Cycle control with a 21-day compared with a 24-day oral contraceptive pill: a randomized controlled trial.

Abstract

To compare bleeding patterns between a 21/7-day triphasic norgestimate/ethinyl estradiol (E2) 25-microgram oral contraceptive pill (OCP) and a 24/4-day drospirenone/ethinyl E2 20-microgram OCP.
In a three-cycle, open-label, multicenter study, healthy, sexually active women were assigned randomly to a 21/7-day (norgestimate/ethinyl E2) or 24/4-day (drospirenone/ethinyl E2) OCP regimen. Randomization was stratified to assure a balanced distribution between regimens for "fresh starts" and "switchers." Bleeding data were collected daily using an interactive voice-response system. Bleeding was defined according to the 2007 U.S. Food and Drug Administration's Reproductive Health Drug Advisory Committee-endorsed criteria.
Across the three cycles, the 21/7-day OCP group (n=165) reported fewer unscheduled bleeding days than did the 24/4-day OCP group (n=167) (mean 4.6 compared with 6.1 days, P=.003). Women using the 21/7-day OCP had significantly fewer episodes of unscheduled bleeding than did those using the 24/4-day OCP (mean 1.47 compared with 2.01, P=.001). Moreover, women using the 21/7-day OCP had a significantly lower absence of scheduled bleeding at each cycle (P<.001). Both regimens were well-tolerated.
A 21-day norgestimate/ethinyl E2 25-microgram regimen results in less unscheduled bleeding and more scheduled bleeding than does a 24-day drospirenone/ethinyl E2 20-microgram regimen.
ClinicalTrials.gov, www.ClinicalTrials.gov, NCT00745901.
I.

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Cycle Control With a 21-Day Compared
With a 24-Day Oral Contraceptive Pill
A Randomized Controlled Trial
Andrew M. Kaunitz, MD, Ronald T. Burkman, MD, Alan C. Fisher, DrPH,
and Katherine D. LaGuardia, MD, MPH
OBJECTIVE: To compare bleeding patterns between a
21/7-day triphasic norgestimate/ethinyl estradiol (E2) 25-
microgram oral contraceptive pill (OCP) and a 24/4-day
drospirenone/ethinyl E2 20-microgram OCP.
METHODS: In a three-cycle, open-label, multicenter study,
healthy, sexually active women were assigned randomly
to a 21/7-day (norgestimate/ethinyl E2) or 24/4-day (dro-
spirenone/ethinyl E2) OCP regimen. Randomization was
stratified to assure a balanced distribution between reg-
imens for “fresh starts” and “switchers.” Bleeding data
were collected daily using an interactive voice-response
system. Bleeding was defined according to the 2007 U.S.
Food and Drug Administration’s Reproductive Health
Drug Advisory Committee–endorsed criteria.
RESULTS: Across the three cycles, the 21/7-day OCP
group (n?165) reported fewer unscheduled bleeding
days than did the 24/4-day OCP group (n?167) (mean 4.6
compared with 6.1 days, P?.003). Women using the
21/7-day OCP had significantly fewer episodes of un-
scheduled bleeding than did those using the 24/4-day
OCP (mean 1.47 compared with 2.01, P?.001). Moreover,
women using the 21/7-day OCP had a significantly lower
absence of scheduled bleeding at each cycle (P<.001).
Both regimens were well-tolerated.
CONCLUSION: A 21-day norgestimate/ethinyl E2 25-
microgram regimen results in less unscheduled bleeding
and more scheduled bleeding than does a 24-day dro-
spirenone/ethinyl E2 20-microgram regimen.
CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.
ClinicalTrials.gov, NCT00745901.
(Obstet Gynecol 2009;114:1205–12)
LEVEL OF EVIDENCE: I
O
have been reduced substantially.1Most of the OCPs
currently prescribed in the United States contain 35
micrograms or less of ethinyl estradiol (E2), and formu-
lations containing as little as 20 micrograms ethinyl E2
are available.2However, although efficacy is compara-
ble with higher-dose formulations, the use of OCPs
containing only 20 micrograms ethinyl E2 has been
associated with less favorable bleeding patterns, which
may include intermenstrual bleeding or spotting or
both, particularly during the first several months of
use.3Women who experience irregular bleeding often
discontinue use of OCPs.4–6A survey of more than
6,000 European women found that those who expe-
rienced bleeding problems during the first 3 months
ver the past 40 years, the doses of estrogen and
progestin in oral contraceptive pills (OCPs)
From the Department of Obstetrics and Gynecology, University of Florida
College of Medicine, Jacksonville, Florida; the Department of Obstetrics and
Gynecology, Baystate Medical Center, Springfield, Massachusetts; and Ortho-
McNeil-Janssen Scientific Affairs, Raritan, New Jersey.
