The oestrogen provocation and GnRH challenge tests were carried out in 5 subjects
with Klinefelter’s syndrome who had no history of previous hormonal therapy. The oestrogen
provocation test consisted of an intramuscular injection of 10 mg of oestradiol valerate
and blood samples were collected daily from day 0 to day 5. In 2 subjects, three GnRH
challenge tests were carried out before (day 0) and on days 2 and 4 after the intramuscular
injection of oestradiol valerate. During each GnRH challenge test, 7 blood samples
were collected at 30-min intervals, 30 min and immediately before and for 150 min
after the bolus dose of GnRH. Plasma concentrations of FSH, LH, testosterone and oestradiol
were measured by established radioimmunoassays. Plasma levels of oestradiol rose significantly
a day following the intramuscular injection of 10 mg of oestradiol valerate, reaching
a peak on day 2 and then falling significantly to lower levels by days 4 and 5, although
these levels were still significantly higher than the corresponding baseline levels.
In the presence of high levels of oestradiol, the high basal levels of FSH were significantly
suppressed, and remained suppressed throughout the 5 days of the study. LH, on the
other hand, had a biphasic response; an initial significant suppression by day 1 persisting
to day 3, but by days 4 and 5 a rebound in basal LH levels was noted. However, the
levels on day 5 were not significantly higher than baseline levels. The pituitary
responsiveness as far as the LH and FSH secretions were concerned reflected the baseline
levels. The results of the present study refuted the claim that a positive oestrogen
feedback exists in men including Klinefelter’s syndrome as a result of the removal
of or reduced testosterone. In addition, the attenuated testosterone feedback in Klinefelter’s
syndrome is responsible for the greatly amplified pituitary responsiveness to the
trophic action of GnRH and this, in part, may be responsible for the elevated levels
of FSH and LH seen in such patients.