Extended cycle combined oral contraceptives and prophylactic frovatriptan during the hormone-free interval in women with menstrual-related migraines.

BACKGROUND: Migraine headaches are a significant problem for American women with many of them suffering from headaches around the time of their menstrual cycle. Women taking oral contraceptives in the standard 21/7 cycle regimen often suffer from headaches around the time of the hormone free intervals (HFIs) as well. Extended oral contraceptive regimens have been shown to decrease the frequency, but not eliminate these headaches. This study is a double-blind, randomized, placebo-controlled pilot study of participants with menstrual-related migraines (MRMs) who were initiated on extended combined oral contraceptives and given frovatriptan prophylactically during HFIs. METHODS: Participants having spontaneous menstrual cycles or taking daily combined oral contraceptives in a 21/7 regimen with MRMs were placed on a contraceptive containing levonorgestrel and ethinyl estradiol. Analyses compared headache scores during pre-study baseline cycles to those in a 168-day extended regimen with placebo versus frovatriptan treatments during HFIs. RESULTS: Daily headache scores decreased (p=0.034) from 1.29 ± 0.10 during pre-study cycles to 1.10 ± 0.14 during extended combined oral contraceptive use. Frovatriptan blocked the increase in headache score over the placebo during HFIs. However, following the withdrawal of frovatriptan, headache scores increased (p>0.01) despite resuming combined oral contraceptive use. CONCLUSIONS: Extended combined oral contraceptive regimen reduces MRM severity. Frovatriptan prevents headaches during HFIs, but is associated with new headache symptoms when withdrawn.

Muchas mujeres podrían preferir un régimen extendido de anticonceptivos orales / Premenstrual symptomatology and oral contraceptives

Los síntomas relacionados con la menstruación son frecuentes en mujeres en edad fértil, incluso en aquellas que están tomando anticonceptivos orales. A pesar de que el diagnóstico de síndrome premenstrual se basa en mujeres que tienen síntomas durante la ovulación, estos síntomas, que incluyen los emocionales, han sido descritos en mujeres que toman anticonceptivos por vía oral en un régimen 21/7. En una investigación en mujeres que utilizan un régimen extendido de anticonceptivos orales (que omite los siete días de intervalo libre de hormonas) y contiene drosperinona y etinilestradiol se halló una mejoría en los síntomas relacionados con la menstruación, incluidos los afectivos. El mayor inconveniente de los regímenes extendidos es el molesto inconveniente del sangrado intermenstrual. Se ha demostrado que el intervalo de tres días libre de hormonas, en los casos de problemas de sangrado prolongado, resuelve más a menudo los casos de pérdidas que la toma continua de comprimidos activos. Un régimen extendido es un plan terapéutico aceptable para muchas mujeres porque es una modificación o una reanudación de un tratamiento previamente utilizado en oposición al agregado de medicación psicotrópica.

Frequency and management of breakthrough bleeding with continuous use of the transvaginal contraceptive ring: a randomized controlled trial.

OBJECTIVE: To assess bleeding patterns with continuous use of the transvaginal contraceptive ring. METHODS: We did a prospective analysis of daily menstrual flow during a 21/7 cycle followed by 6 months of continuous use and institution of a randomized protocol to manage breakthrough bleeding/spotting. Seventy-four women completed the baseline 21/7 phase and were randomized equally into two groups during the continuous phase. Group 1 was instructed to replace the ring monthly on the same calendar day with no ring-free days. Group 2 was instructed to use the same process, but if breakthrough bleeding/spotting occurred for 5 days or more, they were to remove the ring for 4 days, store it, and then reinsert that ring. RESULTS: Sixty-five women completed the continuous phase with reduced average flow scores in the continuous phase compared with the 21/7 phase (P<.02). Most patients had no to minimal bleeding during continuous use, with group 2 experiencing a statistically greater percentage of days without breakthrough bleeding or spotting (95%) compared with group 1 (89%) (P=.016). Instituting a 4-day hormone-free interval was more (P<.001) effective in resolving breakthrough bleeding/spotting than continuing ring use. CONCLUSION: A reduction in bleeding occurred during continuous use with replacement of the transvaginal ring compared with baseline 21/7 use. Continuous vaginal ring use resulted in an acceptable bleeding profile in most patients, reduction in flow, reduction in pelvic pain, and a high continuation rate.