Funded by Ortho-McNeil-Janssen Scientific Affairs, Raritan, New Jersey.
The authors thank the co-investigators for patient recruitment, clinical evalua-
tion, and all necessary data-monitoring and collection: Catherine Dean, Nigel
Dalahunty, Janet Gersten, Phillip Hadley, Raymond Hampton, Frederick
Jenkin, Vicki Kalen, Rebecca Knight, Samuel McNeeley, Edmond Pack, Howard
Reisman, James Rice, Benton Satterfield, Larry Seidman, Herbert Soper,
Louise Taber, Steven Thackeray, and Wallace Wilkerson.
Presented in part at the 57th Annual Clinical Meeting of the American College
of Obstetricians and Gynecologists, May 2–6, 2009, Chicago, Illinois.
Corresponding author: Andrew M. Kaunitz, MD, 4555 Emerson Expressway,
Suite 220, Jacksonville, FL 32207; e-mail: andrew.kaunitz@jax.ufl.edu.
Financial Disclosure
Dr . Kaunitz consults with Johnson & Johnson (New Brunswick, NJ) and Bayer
HealthCare (Wayne, NJ). His department receives funding for conducting
clinical trials from Johnson & Johnson and Bayer HealthCare. Dr. Burkman
has received research support from the Eunice Kennedy Shriver National
Institute of Child Health and Human Development (Rockville, MD), Yale
University (New Haven, CT), and Ortho-McNeil (Raritan, NJ), and he is a
consultant for Ortho-McNeil, Columbia Laboratories (Livingston, NJ),
Veritech Corporation (East Longmeadow, Massachusetts), and Schering-
Plough (Kenilworth, NJ). Drs. Fisher and LaGuardia are employees of
Johnson & Johnson.
© 2009 by The American College of Obstetricians and Gynecologists. Published
by Lippincott Williams & Wilkins.
ISSN: 0029-7844/09
VOL. 114, NO. 6, DECEMBER 2009OBSTETRICS & GYNECOLOGY
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were twice as likely to stop OCP use as those who did
not report bleeding problems during this time.4
It has been suggested that extending the duration
of active hormonal treatment from 21 to 24 days may
decrease the duration and intensity of withdrawal
bleeding and reduce intermenstrual bleeding and
spotting.7Results of one head-to-head comparison of
21-day and 24-day regimens of norethindrone ace-
tate/ethinyl E2 20 micrograms showed that, although
the mean cumulative days of withdrawal bleeding
over cycles 2 to 6 was less with the 24-day regimen
than with the 21-day regimen, the mean number of
days of unscheduled bleeding was not reduced signif-
icantly until cycle 6.7Although the unscheduled
bleeding pattern with a 21-day regimen of norethin-
drone acetate/ethinyl E2 20 micrograms appears to
be similar to that of a 24-day regimen of norethin-
drone acetate/ethinyl E2 20 micrograms, using old
definitions, it is inferior to that with the 21-day
norgestimate/ethinyl E2 25-microgram regimen.7,8
Little has been published about bleeding patterns
with another 20 micrograms ethinyl E2 OCP with a
24-day regimen and containing 3 mg of drospirenone
(drospirenone/ethinyl E2 20 micrograms). Results of
a noncomparative trial with a 24-day regimen of
drospirenone/ethinyl E2 20 micrograms suggested a
favorable bleeding profile9; however, a comparative
trial of a 24-day regimen of drospirenone/ethinyl E2
20 micrograms and a 21-day regimen of desogestrel
150 micrograms/ethinyl E2 20 micrograms found no
significant difference in bleeding/spotting episodes.10
The aforementioned studies used various defini-
tions of measuring bleeding patterns that are not
similar to those recently recommended by Mishell
and colleagues and endorsed by the U.S. Food and
Drug Administration’s (FDA) Reproductive Health
Drugs Advisory Committee.11–13The present study
was undertaken to compare bleeding patterns with a
21/7-day regimen of norgestimate/ethinyl E2 25 mi-
crograms(ORTHOTRI-CYCLENLO,Ortho-McNeil-
Janssen Pharmaceuticals, Inc., Raritan, NJ) and a
24/4-day regimen of drospirenone/ethinyl E2 20 mi-
crograms (YAZ, Bayer HealthCare LLC, Wayne, NJ).
