ORIGINAL RESEARCH ARTICLE
Low Dose Oral Contraceptives and
Quality of Life
C. Egarter,* M.A. Topcuoglu,* M. Imhof, and J. Huber
This study investigated the effects of a low dose oral
contraceptive (OC) (Mercilon) on womens satisfaction
and quality of life based on a detailed questionnaire. A
total of 614 first-time users of oral contraceptives were
enrolled by 102 gynecologists for a treatment period of 4
months. The Quality of Life Enjoyment and Satisfaction
Questionnaire (Q-LES-Q) was filled in both before and
during pill intake. The total quality of life score was
significantly increased under OC intake. In contrast to
older preparations, modern low dose OCs appear to act
favorably on a number of psychological parameters,
thus increasing satisfaction with various aspects of daily
life and, consequently, improving quality of life.
CONTRACEPTION 1999;59:287291 1999 Elsevier Science
Inc. All rights reserved.
KEY WORDS: low dose OC, quality of life
Introduction
B
eyond being an effective method of birth con-
trol, oral contraceptives (OC) offer additional
recognized benefits, including a significant re-
duction of menstrual abnormalities and iron defi-
ciency, a reduced incidence of functional ovarian
cysts, and protection against benign breast disease.1
Current data support a relationship between oral
contraceptives and psychological well-being. Reduced
fear of unwanted pregnancy, and the resulting re-
duced psychological stress and improved sexual expe-
rience, are probably key elements in the improve-
ment in psychological well-being under OC
treatment. However, there have also been reports
suggesting that oral contraceptives exert a number of
adverse psychological and psychosomatic effects,
causing heightened vulnerability to irritability, a
lack of drive, depressive mood changes, and loss of
libido.2,3
*Department of Obstetrics and Gynecology and Department of Gynecologic
Endocrinology and Assisted Reproduction, University of Vienna, Vienna, Austria
Name and address for correspondence: Univ.-Prof. Dr. Christian Egarter,
Department of Obstetrics and Gynecology, University of Vienna, Wahringer
Gurtel 18-20, 1090 Vienna, Austria; Tel.: 43/1/40400-2863; Fax: 43/1/
40400-2861
Submitted for publication January 26, 1999
Revised April 22, 1999
Accepted for publication April 22, 1999
1999 Elsevier Science Inc. All rights reserved.
655 Avenue of the Americas, New York, NY 10010
Earlier in the use of oral contraceptives, a large
body of data accumulated suggesting that they caused
several psychological side effects, with the majority
of these reports not differentiating between the rela-
tive estrogen and progestin contents in various com-
bination OC. Whereas some studies suggested that
the mental side effects of combined oral contracep-
tives were attributable to the progestin component,4
most of them supported a link to estrogen.5 Interest-
ingly, most of these early studies reported a high
incidence of adverse psychological effects with OC
use, such as depressive mood changes and impaired
sexual functioning, with the number of women expe-
riencing such symptoms ranging from 5% to 40%.3
With the advent of low dose OC, the incidence of
mood-changing side effects seemed to decrease, and
interest in the effects of oral contraceptives on central
nervous parameters began to dwindle.6 With regard to
the small proportion of women experiencing mood
alterations or sexual dysfunction during low dose OC
intake, it has been speculated that they may have a
genetically determined predisposition, and a large
scale twin study attempted to validate this view.7
The medical literature provides only scant informa-
tion on the effects of oral contraceptives on overall
quality of life. However, because the acceptability of
OC to the user is paramount to ensure maximum
efficacy, we set out to detail the impact of estrogen on
general well-being and quality of life.