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.

Comparison of scales for evaluating premenstrual symptoms in women using oral contraceptives.

STUDY OBJECTIVE: To compare two scales used in research to evaluate daily premenstrual mood symptoms during use of a monophasic oral contraceptive. DESIGN: Subanalysis of data from a prospective study. SETTING: University-affiliated medical center. SUBJECTS; One hundred two reproductive-aged (18-48 yrs) women taking a monophasic oral contraceptive containing ethinyl estradiol and drospirenone in the standard 21-7 fashion (21 days of hormones followed by 7 days of placebo), and who had self-identified premenstrual symptoms of headache, mood changes, or pelvic pain. INTERVENTION: Subjects completed a single-item questionnaire, the Scott & White Daily Diary of Symptoms, and a multiple-item questionnaire, the Penn State Daily Symptom Report (DSR), to assess their premenstrual symptoms. The Scott & White diary used a visual analog scale of 0-10 to assess pelvic pain, headache, and mood (a composite of anxiety, depression, and irritability). The Penn State DSR contained 17 items: 10 behavioral and seven physical components, each rated on a scale of 0-4, with one item that specifically rated mood swings. MEASUREMENTS AND MAIN RESULTS: Scores from the two scales were compared by using Spearman correlation coefficients, the Kendall W for concordance, and linear regression of ranked sums for study cycles. The Scott & White mood score significantly correlated with the total of the 17 items on the Penn State DSR, as well as the 10 behavioral items, the seven physical items, and the single mood-swing item (p<0.0001); specific coefficients of concordance were 0.44, 0.23, 0.10, and 0.28, respectively, and R2 values were 0.39, 0.39, 0.30, and 0.34, respectively. The daily Scott & White mood score was positively correlated with all 17 elements of the Penn State DSR (0.25-0.57). The greatest correlation was seen with the mood-swing element. Both instruments demonstrated the same patterns during the 21-7 oral contraceptive cycle, with symptoms increasing immediately before and peaking during the 7-day hormone-free interval. CONCLUSION: A single-item daily mood score using a rating scale of 0-10 was concordant with a relatively complex 17-element symptom index and demonstrated the same pattern of change during cycles of oral contraception. The simple scoring system offers an advantage, especially in clinical studies of long duration.

Evaluation of pituitary-ovarian axis suppression with three oral contraceptive regimens.

BACKGROUND: The study was conducted to evaluate follicular development and hormone patterns with three oral contraceptive (OC) regimens before, during and after the 7-day hormone-free interval (HFI) or 7-day ethinyl estradiol (EE)-supplemented interval. STUDY DESIGN: The study is a single-center, open-label, prospective, randomized trial to evaluate pituitary-ovarian suppression with three OC regimens containing identical hormones: 30 mcg of EE and 150 mcg of levonorgestrel (LNG). METHODS: After a standard 21/7 OC baseline cycle, subjects were randomized to one of three treatment groups: (1) three 21/7-day cycles of 150 mcg LNG/30 mcg EE for 21 days followed by 7 days of placebo (n=10); (2) one 84/7-day cycle of 150 mcg LNG/30 mcg EE for 84 days followed by 7 days of placebo (n=12) and (3) one 84/7EE-day cycle of 150 mcg LNG/30 mcg EE for 84 days followed by 7 days of 10 mcg EE (n=11). Estradiol; follicle-stimulating hormone (FSH); luteinizing hormone and inhibin-B levels, ovarian follicles and daily symptom diaries were collected. RESULTS: Compared to subjects receiving placebo during the 7-day HFI, those receiving EE demonstrated reductions (p<.05) in both FSH and estradiol. Number of developing follicles was less after the 7-day EE interval compared to that after 7-day HFI. Subjects on the 84/7 and 84/7EE regimens reported less (p=.03) daily menstrual flow than those on the 21/7-day regimen. A trend (p=.06) toward reduced headaches during the 7-day EE-supplemented interval was noted. CONCLUSIONS: Supplementation of the standard 7-day HFI with 10 mcg EE after 84 days of an extended OC decreased FSH levels and decreased the number of developing follicles.