The FDA-endorsed terminology and definitions for
bleeding variables were used for this trial.12In addi-
tion, bleeding information was collected using an
interactive voice-response system.12
MATERIALS AND METHODS
This randomized, open-label, active-controlled study
was conducted at 20 centers in the United States. The
protocol was approved by central or local institutional
review boards. Eligible participants included healthy,
nonpregnant, nonlactating, sexually active women
aged 18 to 45 years seeking oral hormonal contracep-
tion. Among participants aged 35 to 45 years, only
those who were nonsmokers were included. Eligible
participants had regular menstrual cycles, including at
least one normal menstrual period (typical in duration
and amount of flow for the participant) within 35 days
of the first study visit, a negative Chlamydia test (urine
or cervical swab), and a Pap test without evidence of
moderate to severe dysplasia or any malignancy within
the preceding 12 months. All eligible participants gave
written informed consent. Exclusion criteria included a
history or presence of disorders commonly accepted as
contraindications to steroid hormone therapy, an un-
treated thyroid disorder, or a body mass index greater
than 40 kg/m.2Also excluded were participants who
previously discontinued norgestimate/ethinyl E2 or
drospirenone/ethinyl E2 owing to breakthrough bleed-
ing, received depot medroxyprogesterone acetate or
other hormonal injectables within 6 months of screen-
ing or other hormonal implants in place or removed
within 60 days of screening, or had used a steroid-
containing intrauterine device within 3 months before
screening.
The sample size for this study was based on
information from prior studies on total number of
bleeding days across cycles 1 to 3.14,15The mean for
the total bleeding days was expected to be 22.2
(standard deviation 7.8) for drospirenone/ethinyl E2
and 18.9 (standard deviation 6.9) for norgestimate/
ethinyl E2. Based on a mean difference of 3.3 days
and a conservative pooled standard deviation of 7.8,
119 participants in each group would have 90%
power to show a difference between treatment groups
at an alpha level of 0.05 (two-tailed).
Using a computer-generated randomization sched-
ule, participants were randomly assigned 1:1 to treat-
ment with study medication for three 28-day cycles,
with randomization stratified by center and recent
hormonal contraceptive exposure (ie, fresh starts
compared with switchers). Fresh starts were defined
as women who had not been on a hormonal contra-
ceptive for 60 days or more, and switchers were
defined as those who had been on a hormonal contra-
ceptive within the previous 60 days.
Bleeding patterns and adherence were evaluated
from data recorded daily from day 1 to day 85 using
an interactive voice-response system–based diary.
Participants responded to the following questions: 1)
Did you take your birth control pill yesterday? 2) Did
you have any vaginal blood loss yesterday? If yes, 3)
Please describe the blood loss (reported as light,
medium, or heavy), 4) Did you use any sanitary
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protection (for example, tampon, pad, or pantiliner)
for your blood loss yesterday? If participants missed
calling on a particular day, they were contacted daily
by the study site with a reminder. Participants were
allowed to enter diary data into the interactive voice-
response system for up to 7 days after the expected
date (backfilled data). The following questions were
asked for backfilled data: 1) Did you take your birth
control pill on (read out day, date)? 2) Did you have
any vaginal blood loss on that date? Data not entered
within 7 days were classified as missing.
Bleeding was defined according to the 2007
FDA’s Reproductive Health Drug Advisory Commit-
tee–endorsed criteria with one exception—an un-
scheduled bleeding episode was defined using the
Belsey/World Health Organization definition (see
Table 1).12,16Because days 1 through 7 of cycle 1 were
excluded from the analysis of bleeding per the FDA-
endorsed criteria, only those participants who took
study medication for at least 7 days and had postbase-
line bleeding data after day 7 were included in the
analysis of cycle control.12The primary efficacy vari-
able was the participant’s total number of unsched-
uled bleeding days during cycles 1 through 3 as
recorded daily using the interactive voice-response
system diary. Secondary efficacy variables analyzed
for each of cycles 1 to 3 and cumulatively included: 1)
incidence of unscheduled bleeding, 2) mean number
of unscheduled bleeding episodes, 3) incidence of
scheduled bleeding, and 4) mean number of sched-
uled bleeding days. In the cycle analysis, unscheduled
bleeding episodes may be bounded by scheduled
bleeding days. Other secondary efficacy variables
included the incidence of total bleeding during days 8
to 84 and participant satisfaction with the OCP regi-
men rated at the end of the study as very satisfied,
somewhat satisfied, neither satisfied nor dissatisfied,
somewhat dissatisfied, or very dissatisfied.
Adverse-event data were collected and reported
according to the Guideline for Good Clinical Prac-
tice.17Vital-signs data (blood pressure and pulse),
physical examinations, and body weight measure-
ments (including body mass index) were obtained at
the screening visit and at the end of treatment. In
addition, as noted in the prescribing information for
drospirenone/ethinyl E2 20 micrograms, participants
randomly assigned to this group who were taking any
medications that might increase serum potassium
levels had their level measured during the first month
of concomitant medication use (between days 15 and
28 of starting study medication).
The evaluation of bleeding patterns was based on
the intent-to-treat population, defined as all randomly
assigned participants who took the study drug and for
whom there was postbaseline bleeding data after day
7. The mean, median, and frequency of unscheduled,
scheduled, and total bleeding days were presented by
treatment for each cycle and across all three cycles.
The number of unscheduled and scheduled bleeding
days, number of unscheduled bleeding episodes, and
overall participant satisfaction were compared be-
tween the two treatment groups using the Mann-
Whitney-Wilcoxon test. The incidence of scheduled
and unscheduled bleeding in the two treatment
groups was compared using Fisher exact test. The
extent of exposure to study medication in each treat-
ment group was determined by calculating the num-
ber of days exposed to study medication using the
date of the last and first treatment day. Safety was
evaluated in all participants who took the study
medication and provided postbaseline safety data.
Treatment-emergent adverse events in both treatment
groups were summarized. Mean changes in blood
pressure and body weight in the two treatment groups
were compared by a two-sample t test. A post hoc
Table 1. Terminology and Definitions for Bleeding
Variables12,16
Term 12Definition12,16
Bleeding Evidence of blood loss that requires the use
of sanitary protection with a tampon,
pad, or pantyliner12
Evidence of minimal blood loss that does
not require new use of any type of
sanitary protection including pantyliners12
One or more consecutive days during
which blood loss (bleeding or spotting)
has been recorded; each episode being
bounded by bleeding/spotting-free
days14*
Any blood loss that occurs during a
hormone-free interval regardless of the
duration of the regimen and that may
continue into days 1–4 of the next cycle
of oral contraceptive pill therapy12
Any blood loss that occurs while taking
active hormones, regardless of the
duration of the regimen, with the
exception of blood loss that begins during
the hormone-free interval and continues
through days 1–4 of the subsequent
active cycle and blood loss reported
during days 1–7 of the first cycle of oral
contraceptive pill therapy12
No bleeding or spotting; replaces the term
amenorrhea12
Spotting
Episode of
bleeding/
spotting
Scheduled
bleeding
Unscheduled
bleeding
Absence of all
bleeding and
spotting
* An unscheduled bleeding episode may be bounded by scheduled
bleeding day(s).
VOL. 114, NO. 6, DECEMBER 2009 Kaunitz et al Cycle Control: 21-Day vs 24-Day OCP Regimen
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analysis of the primary endpoint was performed in
which the demographic variables smoking and weight
were incorporated separately as covariates.
RESULTS
The participant flow diagram shows the number of
participants enrolled in the study and their disposition
(Fig. 1). Between May 27, 2008, and June 30, 2008, a
total of 355 women were assigned randomly to either
a 21/7-day norgestimate/ethinyl E2 (n?178) or a
24/4-day drospirenone/ethinyl E2 (n?177) OCP reg-
imen. Eleven women in the 21/7-day group and 10
women in the 24/4-day group failed to meet inclusion
criteria. All 334 women who took the study medica-
tion (n?167 in each study group) were included in the
safety analysis.
The treatment groups were comparable in age,
racial distribution, and previous contraceptive history
(Table 2). More than 50% of participants in each
treatment group had used hormonal contraception
within the 60 days before enrollment. Participants in
the 24/4-day drospirenone/ethinyl E2 group weighed
more and had a greater body mass index than did
participants in the 21/7-day norgestimate/ethinyl E2
group. There were twice as many smokers in the
24/4-day drospirenone/ethinyl E2 group compared
with the 21/7-day norgestimate/ethinyl E2 group (11
participants compared with 22 participants). How-
ever, the majority of participants in each treatment
group were nonsmokers.
There were 165 efficacy-evaluable participants in
the 21/7-day norgestimate/ethinyl E2 group and 167
in the 24/4-day drospirenone/ethinyl E2 group. Two
participants in the 21/7-day norgestimate/ethinyl E2
group were excluded from the efficacy analysis be-
cause bleeding data beyond day 7 were not available.
The mean number of days exposed to the study drug
was 80.9?14.82 in the 21/7-day norgestimate/ethinyl
E2 group and 82.0?11.33 in the 24/4 drospirenone/
ethinyl E2 group.
More than 95% of participants in both groups
called in one or more data responses late (backfilled
within 7 or fewer days of scheduled date). However,
fewer than 5% of participants in both groups had any
missing data. Of more than 13,000 data points in each
treatment group, approximately 19% were backfilled
and fewer than 0.1% of the data points in either group
were missing. Hence, use of the interactive voice-
response system resulted in complete data for all but
Randomized to treatment
N=355
Screen failures: n=11
Did not meet inclusion
criteria: 2
Other: 7*
Pregnant: 2
21/7-day norgestimate/
ethinyl estradiol
n=178
24/4-day drospirenone/
ethinyl estradiol
n=177
Screen failures: n=10
Did not meet inclusion
criteria: 3
Other: 3*
Pregnant: 4†
Received study drug
n=167
Received study drug
n=167
Completed‡
n=154
Completed
n=156
Discontinued: n=13
Adverse event: 3
Lack of compliance: 2
Withdrew consent: 1
Lost to follow-up: 7
Discontinued: n=11
Adverse event: 4
Lack of compliance: 2
Protocol violation: 1
Lost to follow-up: 4
Fig. 1. Participant flow. 21/7-day norgestimate/ethinyl
E2?triphasic norgestimate?ethinyl E2 25 micrograms; 24/
4-day drospirenone/ethinyl E2?drospirenone 3 mg?ethinyl
E2 20 micrograms. *Included participants in either treatment
group who did not take any study medication for any other
reason.
pregnancy test. The reason given on the case-report form for
discontinuation was other. One participant failed screening
because she was lost to follow-up. The woman was reported
to have had a positive pregnancy test, but the result was not
captured in the database.‡One woman who completed the
study had a positive pregnancy test at the final study visit.
Kaunitz. Cycle Control: 21-Day vs 24-Day OCP Regimen. Obstet
Gynecol 2009.
†One participant failed screening owing to positive
Table 2. Demographic and Baseline
Characteristics
21/7-Day
NGM/EE
(n?167)
24/4-Day
DRSP/EE
(n?167)
Age (y)
Race
White
Black or African
Asian
Other
Weight (lb)
Body mass index (kg/m2)
Smoking status
Smoker
Nonsmoker
Previous HC status
Fresh start‡
Switcher§
27.4 (?6.80) 27.3 (?6.59)
128 (76.6)
20 (12.0)
8 (4.8)
11 (6.6)
147.6 (?30.10)
24.7 (?4.48)
126 (75.4)
28 (16.8)
4 (2.4)
9 (5.4)
156.7 (?35.38)*
26.6 (?5.47)†
11 (6.6)
156 (93.4)
22 (13.2)
145 (86.8)
72 (43.1)
95 (56.9)
74 (44.3)
93 (55.7)
NGM/EE, norgestimate/ethinyl estradiol; DRSP/EE, drospirenone/
ethinyl estradiol; HC, hormonal contraceptive.
Data are mean (?standard deviation) or n (%).
Statistically significant difference between groups:
* P?.014.
†P?.001.
‡No HC within 60 days of study drug start.
§Used HC within 60 days of study drug start.
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15 participants, seven in the norgestimate/ethinyl E2
group and eight in the drospirenone/ethinyl E2 group.
Bleeding data for the two treatment groups are
summarized in Table 3. The mean number of days of
unscheduled bleeding in cycles 2 and 3 and across all
three cycles was significantly greater in the 24/4-day
drospirenone/ethinyl E2 group compared with the
21/7-day norgestimate/ethinyl E2 group (P?.005 and
P?.001, cycle 2 and 3, respectively, P?.003 cumula-
tively). Over the three cycles, participants in the
21/7-day norgestimate/ethinyl E2 group experienced
approximately 1.5 fewer days of unscheduled bleed-
ing than did those in the 24/4-day drospirenone/
ethinyl E2 group (4.6 compared with 6.1 days). Cu-
mulatively, 55 (33.3%) participants in the 21/7-day
norgestimate/ethinyl E2 group and 29 (17.4%) partic-
ipants in the 24/4-day drospirenone/ethinyl E2 group
did not experience any unscheduled bleeding epi-
sodes (Fig. 2). The number of unscheduled bleeding
episodes was significantly less in the 21/7-day norg-
estimate/ethinyl E2 group than in the 24/4-day dro-
spirenone/ethinyl E2 group over the course of three
cycles (1.47 compared with 2.01, P?.001). In a post
hoc analysis controlling for weight and smoking sep-
arately, no difference from the primary endpoint
finding was seen.
Participants in the 21/7-day norgestimate/ethinyl
E2 group experienced more days of scheduled bleed-
ing than did those in the 24/4-day group throughout
the cycles; however, data collection stopped on day
28 of cycle 3, resulting in truncation of results on the
duration of scheduled bleeding (Table 3). The mean
number of days of scheduled bleeding was signifi-
cantly greater in the 21/7-day norgestimate/ethinyl
Table 3. Unscheduled, Scheduled, and Total Bleeding Days (Intent-to-Treat Population)
21/7-Day NGM/EE
(n?165)
24/4-Day DRSP/EE
(n?167)
P
Mean (SD)MedianMean (SD) Median
Unscheduled bleeding days
Cycle 1
Cycle 2*
Cycle 3†
Cumulative
Scheduled bleeding days
Cycle 1
Cycle 2*
Cycle 3†
Cumulative
Total bleeding days‡
Cycle 1
Cycle 2*
Cycle 3†
Cumulative
1.9 (3.14)
1.3 (2.49)
1.4 (2.33)
4.6 (5.53)
0.0
0.0
0.0
2.0
2.0 (3.53)
1.9 (2.86)
2.4 (2.86)
6.1 (6.07)
0.0
1.0
1.0
4.0
.970
.005
.001
.003
4.3 (2.09)
4.0 (2.15)
3.1 (2.09)
11.2 (5.40)
5.0
4.0
4.0
12.0
3.2 (2.35)
2.8 (2.40)
1.2 (1.30)
7.0 (4.80)
4.0
3.0
1.0
8.0
?.001
?.001
?.001
?.001
6.2 (3.88)
5.3 (2.66)
4.6 (2.64)
15.8 (6.58)
5.0
5.0
4.0
14.0
5.2 (4.45)
4.6 (3.25)
3.6 (3.10)
13.2 (6.90)
5.0
4.0
3.0
11.0
.003
.006
?.001
?.001
NGM/EE, norgestimate/ethinyl estradiol; DRSP/EE, drospirenone/ethinyl estradiol.
* 21/7-day group: n?160, 24/4-day group: n?165.
†21/7-day group: n?157, 24/4-day group: n?159.
‡Scheduled?unscheduled bleeding days.
0
01
Number of unscheduled bleeding episodes
23456789
5
10
15
Patients (%)
20
25
30
35
33.3
17.4
27.9
24.6
29.9
13.9
12.713.2
7.96.6
4.24.8
01.2000
1.8
00.6
21/7-day norgestimate/ethinyl estradiol (n=165)
24/4-day drospirenone/ethinyl estradiol (n=167)
Fig. 2. Unscheduled bleeding epi-
sodes across three cycles. Women
using the 21/7-day oral contraceptive
regimen had statistically significantly
fewer mean numbers of unscheduled
bleeding episodes than those using
the 24/4-dayoralcontraceptiveregimen
(1.47 compared with 2.01, P?.001).
Kaunitz. Cycle Control: 21-Day vs 24-Day
OCP Regimen. Obstet Gynecol 2009.
VOL. 114, NO. 6, DECEMBER 2009 Kaunitz et al Cycle Control: 21-Day vs 24-Day OCP Regimen
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