International Journal of Obesity (2005) 29, 12521258

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PAPER
Weight, fat mass, and central distribution of fat
increase when women use depot-
medroxyprogesterone acetate for contraception
MK Clark1*, JS Dillon2, M Sowers3 and S Nichols1
1
College of Nursing, University of Iowa, Iowa City, IA, USA; 2Department of Internal Medicine, Roy J and Lucille A Carver
College of Medicine, University of Iowa and Iowa City Veterans Affairs Medical Center, Iowa City, IA, USA; and 3School of
Public Health, University of Michigan, Ann Arbor, MI, USA

OBJECTIVE: To compare longitudinal changes in weight, body fat, and ratio of central to peripheral fat mass among first-time
depot-medroxyprogesterone acetate (DMPA) users to women using no hormonal contraception, and to evaluate user
characteristics associated with that change.
DESIGN: Prospective longitudinal study.
SUBJECTS: Healthy women, aged 1835 y, using DMPA for contraception (n 178) and women using no hormonal
contraception (n 145).
MEASUREMENTS: Weight, body fat, and the central distribution of fat, measured at 3-month intervals for 30 months, by
electronic scale and dual-energy X-ray absorptiometry (DEXA). The ratio of central to peripheral distribution of body fat was
computed by dividing the body fat in the conventional DEXA trunk region of interest (ROI) by the ROIs that encompass the
arms, hips and legs.
RESULTS: Women using DMPA had a significantly greater increase in all measures of fatness than women using no hormonal
method of contraception (Po0.03). The observed weight of DMPA users increased from a mean of 69.4 kg (s.d. 16.9) at
baseline to 75.5 kg (s.d. 25.0) at 30 months; an increase of 6.1 kg (8.8.%). Fat mass increased from a mean of 25.3 kg
(s.d. 12.6 kg) at baseline to 31.4 kg (s.d. 17.8); an increase of 6.1 kg (23.6%) in DMPA users. The ratio of central to
peripheral fat mass in DMPA users changed from 0.95 (s.d. 0.155) at baseline to 1.01(s.d. 0.198) at 30 months. In contrast,
weight, fat mass and the ratio of central to peripheral fat mass of control participants remained virtually unchanged over the
same time period. Women with higher baseline physical activity levels had a smaller increase in body fat (P 0.003) and the fat
ratio (P 0.03), but not weight (P 0.48). No other user characteristics including, smoking, past oral contraceptive use or
previous pregnancies predicted change in level of fatness.
CONCLUSIONS: This study has demonstrated a change in body composition toward greater fatness and toward a central
redistribution of fat among DMPA users as compared to controls and provides important information to be used when
counseling women regarding contraceptive methods. Given the potential long-term implication of these changes, further study
is recommended to determine whether the gains in fatness are reversed following DMPA discontinuation and to examine the
role of progestins in the development and maintenance of obesity.
International Journal of Obesity (2005) 29, 12521258. doi:10.1038/sj.ijo.0803023; published online 28 June 2005

Keywords: DMPA; contraception; fat mass; central obesity; DEXA

Introduction obesity is developing at increasingly younger ages.1 Further-

Obesity and overweight are becoming the most important
public health problems in the United States. More than 60%
of the adult US population is now overweight or obese, and
*Correspondence: Professor MK Clark, College of Nursing, 434 NB,
University of Iowa, Iowa City, IA 52242, USA.
E-mail: mary-clark@uiowa.edu
Received 15 October 2004; revised 28 April 2005; accepted 29 April 2005;
published online 28 June 2005
more, evidence suggests that overweight children and
adolescents remain overweight or become obese as adults.2
The causes of overweight and obesity are multifactorial;
however, one potential contributor to weight gain in
adolescents and young adult women is their choice of
hormonal contraception.
Depot-medroxyprogesterone acetate (DMPA) is a proges-
tin-only injectable contraceptive administered every 1113
weeks; it is used by approximately 11% of women choosing