Long-term assessment of symptomatology and satisfaction of an extended oral contraceptive regimen.

OBJECTIVE: The study was conducted to assess hormone withdrawal symptoms, patient acceptance and occurrence and management of bleeding with an extended oral contraceptive (OC) regimen. METHODS: Subjects were placed on an OC containing 3 mg drosperinone (DRSP) and 30 microg ethinyl estradiol (EE), in the standard 21/7 fashion for two cycles, before converting to an extended pattern of OC for women who indicated they had menstrually related symptoms such as headaches, cramping and mood swings (52 weeks with phone-call follow-up 6 months later). Daily assessments of bleeding, headache, pelvic pain, mood and number of pain pills were recorded. Results are reported as means with S.E., and values were compared using analysis of variance with Dunnett's post hoc test for comparison with 21/7 cycle, Duncan's post hoc test for comparison of changes during the course of the extended regimen and Pearson's chi-square for comparison of proportions. RESULTS: Of the 111 women who began the extended OC regimen, 80 completed 1 year of use. Mood scores, headache scores and pelvic pain were all improved in the extended OC intervals, compared to the 21/7 cycle (p<.001 for all comparisons). Improvement in symptoms persisted throughout the 1 year extended regimen. The findings indicated that 53.7% of subjects had no breakthrough bleeding or breakthrough spotting (BTB/BTS) during any given 28-day interval of the extended regimen. BTB/BTS decreased in the second half compared to the first half of the extended regimen. To manage BTB/BTS, instituting a 3-day hormone-free interval (HFI) was significantly more effective than continuing OCs (p<.001). At the 6-month follow-up, most subjects had continued the extended regimen on their own with a high level of satisfaction. CONCLUSIONS: An extended OC regimen containing DRSP/EE significantly improved mood, headaches and pelvic pain scores throughout the 1 year of use, compared to a 21/7 cycle. Sustained BTB/BTS episodes occurred in 45 subjects (56%), decreasing in the second half of the study and effectively managed with a 3-day HFI.

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.

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.

Outcomes of extended oral contraceptive regimens with a shortened hormone-free interval to manage breakthrough bleeding.

OBJECTIVE: To evaluate in a clinical practice setting the acceptance, continuation and variability of extending the active interval of oral contraceptives (OCs) with introduction of a shortened hormone-free interval (HFI) to manage breakthrough bleeding. METHODS: A retrospective review was undertaken of patients seen by one obstetrician/gynecologist and counseled on extending the active interval of OCs with a shortened HFI of 3-4 days to manage bleeding. Electronic medical records were searched for the phrase "extending the number of active pills" for patients counseled between January 1, 2000, and January 31, 2003, with follow-up through January 31, 2004. A structured query of each patient's initial and follow-up records was performed. RESULTS: The 220 patients counseled on the extended regimen were 14-52 years of age (mean 36.4, SD 9.3 years). At initial counseling before extending, the majority of patients cited more than one reason for using OCs in the standard fashion with 59% using OCs for noncontraceptive reasons. Reasons for extending the active interval of OCs included premenstrual symptoms (45%), dysmenorrhea/pelvic pain (40%), heavy withdrawal bleeding (36%), menstrual associated headaches (35%), convenience (13%), acne associated with menses (10%) and other (15%). Of the 181 patients with follow-up data, 174 (96%) attempted an extended regimen with 121 (67%) continuing to do so at last follow-up. Follow-up intervals ranged from 0.3 to 3.8 years (mean 1.6 years). Using Kaplan-Meier product limit survival analysis, 60% of patients continued using extended patterns of OCs for more than 2 years. For 121 currently extending, the HFI varied from 0 to 7 days with 88% utilizing a 0 to 4 day HFI. CONCLUSIONS: Sixty percent of patients offered extending the active interval and shortening the HFI of OCs initiate and continue this pattern for more than 2 years without serious sequelae or pregnancy while individually directing both the number of days of continuous pills and the length of the HFI.