Greater inhibition of the pituitary--ovarian axis in oral contraceptive regimens with a shortened hormone-free interval.
OBJECTIVE
Our objective was to test the hypothesis that shortening the hormone-free interval (HFI) between cycles of 21 days of oral contraceptives (OCs) reduces pituitary secretion of gonadotropins and ovarian production of estradiol and inhibin-B.


METHODS
We used a prospective trial design comparing the standard 7-day HFI and shortened HFI during cycles, with an OC containing 0.03 mg of ethinyl estradiol and 3 mg of drospirenone.


METHODS
Twelve current OC users initially utilized an OC in the standard fashion, with 21 days of active pills and a 7-day HFI, followed by 21 days of active pills with randomization to either a 3-day or a 4-day HFI. Nine daily blood samples were obtained for the measurement of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol and inhibin-B, beginning with active pill 21 days before each HFI of the two cycles. Analysis of variance was used to compare hormones for 9 days bracketing the standard 7-day HFI and to compare, within individuals, the 7-day HFI and the subsequent shortened HFI.


RESULTS
During the 7-day HFI, all four hormones significantly (p>.001) increased from baseline. FSH increased beginning on HFI Day 4, inhibin-B increased beginning on HFI Day 5, and LH and estradiol increased beginning on HFI Day 6. Subjects randomized to the 3-day or the 4-day HFI did not differ with regard to age and body size (p=.88) or initial hormone level (p=.67). Greater pituitary and ovarian suppression was seen with the shortened HFI for all four hormones (p<.001). Hormone levels in the 7 days after the last active pill of the second cycle did not differ (p>.4) between the 3-day and the 4-day HFI groups.


CONCLUSIONS
Shortening the HFI from 7 days to 3 or 4 days blunts increases in the pituitary-ovarian axis during cycles of OC use.
Willis
Sherilyn A
SA
Departments of Obstetrics and Gynecology, Pathology, and Medical Biochemistry and Genetics, Scott and White Memorial Hospital and Clinic, Temple, TX 76508, USA.
Kuehl
Thomas J
TJ
Spiekerman
A Michael
AM
Sulak
Patricia J
PJ
D000328:Adult; D003276:Contraceptives, Oral / Q000008:administration & dosage*; D004958:Estradiol / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D007265:Inhibins / Q000097:blood; D007986:Luteinizing Hormone / Q000097:blood; D010053:Ovary / Q000187:drug effects / Q000502:physiology*; D010902:Pituitary Gland / Q000187:drug effects / Q000502:physiology*; D011446:Prospective Studies
D003276:Contraceptives, Oral; C422364:inhibin B; D004958:Estradiol; D007265:Inhibins; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone