Effects of ethinyloestradiol on plasma levels of pituitary gonadotrophins, testicular steroids and sex hormone binding globulin in normal men.

Daily measurements of plasma FSH, LH, prolactin, testosterone, 17 beta-oestradiol and sex hormone binding globulin (SHBG) activity were made in eight healthy, normal men during treatment with oral ethinyloestradiol (EE2) in a dose of 30 micrograms/day for 5 days following a 5-day control period. No significant changes in plasma levels of FSH and prolactin during oestrogen treatment occurred. In contrast, plasma concentrations of both LH and testosterone showed a biphasic pattern. Following an initial suppression during the first 3 days of oestrogen treatment both LH and testosterone increased again to baseline values despite continuation of oestrogen administration. The secondary rise of both hormones was associated with (and probably resulted from) a nearly 100% increase in the plasma concentration of SHBG binding activity, and hence reduction of free testosterone index (FTI). Unlike testosterone, plasma 17 beta-oestradiol during EE2 administration did not show a biphasic pattern, but a progressive decline that was positively correlated with the fall in FTI. The rapidity of onset and magnitude of the observed rise in SHBG levels emphasizes the need for measurement of this binding protein (or the free testosterone fraction) in studies on feedback regulation of gonadotrophins employing exogenous EE2 in human males. The observed increase of SHBG to supraphysiological values suggests that currently employed EE2 doses in such studies may be less 'physiologic' than is often assumed.