Comparison of serum and cervical mucus hormone levels during hormone-free interval of 24/4 vs. 21/7 combined oral contraceptives.
BACKGROUND
This study analyzes levels of progesterone, estradiol, norethindrone (NET) and ethinyl estradiol (EE) in serum and levels of NET in cervical mucus on the last day of the hormone-free interval (HFI) in users of 24/4 [norethindrone acetate (NETA)/EE-24] vs. 21/7 (NETA/EE-21) regimens.


METHODS
This was a randomized controlled, crossover, equivalency trial. Subjects were randomized to receive NETA/EE-24 or NETA/EE-21 for 2 months and then switched between study drugs. Blood and cervical mucus samples were obtained on Days 12-16 and on the last day of the HFI.


RESULTS
From April 2010 to November 2011, 32 subjects were enrolled with 18 subjects completing all study visits. There were no statistically significant differences in either day 12-16 (p=.54) or last hormone-free day (p=.33) cervical mucus NET concentrations between the regimens. On the last day of the HFI, median serum progesterone levels did not differ significantly; however, users of NETA/EE-24 had higher levels of serum NET (p<.001) and users of NETA/EE-21 had higher levels of serum estradiol (p=.01).


CONCLUSIONS
This data supports the fact that inhibition of the pituitary-ovarian axis occurs during oral contraceptive use and during the HFI. We demonstrated that a reduced HFI of 4 days resulted in better suppression of the ovarian hormone production, thereby reducing the risk of ovulation and potential contraceptive failure.
Department of Obstetrics and Gynecology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Heather
H
Fels
Rachel
R
Steward
Alexander
A
Melamed
Anna
A
Granat
Frank Z
FZ
Stanczyk
Daniel R
DR
Mishell
D000328:Adult; D002582:Cervix Mucus / Q000187:drug effects* / Q000378:metabolism; D003277:Contraceptives, Oral, Combined / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics* / Q000494:pharmacology; D003278:Contraceptives, Oral, Hormonal / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics* / Q000494:pharmacology; D018592:Cross-Over Studies; D004958:Estradiol / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism*; D004997:Ethinyl Estradiol / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology; D005260:Female; D005498:Follicular Phase; D006801:Humans; D009640:Norethindrone / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology; D000077563:Norethindrone Acetate; D010053:Ovary / Q000187:drug effects* / Q000378:metabolism; D034445:Ovulation Inhibition / Q000187:drug effects; D010352:Patient Dropouts; D010902:Pituitary Gland / Q000187:drug effects* / Q000378:metabolism; D011374:Progesterone / Q000097:blood / Q000378:metabolism*; D016037:Single-Blind Method; D014018:Tissue Distribution; D055815:Young Adult
D003277:Contraceptives, Oral, Combined; D003278:Contraceptives, Oral, Hormonal; D004997:Ethinyl Estradiol; D011374:Progesterone; D004958:Estradiol; D000077563:Norethindrone Acetate; D009640:Norethindrone