Examination of Extended Cycle Hormonal Contraception · Web viewThe extended use of steroidal...

Running head: EXTENDED CYCLE HORMONAL CONTRACEPTION 1

Examination of Extended Cycle Hormonal Contraception

Angelina Skokan

Georgetown University

Research Evidence and Best Practices in Health Care

NURO 540

Chaplin

November 9, 2015

EXTENDED CYCLE HORMONAL CONTRACEPTION 2

Examination of Extended Cycle Hormonal Contraception

The extended use of steroidal hormones to suppress menstruation pre-dates the use of

such hormones for contraception (Junod & Marks, 2002). Initially used to help women who

suffered from hematologic and other conditions that caused abnormally heavy and prolonged

menstruation, “The Pill”, marketed first as Enovid, was not approved for the indication of

suppressing ovulation until 1960 (Junod & Marks, 2002). Additionally, the social mores and

customs of the 1950’s, in America and the world beyond, affected the arbitrary development of a

normal “cycle” of Enovid to mimic the woman’s natural menstrual cycle, and allowed for

withdrawal bleeding to occur every fourth week. One of the developers of the first oral

contraceptive, John Rock, was a devout Roman Catholic and reasoned that normally mimicking

a woman’s 28-day cycle would simply be an extension of the “Rhythm Method” and could,

therefore, be approved by the Pope (Gladwell, 2000).

Present day patients and providers, however, are less concerned with “pleasing the Pope”,

and more concerned with patient experience. Patient satisfaction and patient-centered care have

become the cornerstones of our health care system. Clearly, with initiatives to improve the

quality of health care that include the Triple Aim, enhancing patient experience, improving the

health of populations, and reducing cost (Berwick, Nolan, & Whittington, 2008), mutually

identifying avenues to improve experience should be a goal of primary providers. It follows, that

women’s health care providers should provide options to their clients that would allow for

control and free choice regarding all aspects of their health care, including care regarding their

menstrual cycle and menstrual-related symptoms.


PICOT Question

One question considered often in primary care regarding women’s reproductive health

surrounds method and options in birth control. While type of hormone and their side effects and

safety is discussed often when considering birth control, menstrual suppression is not routinely

offered (Association of Reproductive Health Professionals [ARHP], 2005). A practitioner may

wish to consider offering complete suppression of menses as an option for women who desire

birth control or control of their premenstrual symptoms, regardless of whether they have a

medical condition that dictates such suppression. In women who use combined hormonal

contraception (P), how does extended use of hormone (I) compare to traditional methods that

allow for monthly withdrawal bleeding (C) with regard to patient adherence, satisfaction,

changes in objective body measurements, and menstruation related symptoms (O) over at least

six months (T)?

The population of interest is any woman of childbearing age who uses combined

hormonal contraception. A conventional definition of any adult woman between the ages of 18

and 50 was considered for this review, and studies with women participants outside these age

restraints, for example research on adolescents, were not included. Any method of combined

hormonal contraception including oral, transdermal, implantable, or intrauterine was considered,

as various methods of these contraceptives could be offered to patients.

“Extended Use” of combined hormonal contraceptives refers to a variety of patterns of

menstrual suppression beyond the traditional 24- to 28-day cycle. These patterns include

“continuous”, with no hormone free periods, “extended”, with withdrawal bleed every two to

three months or longer, and “tailored methods”, allowing for flexibility of the woman’s choice of

avoiding bleeding at inopportune times. For the purposes of this evidence review, any method of


menstrual suppression beyond 28 days was included as “Extended Use” and “Continued Use”

provided no hormone free intervals. Similarly, any method of contraceptive use that followed

the traditional pattern of cyclic administration, combined hormone for 21 days followed by a

hormone free period of either three or seven days, was considered “traditional” or “cyclic use

allowing for monthly withdrawal bleeding”.

The outcomes of this review of evidence are broad, allowing for a full investigation of the

differences between the comparison interventions. Each individual woman comes to the

provider with different health needs and desires, therefore, fully investigating these differences

will allow for unique and patient-specific recommendations for plan of care and mutuality.

Research that studied patient adherence to treatment, patient satisfaction, continuation of

treatment, changes in objective body measurements, and menstruation-related symptoms was

included. Objective body measurements examined for this review compared values for

coagulation factors, bleeding or clotting times, lipid or other metabolic measurements, vital

signs, and weight. Menstruation-related symptoms experienced by women encompasses a range

of issues, including headache, breast tenderness/soreness, pelvic pain and cramping,

breakthrough bleeding, abnormal or heavy bleeding, dysphoria, bloating, fatigue, or irritability.

All symptoms were considered because each client may place different levels of importance on

the various symptoms in her experience, and best meeting her individual needs depends on

careful consideration of a multitude of factors.

