Pulsatile luteinizing hormone patterns in long term oral contraceptive users.
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.
Hemrika
D J
DJ
Department of Reproductive Endocrinology and Fertility, O. L. Vrouwe Gasthuis, Amsterdam, The Netherlands.
Slaats
E H
EH
Kennedy
J C
JC
de Vries Robles-Korsen
T J
TJ
Schoemaker
J
J
D000328:Adult; D000704:Analysis of Variance; D003277:Contraceptives, Oral, Combined / Q000494:pharmacology*; D017135:Desogestrel / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology; D006801:Humans; D015592:Immunoradiometric Assay; D016912:Levonorgestrel / Q000494:pharmacology*; D007986:Luteinizing Hormone / Q000097:blood / Q000378:metabolism*; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors
D003277:Contraceptives, Oral, Combined; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol; D016912:Levonorgestrel; D017135:Desogestrel; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone