Disappearance of Endogenous Luteinizing Hormone Is Prolonged in Postmenopausal Women1

• Published in: The journal of clinical endocrinology and metabolism Vol. 84; no. 2; pp. 688 - 694
• Main Authors: Sharpless, Julie L, Supko, Jeffrey G, Martin, Kathryn A, Hall, Janet E
• Format: Journal Article
• Language: English
• Published: Endocrine Society 01-02-1999
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jcem.84.2.5433

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 α-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 sc,
at doses of 5, 15, 50, and 150 μg/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 μg/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-μg/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.