Significance of the Problem

Virtually all post-pubescent females, absent a condition that causes amenorrhea,

experience menstruation and, therefore, some symptom associated with the monthly fluctuations


and surges of hormones. If nothing else, they experience the bleeding that many women find a

nuisance or distraction.

We can assume most people want to avoid pain. Many studies in the United States and

other developed countries have attempted to estimate the prevalence of dysmenorrhea, or painful

periods, just one of the symptoms associated with menstruation. Reviews of these studies have

reported how difficult and varied it is to estimate this prevalence. In one such review, authors

examined 15 studies from 2004 to 2012 and found that a range of 16% to 91% of women of

reproductive age report symptoms of dysmenorrhea and of those studied, 2% to 29% have severe

pain related to their menstruation (Ju, Jones, & Mishra, 2014). Authors of this review suggest

that the real prevalence between these studies should be estimated at 37% to 91% owing to the

poor methods of the study reporting the least percent and the sample bias of the second least

percent (Ju et al., 2014). This would align with the World Health Organization’s review and

published dysmenorrhea prevalence rates of 45% to 97% (Lacovides, Avidon, & Baker, 2015).

Even with these large discrepancies, it is safe to assume that one third to one half of all women in

the world experience pain related to their menstrual cycles.

The only recent cost analyses study directly comparing economics of extended cycle

regimens to monthly cyclic regimens was published in 2003. Researchers considered direct and

indirect costs including, but not limited to, costs of feminine hygiene products, pregnancy tests,

iron-replacement, co-pays for clinic visits, analgesics, loss of work, and more, and they estimate

a reduced cost to society and to the woman for those following extended regimens (Braunstein,

Hausfeld, Hausfeld, & London, 2003). In this study, researchers were estimating costs without

really investigating the frequency the items and services were really needed in each group.

Further, authors assumed the cost of each contraceptive pill was uniform but, if a woman is


prescribed a formulation specific to an extended regimen, or if they choose an intrauterine device

or injection, the cost varies.

Another recent study was specific to costs relating to heavy menstrual flow. Jensen and

colleagues found that there was significant direct cost burden, with access to medical care,

products, and procedures, and indirect cost burden, with loss of work and absenteeism from

school, associated with heavy menstrual flow compared to normal flow (Jensen et al., 2012).

This difference was estimated to be $2,607 more per woman per year than cost to the control

group. Authors additionally note that less than three per cent of the women with heavy flow

received treatment with the extended regimen, hormone-containing intrauterine device, which

has been shown to decrease heavy bleeding (Blumenthal, Dawson, & Hurskainen, 2011). Most

received surgery as primary treatment (Jensen et al., 2012), which had a considerable effect on

cost. An older study, widely referenced in even the most recent reviews, suggests there are

approximately 600 million lost work hours related to menstruation-related symptoms and $2

billion per year in lost productivity (Daywood, 1984). This study, published on the cusp of

widespread use of non-steroidal anti-inflammatory (NSAID) medicines, may overestimate the

effect of menstrual-related pain on loss of work time and productivity as NSAIDs relieve pain in

this population quiet effectively and are now the gold standard (Majoribanks, Ayeleke, Farquhar,

& Proctor, 2015).

Pain, however, is not the only symptom that causes distress and decreased quality of life.

Symptoms of bloating, mastalgia, dysphoria and depression can be equally debilitating and

harder to attribute solely to hormone fluctuations surrounding reproductive cycles. In any case,

pain and depressed or otherwise altered moods are real conditions that contribute to lost time at

work, causing considerable economic burden on society, the woman, and her family.


Clearly any strategy that can reduce pain and symptoms of dysmenorrhea should be

explored and offered to women in order to improve the quality of life and decrease costs

associated with loss of productivity.

Search Strategy and Results

In the month of September, 2015 the author searched computerized databases CINAHL,

EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and PubMed. In

addition, a hand search of the reference lists of the two systematic reviews found (Edelman,

Micks, Gallo, Jensen, & Grimes, 2014 and Mendoza et al., 2014) was conducted to identify any

other possible studies. Population, Intervention, Comparison, and Outcomes were identified

prior to the search in order to guide the selection of keywords and the inclusion and exclusion of

studies. The details of the search strategy can be found in figure 1.

For the CINAHL search, terms used were “menstrual cycle” or “extended cycle” AND

“patient satisfaction”; “menstrual suppression”; and “contraceptive” AND “withdrawal bleeding”

with limits to five years, English language, and adult.

For the EMBASE search, terms used were “combined oral contraceptive” AND “patient

compliance”, and “cyclic oral contraceptives” AND “dysmenorrhea” with limits to five years,

adult, and clinical trials.

For the CENTRAL search, terms used were “Ethinyl Estradiol” OR “Extended Cycle

Contraceptive” OR “levonorgestrel” OR “contraceptives, oral, combined” AND “satisfaction”

with limits to 5 years.

For the PubMed search, terms used were “extended cycle contraceptive” with limits to 5

years, and clinical trials. One article found (Wiegratz et al., 2011) was used to “Find Similar”

articles.


The total number of articles considered was 232 with most eliminated due to intervention,

comparison, or population not congruent with the identified PICOT concepts. Most from the

hand search of reference lists were eliminated for date preceding the five-year limit, duplicate, or

because they were not a clinical trial. Only one study was eliminated before reviewed, as the

author could not obtain the study in spite of requesting it through a library loan and searching for

full text on the Internet. A total of nine primary studies and one Cochrane Review were retained

for this evaluation. The studies included seven randomized, controlled trials of which one was

double-blinded. One study was a qualitative study in the Phenomenological tradition, one was a

prospective, cross-over study, and the last was the Cochrane Review.

Critical Appraisal of the Literature

The author appraised the nine primary studies and one systematic review. Data was

extracted, and details can be found summarized in Table A and Table B. A second reviewer was

not used in this study, which is a limitation of the findings.

Conceptualization of the Problem

Contraception has been studied for years and there exists a standard, cyclic regimen of

contraception that follows the normal reproductive pattern and allows monthly withdrawal

bleeding. This variable is standard throughout the studies in this review, was always the main

comparison treatment, and a criterion for inclusion. Extended regimens always extend the

hormone-free interval (HFI) past the traditional monthly cycle, but regimens differed across

studies. Some fixed a HFI at 84 days and some were more “flexible” and allowed either the

unexpected spotting to dictate the HFI or the woman herself to decide when the HFI would be

initiated. All ten studies clearly described their examined regimens, and all seem comparable if


followed. Most authors recognized that allowing for decision and control of the participants’

cycles was an overreaching goal for care.

Outcomes and how they were measured did not always allow for comparison. For

example, when satisfaction with regimen was studied, it was likely to be assessed with a 3- to 5-

point Likert scale at the end of the study period. Most that studied satisfaction just asked “how

satisfied were you with the regimen”, and did not indicate any exploration about what

participants meant by being “satisfied”. In other words, the concept of “satisfaction” was not

clearly developed in any study.

Formulations of hormones varied across studies as well, and some studies varied the

hormone formulation between treatment and comparison regimen. It is difficult to assess,

therefore, whether the relief of symptoms was due to the specific formulation used or to the

extended regimen and minimization of hormone fluctuation. It is especially difficult to attribute

outcomes in studies that varied formulation of hormone between extended and cyclic regimens.

Pain, as one of the symptoms studied, was not always measured the same, either. At

times the participant was asked to rank severity of pain using a Likert scale, other times pain was

assessed with the use of one of the validated scales administered to participants.

Collection of data was not always uniform, although six out of the ten had participants

keep a daily diary to record information. Assuming the diaries were kept up date, they could be

extremely useful in collecting symptom information, including severity ratings, at the time of

experiencing those symptoms. Some studies collected objective data through laboratory results

and Doppler ultrasound procedures. Popular symptom questionnaires included the validated

Moos Menstrual Distress Questionnaire (MMDQ) and the Psychological General Well-Being


Index (PGWBI) as well as Visual Analog Scales (VAS). One study used a non-validated scale

that was compared to the PGWBI.

Findings

The author attempted to extract findings directly relating to the outcomes identified in the

PICOT question. These findings included satisfaction, adherence, objective body measurements,

and menstruation related symptoms, including bleeding profiles.

Satisfaction. Five of the primary studies reviewed attempted to measure satisfaction of

regimen in some fashion, although not measured with consistency across studies or even

regimens, nor adequately defined. The qualitative study, Graham, Panicker, Shawe, and

Stephenson (2013) described the participants’ experiences without directly scoring an overall

“satisfaction” level of the regimens. Authors identified four themes, two of which suggested the

tailored regimen was satisfying to the participants, while two suggested women were having

trouble adjusting to the reduced or absent bleeding and the unpredictability of the bleeding.

Authors infer that most criticisms of the extended regimens were overridden by the benefit of not

bleeding, and some of the participants needed time to adjust to the regimen (Graham, et al.,

2013, p. 1624).

Jensen, Garie, Trummer, and Elliesen (2012) measured overall satisfaction with regimens

only once, at the final visit, and researchers found that there was no difference in satisfaction

between all three regimens, although inferential statistics are not reported. The majority of

women in the three arms rated high satisfaction and the scale is not provided.

Klipping, Duijkers, Fortier, Marr, and Trummer (2012) administered a satisfaction

questionnaire at the end of the study. This satisfaction survey was not administered to the

conventional arm participants, but only to the two arms with the extended regimens. The


satisfaction survey is not described, but overall, 95.5% of the flexible regimen arm and 90.7% of

the fixed extended regimen arm were “Quite” or “Very” satisfied. These are listed together as

one percentage because it is not clear which is higher on the authors’ scale.

Seidman et al. (2010) asked participants to record overall satisfaction with their patterns

of bleeding and severity of symptoms with a 100 mm visual analog scale (VAS). These were

completed after each extended-regimen cycle. In this crossover study, the participants did not

rate satisfaction at the end of each conventional cycle, which preceded the extended cycles.

Overall 73.5% were satisfied with their extended regimen after the first cycle and this decreased

to 65.5% at the end of the study.

In Stephenson et al. (2013), satisfaction of the regimen was again addressed, and this

time was compared to the conventional arm. Participants were asked to rate satisfaction of the

regimen overall, and to rate their satisfaction with the bleeding pattern of their regimen.

Although participants in both regimens reported high satisfaction, the satisfaction of both the

overall regimen and of the bleeding patterns was significantly lower in the tailored arm (P = .026

and P = .007 respectively, Stephenson et al., 2013, p. 529).

Weigratz et al. (2011) assessed satisfaction, which they term “acceptance”, at the last

visit and with a 7-point Likert scale. Although they do not elaborate, they claim that overall

acceptance of the regimens was similar and high.

The Cochrane Review reports similar findings that while some studies do not mention

satisfaction, most report high satisfaction with any method. This review found a similar pattern

in the more recent studies. It appears that most women report high satisfaction regardless of the

regimen.


Adherence. Overall, adherence is measured inconsistently, not commonly, and defined

and operationalized in dissimilar ways. Only four trials discuss adherence, and none of these are

detailed enough to significantly find differences between regimens. More research is needed to

determine if extended and flexible regimens are difficult to follow or if compliance with

treatment regimens is a problem in general.

The experience of women in the Graham et al. (2013) qualitative study suggests women

interviewed found the extended regimen easier to adhere to, as there were few intervals where

there were breaks in hormone and, therefore, fewer opportunities to forget to restart a pack of

pills.

Jensen et al. (2012) report that 10% of all participants did not follow their regimen

exactly. In this 3-arm study with 2 flexible regimens and a conventional regimen, researchers

observed some participants taking early and late hormone free intervals (HFIs), behaving like

other regimens, and confounding the findings. Based on this, authors stress the importance of

“having the ability to control when withdrawal bleeding occurs” (Jensen, Garie, Trummer, &

Elliesen, 2012, p. 117).

Klipping et al. (2012) followed compliance to treatment in the participant daily diary. It

is not discussed, but it appears from a figure that only 11 total participants deviated from their

respective protocol (Klipping et al., 2012, p. 75).

Stephenson et al. (2013) only reported adherence to the extended regimen and it was

measured two ways. Data on number of days after spotting the participant started a HFI and on

how many days of bleeding occurred before the HFI was initiated was abstracted from the

diaries. Stopping on time happened only 20% of the time and stopping after the correct number


of bleeding days happened only 32% of the time. Clearly the protocol, as directed, was not being

followed.

Wiegratz et al. (2011) lump protocol deviators and drop outs together in their figure of

disposition of volunteers (Wiegratz et al., 2011, p. 136). The conventional regimen lost 16% of

volunteers compared to 31% in the extended regimen. This is not discussed in their paper.

Important to note, both Klipping et al. (2012) and Stephenson et al. (2013) include

protocol deviators in the full analysis set (FAS) for primary outcomes.

Objective body measurements. While vital signs and other objective measurements

were collected regularly, these measurements were not always a primary outcome for these

studies.

Some studies examined biological markers such as lipid profile numbers, coagulation

factors and hemostatic markers, and bone density markers as these values can be affected by the

use of hormones. Researchers in these studies attempted to detect differences between cyclic use

and extended use of hormone that would indicate an increased risk for developing a disease or

adverse event. In Nappi et al. (2014), the main outcome studied was changes to participants’

baseline prothrombin F1 + 2 levels and they found that length of the cycle had less of an effect

on most parameters studied than the progestin selectivity and activity did (p. 292). After a full

year of study, Rad et al. (2011) found that there was a similar effect between regimens on

participants’ metabolic profile, with significant increases (P < 0.05, p 91) in sex hormone

binding globulin and protein C antigen percentage in the extended regimen group. Authors of

this study also looked at some coagulation factors and found a significant reduction (P < 0.05, p

91) in d-Dimer in the extended group. The low numbers of participants in this study, however,

could mean results were due to chance.


The examined markers and levels do not necessarily indicate disease or even elevated

risk for adverse events like venous thromboembolism (VTE) or other vascular disease.

Examining prospectively, for a longer time and in a larger sample, looking for endpoints such as

VTE would afford better clinical information.

One objective measurement that may have significant meaning to American females is

body weight and very few of the studies examined differences in weight gain. Additionally,

most studies only span a six-month period, which may not be long enough to observe a

significant difference. Dmitrovic et al. (2013) studied pain as the primary outcome but

discovered a significant increase (p.13) in weight in the extended regimen group over six

months. Weight gain differences in Stephenson et al. (2013) were not significant over the 12-

month study (p. 529). Interestingly, Rad et al. (2011), who studied lipid profile differences as a

main outcome and obtained a baseline weight of participants, did not report body weight at the

end of the 12-year study.

Menstruation related symptoms. Pain is a significant menstruation related symptom

that is often evaluated in studies yet only four studies in this review examined pain. Dmitrovic et

al. (2013) focused their study on the perception of pain. They found that the continuous regimen

outperformed the traditional regimen in reducing the perception of pain significantly (P < 0.001,

p. 10) but the difference was lost (P = 0.05) at 6 months. This study had a low number of

participants and was only six months in length. Graham et al. (2012) finds that women report,

subjectively, a reduction in pain on the extended regimen. Klipping et al. (2012) report pain

frequencies, but do not compare regimens. Seidman et al. (2010) found that between regimens,

PGWBI scores, which included pain, did not differ significantly.


Psychological wellbeing is another issue that may be important to women and the

clinicians that prescribe their hormonal contraception medicines. Two studies used the validated

PGWBI to assess this in their participants. Klipping et al. (2012) lists the change in the PGWBI

score for each arm of their study, but does not discuss this further (p. 80). They do not provide

comparison statistics between their groups. Seidman et al. (2010) found no significant changes

in PGWBI scores at the end of the extended cycle portion of their six-month crossover.

Seidman et al. (2010) did, however, find significant (P < 0.005, p. 400) decreases in the

incidence of many other menstruation-related symptoms, including bloating, breast tenderness,

depressed mood, and menorrhagia from the enrollment into the study. These participants,

however, were crossed over after two traditional cycles and did not complete a questionnaire

between the cross over of regimens. Stephenson et al. (2013) report no difference between

regimens regarding a list of 11 symptoms with the exception of the loss of interest in sex, which

was increased (P = 0.04, p 529) in the tailored regimen at 12 months.

Bleeding Profiles. The bleeding profile of participants seemed to be the aspect of

menstrual suppression symptomatology at the forefront of recent literature. Six of the nine

primary studies examined participants’ bleeding patterns as a primary or secondary outcome, and

the qualitative study identified bleeding in two of their four themes.

Two of the studies defined breakthrough bleeding using the World Health Organization

definition as bleeding that was unplanned and that requires sanitary protection as opposed to

spotting which does not (Besley, Machin, & D’Arcagues, 1986). Three primary studies that

examined bleeding profiles either used their own subjective scales, and one study defined

episodes based on numbers of days where bleeding or spotting was noticed surrounded by at


least two bleed-free days before and after. These varied definitions make aggregation of the data

difficult.

Graham et al. (2012) describe that the experience of women on extended cycle regimens

involves an adjustment to reduced or absent bleeding and to the unpredictability of bleeding.

Dmitrovic et al. (2012) report a significant increase (P = 0.003, p. 14) in spotting days with the

continuous cycle. Jensen et al. (2012) report no difference in intensity of withdrawal bleeding

across regimens but the mean number of bleeding/spotting days was significantly lower (P <

0.0001, p. 115) in the flexible regimen. Klipping et al. (2012) reports similar results of

significantly fewer (P < 0.0001, p. 77) bleeding/spotting days in the flexible regimen compared

to conventional. Seidman et al. (2010), Stephenson et al. (2013), and Wiegratz et al. (2011) all

report less bleeding in the extended or flexible regimens, however they either compare to pre-

study profiles or do not compare statistically with the cyclic regimens.

The decreased amount of bleeding in the extended regimens is not surprising, as there are

fewer days that women are hormone-free. It would be more informative if studies did not count

the expected bleeds during hormone-free intervals and looked at unexpected bleeding and

spotting. This may be more concerning and distressful to women.

Methodological Rigor

Seven of the nine primary studies in this review were randomized, controlled trials. All

but one of these was rated 2b per LEGEND after careful critique (see Appendix C, Clark,

Burkett, & Stanko-Lopp, 2009). The review also included one clinical trial that was designed in

a crossover fashion, on qualitative study and a Cochrane Review. Decisions on ratings of all

studies in this review followed the tools provided on the Cincinnati Children’s Website

(http://www.cincinnatichildrens.org/service/j/anderson-center/evidence-based-care/legend/).


Primary outcomes and measurements differed amongst the studies therefore, the evidence

as a whole cannot be completely combined as an aggregate. This is partly due to the broad

nature of the PICOT question and is a natural problem the clinician may face serving a

heterogeneous population. Every patient comes in with a different set of values and needs and

must be evaluated based on their individuality. Looking at a similar problem from different

perspectives will help provide a general guideline that can be tailored to suit the individual seen

in the clinic.

