Endocrine Abstracts

Context: In men, a decline of mean circulating testosterone level is seen with increasing age. This decline is associated with an increase in the mean levels of LH and FSH, albeit insufficient to maintain testosterone at its original level. It has been speculated that a higher sensitivity of the hypothalamus and/or pituitary for the feedback effect of circulating testosterone in older men is responsible.

Objective: To compare the effect of experimentally varied plasma levels of estradiol on the LH and FSH secretion in young and old men, in almost absence of testosterone.

Methods: In 10 healthy, castrated young men and 11 healthy, castrated old men (both male-to-female transsexuals after gonadectomy) plasma estradiol levels were experimentally varied with estradiol patches (the first week 100?g/day, the second week 50?g/day, the third week 25?g/day and the fourth week no patch was applied). We monitored plasma levels of LH and FSH after every week.

Results: The mean plasma bioavailable E2 levels in the two groups ranged between 13.6 and 104.0 pmol/l. LH and FSH were inversely related to peripheral estradiol levels. Mean LH and FSH levels were lower in the old group at all time points however, the difference only reached statistical significance in the last week of the study when no patch was applied and estradiol levels were extremely low.

Conclusions: Circulating E2 levels markedly inhibit gonadotropin release in both young and older men. Observations that the difference between gonadotropin levels of young and old men is highest when E2, T and inhibin levels are very low, does not support the hypothesis of an age related increasing sensitivity of the hypothalamus for the negative feedback of E2, but rather supports the hypothesis of a deficient hypothalamic feed-forward drive.