Dj. Hemrika et al., THE RESPONSE OF THE PITUITARY-OVARIAN AXIS TO PULSATILE ADMINISTRATION OF GONADOTROPIN-RELEASING-HORMONE IN LONG-TERM ORAL-CONTRACEPTIVE USERS, American journal of obstetrics and gynecology, 170(2), 1994, pp. 462-468
OBJECTIVE: Our purpose was to differentiate between pituitary and hypo
thalamic feedback effects of oral contraceptives. STUDY DESIGN: Twenty
micrograms of gonadotropin-releasing hormone was administered intrave
nously at 90-minute intervals for 4 days to 14 long-term users of a co
mbined oral contraceptive (30 mu g of ethinyl estradiol and 150 mu g o
f levonorgestrel), starting at different moments in the pill cycle. On
the fourth day of administration the pulsatile release of luteinizing
hormone was determined by blood sampling every 10 minutes for 6 hours
. The sensitivity of the pituitary was determined before, during, and
after treatment with gonadotropin-releasing hormone by a 100 mu g gona
dotropin-releasing hormone challenge test. On each sampling day serum
estradiol, progesterone, and prolactin levels were measured, and ovari
an ultrasonography was performed. RESULTS: After 4 days of pulsatile g
onadotropin-releasing hormone administration every exogenous gonadotro
pin-releasing hormone bolus was followed by an endogenous luteinizing
hormone pulse of high amplitude (median 3.30 U/L). Both serum luteiniz
ing hormone and follicle-stimulating hormone levels increased signific
antly (p < 0.001). The increase in follicle-stimulating hormone levels
was accompanied by an increase in serum estradiol (p < 0.01). The lut
einizing hormone response to a 100 mu g bolus of gonadotropin-releasin
g hormone decreased during gonadotropin-releasing hormone treatment (p
< 0.01), whereas the follicle-stimulating hormone response did not ch
ange. CONCLUSION: Pituitary sensitivity is not impaired during oral co
ntraceptive use, suggesting that oral contraceptives exert their negat
ive feedback effects predominantly at the hypothalamic level.