Seven of the nine primary studies sampled from multiple centers. The Cochrane Review

included studies from multiple centers. Sampling from multiple centers reduces bias and allows

greater generalizability (Polit & Beck, 2012). Most of the samples, however, were healthy adult

women. Not everyone coming into the clinic is healthy and menstrual suppression for reasons

other than personal choice is often considered. For example, a women suffering pelvic pain or

dysmenorrhea may benefit from an absence of hormonal fluctuations to a greater extent than

would a healthy woman. Only one study reviewed, Dmitrovic et al. (2012), examined a sub

group of this population.

Four of the primary studies were Phase III trials. The intent of these researchers is to

demonstrate safety and efficacy of their formulation of hormone for use in various regimens or

conditions. This could introduce bias and threaten validity.

Strengths and Limitations

This study attempted to critically review recent studies relating to menstrual suppression

in order to best care for patients in the clinical setting. The search was thorough, using four

databases and additional hand searches, and limited to studies within the past five years.


Seven of the primary studies were randomized, controlled trials. Randomization is key to

reducing bias in research (Polit & Beck, 2012).

Not all studies meeting the inclusion criteria were reviewed due to time constraints and

only a single reviewer. Data, therefore, is not exhaustive and key patterns may not have

emerged.

Studies on adolescents were excluded which is a limitation. Clinicians do not only see

adults, and adolescents often present with quite severe menstruation related symptoms. These

symptoms often decrease over years and after parity, and knowledge of best evidence to treat this

population of a clinical practice would certainly be desired. Adolescents often do not have the

years of experience or knowledge about managing their symptoms and health needs as do adults.

Three out of eight primary studies evaluated were six months in duration and findings in

these studies may have been due to chance. Generally, the greater the sample size, the greater

the power (Polit & Beck, 2012). The “extended regimens” were on average three months

duration therefore, only two cycles would be observed in these studies.

While several of the studies report conducted a priori power analyses, often the drop out

rate decreased the sample size to below the recommended number for sufficient and planned

power. Jensen et al. (2012) and Seidman et al. (2010) do not report a power analysis. Graham et

al. (2012) report data saturation (p. 1622). Dmitrovic et al. (2012), Klipping et al. (2012), Nappi

et al. (2014), and Stephenson et al. (2013) all report conducting the analyses or using guidelines,

yet the numbers of participants completing the studies exceeds the planned dropout rates,

resulting in insufficient power. Only Rad et al. (2011) and Weigratz et al. (2011) end the study

with sufficient power as planned.


Two of the studies, Klipping et al. (2012) and Weigratz et al. (2011) used descriptive

statistics for the majority of their data. Klipping et al. (2012) did use inferential statistics for

their main outcome, however Weigratz et al. (2011) did not use inferential statistics at all.

Without the use of inferential statistics, it is difficult to generalize to the larger population of

interest. Additionally, one of the studies reviewed was qualitative in design and, although it

contained rich descriptions, it still leaves the consumer with the weight of what to do about

external validity.

Summary Statement Regarding Strength of the Evidence

Based on the evidence available in this review, it is still difficult to determine whether

differences, if any, exist between extended regimens and traditional, cyclic regimens. Many of

the trials in this body of evidence were not conducted for long enough periods, nor were

completed with sufficient power, to reasonably conclude a change in practice is warranted.

Additionally, the focus of many of these studies was on bleeding profiles and additional research

examining patient satisfaction, incidence of symptoms, and pattern of unexpected bleeding is

needed.

Based on the current evidence in this review, extended regimens of combined hormonal

contraception are reasonable alternatives to traditional, cyclic regimens. The extended regimens

may have improved pain and bleeding profiles, however, more research is needed to detect

significant differences. While patient satisfaction was high for all regimens in this body of

evidence, often it was not compared between regimens or explored in depth. Adherence,

experience of symptoms, and changes in objective body measurements appeared similar between

regimens in this body of evidence as well.


In addition to being used to grade each of the studies in this review, LEGEND was also

used to grade the total body of evidence, and the author assigned the level of Moderate to the

evidence as a whole ("Grading," 2012). Factors that led to this grading included the individual

LEGEND grades of the 10 studies, the fact that consistent results were observed with minor

exceptions, threats to internal validity inferred, risks of bias appraised, inadequate power in the

majority of studies, heterogeneity of interventions and measurements, inability to generalize to

the larger population in some of the studies, and statistical inconsistencies.

Conclusion

In the pursuit of exceptional patient care, this review attempted to determine any

differences between the extended and conventional cyclic regimens of combined hormonal

contraception. Identifying any differences and working with the woman who comes into the

clinic to clarify goals and desires will help the clinician provide the best possible, individualized

treatment plans.

