The gonadotrophin response to naloxone infusion has been investigated in three adult males, and three adult females in the early follicular phase. The frequency of LH secretory episodes and the mean LH levels increased in both sexes. The data suggest that the pulsatile release of LH is under inhibitory opiate control.

Endogenous opiates are involved in the control of pituitary gonadotrophin and PRL secretion, and possibly of food intake. Both hyperprolactinaemia and weight loss (especially in anorexia nervosa) are frequently associated with amenorrhoea and an absence of gonadotrophin pulsatility. Since it has been suggested that increased endogenous opiate tone may operate in both conditions, we infused high-doses of naloxone into twelve patients with amenorrhoea of whom five had hyperprolactinaemia and seven had weight-loss related amenorrhoea. Eleven of the twelve patients had low levels of oestradiol (less than 50 pmol/l). Naloxone induced a marked rise in both LH and FSH levels in all of the five hyperprolactinaemic patients. In contrast, the patients with weight-loss amenorrhoea responded to naloxone with only a small or no rise in gonadotrophins. There was no consistent change in PRL in either group of patients. It is concluded that in hyperprolactinaemia, but not weight-loss amenorrhoea, there is an important endogenous opiate-mediated tonic inhibition of secretion of hypothalamic gonadotrophin releasing hormone.

Endogenous opiates are involved in the control of pituitary gonadotrophin and PRL secretion, and possibly of food intake. Both hyperprolactinaemia and weight loss (especially in anorexia nervosa) are frequently associated with amenorrhoea and an absence of gonadotrophin pulsatility. Since it has been suggested that increased endogenous opiate tone may operate in both conditions, we infused high-doses of naloxone into twelve patients with amenorrhoea of whom five had hyperprolactinaemia and seven had weight-loss related amenorrhoea. Eleven of the twelve patients had low levels of oestradiol ( < 50 pmol/l). Naloxone induced a marked rise in both LH and FSH levels in all of the five hyperprolactinaemic patients. In contrast, the patients with weight-loss amenorrhoea responded to naloxone with only a small or no rise in gonadotrophins. There was no consistent change in PRL in either group of patients. It is concluded that in hyperprolactinaemia, but not weight-loss amenorrhoea, there is an important endogenous opiate-mediated tonic inhibition of secretion of hypothalamic gonadotrophin releasing hormone.

The effect of food on the bioavailability of 6-mercaptopurine (6-MP) has been investigated. Seven patients were studied on two separate occasions. On the first occasion 6-MP was administered p.o. after an overnight fast and on the second, 15 min after a standard breakfast. 6-MP concentrations were determined by high-performance liquid chromatography. Variable plasma drug levels were observed between individual subjects in the fasting state. The peak levels of 6-MP were lower and took longer to be achieved following administration after a standard breakfast than after an overnight fast. In two subjects levels were undetectable (less than 20 ng/ml). In view of these observations it is suggested that 6-MP should be administered before food if maximum blood levels are to be achieved.

The role of endogenous opiate peptides in puerperal hyperprolactinaemia, and in the control of TSH in hypothyroidism, has been investigated. Although exogenous opioids raise prolactin and TSH levels, 16 mg naloxone administered to women on days 2-4 of the puerperium produced no significant change in serum prolactin and the same dose of naloxone had no significant effect on serum TSH in six primary hypothyroid patients. There is little evidence that endogenous opioid peptides are major modulators of prolactin or TSH in man under these conditions.