Dj. Hemrika et al., PULSATILE LUTEINIZING-HORMONE PATTERNS IN LONG-TERM ORAL-CONTRACEPTIVE USERS, The Journal of clinical endocrinology and metabolism, 77(2), 1993, pp. 420-426
Oral contraceptives (OC) inhibit folliculogenesis by a central suppres
sive action on the release of gonadotropins. To characterize the natur
e of these central effects, we studied 40 long term OC users on 3 diff
erent OCs: two monophasic preparations with 30 mug ethinyl estradiol a
nd 150 mug 1-norgestrel (group 1; n = 15), 150 mug desogestrel (group
2; n = 10), and a triphasic formulation containing 30-40 mug ethinyl e
stradiol and 50, 75, and 125 mug 1-norgestrel (group 3; n = 15). Blood
sampling at 10-min intervals during 6-h periods was performed at diff
erent moments in the pill cycle. Thirteen healthy volunteers with regu
lar ovulatory cycles served as normal controls. FSH and LH were measur
ed by a sensitive immunoradiometric assay. Pulsatile LH release was ob
served in all OC users. Mean serum LH and FSH levels, number of LH pul
ses 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, wherea
s LH levels progressively declined in groups 1 and 2 from day 8 onward
. In group 3, however, LH levels were only significantly suppressed af
ter day 13. The number of LH pulses per 6 h decreased in all groups st
arting on day 2, whereas the amplitude of LH pulses increased. A subst
antial percentage of LH pulses observed in OC users after day 1 were o
f 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) modulat
ion of LH pulse amplitudes, and subsequently of serum LH levels, is ma
inly mediated by a dose- and time-dependent effect of the gestagenic c
omponent of the OC; and 5) after the 7-day pill-free interval, a norma
l early follicular phase pulse pattern is found, even in long term OC
users, suggesting that in this period, most of the steroidogenic feedb
ack effects wear off.