hormonal contraception.3 Weight gain is a commonly
reported side effect and is cited second only to irregular
bleeding as the primary reason for DMPA discontinuation.46
Published studies of weight changes among DMPA users
are inconsistent. Some studies report no weight changes
unique to DMPA users710 while others find average weight
gains as high as 9 kg in 2 y or less.6,1114 Most of these studies
have used either retrospective designs or did not include
controls in the prospective design. Thus, it is difficult to
discern if the weight changes, or lack thereof, are due to
the potential weight-related dropout bias in the retrospec-
tive studies, or to the failure to discriminate DMPA-related
weight gain from usual weight gain in uncontrolled
prospective studies. The only prospective, controlled study
of DMPA-related weight gain reported no change in weight
between the DMPA and the control group. However, in
that study the sample size was limited to 11 DMPA
users and controls who were followed for a single,
3-month DMPA injection period.9 None of these pub-
lished studies has included measures of fat mass or its
distribution.
DMPA-related increases in weight or fat mass during late
adolescence and young adulthood, if substantial, may
increase the future risk of obesity. Understanding the
magnitude of weight and other body composition changes
among DMPA users is important in order to better appreciate
that risk. Accordingly, the purpose of this study was to
longitudinally characterize the 30-month changes in mea-
sures of fatness (weight, fat mass, and the ratio of central
to peripheral fat) in a large number of women using either
DMPA or no hormonal contraception.
Methods
Body composition was measured as part of a prospective
longitudinal study evaluating bone mineral density (BMD)
changes among women, aged 1835 y, with and without
DMPA use. 15 The study enrolled 323 women over 18 months
beginning April 2000, including 178 women who newly
initiated DMPA 150 mg for contraception and 145 control
participants who used no hormonal contraception. Partici-
pants were recruited from family planning and gynecology
clinics, newspaper advertisements, dormitories, residence
halls, workplaces, local business establishments, and by
word-of-mouth. Potential enrollees were excluded if they
did not meet the age requirement; had fewer than nine
menstrual cycles per year; were pregnant or breastfeeding
in the 6-month period prior to study baseline; reported a
history of infertility, seizure disorder, thyroid disease,
autoimmune diseases, diabetes, or eating disorders; were
regularly (more than two times per week) using oral or
inhaled steroid medication; or had ever used DMPA or
Norplant. The University of Iowas Institutional Review
Board approved the study and all enrollees gave informed
Fat and DMPA
MK Clark et al
1253
consent prior to participation and received monetary
compensation for their participation.
Study participants were evaluated at 3-month intervals for
up to 30 months. DMPA users completed the baseline visit
within 1 week of the initial injection. Subsequent visits were
scheduled to correspond with DMPA injections, which
averaged 84 days apart. Control participants were evaluated
between day 1 and day 7 of the follicular phase of their
menstrual cycles and their average visit interval was 93 days.
As a result of the difference in average visit intervals, over
the 30-month observation period the maximum number of
possible visits for DMPA users was 12, while the maximum
number for controls was 11 visits.
A total of 139 (78.1%) of DMPA users and 114 (78.6%)
control participants completed the entire 30 months of
observation. Not all of those who completed the entire
observation period maintained their contraceptive status.
The DMPA discontinuation rate averaged 6.8% per visit
during the first year and 6.4% per visit during the second
year. Persistent vaginal bleeding, weight gain, and desire to
become pregnant were the primary reasons for DMPA
discontinuation. For controls, the hormonal contraceptive
initiation rate averaged 6.3% per visit during the first year
and 7.2% per visit during year 2. Measures of baseline fat
mass, lean mass, and weight did not differ between those
participants who remained in the study and maintained
their original contraceptive status and those who either quit
the study or changed contraceptive status (discontinued
DMPA or began hormonal contraceptives). Data for all
participants were included in the analyses until a participant
either quit the study or changed contraceptive status, at
which point data for that individual was censored. The
analyses included data from 1277 visits for DMPA-users and
1027 visits for controls, and average of 7.2 visits per person
for each of the groups. This provides a 90% power to detect
yearly increases of 1.1 kg (4.5%) in fat mass, 1.5 kg (2.1%) in
weight, and a 0.0154 change in fat ratio.
Measurements
Participants were weighed on an electronic scale (Tanita
Corp, Arlington Heights, IL, USA) in light clothing without
shoes. The scale precision was monitored daily by comparing
the actual scale value to that of a standard 50 pound weight.
Total fat and lean mass were measured with dual-energy
X-ray absorptiometry (DEXA) (GE Lunar Prodigy,t Madison,
WI). The precision of our body fat measures, determined by
comparing same day, repeated measurement of body fat on
26 individuals taken by two different technicians, was 1.4%.
The DEXA standard trunk region of interest (ROI) includes
chest, abdomen, and pelvis and was used as an indicator
of central obesity. The trunk ROI has a high correlation
(r 0.77, Po0.001) with intra-abdominal adipose tissue, as
measured by CT16 and with visceral abdominal fat measured
by MRI (r 0.825, Po0.01).17 In order to determine whether
there was a preferential deposition of fat in the central
International Journal of Obesity
 Fat and DMPA
MK Clark et al
1254
region, a ratio of central to peripheral distribution of body
fat (fat ratio) was computed by dividing the body fat in the
conventional DEXA trunk ROI by the combined fat mass in
the ROIs that encompass the arms, hips, and legs. Quality
assurance checks for the densitometer were performed daily
using a calibration block consisting of tissue-equivalent
material with three bone-simulating chambers. Mean base-
line fat values of new enrollees was computed every 2 weeks
and compared overtime to identify systematic changes in
fat mass that may indicate machine drift. For this, trend
analyses based on regression approaches were used to
compute and evaluate the slope change over time; the slope
remained within 0.2% over the entire 18-month enrollment
period.
Demographic, reproductive, medical, smoking, physical
activity and alcohol consumption histories were obtained
through structured interviews at baseline and updated at
each follow-up visit. Average weekly physical activity for the
between-visit interval was estimated through self-report of
type, duration, and frequency of activity. Energy expenditure
for each activity was converted to metabolic equivalent tasks
(METs) as described by Ainsworth.18 METs represent the
energy expended during selected activities relative to that
expended during rest.18
Statistical analyses
The characteristics of participants, at baseline, were de-
scribed using means or medians for continuous variables (eg
age, fat mass, and lean mass) and frequencies were calculated
for categorical variables (eg prior oral contraceptive use, prior
pregnancy, and smoking). Differences between the two
groups, at baseline were evaluated using t-tests for normally
distributed continuous variables and the Wilcoxon or w2 test
for non-normally distributed (physical activity) or catego-
rical variables.
Plots were developed to describe the observed change in
the measures of fatness over time. Longitudinal analyses of
the repeated measurements of fatness were used to model
change and to test its association with DMPA use. This was
completed using the SAS Procedure Mixed. Models included
DMPA-use as a main effect, as well as a time-by-contraceptive
group interaction. This estimated the rate of change in
measures of fatness in the DMPA group as compared to the
non-DMPA group. Quadratic time terms were included in all
models to determine the linearity of changes in body
composition over time. Fixed covariates considered in the
models included age at baseline, age at menarche, number of
pregnancies, previous oral contraceptive use, and smoking
status. Physical activity at each follow-up visit was included
as a time-dependent covariate. The longitudinal analyses
take into account the multiple observations over time and
the within-person autocorrelation that occurs with these
multiple observations. These analyses allow for variation in
the number and spacing of observations across time that is
inherent in longitudinal studies.19
Results
The population was predominantly white (n 278, 86. 1%)
with 22 women (6.8%) designating themselves as black
or African American, nine (2.7%) as Asian, six (1.9%) as
American Indian, and eight (2.5%) as being of more than
one race. The mean age was 22.1 y (s.d. 4.1). There were no
significant differences between the DMPA users and controls
in age or race/ethnicity.
As seen in Table 1, DMPA users and nonusers were
comparable with respect to weight, fat mass, lean mass,
and ratio of central to peripheral fat mass at baseline.
Likewise, at baseline, both groups were comparable with
respect to self-reported cigarette smoking, physical activity,
and age. DMPA users were significantly more likely to have

