Human Pituitary Gonadotropin Index. I. Standardized LRH Test Criteria for Evaluation of Functional Amenorrhea+

Abstract

LRH test were carried out by giving 339 amenorrheic women and 74 normally menstruating volunteers an intravenous injection of 25 mug LRH (Hoe 471). Plasma LH and FSH were measured by RIA in two laboratories (Tuebingen and Ulm) using two standard reference preparations: LER 907 and 2nd IRP-HMG. The average conversion factors between the two standard preparations were calculated at 5.0 for LH and 25.0 for FSH. Furthermore, the estradiol-17beta levels were measured in 139 out of the 339 patients immediately before and 60 minutes after LRH injection. Taking the episodic and cyclic plasma gonadotropin fluctuations into consideration a shorthand system classifying the gonadotropin baseline (BI-BIV) and LH responses to 25 mug LRH (R0-R2) has been established and is referred to as Human Pituitary Gonadotropin Index (HPGI). It is possible to achieve reproducible gonadotropin results in two different laboratories using two different standard reference preparations. Two separate, randomly selected groups of amenorrheic women were found to have the same percent distribution of the HPGI. A correlation coefficient of r equal 0.67 between basal and LRH stimulated plasma LH levels does not sufficiently characterize the individual LH response behavior. A significant increase of plasma LH and FSH within the test period (60') reveals that the iv administration of 25 mug LRH represents an adequate dose for the LRH test in women. The HPGI which characterizes the functional state of gonadostat, may become a useful diagnostic index for evaluating women with anovulatory disease before, during, and after therapy.

Modulation of Pituitary LH and Prolactin Pools in Amenorrheic Women I. Effects of High Dose Estrogen or Gestagen Treatment

“…LH was determinded by radioimmunoassay and results expressed as Mg/1 of the N1H standard preparation LER-907 (Keller et al 1975). The radioimmunoassay procedures for determination of (E 2 ) and (P) as well as levels observed in normally cycling women are given elsewhere (Friedrich, Jaeger-Whitegiver, Bieder, Halver-Schmidt, Pertte, Pallai, Eller, Schindler 1974;Keller et al 1975;Bohnet, Dahlin, Keller, Friedrich, Schindler, Wyss, Schneider 1976b;Bohnet, Hanker, Horowski, Wickings and Schneider 1979); results were expressed in terms of pmol/1 and nmol/1 respectively. PRL was measured in a homologous radioimmunoassay system using the MRC standard preparation 71/222 (fnU/1) as described earlier (Franchimont, Donrey, Ligros, Reuter, Vrindts-Gevaert, van Cauwenberge, Remacle, Gaspard and Colin 1976;Bohnet, Miihlenstedt, Hanker and Schneider 1977).…”

“…While the administration of small doses of estrogen and/or progesterone increases the functional gonadotropin capacity (Yen, Vandenberg, Siler 1974a;Jaffe and Keye 1974;Wang and Yen 1975;Lasley, Wang and Yen 1975), high doses of these hormones decrease the pituitary LH content as judged from LH-RH stimulation tests (Vandenberg, De Vane and Yen 1974;Thompson, Arfania and Taymor 1973;Taymor, Thompson, Berger and Patten 1974;Wang, Lasley and Lein 1976a;Wang, Lasley and Yen 1976b;Mishell, Kharma, Thorneycroft and Nakamura 1977). Based on the response to a single injection of LH-RH several investigators suggested classifications of amenorrheic women (Taymor et al 1974;Aono, Ninagawa, Kinugasa, Miyake and Kuracchi 1974;Keller et al 1975;Van de Kerckhove, Dhont and van Eyck 1975). There is, however, little information on the total pituitary gonadotropin capacity in hypogonadal women and its modulation by exogenously given sex steroids administered for endometrial bleeding tests.…”

Human Pituitary Gonadotrophin Index

“…In this present study women with functional amenorrhoea were treated with LHRH to investigate its effect on hypothalamo-pituitary-gonadal function. Pituitary gonadotrophic function was judged by the release of LH and FSH in a standardized LHRH test designed in our laboratories (Keller et al, , 1975. Gonadal function was evaluated by recording plasma oestradiol and progesterone concentrations before and after LHRH treatment.…”

“…The HPGI objectively characterizes the functional state of the gonadostat in that (1) the actual gonadotrophin reserve as reflected by the response pattern (R) seems to be a better reflection of pathophysiology than basal gonadotrophin levels (B); (2) when looking at the changes in FSH/LH ratio in LHRH tests, a midcycle type change to a ratio of less than I, as required for ovulation, is only found in the patients with R 2 indices; (3) the peripheral oestradiol levels were found to increase not only with B but also with R indices. The relative importance of the R index is apparent from the abundance of R 2 in normal cycling volunteers as compared to amenorrhoeic patients in whom B I is associated with only 24% of R 2 (as com-pared to 44% in normals), B I1 with 50% (72%) and B I11 with 90% (96%) (Keller et al, , 1975.…”

“…The results were expressed in terms of eithern g/ml of LER-907 or miu/ml of 2nd IRP-HMG. The conversion factors between these standard preparations were calculated to be 5.0 for LH and 25.0 for FSH on average (Keller et al, , 1975. Plasma oestradiol and progesterone were measured by radioimmunoassay employing highly specific antisera .…”