Patterns of LHβcf among women in health and disease

Abstract

Urine based gonadotropin assays provide a practical means of analyzing hormone secretion patterns. While research protocols have revealed pulsatile patterns of gonadotropins such as LH in the blood, these assays are of limited clinical use since daily venipuncture sampling is not feasible outside of a research environment. However, collection of several urine samples provides a method to achieve the same visualization of gonadotropin patterns in patients using a convenient and generally applicable technique based on analysis of the highly stable hLHβcf for monitoring LH and hCGβcf for monitoring pituitary hCG. We demonstrated that two different sampling techniques for analyzing these gonadotropin metabolites yielded the same information on their excretory patterns, either sampling of spot urines or collecting first morning void urines for several days. Next, we studied the core excretory patterns in several populations: menstruating and postmenopausal women from the general population, and two populations of women from a fertility center, one of which had polycystic ovaries (PCO). The PCO population was also subdivided into those with and without insulin resistance (IR). It was found that our hLHβcf assay did not measure the form of the LH core (vhLHβcf) produced in subjects who were homozygous for a variant form of LH (v-LH). None of our patients tested were homozygous for the variant form of LH. It was also found that in most non-PCO (NPCO) patients, the hLHβcf peak lasted for 7-9 days while among the PCO patients this peak frequently lasted for less than 7 days and an erratic pattern tended to appear. The overall differences in patterns between the PCO and NPCO patients were confirmed by spectral statistical methods. The prevalence of certain characteristic hLHβcf patterns may be higher among women with PCO with a more severe clinical presentation. Use of urinary analysis of gonadotropin metabolites, especially hLHβcf, may supplement subjective ultrasound studies with more sensitive biochemical measurements.

First Morning Voided Urinary Gonadotropin Measurements as an Alternative to the GnRH Test

“…A potential limitation of FMV U-LH assays is the fact that a large part of LH immunoreactivity in urine consist of a fragment of the LHβ subunit called the core fragment (LHβcf) [32]. Different assays recognize this fragment to variable degrees, and therefore the measured LH concentrations are highly dependent on the assay used [33].…”

Polycystic ovarian syndrome: clinical and biological diagnosis

“…Parmi celles-ci signalons un retrocontrôle négatif altéré aux progestatifs qui de toutes façons sont sécrétés insuffisamment du fait de l'anovulation (21)(22)(23). Les taux de LH peuvent être influencés par la plus ou moins forte proximité d'une ovulation (qui normalise transitoirement la LH), par l'index de masse corporel (le taux étant plus élevé chez les femmes minces avec SOPMK), par l'hyper-insulinisme et par le système de dosage utilisé (24,25). Sur la base de ces données, la mesure des taux de LH plasmatique ne doit pas être considérée comme nécessaire pour le diagnostic clinique du SOPK.…”

Immunoreactive LH in long‐term frozen human urine samples

“…Yet, despite the reduced absolute LH measurements by the IF immunoassay, both LH immunoassays displayed sufficiently similar patterns of urine LH measurements to confirm the findings of the original study that hCG administration produces LH suppression. [30][31][32] This diversity reflects the metabolism of the gonadotropins which produces nicked dimers and free sub-units including the core fragment. Similar findings were reported for serum LH measurements where the performance of the ICL was reported to be more sensitive and accurate compared to the IF immunoassay for the determination of reference range during sexual development in normal children.…”

“…These discrepancies between LH immunoassays most probably reflect the diversity of immunoreactive LH species in human urine compared with the bloodstream. [30][31][32] This diversity reflects the metabolism of the gonadotropins which produces nicked dimers and free sub-units including the core fragment. Like hCG where the metabolism is more fully characterized, [33] the homologous LH heterodimer is metabolized and excreted in the urine in various fragments which are largely in the forms of free sub-units and fragmented forms of LHb.…”