh replacement for >12 months. Fat percentage increased from 31.5 ± 9.5% to 33.8 ± 9.0% (mean difference 2.3, P = 0.003). BMI decreased only in subjects <60 years (P = 0.014). Glucose, total cholesterol, and LDL-cholesterol levels did not change; however, the percentage of patients on statins increased slightly from 39% to 44%. HDL-C concentration increased only in patients <60 years (mean difference 0.2, P = 0.043). Lumbar spine BMD did not change; however, femoral neck BMD and bone turnover markers decreased in subjects <60 years (P = 0.001). Systematic review included eight studies (n = 166 patients) with a follow-up duration of 6-18 months. Of the eight studies, three qualified as low risk of bias and five as having an intermediate risk of bias. None of the studies reported handling of statins, bisphosphonates, and glucose-lowering medication or excluded patients using these medications. Conclusions: In this study, discontinuation of rhGh replacement resulted in metabolic changes only in patients <60 years after 3 years. Further research warrants to determine the optimal strategies for (dis)continuation of rhGh replacement in adult patients with GHD.

“…At present, data on long-term efficacy and safety of rhGH replacement are limited and uncontrolled for the effect of aging (5, 6,7,8,9,10,11,12,13,14,15,16,17,18). Recently, we have reported a further increase in BMI and MS prevalence despite 10 years of rhGH replacement (19).…”

Section: Introductionmentioning

confidence: 99%

Abnormal metabolic phenotype in middle-aged GH-deficient adults despite long-term recombinant human GH replacement

Claessen

Appelman‐Dijkstra²,

Pereira³

et al. 2014

Background: Adult GH deficiency (GHD) is associated with increased cardiovascular mortality. Recombinant human GH (rhGH) replacement has beneficial short-term metabolic effects. Although these positive effects sustain during longer follow-up, the prevalence of the metabolic syndrome (MS) remains increased in comparison with population data not adjusted for the higher mean BMI in GHD adults. Objective: To explore whether middle-aged patients with proposed physiological rhGH replacement have been normalized with respect to MS and its individual components in comparison with the general population, adjusted for age, sex, and BMI. Methods: One hundred and sixty-one GHD patients (aged 40-70 years) were studied before the start and after 5 years of rhGH replacement, and were compared with 1671 subjects (aged 45-66 years) from the general population (NEO Study). Results: MS proportion in GHD patients was 41.0% before the start of rhGH suppletion, increasing to 53.4% after 5 years (PZ0.007). Despite chronic rhGH replacement, GHD patients had a 1.3-times higher MS proportion than the general population, independently of age, sex, and BMI (95% CI 1.1-1.5, PZ0.008). The GHD population showed a different metabolic profile than the general population with similar BMI: an increased risk of hypertriglyceridemia (adjusted prevalence ratio (PR) 2.0, 95% CI 1.7-2.3) and low HDL-C (adjusted PR 1.8, 95% CI 1.5-2.2), but less hyperglycemia (adjusted PR 0.5, 95% CI 0.4-0.7). Conclusions: Despite 5 years of rhGH replacement, GHD patients still have a different metabolic profile and more frequently MS than the general population. These differences were independent of BMI, and resemble the unfavorable metabolic profile of untreated GHD patients, pointing to question the long-term benefits of rhGH replacement.