Growth hormone kinetics in polycystic ovary syndrome

Kaltsaset al. (1998), performed an interesting study to determine the effects of gonadotrophin-releasing hormone agonist (GnRHa) administration on growth hormone releasing hormone (GHRH) stimulated release in women with polycystic ovary syndrome (PCOS). In both the PCOS and control groups, the growth hormone response to GHRH was significantly smaller after treatment with GnRHa than before treatment, but more so in the PCOS group. This suppression of the growth hormone response to GHRH following GnRHa administration in women with PCOS lead them to ask the clinically relevant question of whether the addition of growth hormone to the gonadotrophin regimen may be needed during ovulation induction with GnRHa in these patients. It is unfortunate that this was left as an open question as a glance at Homburget al. (1995) in which we published the results of a randomized, double-blind, placebo controlled trial of adjuvant growth hormone for induction of ovulation with GnRHa and gonadotrophins in PCOS, would have provided the answer. Our study was performed for the very reasons which prompted Kaltsas et al. to ask the question, i.e. women with PCOS have a disturbance of growth hormone kinetics; those who are obese and some of normal weight have lower than normal adult circulating concentrations of growth hormone (Prelevicet al., 1992; Insleret al., 1993; Moraleset al., 1996); and a reduced pituitary reserve of growth hormone (Ovesen et al., 1992), usually associated with insulin resistance, hyperinsulinaemia, and a reduction of insulin-like growth factor binding protein-1 (IGF-BP1) serum concentrations (Homburg et al., 1992). Treatment involving GnRHa further reduces pituitary reserves of growth hormone (Word et al., 1990; Kaltsas et al., 1998). Finally, follicular fluid concentrations of IFG-I are decreased in PCOS compared with normally ovulating women when stimulated with gonadotrophins (Volpe et al., 1992). In our study (Homburget al., 1995), 30 women with PCOS were given adjuvant growth hormone or placebo during GnRHa/gonadotrophin therapy. Other than a GH-induced increase in serum insulin and IFG-I concentrations, there were no significant differences between the growth hormone and placebo groups in gonadotrophin requirement to attain ovulation, serum oestradiol concentrations, number of growing follicles induced, nor in ovulation or pregnancy rates. We concluded that although growth hormone kinetics are abnormal and growth hormone pituitary reserves are suppressed in women with PCOS receiving GnRHa, the addition of growth hormone to this treatment regimen does not bestow any potential clinical benefit. These findings however, do not rule out the possible involvement of growth hormone in the pathogenesis of women with PCOS, predominantly in those of normal weight with no insulin resistance and normal insulin levels and who have an increased pituitary secretion and relatively high concentrations of growth hormone (Prelevicet al., 1992). Indeed, these lean women with PCOS were found to have a mean growth hormone pulse amplitude that was elevated by 30% in comparison with