GONADOTROPHIN RESPONSES TO GnRH PULSES IN HYPOGONADOTROPHIC HYPOGONADISM: LH RESPONSIVENESS IS MAINTAINED IN THE PRESENCE OF LUTEAL PHASE CONCENTRATIONS OF OESTROGEN AND PROGESTERONE

LH pulse secretion changes during the menstrual cycle from a rapid regular pattern in the follicular phase to a slower and irregular pattern in the luteal phase. To determine whether the irregular LH pulse pattern in the luteal phase reflects altered GnRH secretion or altered pituitary responsiveness to GnRH, we gave low dose GnRH pulses (25 ng/kg i.v.) every 2 h or every hour for 10 or 12 d to three women with isolated GnRH deficiency. After 4 d of GnRH alone, oestradiol (E 2 ) was given and after 6 d progesterone (P) was added to mimic the hormonal milieu of the luteal phase. LH and FSH were measured every 4 h throughout and also every 20 min for 6 or 12 h, before and after GnRH alone (day 0 and day 4), after E 2 (day 6), and after E 2 + P (day 10 and day 12). Both GnRH pulse frequencies resulted in a rapid increase in plasma FSH to peaks on day 4 (every 2 h) and day 2 and 3 (every hour). FSH concentrations then declined as plasma E 2 rose to 50–80 pg/ml reflecting the selective inhibitory effect of E 2 on FSH release. Plasma LH was also increased after the hourly GnRH injections and this regimen was associated with a more rapid rise in E 2 reflecting follicular maturation. In contrast to the differences in mean hormone concentrations, administration of GnRH at both frequencies resulted in sustained one-on-one responsiveness of LH that was maintained in the presence of both oestrogen and progesterone at mid-luteal phase concentrations. We conclude that the slow frequency of LH pulses observed during the luteal phase reflects decreased GnRH pulse frequency rather than impaired pituitary responsiveness to GnRH.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74947/1/j.1365-2265.1987.tb00786.x.pd

Levonorgestrel Plasma Levels During Continuous Administration With Different Models Of Subdermal Implants

Plasma concentrations of levonorgestrel were determined in women using subdermal levonorgestrel implants. One group had 6 Silastic ® capsules† † Silastic® supplied by Leiras Pharmaceutical, Turku, Finland. (NORPLANT), one group had 4 and one group had 6 covered Silastic® rods for variable lengths of time. Levonorgestrel concentrations remained constant around 0.4 ng/ml up until 6 years of use in the Norplant group. The observation period was shorter for the covered rods; plasma concentrations were, however, constant around 0.55 ng/ml and 0.70 ng/ml for 3.5 years with the 4 rods and 6 covered rods, respectively. The difference in mean levonorgestrel concentrations between the three groups were statistically significant (p < 0.0005). Plasma levels of levonorgestrel were twice to three times higher in blood obtained from the arm with the implants compared to the levels found in the other arm. The application of a tourniquet for variable periods before blood sampling did not influence the plasma concentrations of levonorgestrel. © 1983.272123130Segal, Croxatto, Single administration of hormones for long-term control of reproductive function (1967) Presentation at the XXIII Meeting of the American Fertility Society, , April 14–16, Washington DCAlvarez, Robertson, Montes de Oca, Sivin, Brache, Faundes, Comparative clinical trial of the progestins R-2323 and levonorgestrel administered by subdermal implants (1978) Contraception, 18, pp. 151-162Coutinho, da Silva, Mattos, Nielsen, Osler, Wiese, Holma, Sivin, Contraception with long acting subdermal implants. I. An effective and acceptable modality in international clinical trials (1978) Contraception, 18, pp. 315-333Coutinho, da Silva, Mattos, Nielsen, Osler, Wiese, Holma, Sivin, Contraception with long acting subdermal implants. II. Measured and perceived effects in international clinical trials (1978) Contraception, 18, pp. 335-353Faundes, Brache de Mejias, Leon, Robertson, Alvarez, First year clinical experience with six levonorgestrel rods as subdermal contraception (1979) Contraception, 20, pp. 167-175Croxatto, Diaz, Miranda, Elamsson, Johansson, Plasma levels of levonorgestrel in women during long-term use of NORPLANT (1980) Contraception, 22, pp. 583-596Weiner, Victor, Johansson, Plasma levels of d-norgestrel after oral administration (1976) Contraception, 14, pp. 563-57