Today, the most commonly used oral contracep-
tives contain lower doses of sex steroids to minimize
potential side effects. This is why we chose a low dose
monophasic oral contraceptive containing 20 g ethi-
nyl estradiol and 150 g desogestrel (Mercilon, NV
Organon, the Netherlands) to investigate the impact
of oral contraceptives on the quality of life. Large
scale clinical studies have shown this preparation to
be a reliable oral contraceptive that effectively sup-
presses follicle development and ovulation.8,9 It is
comparable to other low dose pills with regard to the
Pearl index and cycle control.8,9 Because of the lower
estrogen dose, estrogen-related subjective side effects
are rare. Moreover, this combination oral contracep-
tive has minimal effects on the carbohydrate and
lipoprotein metabolism.10
ISSN 0010-7824/99/$20.00
PII S0010-7824(99)00040-2
288 Egarter et al.
Table 1. The Quality of Life and Enjoyment Question-
naire (Q-LES-Q)*
During the past week, how satisfied have you been with
your . . .
. . . physical health?
. . . mood?
. . . work/school?
. . . household activities?
. . . relationships to your friends and colleagues at work/
school?
. . . family relationships?
. . . leisure time activities (sports, hobbies)?
. . . ability to function in daily life?
. . . sex life?
. . . living/housing situation?
. . . your vision in terms of ability to do work or hobbies?
. . . overall sense of well-being?
How would you rate your overall satisfaction and
contentment during the past week?
Consists of a total of 13 questions, with item scores ranging from 1 to 5
(very dissatisfied, dissatisfied, fairly satisfied, satisfied, and very satisfied)
and total scores for each respondent from 13 to 65 points.
This study was undertaken to determine the toler-
ability of this preparation in first time users of oral
contraceptives and to evaluate its effects on patient
satisfaction and quality of life.
Patients and Methods
The study protocol provided for non hospital based
physicians to include 600 first time users of oral
contraceptives into this open multicenter study. Ex-
clusion criteria were anemia or present thromboem-
bolism, severe diabetes mellitus, severe hypertension,
hepatic dysfunction, hormone-dependent tumors, and
pregnancy. Adipose patients and smokers 35 years
of age were allowed to be enrolled. Other possible risk
factors, such as alcohol consumption or varicose
veins, were recorded. Patients received a preparation
containing 20 g ethinyl estradiol and 150 g deso-
gestrel for 4 months.
Before the beginning of treatment, womens men-
strual history was obtained. Moreover, body weight,
blood pressure, known risk factors for the develop-
ment of cardiovascular disease (such as obesity,
smoking, and alcohol consumption), as well as any
concomitant medication were documented. Quality
of life was assessed using a self-administered, detailed
questionnaire (Quality of Life Enjoyment and Satis-
faction Questionnaire, Q-LES-Q) (Table 1).11 At the
follow-up examination at 4 months, subjects cycle
length, duration of menses, body weight, and blood
pressure were documented once more, and subjects
again completed the Q-LES-Q. Any adverse events
experienced during pill intake and the subjects over-
all perception of the prescribed OC were also
recorded.
Contraception
1999;59:287291
Statistical Analysis
The statistical analysis was based on the intention to
treat principle, and an explorative analysis approach
was chosen. All data items from the case report forms
collected in this study were analyzed at least descrip-
tively. As the observed patient compliance was ex-
tremely high (98.4%), possible maximum bias assess-
ment revealed that the application of the last value
technique should be permissible for practical pur-
poses without the risk of introducing any remarkable
bias.
The rationale for the choice of an exploratory
analysis strategy in this study can be justified by the
local legal safety requirements for the analysis of
postmarketing surveillance projects, which state the
priority of safety aspects over efficacy issues (which,
in addition, usually are heavily confounded with
safety). Therefore, nominal risks of 5% have been
taken as the critical limit to avoid an excessive (and
thus unethical) number of patients exposed to the
study drug with respect to safety aspects.