The specific intention of this review was to determine if providing the option of

menstrual suppression should be standard, regardless of whether the woman requests birth

control. Nine primary studies and one systematic review were critically appraised in order to

compare traditional cyclic methods of combined hormonal contraception with extended regimens

with regard to patient adherence, satisfaction, changes in objective body measurements, and

menstruation-related symptoms with the intent to uncover any differences or benefits that might

arise with menstrual suppression.

While extended and flexible regimens seem like reasonable and safe options, and may

provide a reduction in pain and bleeding/spotting, there is not overwhelming evidence that


menstrual suppression should be offered routinely without further investigation. Many studies

conveyed the importance of attendance to the woman’s desire for control over her reproductive

cycle. Offering open dialogue to clients, exploring their expectations, tolerances, and needs, and

educating them on what to expect from the various regimens may be the most important factor in

ensuring adherence, satisfaction, and the therapeutic relationship the woman deserves.


References

About RevMan . (n.d.). Retrieved October 15, 2015, from

http://tech.cochrane.org/revman/about-revman-5

Association of Reproductive Health Professionals. (2005). Continuous regimen contraception

[Greenburg Quinlan Rosner Survey 2005]. Retrieved from

http://www.arhp.org/uploadDocs/2005menstruationsurvey_fullreport.pdf

Berwick, D. M., Nolan, T. W., & Whittington, J. (2008, May). The Triple Aim: Care, health,

and cost. Health Affairs, 27(3), 759-769. http://dx.doi.org/10.1377/hlthaff.27.3.759

Besley, E. M., Machin, D., & D’Arcagues, C. (1986). The analysis of vaginal bleeding patterns

induced by fertility regulating methods. World Health Organization special programme

of research, development and research training in human reproduction. Contraception,

34(3), 253-260.

Blumenthal, P. D., Dawson, L., & Hurskainen, R. (2011, March). Cost-effectiveness and quality

of life associated with heavy menstrual bleeding among women using the levonorgestrel-

releasing intrauterine system. Intl J Gynaecol Obstet, 112(3), 171-178.

http://dx.doi.org/10.1016/j.ijgo.2010.08.025

Braunstein, J. B., Hausfeld, J., Hausfeld, J., & London, A. (2003, October). Economics of

reducing menstruation with trimonthly-cycle oral contraceptive therapy: Comparison

with standard-cycle regimens. Obstet Gynecol, 102(4), 699-708.

http://dx.doi.org/10.1016/S0029-7844(03)00738-5

Clark, E., Burkett, K., & Stanko-Lopp, D. (2009, December). Let evidence guide every new

decision (LEGEND): An evidence evaluation system for point-of-care clinicians and


guideline development teams. Journal of Evaluation in Clinical Practice, 15(6), 1054-

1060. http://dx.doi.org/10.1111/j.1365-2753.2009.01314.x

Cresswell, J. W. (1998). Cresswell’s evaluative criteria. Retrieved October 28, 2015, from

http://www.qualres.org/HomeCres-3682.html

Daywood, M. Y. (1984, July 13). Ibuprofen and dysmenorrhea. American Journal of Medicine,

77(1A), 87-94. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/6380282

Dmitrovic, R., Kunselman, A. R., & Legro, R. S. (2012, June). Continuous compared with cyclic

oral contraceptives for the treatment of primary dysmenorrhea: A randomized controlled

trial. Obstet Gynecol, 119(6), 1143-1150.

http://dx.doi.org/10.1097/AOG.0b013e318257217a

Edelman, A., Micks, E., Gallo, M. F., Jensen, J. T., & Grimes, D. A. (2014). Continuous or

extended cycle vs. cyclic use of combined hormonal contraceptives for contraception.

Cochrane Database of Systematic Reviews, 2014(7), 1-92.

http://dx.doi.org/10.1002/14651858.CD004695.pub3

Gladwell, M. (2000, March 13). John Rock’s Error. The New Yorker, 52-58. Retrieved from

http://www.newyorker.com/magazine/2000/03/13/john-rocks-error-2

Grading a body of evidence. (2012). Retrieved from

file:///Users/Angelina/Downloads/Grading.BodyOfEvidence-FINAL%20(1).pdf

Graham, C. A., Panicker, S., Shawe, J., & Stephenson, J. (2013, March 22). Women’s

experiences with tailored use of a combined oral congraceptive: A qualitative study.

Human Reproduction, 28(6), 1620-1625. http://dx.doi.org/10.1093/humrep/det078

Jensen, J. T., Garie, S. G., Trummer, D., & Elliesen, J. (2012, December 12). bleeding profile of

a flexible extended regimen of ethinylestradiol/drospirenone in US women: An open-


label, three-arm, active-controlled, multicenter study. Contraception, 86, 110-118.

http://dx.doi.org/10.1016/j.contraception.2011.12.009

Jensen, J. T., Lefebvre, P., Laliberte, F., Sarda, S. P., Law, A., Pocoski, J., & Duh, M. S. (2012).

