Disappearance of endogenous luteinizing hormone is prolonged in postmenopausal women

Pituitary secretion of LH is increased after menopause, but it is not known whether changes in LH clearance also contribute to elevated serum levels. To determine whether the disappearance of endogenous LH is decreased in postmenopausal women (PMW), compared with normal cycling women, GnRH receptor blockade was used to inhibit endogenous secretion of LH and the glycoprotein free alpha-subunit (FAS), and the decline of serum levels was monitored. The NAL-GLU GnRH antagonist ([Ac-D-2Nal1,D-4ClPhe2, D-3Pal3,Arg5,D-4-p-methoxybenzoyl-2-aminobutyric acid6,D-Ala10]GnRH) was administered s.c., at doses of 5, 15, 50, and 150 microg/kg, to 15 euthyroid PMW in 21 studies. Blood was sampled every 10 min, for 4 h before and 8 h after a single sc injection of the GnRH antagonist, followed by hourly samples, ending at 20 h after injection. Results of the maximally suppressive doses (50 and 150 microg/kg) were compared with those of 24 normal cycling women in the early follicular phase and late follicular phase or early luteal phase, and 8 women at the midcycle surge (MCS), who also received these doses of the GnRH antagonist. The best fit curve describing the decay of hormone serum levels after maximal GnRH receptor blockade was determined by nonlinear regression analysis. The elimination of both LH and FAS, after GnRH receptor blockade, exhibited apparent first-order kinetics characterized by a single exponential phase. No differences were seen in percent suppression or half-lives (t1/2) of LH or FAS, between the 50- and 150-microg/kg antagonist doses, in any of the subject populations; and percent suppression of LH was similar across all groups. The t1/2 of LH was prolonged in PMW (139 +/- 35 min, mean +/- est. SD), in comparison with both the MCS (78 +/- 20 min; P < 0.0005) and other cycle stages (57 +/- 28 min; P < 0.0001). However, the disappearance of FAS was not different in PMW, compared with MCS or other cycle stages (t1/2 = 51 +/- 26, 41 +/- 12, and 41 +/- 19 min, respectively). Our conclusions were: 1) Disappearance of endogenous LH after GnRH receptor blockade is significantly prolonged in PMW, compared with the MCS or other cycle stages; 2) The disappearance of FAS is not altered in PMW, suggesting that differences in the disappearance of LH relate to LH microheterogeneity rather than systemic factors.