The European Journal of Contraception & Reproductive

Health Care

ISSN: 1362-5187 (Print) 1473-0782 (Online) Journal homepage: https://www.tandfonline.com/loi/iejc20

Comparison of change in body weight

between contraception containing 30-µg
ethinylestradiol/2-mg chlormadinone acetate
or 30-µg ethinylestradiol/3-mg drospirenone: a
randomised controlled trial

Thanyarat Wongwananuruk, Nalinee Panichyawat, Tachjaree Panchalee,

Preeyaporn Jirakittidul, Surasak Angsuwathana, Korakot Sirimai, Manopchai
Thamkhantho & Gessuda Chiravacharadej

To cite this article: Thanyarat Wongwananuruk, Nalinee Panichyawat, Tachjaree Panchalee,

Preeyaporn Jirakittidul, Surasak Angsuwathana, Korakot Sirimai, Manopchai Thamkhantho &
Gessuda Chiravacharadej (2019): Comparison of change in body weight between contraception
containing 30-µg ethinylestradiol/2-mg chlormadinone acetate or 30-µg ethinylestradiol/3-
mg drospirenone: a randomised controlled trial, The European Journal of Contraception &
Reproductive Health Care, DOI: 10.1080/13625187.2019.1688290

To link to this article: https://doi.org/10.1080/13625187.2019.1688290

Published online: 22 Nov 2019.

Submit your article to this journal

View related articles

View Crossmark data

Full Terms & Conditions of access and use can be found at

https://www.tandfonline.com/action/journalInformation?journalCode=iejc20
THE EUROPEAN JOURNAL OF CONTRACEPTION & REPRODUCTIVE HEALTH CARE
https://doi.org/10.1080/13625187.2019.1688290

RESEARCH ARTICLE

Comparison of change in body weight between contraception containing

30-lg ethinylestradiol/2-mg chlormadinone acetate or 30-lg
ethinylestradiol/3-mg drospirenone: a randomised controlled trial
Thanyarat Wongwananuruka, Nalinee Panichyawata , Tachjaree Panchaleeb, Preeyaporn Jirakittidula,
Surasak Angsuwathanaa, Korakot Sirimaia, Manopchai Thamkhanthoa and Gessuda Chiravacharadeja
a
Family Planning and Reproductive Health Unit, Department of Obstetrics and Gynaecology, Faculty of Medicine Siriraj Hospital,
Mahidol University, Bangkok, Thailand; bDivision of Maternal–Fetal Medicine, Department of Obstetrics and Gynaecology, Faculty of
Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand

ABSTRACT ARTICLE HISTORY

Objectives: The aim of this study was to compare changes in body weight in women using a Received 10 May 2019
combined oral contraceptive (COC) consisting of 30-lg ethinylestradiol (EE) and 2-mg chlormadi- Revised 15 September 2019
none acetate (CMA) or a COC consisting of 30-lg EE and 3-mg drospirenone (DRSP). Accepted 29 October 2019
Methods: This randomised double-blind controlled trial (ClinicalTrials.gov NCT01608698) was con-
KEYWORDS
ducted at a university hospital-based clinic in Thailand between June 2012 and September 2015. A Body weight;
total of 102 women were enrolled in the study, 99 of whom were randomised to EE/CMA (n ¼ 45) chlormadinone acetate;
or EE/DRSP (n ¼ 54). Each participant was treated for six cycles. Body weight and other parameters combined oral
as well as side effects were recorded at baseline and at the end of the third and sixth cycles contraceptives; drospire-
of treatment. none; randomised
Results: A significant difference was observed in mean body weight change between the EE/CMA controlled trial
and EE/DRSP groups from both baseline to third cycle (0.51 ± 1.36 kg vs –0.43 ± 1.56 kg; p ¼ .003)
and baseline to sixth cycle (1.00 ± 1.84 kg vs –0.20 ± 2.23 kg; p ¼ .013). The mean difference in body
mass index and waist circumference had a similar trend to that of the mean difference in body
weight. There was no significant difference in side effects between groups.
Conclusion: A COC containing 30-mg EE/3-mg DRSP tended to confer a significantly more favour-
able change in body weight over a 6-month period compared with a COC containing 30-mg
EE/2-mg CMA, which was associated with an increase in body weight.

Introduction while an antimineralocorticoid effect could balance the

Combined oral contraceptives (COCs) contain both an
oestrogen and a progestin. Weight gain has been reported
to be one of the side effects of COC use and is a common
reason why women discontinue treatment [1]. As a result,
women and clinicians who are concerned about potential
weight gain may be deterred from using this effective
contraceptive method. Several mechanisms of COCs that
may affect weight gain have been proposed, such as an
increase in fluid retention, an increase in fat deposition, an
anabolic effect on increased appetite and an androgenic
effect on muscle mass [2]. Ethinylestradiol (EE), the
type of oestrogen currently used in most COCs, has
mineralocorticoid activity that exerts a stronger stimulatory
effect on the renin–angiotensin–aldosterone system (RAAS)
compared with natural oestrogen. The effect of EE on the
RAAS, which can induce fluid retention, combined with its
effect of increasing fat deposition, may result in weight
gain in COC users. Some progestins also cause water and
salt retention, especially first-generation progestins. Newly
developed progestins with different properties such as
antimineralocorticoid and antiandrogenic activities have
been introduced [3]. Progestins with antiandrogenic activity
may have a favourable effect on acne and/or hirsutism,
mineralocorticoid activity of EE [4] and may reduce fluid
retention, which is one of the proposed mechanisms of
weight gain in COC users.
Drospirenone (DRSP) is a progestin that has both
antiandrogenic and antimineralocorticoid activities, the lat-
ter of which decreases the body’s ability to reabsorb water
[5]. Guang-Sheng et al. [6] compared a COC containing
DRSP with a COC containing desogestrel for 13 cycles in
healthy Chinese women. They observed a significant
improvement in water retention and a significant decrease
in mean body weight in women receiving the COC contain-
ing DRSP, compared with an increase in mean body weight
in women using the COC containing desogestrel. Borges
et al. [4] studied the effect of COCs containing EE and
DRSP, but they reported no significant change in body
weight or blood pressure.
Conversely, chlormadinone acetate (CMA) has slight
glucocorticoid and potent antiandrogenic effects without
antimineralocorticoid activity [3]. Uras et al. [7] found no
difference in body mass index (BMI) between women using
a COC containing CMA and non-hormonal contraceptive
users over six cycles of treatment. In contrast, Pushparajah
et al. [8] observed a mean increase in body weight of
0.6 kg after 13 cycles of combined EE and CMA.

CONTACT Nalinee Panichyawat nalinee.pan@mahidol.ac.th Family Planning and Reproductive Health Unit, Department of Obstetrics and
Gynaecology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
ß 2019 The European Society of Contraception and Reproductive Health
2 T. WONGWANANURUK ET AL.
A 2014 Cochrane review was not able to conclusively
confirm a relationship between COC use and body weight
change [2]. COC formulations that contain new generations
of progestins, DRSP and CMA, are currently widely used.
However, no study has compared the effect of COCs con-
taining these different progestins on weight change as a
primary study objective. Given the variable and sometimes
inconclusive findings reported in previous studies, further
investigation is needed to elucidate the effect of these
agents on body weight, as well as other side effects. The
primary aim of this study was to investigate the effect of
contraceptive treatment with 30-lg EE/2-mg CMA vs 30-lg
EE/3-mg DRSP on body weight change.
Methods
This randomised double-blind controlled trial was con-
ducted between June 2012 and September 2015 at the
Family Planning and Reproductive Health Unit, Department
of Obstetrics and Gynaecology, Faculty of Medicine Siriraj
Hospital, Mahidol University, Bangkok, Thailand. The trial is
registered at ClinicalTrials.gov (NCT01608698). The study
protocol was approved by the Siriraj Institutional Review
Board (COA no. Si 115/2012) and complied with the princi-
ples set forth in the Declaration of Helsinki and all of its
subsequent amendments. Written informed consent was
obtained from all participants.
Women satisfying all the following criteria were eligible
for inclusion: age 19–45 years, BMI <27.5 kg/m2, regular
menstrual cycles, no hormonal or other steroid therapy
3 months prior to enrolment, no known gynaecological dis-
orders and desire for contraception using COCs. Women
having one or more of the following were excluded:
contraindication for COC use, high blood pressure (systolic
blood pressure >140 mmHg and/or diastolic blood pressure
>90 mmHg), abnormal vaginal bleeding, pregnancy, smok-
ing, eating disorder history and/or treatment with a steroid
and/or drug that may interact with COCs.
Intervention
Groups were randomised using simple randomisation soft-
ware, and the computer-generated codes were concealed
in opaque envelopes. There were two COC treatment
groups: (1) 30-lg EE and 2-mg CMA (EE/CMA) and (2) 30-
lg EE and 3-mg DRSP (EE/DRSP). Both study drugs had
identical capsules and packaging. The study participants
and study observers were blinded to the group assign-
ments. The participants were instructed to take one tablet
per day for 21 days, followed by a 7-day tablet-free interval
during which withdrawal bleeding would be expected.
After finishing the 7-day tablet-free interval, the 21-day tab-
let intake regimen was restarted, regardless of whether
withdrawal bleeding had stopped, for a total of six treat-
ment cycles. The second and third visits were scheduled on
days 5–7 of the 7-day tablet-free interval at the end of the
third and sixth cycles of treatment, respectively. The partici-
pants received a 3-month COC prescription at the first visit
and a 3-month COC prescription at the second visit.
Baseline characteristics were collected and recorded during
the first visit by a study nurse. Body weight, BMI, waist cir-
cumference, blood pressure and side effects were recorded
at each follow-up visit, and participants were asked to
bring their menstrual record card and their remaining
COCs for evaluation of drug compliance.
Body weight was measured on the morning of each visit
after an overnight fast, using the Economical Digital
Physician Scale (Health O meter; McCook, IL, USA). Prior to
weight measurement, participants had to fully disrobe and
wear a pre-weighed gown so that the participant’s weight
could be measured exactly. Waist circumference was meas-
ured, with the participant in the standing position, at the
midpoint between the lower margin of the least palpable
rib and the top of the iliac crest and all measurements
were performed by the same research nurse. Blood pres-
sure was measured after the participant had rested in the
seated position for 5 min, using the same calibrated digital
blood pressure device (Omron HEM-7203; Omron
Healthcare Corporation, Kyoto, Japan) at each visit.
Participants were instructed not to change their diet or
physical activity habits during the study period.
Bleeding patterns were defined according to the criteria
established by the World Health Organization [9].
Unscheduled vaginal bleeding/spotting was recorded.
Withdrawal bleeding was defined as any vaginal bleeding/
spotting that occurred during the pill-free period. Vaginal
bleeding was defined as any bleeding that required the
use of a sanitary pad, while spotting was defined as any
bleeding that did not require the use of a sanitary pad.
Participants were instructed to record their bleeding or
spotting on a daily menstrual record card. Severity of acne
was assessed by the study investigator and classified as
none, mild, moderate or severe, according to lesion num-
ber and characteristics [10]. Side effects that were noted
from specific questions asked by investigators or that were
spontaneously reported by participants were recorded.
Sample size calculation
The sample size calculation was based on data from a pre-
vious study [7] of EE/CMA over six cycles, with a pooled
standard deviation (SD) of weight in EE/CMA users of 1.6.
The sample size was calculated for a power of 80% with a
two-sided type I error of 0.05 to detect a statistically signifi-
cant difference in mean body weight change of 1 kg
between the two study COCs. The estimated dropout rate
was 20%. The total sample size was 42 participants
per group.
Statistical analysis
Data analyses were performed using PASW Statistics, ver-
sion 18.0 for Windows (SPSS, Chicago, IL, USA). Descriptive
statistics were used to summarise demographic data. Data
are presented as means ± SD or numbers and/or percen-
tages. Normality of data distribution was tested using the
Kolmogorov–Smirnov test. The paired t test and
Mann–Whitney U test were used to compare mean differ-
ences within groups; the unpaired t test was used to
compare mean differences in body weight change between
groups as a primary outcome. A p-value <.05 was regarded
as statistically significant.
 THE EUROPEAN JOURNAL OF CONTRACEPTION & REPRODUCTIVE HEALTH CARE 3

Results circumference between baseline and the two post-baseline

One hundred and two women were included at the screen-
ing visit; however, three women reversed their decision
and decided not to participate because of the inconveni-
ence associated with the two required follow-up visits. The
remaining 99 women were included in the study.
Randomisation software allocated 45 participants to the EE/
CMA group and 54 participants to the EE/DRSP group.
Both groups were followed-up at the third cycle (43 partici-
pants in the EE/CMA group and 50 participants in the EE/
DRSP group) and the sixth cycle (36 participants in the EE/
CMA group and 44 participants in the EE/DRSP group)
(Figure 1). The participants who were lost to follow-up
could not be contacted by either telephone or mail. The
baseline characteristics of the participants showed no sig-
nificant differences between groups (Table 1). Mean BMI,
waist circumference and blood pressure were within nor-
mal ranges.
An intention-to-treat analysis compared the mean
change in body weight between baseline and the two fol-
low-up visits (data not shown). Between baseline and the
third cycle visit, the mean change in body weight was sig-
nificantly different between the EE/CMA and EE/DRSP
groups (0.49 ± 1.33 kg vs –0.40 ± 1.51 kg, respectively;
p ¼ .003). Similarly, between baseline and the sixth cycle
visit, the mean change in body weight was significantly dif-
ferent between the EE/CMA and EE/DRSP groups
(0.86 ± 1.82 kg vs –0.18 ± 2.07 kg, respectively; p ¼ .011).
A per protocol analysis of the comparison of mean dif-
ference in body weight change, BMI and waist
Assessed for eligibility (n=102)
visits in both groups is shown in Figure 2. The mean
change in body weight was significantly different between
the EE/CMA and EE/DSRP groups, between both baseline
and the third cycle (0.51 ± 1.36 kg vs –0.43 ± 1.56 kg,
respectively; p ¼ .003) and baseline and the sixth cycle
(1.00 ± 1.84 kg vs –0.20 ± 2.23 kg, respectively; p ¼ .013).
At the third cycle, 23.3% of women in the EE/CMA
group experienced a weight reduction, compared with
60.0% in the EE/DRSP group, while 76.7% of women in the
EE/CMA group and 36.0% in the EE/DRSP group experi-
enced a weight increase (p < .001). At the sixth cycle,
22.9% of women in the EE/CMA group experienced a
weight reduction, compared with 43.2% in the EE/DRSP
group, while 74.3% of women in the EE/CMA group and
56.8% in the EE/DRSP group experienced a weight
increase (p ¼ .074).
Other factors compared between time points by group
are shown in Table 2. Specifically, there were no significant
differences between groups with regard to blood pressure,
breast tenderness, headache, gastrointestinal discomfort or
acne severity. No participants in either group reported
unscheduled or breakthrough bleeding or pregnancy.
Discussion
Differences and similarities in relation to other studies
One of the side effects of COC use is increasing body
weight, which can influence failure to comply with contin-
ued contraceptive use, especially among young women of
reproductive age [11,12]. Our study compared the effect of
two COCs with different progestin properties (CMA and
DRSP) on weight change. We found that mean body

Declined to participate (n=3) Table 1. Baseline characteristics of the two study groups.
EE/CMA EE/DRSP
Characteristic (n ¼ 45) (n ¼ 54) p-value
99 participants Age (years) 30.62 ± 5.08 28.91 ± 4.86 .090
Body weight (kg) 54.80 ± 7.64 54.70 ± 8.54 .819
BMI (kg/m2) 21.97 ± 2.94 21.82 ± 3.16 .953
Waist circumference (cm) 72.45 ± 12.62 75.00 ± 8.97 .245
Previous contraceptiona .696
Informed consent obtained COC 23 (51.1) 27 (50.0)
Depot medroxyprogesterone 1 (2.2) 0
acetate
Intrauterine device 6 (13.3) 6 (11.5)
Implant 1 (2.2) 1 (1.9)
Randomised to two groups Other method 14 (31.1) 18 (33.3)
Acneb .601
None 23 (52.3) 25 (46.3)
Mild 12 (27.3) 22 (40.7)
Moderate 8 (18.2) 6 (11.1)
Severe 1 (2.3) 1 (1.9)
30 µg EE/2 mg CMA 30 µg EE/3 mg DRSP Education .832
(n=45) (n=54) Primary school 2 (4.4) 3 (5.6)
High school 22 (48.9) 29 (53.7)
Bachelor’s degree or higher 21 (46.7) 22 (40.7)
Lost to follow-up (n=2) Lost to follow-up (n=4) Occupation .689
Government employee 6 (13.3) 6 (11.1)
Follow-up at third cycle Follow-up at third cycle Business owner 1 (2.2) 5 (9.3)
(n=43) (n=50) Employee 24 (53.3) 26 (48.1)
Others 14 (31.1) 17 (31.5)
Income status .183
Lost to follow-up (n=7) Lost to follow-up (n=6) Inadequate 2 (4.4) 1 (1.9)
Adequate with no savings 13 (28.9) 25 (46.3)
Follow-up at sixth cycle Follow-up at sixth cycle Adequate with savings 30 (66.7) 28 (51.9)
(n=36) (n=44) Data are means ± SD or n (%).
a
Missing data: n ¼ 52 in the EE/DRSP group.
Figure 1. Flow diagram of the study protocol.
b
Missing data: n ¼ 44 in the EE/CMA group.
4 T. WONGWANANURUK ET AL.

(A) 1.2 n=36

1.00±1.84
1 EE/CMA

Mean difference in body weight (kg)

EE/DRSP
0.8
n=43
0.6 0.51±1.36

0.4

0.2

0 n=44
–0.20±2.23
-0.2
n=50
–0.43±1.56
-0.4

-0.6
Between baseline and third cycle* Between baseline and sixth cycle*

(B) 0.6
n=36
Difference in body mass index (kg/m2)

0.48±0.08
0.5
EE/CMA
0.4
n=43 EE/DRSP
0.3 0.26±1.03

0.2

0.1
n=44
0
–0.08±0.87
n=50
-0.1 –0.17±0.58
-0.2

-0.3
Between baseline and third cycle* Between baseline and sixth cycle*

(C) 0.6
n=36
2.90±11.01
Difference in waist circumference (cm)

0.5 EE/CMA

0.4 EE/DRSP
n=43
0.3 1.86±9.93

0.2

0.1

0 n=44
–0.23±4.60
-0.1 n=50
–1.71±3.59

-0.2

-0.3
Between baseline and third cycle* Between baseline and sixth cycle*
Figure 2. Mean ± SD differences in body weight (A), BMI (B) and waist circumference (C) between baseline and the two post-baseline visits (per protocol ana-
lysis). p < .05.

weight increased in EE/CMA users and decreased in EE/ Uras et al. [7] found that mean body weight remained
DRSP users over the six cycles of contraceptive treatment. unchanged, but that fat mass was decreased in the EE/
A Cochrane review stated that the available evidence CMA group from baseline to the sixth cycle of treatment.
was insufficient to determine the effect of combined con- In our study, the majority of participants in the EE/CMA
traceptives on body weight change [2]. A number of stud- group (74.3%) showed an increase in body weight over the
ies have reported different results relating to the effect of six cycles of treatment.
COCs on body weight. Previous studies of EE/CMA showed DRSP has similar antiandrogenic properties to those of
a marginal increase in body weight or a small percentage CMA; however, DRSP has antimineralocorticoid activity but
of the study population who experienced weight gain dur- CMA does not. Several studies have reported the beneficial
ing treatment [8,13,14], while others reported no change in effect of COCs containing DRSP in terms of improving
body weight or BMI during treatment with EE/CMA [15,16]. water retention but without significantly changing BMI
 THE EUROPEAN JOURNAL OF CONTRACEPTION & REPRODUCTIVE HEALTH CARE 5

Table 2. Comparison of variables between time points by group. may reflect natural fluctuations, our results demonstrated
Variable EE/CMA EE/DRSP p-value that the COC containing DRSP had a more favourable
Mean difference in systolic blood pressure (mmHg) effect on weight compared with the COC containing CMA.
Between baseline and third cycle –0.95 ± 10.32 –1.10 ± 11.54 .949
Between baseline and sixth cycle –2.48 ± 9.82 –4.79 ± 14.50 .410
Most reproductive-aged women are concerned about
Mean difference in diastolic blood pressure (mmHg) side effects other than body weight gain when choosing a
Between baseline and third cycle –2.16 ± 7.03 –0.14 ± 9.167 .244 COC regimen for contraception. Both regimens in this
Between baseline and sixth cycle –2.83 ± 8.31 0.07 ± 9.26 .150 study provided a reliable method of contraception with no
Breast tenderness .142 reported pregnancies in either group. Moreover, the
At third cycle 28 (65.1) 24 (48.0)
At sixth cycle 12 (33.3) 14 (31.8) participants in both COC groups reported good cycle
Headache .649 control and no unscheduled bleeding. With regard to the
At third cycle 13 (30.2) 16 (32.0)
At sixth cycle 12 (33.3) 17 (38.6) antiandrogenic effect of the two studied COC regimens,
Gastrointestinal discomfort .764 many of the women in our study had mild acne symptoms
At third cycle 9 (20.9) 11 (22.0) at baseline; however, no significant change in acne was
At sixth cycle 5 (13.9) 8 (18.2)
Acne severity observed at the end of the study. In addition, only some
At third cycle .489 minor side effects (i.e., breast tenderness, headache and/or
Worse 5 (11.1) 3 (6.0)
No change 29 (67.4) 32 (64.0)
gastrointestinal discomfort) were reported, but no serious
Improved 9 (20.9) 15 (30.0) side effects were observed. As the regimens investigated in
At sixth cycle .258 this study are two of the most commonly used COCs in
Worse 1 (2.8) 5 (11.4)
No change 24 (66.7) 23 (52.3) routine clinical practice, the results from this trial might
Improved 11 (30.6) 16 (36.4) provide valuable information to both clinicians and users.
Data are means ± SD or n (%).
Third cycle: n ¼ 43 in EE/CMA group and n ¼ 50 in EE/DRSP group.
Sixth cycle: n ¼ 36 in EE/CMA group and n ¼ 44 in EE/DRSP group.
Strengths and weaknesses
The strength of this trial is its randomised, double-blind,
[17,18]. Earlier studies that compared EE/DRSP with COCs controlled design to evaluate body weight change as a pri-
containing other progestins such as desogestrel or levonor- mary outcome. The most notable limitation is the fact that
gestrel reported stable or decreased body weight [6,19,20]. many participants withdrew for various reasons during the
This is similar to our finding of decreased body weight in course of the study. As a result, one of our two study
EE/DRSP users. More specifically, 43.2% of participants in groups had less than the minimum required sample size at
the EE/DRSP group experienced a decrease in body weight the end of the study. Nevertheless, we analysed the data
over the six cycles of treatment. by both intention to treat and per protocol, and the results
Only two studies have compared the effect of EE/DRSP of both analyses demonstrated similar trends. The second
and EE/CMA on body weight change and both of those limitation was the relatively short six cycle study period.
studies reported no significant change between the two Longer-term studies are needed to confirm the findings of
COC groups [21,22]. A recently published study that this study and to further elucidate the effect of COCs on
compared EE/DRSP and EE/CMA for the treatment of acne body weight. In addition, we evaluated body weight out-
and dysmenorrhoea in a Thai population reported no sig- come only, and no other body composition variables were
nificant change in body weight over the six cycles of treat- compared. The fact that COCs are known to affect body
ment in both treatment groups [23]. However, weight composition, including body water and fat, suggests that
change was not the primary objective of the aforemen- analysis of other variables would tell us more about how
tioned studies and the participants were younger than our COCs affect change in body weight. Moreover, our study
study population. This could be a factor that influences lacked a placebo or non-hormonal control group, which is
observed differences in the amount of weight change. suggested by Cochrane for studies of hormonal contracep-
tion and weight change. However, as we aimed to investi-
Findings and interpretation gate and compare the effect on weight change of COCs
with different progestin properties, we did not include a
In this study, the mean difference in body weight signifi- placebo or non-hormonal control group. Finally, as only
cantly decreased (by 0.20 kg) between baseline and the Thai women were recruited to this study, our findings may
third cycle and between baseline and the sixth cycle (by not be observed in studies evaluating women of different
0.43 kg) in the EE/DRSP group. In contrast, the mean differ- racial or ethnic groups.
ence in body weight in the EE/CMA group increased by
0.51 kg between baseline and the third cycle and by 1.0 kg
between baseline and the sixth cycle of treatment. Since
Conclusion
fluid retention is one of the proposed mechanisms of
weight gain in COC users, this finding suggests that the The COC containing 30-mg EE and 3-mg DRSP tended to
stronger antimineralocorticoid effect of DRSP (compared have a significantly more favourable change in decreasing
with CMA) via activation of the RAAS may explain the body weight over a 6-month period, particularly during the
reduced body fluid retention and decrease in body weight first three cycles of use, while the COC containing 30-mg EE
in DRSP users. Even though our weight change findings and 2-mg CMA was associated with a small increase in
were not clinically obvious and a change in body weight body weight.
6 T. WONGWANANURUK ET AL.
Acknowledgements
The authors would like to thank J. Inthawong and M. Vongsiri (Family
Planning and Reproductive Health Unit, Department of Obstetrics and
Gynaecology, Faculty of Medicine Siriraj Hospital, Mahidol University)
for collecting data. The authors are also grateful to J. Pooliam (Clinical
Epidemiology Unit, Faculty of Medicine Siriraj Hospital, Mahidol
University) for assistance with the statistical analyses.
Disclosure statement
No potential conflict of interest was reported by the authors.
Funding
This work was supported by a Siriraj grant for research development,
Faculty of Medicine Siriraj Hospital, Mahidol University
(no. R15532040).
ORCID
Nalinee Panichyawat http://orcid.org/0000-0002-9058-4905
References
[1] Zahradnik HP. Belara – a reliable oral contraceptive with add-
itional benefits for health and efficacy in dysmenorrhoea. Eur J
Contracept Reprod Health Care. 2005;10:12–18.
[2] Gallo MF, Lopez LM, Grimes DA, et al. Combination contracep-
tives: effects on weight. Cochrane Database Syst Rev. 2014;1:
CD003987.
[3] Schindler AE, Campagnoli C, Druckmann R, et al. Classification
and pharmacology of progestins. Maturitas 2003;46:S7–S16.
[4] Borges LE, Andrade RP, Aldrighi JM, et al. Effect of a combin-
ation of ethinylestradiol 30 microg and drospirenone 3 mg on
tolerance, cycle control, general well-being and fluid-related
symptoms in women with premenstrual disorders requesting
contraception. Contraception 2006;74:446–450.
[5] Tan J, Ediriweera C. Efficacy and safety of combined ethinyl
estradiol/drospirenone oral contraceptives in the treatment of
acne. Int J Womens Health 2009;1:213–221.
[6] Guang-Sheng F, Mei-Lu B, Li-Nan C, et al. Efficacy and safety of
the combined oral contraceptive ethinylestradiol/drospirenone
(Yasmin) in healthy Chinese women: a randomized, open-label,
controlled, multicentre trial. Clin Drug Investig. 2010;30:
387–396.
[7] Uras R, Orru M, Etzi R, et al. Evidence that in healthy young
women, a six-cycle treatment with oral contraceptive contain-
ing 30 mcg of ethinylestradiol plus 2 mg of chlormadinone
