Determination of Half-lives of Circulating FSH and LH Glycoforms in Women During GnRH Receptor Blockade

Context: Both FSH and LH circulate as 2 glycoforms, differing in number of glycans: low-N-glycosylated glycoforms, FSHtri and LHdi, and fully N-glycosylated glycoforms, FSHtetra and LHtri.

Objectives: To determine the half-lives of endogenous circulating gonadotropin glycoforms in women during GnRH receptor blockade.

Design/participants: Serum samples were collected in 8 healthy women before and up to 20 hours after administration of the NAL-GLU GnRH antagonist. Three women were in early follicular phase, 2 at mid-cycle phase, and 3 were postmenopausal.

Main outcome measures: The half-life of each glycoform was estimated by monoexponential decay for FSH (n = 8) and LH (n = 5). Data were analyzed using paired t tests.

Results: Half-lives in the circulation of low-N-glycosylated glycoforms of both FSH and LH were shorter than those of the fully N-glycosylated glycoforms (mean; range, FSHtri 343; 116-686 minutes vs FSHtetra 757; 436-1038, minutes, P = 0.0003; LHdi 125, 84-198 minutes vs LHtri 164, 107-235 minutes, P = 0.004). The half-lives of low-and fully N-glycosylated forms of LH were shorter than the corresponding half-lives of FSH glycoforms, P = 0.0008.

Conclusions: For both FSH and LH, low-N-glycosylated glycoforms disappeared from the circulation faster than the fully N-glycosylated. The half-lives of low and fully N-glycosylated forms of LH were shorter than the corresponding half-lives of FSH. The estimated values for half-life in the circulation of total FSH and total LH will depend on the relative amounts of the 2 glycoforms of each hormone and their individual disappearance rates in circulation.