Pituitary-ovarian hormone levels and symptoms in oral contraceptive users: comparison of a 21/7-day and extended regimen.

OBJECTIVE: To compare hormone levels and symptoms during transition from standard to extended oral contraceptive (OC) regimens. STUDY DESIGN: A prospective analysis of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, and inhibin-B levels with symptoms during 21/7-day vs. 168/7-day extended OCs containing 3 mg of drosperinone and 30 mcg of ethinyl estradiol. Blood samples were obtained from 10 subjects in each of 4 weeks in the 21/7 regimen, in the first 6 weeks of the extended regimen, and again the week before, the week of and the week after the 7-day hormone-free interval (HFI) at the end of the extended regimen. RESULTS: All 4 hormones followed a cyclic pattern with decreasing levels during the 3 active pill weeks of the 21/7 cycle, followed by an increase during the 7-day HFI, which continued into the extended regimen. Levels then decreased during the extended regimen and remained low at week 24. During the 7-day HFI after the extended regimen FSH and LH again increased above baseline (p > 0.07). Hormone withdrawal symptoms increased at the end of 21 active pills with increasing severity during the 7-day HFI. CONCLUSION: Absence of pituitary and ovarian suppression associated with HFI leads to fluctuations in hormones and associated hormone withdrawal symptoms.

Headaches and oral contraceptives: impact of eliminating the standard 7-day placebo interval.

OBJECTIVE: The aim was to assess the timing and severity of self-reported headaches in patients utilizing a standard 28-day oral contraceptive (OC) cycle consisting of 21 hormone (estrogen + progestin)-containing pills and 7 placebo pills (ie, 21/7-day cycle) converted to a placebo-free extended OC regimen. METHODS: An open label single-center prospective analysis of headaches recorded daily on a severity scale of 0 to 10, along with the headache item of the Penn Daily Symptom Rating (DSR17) and a weekly modified Migraine Disability Assessment (MIDAS) headache questionnaire, during standard 21/7-day cycles followed by a 168-day extended placebo-free regimen of an OC containing 3 mg of drosperinone and 30 mcg of ethinyl estradiol (DRSP/EE). RESULTS: Of the 114 patients who began the trial, 111 completed the 21/7-day cycle portion of the study. Based on the headaches scales, there were significant differences in headache severity among the 28 days of the standard 21/7 cycles (P < .001). Greater headache severity occurred on days 25 through 28 during the 7-day placebo interval of the 21/7 cycles (P < .05). Of the 111 patients who completed the 21/7 phase of the study, 102 (92%) completed the 168-day extended placebo-free OC regimen. During the first 28 days of the extended placebo-free regimen, daily headache scores decreased (P < .0001) compared to those of the previous 21 active/7 placebo day cycle. The difference on a daily basis was first detected on extended cycle days 25 through 28 (P < .0001) and persisted throughout the remainder of the 168-day regimen. Subjects were divided into 2 groups (severe and mild) based on the median of the total headache score during the 21/7 OC cycle. The group with higher total headache scores demonstrated a significant (P < .0001) reduction in daily headaches beginning in the first 28-day interval of the extended placebo-free regimen, persisting throughout the entire 168-day extended regimen. In contrast, the group with the lower total headache score remained unchanged (P= .79) throughout the extended regimen. Impact of headaches on work, family, and social functions also improved on the extended placebo-free regimen in 6 of 8 measures (P < .05) assessed by weekly headache questionnaires. CONCLUSION: Compared to a 21/7-day OC regimen, a 168-day extended placebo-free regimen of DRSP/EE led to a decrease in headache severity along with improvement in work productivity and involvement in activities. This is a preliminary study and results may not be widely generalizable.

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. DESIGN: 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.

Oral contraceptives and premenstrual symptoms: comparison of a 21/7 and extended regimen.

OBJECTIVE: The purpose of this study was to assess the incidence and severity of premenstrual-type symptoms in patients converted from a 21/7 oral contraceptive (OC) regimen to an extended regimen. STUDY DESIGN: This was a single center prospective analysis of the single item Scott and White (S&W) Mood Scale and the Penn State Daily Symptom Report (DSR17) during a 21/7-day followed by a 168-day extended regimen of an OC containing 3 mg of drosperinone and 30 microg of ethinyl estradiol (DRSP/EE). RESULTS: Of the 114 patients who began the study, 111 completed the preextension 21/7 phase of the study. There were significant differences in severity in the DSR17 and the S&W mood scale among days of the cycle. (P < .0001) The highest values in both scales occurred during the 7-day hormone free interval (HFI) of the 21/7 cycles (P < .001). Of the 111 patients who completed the 21/7 phase of the study, 102 (92%) completed the 168-day extended regimen. During the extended phase of the study, subjects were divided into 2 groups: those with a 100% increase in symptoms from the first half to the second half of the last 21/7 cycle were labeled as high cyclic variability, whereas those with lesser or no cyclic change were labeled as low cyclic variability. There were 55 (54%) with increased cyclic variability in mood scores peaking during the 7-day HFI. Premenstrual-type symptoms measured by both the S&W mood scale and the DSR17 instrument decreased during the extended DRSP/EE OC regimen (P < .0001) compared with the preceding 21/7 cycle, with the greatest improvement detected in the sixth month of continuous OCs (P < .003). The patient group with greatest cyclic variability during the 21/7 regimen demonstrated the most improvement during the 168-day regimen (P < .0001). The single item S&W mood scale was significantly (P < .05) correlated to each of 17 elements of the DSR17 with Spearman R correlation coefficients of 0.25 to 0.57. The greatest correlation coefficient (Spearman's R = 0.66) is with the sum of all 17 items. CONCLUSION: A 168-day extended regimen of DRSP/EE led to a decrease in premenstrual-type symptoms compared with the 21/7-day regimen.

Prospective analysis of occurrence and management of breakthrough bleeding during an extended oral contraceptive regimen.

OBJECTIVE: The purpose of this study was to assess the bleeding patterns of an extended oral contraceptive (OC) regimen and management of breakthrough bleeding/breakthrough spotting (BTB/BTS). STUDY DESIGN: This was a single-center prospective analysis of self-rated menstrual flow during a 21/7-day versus a 168-day extended regimen of on OC containing 3 mg of drosperinone and 30 mcg of ethinyl estradiol (DRSP/EE) with institution of a randomized protocol to manage BTB/BTS. RESULTS: Of the 111 patients initiating the extended OC regimen, 102 (92%) completed the 168-day regimen. Subjects having a heavier daily flow rating during the 21/7-day pre-extension cycle had greater daily flow ratings (P < .001) and tended to have earlier occurrence of BTB during the extended regimen (P = .07) than subjects with lighter daily flow ratings. If BTB/BTS of at least 7 consecutive days occurred, patients were randomized to taking a 3-day hormone free interval (HFI) versus continuing active pills. Instituting a 3-day HFI was significantly more effective in resolving BTB/BTS than continuing active pills (P < .0001). Patients with heavier daily flow ratings during the 21/7-day cycle were not more likely to be randomized for BTB/BTS than those with lighter flow ratings (P = .53). CONCLUSION: A 168-day extended regimen of DRSP/EE had an acceptable bleeding profile with a high continuation rate. Bleeding during the extended cycle was effectively managed with institution of a 3-day HFI.