ABSTRACT
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. STUDY DESIGN: 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). CONCLUSION: 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.
Subject(s)
Cervix Mucus/drug effects , Contraceptives, Oral, Combined/pharmacokinetics , Contraceptives, Oral, Hormonal/pharmacokinetics , Estradiol/metabolism , Ovary/drug effects , Pituitary Gland/drug effects , Progesterone/metabolism , Adult , Cervix Mucus/metabolism , Contraceptives, Oral, Combined/blood , Contraceptives, Oral, Combined/metabolism , Contraceptives, Oral, Combined/pharmacology , Contraceptives, Oral, Hormonal/blood , Contraceptives, Oral, Hormonal/metabolism , Contraceptives, Oral, Hormonal/pharmacology , Cross-Over Studies , Estradiol/analogs & derivatives , Estradiol/blood , Ethinyl Estradiol/blood , Ethinyl Estradiol/metabolism , Ethinyl Estradiol/pharmacokinetics , Ethinyl Estradiol/pharmacology , Female , Follicular Phase , Humans , Norethindrone/analogs & derivatives , Norethindrone/blood , Norethindrone/metabolism , Norethindrone/pharmacokinetics , Norethindrone/pharmacology , Norethindrone Acetate , Ovary/metabolism , Ovulation Inhibition/drug effects , Patient Dropouts , Pituitary Gland/metabolism , Progesterone/blood , Single-Blind Method , Tissue Distribution , Young AdultABSTRACT
BACKGROUND: Few studies have examined the action of combined oral contraceptives (COCs) on cervical mucus. We hypothesized that midcycle cervical mucus of women taking COCs is of poor quality when compared to their own midcycle mucus prior to initiating COCs. We sought to compare the effect upon quality and sperm penetration of the cervical mucus on the last hormone-free day with a 24/4 regimen to a 21/7 regimen. METHODS: This is an open-label, investigator-blinded, randomized, controlled, crossover equivalency study. All subjects received, in random order, 2 months of a 21/7 regimen and 2 months of a 24/4 regimen, each containing 20 mcg ethinyl estradiol and 1 mg norethindrone acetate. Analysis of cervical mucus quality (CMQ) and sperm penetration took place midcycle and on the last day of the hormone-free interval during the second month of each COC treatment. RESULTS: From April 2010 to November 2011, 18 subjects completed all study visits. Mean midcycle CMQ was poor (mean CMQ=1) and did not differ between 24/4 and 21/7 regimens (p=.92). On the last day of the pill-free interval, the quality and sperm penetration were poor with both regimens. CONCLUSION: This study indicates that thickening of cervical mucus is a major mechanism of contraceptive action of COCs and that both 21/7 and 24/4 regimens result in poor quality and impenetrable mucus on the last day of the pill-free interval.
Subject(s)
Cervix Mucus/drug effects , Cervix Uteri/drug effects , Contraceptives, Oral, Combined/pharmacology , Menstrual Cycle , Adult , Cervix Mucus/chemistry , Cervix Mucus/metabolism , Cervix Uteri/metabolism , Chemical Phenomena/drug effects , Contraceptives, Oral, Combined/administration & dosage , Cross-Over Studies , Cryopreservation , Drug Administration Schedule , Ethinyl Estradiol/administration & dosage , Ethinyl Estradiol/pharmacology , Female , Humans , Male , Norethindrone/administration & dosage , Norethindrone/analogs & derivatives , Norethindrone/pharmacology , Norethindrone Acetate , Patient Dropouts , Semen Preservation , Single-Blind Method , Sperm Transport , Viscosity/drug effects , Young AdultABSTRACT
Approximately 25% of elderly patients scheduled for carotid endarterectomy (CEA) develop post-operative cognitive dysfunction (CD). We tested the hypothesis that the plasma levels of matrix metalloproteinase 9 (MMP-9) are predictive of moderate to severe CD after CEA. A total of 73 patients were prospectively enrolled in this Institutional Review Board-approved study. Plasma samples were obtained at baseline and day 1 post-surgery. We measured the plasma concentrations of both MMP-9 and its inhibitor, tissue inhibitor of metalloproteinases 1 (TIMP-1). We estimated the MMP-9 activity by calculating the MMP-9:TIMP-1 ratio. The cognitive performance day 1 post-surgery was quantified with z-scores, using a control group who were undergoing spinal surgery. The criteria used to define CD was performance of >or=1.5 standard deviations worse than the control group; approximately 19% of eligible patients developed CD. Compared to patients without CD, this group had both higher total (81.66+/-12.25 ng/mL versus [vs.] 43.18+/-4.44 ng/mL, p=0.005) and activity (0.88+/-0.24 ng/mL vs. 0.54+/-0.06 ng/mL, p=0.003) MMP-9 levels at baseline. All of the results were adjusted for age, diabetes and neurovascular symptoms.
