The Ratios of Serum Bioactive/Immunoreactive Luteinizing Hormone and Follicle-Stimulating Hormone in Various Clinical Conditions with Increased and Decreased Gonadotropin Secretion: Reevaluation by a Highly Sensitive Immunometric Assay*

Abstract

Serum bioactive and immunoreactive LH and FSH were measured in clinical conditions with increased or decreased gonadotropin secretion. Gonadotropin immunoreactivity was measured using a conventional RIA (I) and an ultrasensitive immunofluorometric method (F). Bioactive (B) LH was assessed by the mouse interstitial cells in vitro bioassay, and B-FSH using the immature rat granulosa cell assay. Acute GnRH stimulation of adult men (n = 6) increased LH levels measured by the different methods 4.3- to 5.3-fold. The B/I ratio of LH increased from 2.34 +/- 0.21 to 3.71 +/- 0.36 (mean +/- SEM) at 120 min (P less than 0.05), but no change was found in the B/F ratio. After ovariectomy of premenopausal women (n = 6), the LH levels increased in 1 week 4- to 6-fold, the B/I ratio from 1.85 +/- 0.22 to 2.59 +/- 0.24, and the B/F ratio from 1.78 +/- 0.22 to 2.90 +/- 0.30 (P less than 0.05 for both). In addition, the LH levels were measured during GnRH agonist treatment of ovarian carcinoma (n = 8), endometriosis (n = 8), and prostatic carcinoma after orchiectomy (n = 8). In the two former groups, serum B-LH decreased in 1 month to undetectable levels (less than 0.5 IU/L), and in the prostate cancer patients to 1.2 (0.8-1.9) IU/L (log mean and range of +/- SEM). The concomitant decline of I-LH was to 1.5-1.9 IU/L in the agonist-treated female patients, and that of F-LH to 0.10-0.15 IU/L; in the prostate cancer patients, respectively, these values were 7-8 and 0.3-0.7 IU/L. The B/I and B/F ratios during the agonist treatments could only be calculated in the prostate cancer patients (in the others, B-LH became undetectable). The B/I ratio decreased from 2.34 +/- 0.5 to 0.14 +/- 0.03 (P less than 0.01), but no suppression was found in the B/F ratio from a pretreatment value of 3.6 +/- 0.8. B-, I-, and F-FSH levels were measured in the GnRH agonist-treated orchiectomized prostate cancer patients. The pretreatment level of B-FSH was 154 (137-175), that of I-FSH was 38.0 (34.4-42.0), and that of F-FSH was 39.8 (35.3-44.9) IU/L. The B/I ratio of FSH was 3.76 +/- 0.49, and the B/F ratio was 3.53 +/- 0.59. The mean B-FSH level decreased during treatment by 87-93.5%, that of I-FSH by 98%, and that of F-FSH by 91.5% (P less than 0.01 for all).(ABSTRACT TRUNCATED AT 400 WORDS)

Comparative Analysis of Different Puberty Inhibiting Mechanisms of Two GnRH Agonists and the GnRH Antagonist Cetrorelix Using a Female Rat Model

“…Supporting this idea are reports that in humans BUS releases bioinactive LH molecules into the circulation that are detected by RIA using polyclonal antibodies but not by immunoassays based on monoclonal antibodies (24,25). This hypothesis of bioinactive LH release caused by GnRH agonists is supported by the observation that sera from women under BUS treatment do not stimulate testosterone production in the mouse interstitial cell in vitro bioassay (26). An alternative explanation for the elevated GnRH agonist-caused gonadotropin levels is that TRIP and BUS may cause a transient flare-up.…”

Autoregulation of the gonadotropin-releasing hormone (GnRH) system during puberty: effects of antagonistic versus agonistic GnRH analogs in a female rat model

“…These molecules do not act in the ovary because they cannot activate their receptors. This possibility is supported by data that GnRH agonist treatment leads to secretion of bioinactive LH molecules into the circulation which are detected by RIAs but not by immunoassays based on monoclonal antibodies (Jaakkola et al 1990, Kwekkeboom et al 1990, Uemura et al 1992. The second possibility is that TRIP stimulates the release of bioactive LH and FSH molecules whose action is counteracted by direct effects of TRIP in the ovary due to an interference with a local ovarian autoregulatory GnRH system.…”

Low-dose human chorionic gonadotropin may improve in vitro fertilization cycle outcomes in patients with low luteinizing hormone levels after gonadotropin-releasing hormone antagonist administration

“…For example, using the same threshold of %0.5 mIU/mL, Merviel et al (67) did not find any significant detrimental effect of low LH levels. Possible explanations for these differing findings include OCP pretreatment, daily versus single dose GnRH antagonist administration (4), variability in the sensitivities of commercially available LH assays, and the fact that biochemical assays of LH do not always accurately reflect LH bioactivity (68). It is also possible that the time of day when the GnRH antagonist is administered and when LH is measured could affect outcomes.…”