A subset of patients have features of both morphological abnormalities. Patients with lipoatrophy experience a loss of SAT, most noticeably in the limbs and face. Patients with fat accumulation typically

have gains of VAT in the abdomen and may have dorsocervical fat pad enlargement. Thus, we feel that if fat atrophy and fat accumulation co-exist in a patient, they should be addressed independently. Our results suggest that GH axis therapy may not be effective for improving SAT. Thus, for patients with both SAT loss and VAT gains, clinicians could consider combined therapy using GH axis drugs for the management of VAT and agents such as thiazolidinediones LDK378 MK0683 cell line for the treatment of SAT loss. Thiazolidinediones, such as pioglitazone, have been shown to be beneficial in the treatment of SAT loss, but their use remains investigational [25]. Additionally, clinicians might consider

pioglitazone in patients with lipoatrophy who have evidence of insulin resistance. This could reduce SAT loss and improve some metabolic abnormalities. The major side effects of GH axis therapies listed in the studies were oedema, arthralgias, myalgias and, less commonly, carpal tunnel syndrome and diabetes mellitus. Although some studies reported no risk of adverse events with treatment, our meta-analyses showed statistically significant increases in the frequencies of oedema and arthralgias in the treatment groups. However, providers must be careful in considering a summary effect of adverse events with these different drugs grouped together. As seen in Figure 4, when considered by itself, tesamorelin did not produce a significant increase in the frequency of arthralgias or oedema. While these summary effects may raise questions about the pathophysiological mechanisms of GH axis drugs, each drug should be considered individually

in terms of its adverse Cyclic nucleotide phosphodiesterase effects. Until more results from large, randomized, placebo-controlled studies are available, clinicians must weigh the benefits and risks of each GH axis agent and individualize treatment for their patients. The large number of participants across the included studies allows us to form some hypotheses and draw some conclusions regarding GH axis drugs. However, because of the limited number of studies available for each specific drug type, we cannot make any definitive statements about the individual effectiveness of GH, GHRH, IGF-1 or tesamorelin. Furthermore, few studies evaluated whether the benefits of the intervention persisted after discontinuation of treatment, which is an important consideration given the costs and potential long-term side effects of the intervention. Lastly, no long-term studies have examined the benefits and consequences of extended use of these drugs.