Context: The common genetic variant of human LH has two mutations and an extra N-linked oligosaccharide chain, a modification expected to affect the half-life in the circulation.

Objectives: Our objectives were to determine the half-lives of variant and wild-type forms of LH during GnRH receptor blockade in heterozygous women and to determine the time-related changes in isoform composition.

Design and Participants: Serum samples were obtained from three healthy women heterozygous for variant LH before and up to 20 h after administration of the NAL-GLU GnRH antagonist.

Main Outcome Measures: The half-lives were estimated by monoexponential decay. The number of sialic acid and sulfonated N-acetylgalactosamine residues per wild-type and variant LH molecule and the distribution of molecules with zero, one, two, or three sulfonated residues were measured.

Results: The variant LH had a half-life that was approximately 40% longer than the corresponding forms of wild-type LH (148 vs. 108 min; P < 0.001). Variant LH had more sialic acid residues per molecule than wild type (3.6 vs. 2.4; P < 0.05), whereas the number of sulfonated residues was similar (1.0 vs. 0.98). The decline in the variant LH during GnRH receptor blockade was associated with a decrease in sulfonated and an increase in sialic acid residues similar to that for in wild-type LH. Isoforms of either variant or wild-type LH with two to three sulfonate groups per molecule had the shortest half-life.

Conclusion: Variant LH remains longer in circulation than wild type during GnRH receptor blockade in heterozygous women, in accord with its higher content of sialic acid.