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Oral contraceptives inhibit ovarian follicular growth by suppressing the release of gonadotropins from the pituitary. We studied basal and gonadotropin-releasing hormone-stimulated gonadotropin release, as well as pulsatile luteinizing hormone (LH) secretion, in ten healthy volunteers who had not used oral contraceptives before. Subjects received either a monophasic preparation containing 30 micrograms of ethinylestradiol and 75 micrograms of gestodene (group 1) or a triphasic formulation containing 30-40 micrograms of ethinylestradiol and 50, 70 and 100 micrograms of gestodene (group 2). Blood sampling at 10-min intervals during 6-h periods was performed on days 1, 8, 15 and 21 of both the first and fourth pill cycle. Thirteen healthy volunteers with regular ovulatory cycles served as normal controls. Both LH and follicle-stimulating hormone (FSH) were measured by a sensitive immunoradiometric assay. Pulsatile LH secretion was observed in all oral contraceptive users. Mean serum LH and FSH levels, number of pulses/6 h and the amplitude of LH pulses on day 1 in both the first and fourth pill cycle did not differ from early follicular phase controls in both groups. The FSH levels were suppressed rapidly in both groups, even in first cycles, while LH serum levels progressively declined in all cycles studied. In both groups, amplitudes of LH pulses decreased from day 8 onwards, with a substantial number of low-amplitude pulses (< 0.75 U/l) interspersed between large-amplitude pulses. On day 1 of the fourth pill cycle a significant number of pulses were of low amplitude.(ABSTRACT TRUNCATED AT 250 WORDS)

The dynamics of luteinizing hormone (LH) and follicle stimulating hormone (FSH) release were investigated in 60 long-term oral contraceptive (OC) users. Five different types of OC, all containing the same amount of estrogens were studied: three monophasic preparations containing levonorgestrel, desogestrel and gestodene, respectively, and two triphasic formulations, containing levonorgestrel or gestodene. Thirteen healthy, normally cycling volunteers served as controls. Blood sampling was performed at 10-min intervals during a 6-h period to determine the pulsatile release of LH. LH and FSH were measured using a sensitive immunoradiometric assay. Pulse patterns were classified on the basis of the overall LH level, as well as on the character of the LH pulses, according to both frequency and amplitude characteristics. Pulsatile LH release was maintained during OC use. After the 7-day pill-free interval, FSH levels as well as the LH pulse patterns were comparable to those of early follicular-phase controls. FSH levels and FSH release in response to a gonadotropin releasing hormone (GnRH) challenge were profoundly suppressed in all OC users, as early as day 8 of the pill cycle. LH release during the pill cycle was characterized by either a low frequency (median 1 pulse/6 h), high amplitude (median 2.5 IU/l) pulse pattern or by a pattern of low-amplitude pulses (median 0.2 IU/l) and low basal LH levels (median 0.2 IU/l). The distribution of these pulse patterns showed marked differences between different OC preparations and depended on both the type and dose regimen of the gestagenic component of the OC.

Oral contraceptives (OC) inhibit folliculogenesis by a central suppressive action on the release of gonadotropins. To characterize the nature of these central effects, we studied 40 long term OC users on 3 different OCs: two monophasic preparations with 30 micrograms ethinyl estradiol and 150 micrograms l-norgestrel (group 1; n = 15), 150 micrograms desogestrel (group 2; n = 10), and a triphasic formulation containing 30-40 micrograms ethinyl estradiol and 50, 75, and 125 micrograms l-norgestrel (group 3; n = 15). Blood sampling at 10-min intervals during 6-h periods was performed at different moments in the pill cycle. Thirteen healthy volunteers with regular ovulatory cycles served as normal controls. FSH and LH were measured by a sensitive immunoradiometric assay. Pulsatile LH release was observed in all OC users. Mean serum LH and FSH levels, number of LH pulses per 6 h, and the amplitude of LH pulses on day 1 of the pill cycle did not differ from early follicular phase control values. FSH levels were rapidly suppressed from day 2 onward in all three groups, whereas LH levels progressively declined in groups 1 and 2 from day 8 onward. In group 3, however, LH levels were only significantly suppressed after day 13. The number of LH pulses per 6 h decreased in all groups starting on day 2, whereas the amplitude of LH pulses increased. A substantial percentage of LH pulses observed in OC users after day 1 were of low amplitude (< 0.75 IU/L). From these results, we conclude that 1) pulsatile release of LH is maintained during OC use; 2) FSH levels are suppressed equally early and equally effective by all OCs studied; 3) during OC use, the number of LH pulses per 6 h is reduced; 4) modulation of LH pulse amplitudes, and subsequently of serum LH levels, is mainly mediated by a dose- and time-dependent effect of the gestagenic component of the OC; and 5) after the 7-day pill-free interval, a normal early follicular phase pulse pattern is found, even in long term OC users, suggesting that in this period, most of the steroidogenic feedback effects wear off.

The existence of a short-term pituitary desensitization in luteinizing hormone (LH) release to single doses of luteinizing hormone-releasing hormone (LH-RH) in the ovariectomized rat was recently disclosed. The purpose of the present study was to investigate whether this refractoriness is also present in humans. Blood from six women with amenorrhea of suprapituitary origin was sampled every 10 minutes for 300 minutes for determination of LH and follicle-stimulating hormone (FSH). A pulse of 20 micrograms LH-RH was given intravenously 90 and 210 minutes after the first blood sample, and 2 micrograms LH-RH was given 30, 150, 240, and 270 minutes after t0. The mean maximal increments of LH and FSH were compared. The LH response to a 2-micrograms LH-RH bolus given 30 (t240) or 60 (t150) minutes after a 20-micrograms LH-RH pulse was significantly decreased, compared with the initial response to this dose at t30. For both LH and FSH, the response to 2 micrograms LH-RH given 30 minutes after the 20-micrograms pulse (t240) was almost absent, compared with 60 (t150) minutes after the 20-micrograms dose. We conclude that a short-term pituitary refractoriness to LH-RH is present after administration of single pulses of LH-RH in women with amenorrhea of suprapituitary origin and pulses of LH-RH in the physiologic range (2 micrograms) given to these women do not always generate LH and FSH increments that are identifiable as significant hormone pulses.

The aim of the study was to test the hypothesis that in serial determinations of concentrations of LH and FSH involving blood samples taken every minute, the observed pulses of LH and FSH which last less than 3-4 min might not be a physiological phenomenon but part of the 'noise' of the radioimmunoassay or blood-sampling technique. Blood was sampled every minute for a period of 90 min in six men. During the first 45 min, blood was sampled by means of vacuum tubes only. During the second 45 min, sampling took place with a syringe via a rubber stopper, either using a tourniquet (n = 3) or flushing the cannula with heparinized saline. Three criteria were used to identify variations in the patterns of LH and FSH as true hormonal changes. First, a threshold was used which had to be exceeded by the difference between nadir and maximum values before a pulse could be identified. An average of approximately six pulses per 90 min was found in both the LH and FSH series. The majority of these pulses lasted less than 3-4 min. In two subjects, larger LH pulses of longer duration were measured. Secondly, differences between duplicate measurements of nadir and/or maximum values of more than one-third of the amplitude of a pulse were considered unacceptable. This involved about 75% of the pulses. Thirdly, the reproducibility of the hormone variations was estimated. In one subject, concentrations of LH were measured four times in four separate assays.(ABSTRACT TRUNCATED AT 250 WORDS)