For the evaluation of the primary study results, a
total of 21 statistical tests were done. The application
of the Bonferroni-Holm global risk adjustment did
not show any need for statistical decision change, as
the Wilcoxon signed rank test associated z-values
were in the range of 513 for the main end points in
this study, which are shown with associated p values
0.001. For the safety parameters (and some of the
discussed items of the QOL scale), where for possibly
disguised safety problems the nominal p value ap-
proach is mandatory, some of the low p values in the
range from 0.05 to 0.01 of course vanish after the
application of the Bonferroni-Holm correction. How-
ever, it was believed to be appropriate to publish the
results on the nominal levels because no indica-
tions for statistically significant deteriorations in any
of those secondary details were observed and it was
found interesting to exclude the sampling error at
least on the nominal level to have contributed to
these improvements. With this approach, a fair com-
promise between efficacy and safety aspects was
believed to be provided. Detailed considerations on
the hysteresis loop analysis have been reported previ-
ously.12 Each physician was supposed to enroll at
least five patients into the study.
Results
Between January 1997 and May 1998, 614 women
were included in the study by a total of 102 office-
based gynecologists. The mean age of the patients was
22.5 6.7 years, mean cycle length was 30.4 9.9
days, and mean duration of menses was 5.4 1.3
days. Of the women, 9% were found to be obese and
Contraception
1999;59:287291
Figure 1. Mean scores of each of the 13 items of the
Quality of Life and Enjoyment Questionnaire before and
after 4 months of treatment with a low dose oral contracep-
tive.
37% were smokers. Alcohol abuse was documented
in 1% of participants. Other risk factors for the use of
oral contraceptives were present in 5% of women,
with varicose veins being most common.
The follow-up examination took place after a me-
dian of 126 days, with the study protocol providing for
a follow-up visit in month 4 of treatment. Ten pa-
tients failed to return for review at the follow-up
examination, resulting in a drop-out rate of 1.6%.
By the time of the follow-up examination, the mean
cycle length had decreased significantly to 27.5 1.7
days (p 0.001), and the median duration of menses
had dropped significantly to 4.1 1.1 days (p 0.001).
Neither the systolic and diastolic blood pressure nor
the median body weight were statistically signifi-
cantly modified by OC use.
Figure 1 shows the mean changes in the quality of
life, with scores ranging from 1 (very dissatisfied) to 5
(very satisfied). Thus, the total score could vary from
13 to 65, with decreasing scores representing lower
levels of satisfaction. The total quality of life score
Low Dose OC and Quality of Life 289
Figure 2. Hysteresis loop analysis of the total score. The
shift to the right of the curve after 4 months of OC use
corresponds to an improvement in the quality of life.
showed a highly significant increase from 52.5 7.0
at baseline to 53.9 6.8 after 4 months of OC use
(p 0.001). Hysteresis loop analysis of the cumulative
frequency distributions at baseline and at the end of
the study revealed that the proportion of women with
total quality of life scores of 45 dropped from 14% at
baseline to 9% in month 4 of OC use (Figure 2), which
may be interpreted as a decrease in the proportion of
women with a comparatively poor quality of life.
Similarly, the proportion of women with total quality
of life scores of 57 or higher, who may be considered
to have a particularly good quality of life, increased
from 17% to 22% during the 4 months of OC use.
Furthermore, the intraindividual changes noted
across the 4 months of OC use suggest that 56% of
women experienced an improvement, 18% experi-
enced no change, and 26% experienced a deteriora-
tion of their quality of life.
With regard to the subjects social and family rela-
tionships, living and housing situation, and vision, no
significant changes were noted after 4 months of OC
intake. Adverse effects were reported by 23% of the
study participants, with bleeding irregularities being
most frequent, followed by weight gain, headache,
breast tenderness, and gastrointestinal complaints. Of
the women, 88% stated that they intended to con-
tinue taking the prescribed oral contraceptive beyond
the study period. A total of 49 patients (8%) stated the
reasons for discontinuing oral contraceptives after
completion of the study; it is important to note here
that 10 of these 49 women reported not currently
needing contraceptive protection.