acetate reduces fat mass. Contraception 2009;79:117–121.
[8] Pushparajah DS, Rohm P, Hoschen K, et al. Safety data and
beneficial effects of the combined oral contraceptive ethinyles-
tradiol 0.03 mg/chlormadinone acetate 2 mg (BelaraV R ): a 13-
cycle, observational study in routine clinical practice. Clin Drug
Investig. 2011;31:121–134.
[9] Belsey EM, Machin D, d’Arcangues C. 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. 1986;34:253–260.
[10] Noppakun N, Timpatanapong P, Sindhupak W, et al. Clinical
practice guideline for acne (in Thai). 2011. [cited 2011
September 28]. Available from: www.dst.or.th/files_news/001-
Guideline_Acne_2011.pdf.
[11] Oddens BJ. Women’s satisfaction with birth control: a popula-
tion survey of physical and psychological effects of oral contra-
ceptives, intrauterine devices, condoms, natural family
planning, and sterilization among 1466 women. Contraception.
1999;59:277–286.
[12] Lindh I, Blohm F, Andersson-Ellstrom A, et al. Contraceptive use
and pregnancy outcome in three generations of Swedish
female teenagers from the same urban population.
Contraception. 2009;80:163–169.
[13] Schramm G, Steffens D. A 12-month evaluation of the CMA-
containing oral contraceptive Belara: efficacy, tolerability and
anti-androgenic properties. Contraception. 2003;67:305–312.
[14] Zahradnik HP, Hanjalic-Beck A. Efficacy, safety and sustainability
of treatment continuation and results of an oral contraceptive
containing 30 mcg ethinyl estradiol and 2 mg chlormadinone
acetate, in long-term usage (up to 45 cycles) – an open-label,
prospective, noncontrolled, office-based phase III study.
Contraception. 2008;77:337–343.
[15] Anthuber S, Schramm GA, Heskamp ML. Six-month evaluation
of the benefits of the low-dose combined oral contraceptive
chlormadinone acetate 2 mg/ethinylestradiol 0.03 mg in young
women: results of the prospective, observational, non-interven-
tional, multicentre TeeNIS study. Clin Drug Investig. 2010;30:
211–220.
[16] Schramm GA, Schrah G. The efficacy and safety of an oral
contraceptive containing chlormadinone acetate: results of a
pooled analysis of noninterventional trials in adult and adoles-
cent women. Contraception. 2011;84:390–401.
[17] Fruzzetti F, Lazzarini V, Ricci C, et al. Effect of an oral contra-
ceptive containing 30 microg ethinylestradiol plus 3 mg dro-
spirenone on body composition of young women affected by
premenstrual syndrome with symptoms of water retention.
Contraception. 2007;76:190–194.
[18] Endrikat J, Sandri M, Gerlinger C, et al. A Canadian multicentre
prospective study on the effects of an oral contraceptive con-
taining 3 mg drospirenone and 30 microg ethinyl oestradiol on
somatic and psychological symptoms related to water retention
and on body weight. Eur J Contracept Reprod Health Care.
2007;12:220–228.
[19] Oelkers W, Helmerhorst FM, Wuttke W, et al. Effect of an oral
contraceptive containing drospirenone on the renin–angioten-
sin–aldosterone system in healthy female volunteers. Gynecol
Endocrinol. 2000;14:204–213.
[20] Suthipongse W, Taneepanichskul S. An open-label randomized
comparative study of oral contraceptives between medications
containing 3 mg drospirenone/30 mg ethinylestradiol and 150
microg levonorgestrel/30 mg ethinylestradiol in Thai women.
Contraception. 2004;69:23–26.
[21] Lello S, Primavera G, Colonna L, et al. Effects of two estropro-
gestins containing ethynilestradiol 30 mg and drospirenone
3 mg and ethynilestradiol 30 mg and chlormadinone 2 mg on
skin and hormonal hyperandrogenic manifestations. Gynecol
Endocrinol. 2008;24:718–723.
[22] Sabatini R, Orsini G, Cagiano R, et al. Noncontraceptive benefits
of two combined oral contraceptives with antiandrogenic prop-
erties among adolescents. Contraception. 2007;76:342–347.
[23] Jaisamrarn U, Santibenchakul S. A comparison of combined
oral contraceptives containing chlormadinone acetate versus
drospirenone for the treatment of acne and dysmenorrhea: a
randomized trial. Contracept Reprod Med. 2018;3:5.