Cost burden and treatment patterns associated with management of heavy menstrual

bleeding. Journal of Women’s Health, 21(5), 539-547.

http://dx.doi.org/10.1089/jwh.2011.3147

Ju, H., Jones, M., & Mishra, G. (2014). The prvelance and risk factors of dysmenorrhea.

Epidemiology Review, 36, 104-113. http://dx.doi.org/10.1093/epirev/mxt009

Junod, S. W., & Marks, L. (2002, April). Women’s trials: The approval of the first oral

contraceptive pill in the United States and Great Britain. Journal of the History of

Medicine, 57, 117-160. Retrieved from

http://ethique-tic.fr/2013/wp-content/uploads/1/2013/02/JunodMarks-pill02.pdf

Klipping, C., Duijkers, I., Fortier, M. P., Marr, J., Trummer, D., & Elliesen, J. (2012, February

10). Contraceptive efficacy and tolerability of ethinylestradiol 20 mcg/drospirenone 3mg

in a flexible extended regimen: An open-label, multicentre, randomised, controlled

study. J Fam Plann Reprod Health Care, 38, 73-83. http://dx.doi.org/10.1136/jfprhc-

2011-100213

Lacovides, S., Avidon, I., & Baker, F. C. (2015, November 21). What we know about primary

dysmenorrhea today: A critical review. Hum Reprod Update, 6, 762-778.

http://dx.doi.org/10.1093/humupd/dmv039

Majoribanks, J., Ayeleke, R. O., Farquhar, C., & Proctor, M. (2015, July 30). Nonsteroidal anti-

inflammatory drugs for dysmenorrhea (Review). Cochrane Database of Systematic

Reviews. Retrieved from http://ovidsp.tx.ovid.com.proxy.library.georgetown.edu/sp-


3.17.0a/ovidweb.cgi?

&S=EHJOFPIHHFDDJLMINCJKEGOBPOIIAA00&Link+Set=S.sh.38%7c1%7csl_114

54392

Mendoza, N., Lobo, P., Lertxundi, R., Correa, M., Gonzalez, E., Salamanca, A., & Sanchez-

Borrego, R. (2014). Extended regimens of combined hormonal contraception to reduce

symptoms related to withdrawal bleeding and the hormone-free interval: A systematic

review of randomised and observational studies. Eur J Contracept Roprod Health Care,

19, 321-339. http://dx.doi.org/10.3109/13625187.2014.927423

Nappi, R. E., Paoletti, A. M., Volpe, A., Chiovato, L., Howard, B., Weiss, H., & Ricciotti, N.

(2014). Multinational, multicentre randomised, open-label study evaluating the impact of

a 91-day extended regimen combined oral contraceptive, compared with two 28-day

traditional combined oral contraceptives, on haemostatic parameters in healthy women.

The European Journal of Contraception and Reproductive Health Care, 19(4), 285-294.

http://dx.doi.org/10.3109/13625187.2014.918596

Polit, D. F., & Beck, C. T. (2012). Nursing research: Generating and assessing evidence for

nursing practice (9th ed.). Philadelphia, PA: Walters Kluwer Health: Lippincott

Williams & Wilkins.

Rad, M., Kluft, C., De Kam, M. L., Meijer, P., Cohen, A. F., Grubb, G. S., ... Burggraaf, J.

(2011, April). Metabolic profile of a continuous versus a cyclic low-dose combined oral

contraceptive after one year of use. The European Journal of Contraception and

Reproductive Health Care, 16, 85-94. http://dx.doi.org/10.3109/13625187.2011.556761

Seidman, D. S., Yeshaya, A., Ber, A., Amodai, I., Feinstein, I., Finkel, I., ... Wolman, I. (2010,

July). A prospective follow-up of two 21/7 cycles followed by two extended regimen


84/7 cycles with contraceptive pills containing ethinyl estradiol and drospirenone. IMAJ,

12, 400-404. Retrieved from http://www.ima.org.il/IMAJ/ViewArticle.aspx?

year=2010&month=07&page=400

Stephenson, J., Shawe, J., Panicker, S., Brima, N., Copas, A., Sauer, U., ... O’Brien, P. (2013,

March 30). Randomized trial of the effect of tailored versus standard use of the combined

oral contraceptive pill on continuation rates at 1 year. Contraception, 88, 523-531.


Wiegratz, I., Stahlberg, S., Manthey, T., Sanger, N., Mittmann, K., Lange, E., ... Kuhl, H. (2011,

January 6). Effect of extended-cycle regimen with an oral contraceptive containing 30

mcg ethinylestradiol and 2 mg dienogest on bleeding patterns, safety, acceptance and

contraceptive efficacy. Contraception, 84, 133-143.



Figure 1. Detail of search strategy


Appendix C

Let Evidence Guide Every New Decision Table

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