Discussion
The results of the present investigation, the first to
assess a low dose oral contraceptive in the light of
290 Egarter et al.
patient satisfaction and quality of life considerations,
demonstrate a significant improvement in quality of
life as assessed using a detailed questionnaire. With
the exception of subjects social and family relation-
ships, living and housing situation, and vision, all
other quality of life parameters were distinctly im-
proved by OC use, resulting in a significant improve-
ment in the summary scores of satisfaction and, thus,
in the quality of life. The Quality of Life Enjoyment
and Satisfaction Questionnaire11 we used in the cur-
rent study has already been shown in other clinical
areas to be a reliable and valid measure of a patients
perception of her/his ability to function in various
dimensions of daily life that enables investigators to
easily obtain sensitive measures of the degree of a
patients satisfaction.
The improvement in patient satisfaction and qual-
ity of life noted in this study is an important factor in
terms of both the acceptability of an OC and patient
compliance. Research into the level of compliance
with chronic treatments for a wide variety of disor-
ders has shown that no consequence of noncompli-
ance with a given treatment regimen is severe enough
to motivate patients to strictly adhere to the pre-
scribed regimen over extended periods of time.13 Even
the fear of pregnancy does not appear to improve
compliance with OC over adherence to other chronic
medical treatments.14 In this light, the improvement
in the quality of life reflected in our results may
certainly be considered an important prerequisite for
long term compliance.
The reasons for this impressive improvement in
satisfaction and quality of life in users of low dose
oral contraceptives are, of course, difficult to pin-
point, although the absence of fear of an unwanted
pregnancy as well as other well established advan-
tages of OC, such as improved cycle control, short-
ened duration of menses, and an alleviation of pre-
menstrual complaints, most probably play key roles.
The mechanisms whereby estrogens and progestins
act on the central nervous system, and in turn on the
quality of life, have not been clearly elucidated. Based
on studies that have identified alterations in specific
neurotransmitter systems in women with psychiatric
disturbance,15 most researchers have focused on the
effects of steroid hormones on the limbic system.
Fink et al., in a recent study in rodents, concluded
that estrogen stimulates a marked increase in dopa-
mine and serotonin receptors in the cerebral cortex
and nucleus accumbens,16 areas of the brain that are
assumed to play a primary role in regulating emotion
and neuroendocrine control mechanisms. Moreover,
they found that estrogen increases the neuropeptide
vasopressin, possibly resulting in enhanced olfactory
and social memory. Other research groups have dem-
Contraception
1999;59:287291
onstrated that estrogen reduces monoamine oxidase
activity, thereby increasing neuronal excitability,17
whereas progesterone appears to partially negate this
effect. Numerous other findings, many coming from
animal studies, have suggested other effects, such as
alterations in the numbers of receptor-binding sites or
direct effects on neuronal firing.15 Overall, steroid
hormones exert complex effects on the central ner-
vous system, with OC containing higher doses of
estrogen more likely to have a negative rather than a
stimulatory effect on mood. Moreover, studies on the
relationship between psychological symptoms and
changes in estrogen and progesterone levels across the
menstrual cycle have provided evidence that relative
changes in estrogen levels, whether increasing or
decreasing, may have a role in the development of
psychological disturbances.18
In conclusion, modern low dose oral contraceptives
have demonstrated beneficial effects on certain as-
pects of the menstrual cycle, including cycle control
and the duration of menses. Moreover, they may have
a beneficial and stimulatory effect on a variety of
psychological parameters, which may explain the
improvement in satisfaction and quality of life ob-
served in this study. This is why there has in recent
years been increased interest in using hormonal ther-
apies in women with previous psychiatric distur-
bances, such as seasonal affective disorder,19 to allow,
hopefully, for improved maintenance of the psycho-
logical well-being and quality of life of these women
and to ultimately prevent the potential deterioration
of these disorders.
cknowledgments
We thank all gynecologists enrolling women into this
study and DI Kurt Neumann for statistical calcula-
tions.
This study was supported by a grant from Organon
GesmbH, Austria.
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