Pharmacological aspects of growth hormone replacement therapy: route, frequency and timing of administration

Two or three weekly, daytime intramuscular injections of GH has been the traditional treatment of GH deficiency since the first studies. A recent reevaluation of the feasibility of subcutaneous GH injections revealed no side-effects, but a very strong preference by the patients for the subcutaneous route, and also an increase in growth rate in studies where the patients received daily injections given in the evening. That could indicate that the route, frequency and timing of GH administration may be of clinical importance. Subcutaneous injections result in a slower absorption, a smaller peak value, and a prolonged serum disappearance phase compared to intramuscular injections. This extends the periods of elevated serum GH levels in the patient, which might be advantageous. On the other hand, a reduced bioavailability of GH by the subcutaneous route has also been reported. The frequency of subcutaneous injections correlates positively with growth rate in animal studies. This is commonly ascribed to a closer resemblance to the endogenous pulsatile pattern. However, frequent subcutaneous injections do not induce a pulsatile pattern, but a pattern which is intermediary between continuous and true pulsatile administration. In a short-term patient study, we observed that pulsatile and continuous intravenous administration of GH generated identical increases in serum insulin-like growth factor I, which suggests that both pulsatory and constant, small elevations in serum GH are important for its actions. Concerning the time of administration, evening GH injections yield a more physiological pattern, and it has been shown that evening GH administration induces increased nitrogen retention and is more successful in normalizing circadian patterns of pertinent hormones and metabolites.(ABSTRACT TRUNCATED AT 250 WORDS)