Table 1 Baseline characteristics of participants by group status

Women using DMPA Control women (no current hormonal contraceptive use)
n 178 n 145

x s.d. x s.d. P-value

Age (y) 21.9 4.0 22.2 4.3 0.67

Height (cm) 166.6 6.3 167.4 6.3 0.26
Weight (kg) 69.4 16.9 67.9 14.9 0.40
Lean mass (kg) 41.2 5.2 41.7 5.3 0.38
Fat mass (kg) 25.3 12.6 23.4 10.8 0.16
Fat ratio (trunk/(arms+legs+hips)) 0.953 0.1552 0.948 0.1772 0.81
Physical activity (METs week) 29.28 25.66 35.38 30.63 0.09
Age at menarche (y) 13.7 2.3 13.7 2.4 0.92

N % N % P-value
Hx of amenorrhea Z3 months 15 8.4 15 10.4 0.54
Ever pregnant 38 21.4 16 11.0 0.01
OCs Z3 months 123 69.1 57 39.3 o0.001
Current smoking 40 22.5 23 15.9 0.14

International Journal of Obesity


previously used oral contraceptives (69 vs 39%, Po0.001)
and to have ever been pregnant (21 vs 11%, Po0.01).
The observed and modeled 30-month changes in body
composition measures for the comparison groups are shown
in Figures 1 and 2. In all cases, the observed and modeled
changes were very similar indicating robust modeled values.
Women using DMPA had a significantly greater increase in
all measures of fatness than women using no hormonal
method of contraception (Po0.03). The observed weight of
DMPA users increased steadily from a mean of 69.4 kg
(s.d. 16.9) at baseline to a mean of 75.5 kg (s.d. 25.0) at
30 month; an increase of 6.1 kg (8.8.%), while the weight
of controls remained virtually unchanged (Figure 1, upper
section). Notably, the increase in weight observed with
the DMPA users was solely related to an increase in fat
mass. The amount of lean mass did not change over the 30
months for either the DMPA users or controls (Figure 1,
middle section). Fat mass increased among DMPA users
from a mean of 25.3 kg (s.d. 12.6 kg) at baseline to 31.4 kg
(s.d. 17.8); an increase of 6.1 kg (23.6%) at 30 months,
compared to negligible changes in fat mass among the
controls (Figure 1, lower section). Furthermore, among
DMPA users, the ratio of central to peripheral fat mass
changed from 0.95 (s.d. 0.155) at baseline to 1.01
(s.d. 0.198) at 30 months; there was no observed change
among the controls (Figure 2).
Fat and DMPA
MK Clark et al
1255
Longitudinal models were used to identify characteristics
that might influence the changes in weight, fat mass, and fat
ratio (Table 2). The length of time using DMPA (time*DMPA)
was the best predictor of change in all measures of fatness
(P o0.03) Women with greater physical activity levels had
smaller increases in fat mass (P 0.003) and fat ratio
(Po0.0001), but not weight (P 0.48). Women with larger
central distribution of fat at baseline had greater increases
in the fat ratio over 30 months (Po0.0001). No other
characteristics, including baseline weight, baseline fat mass,
prior oral contraceptive use, previous pregnancy or smoking,
were significant predictors of change in weight, fat mass, or
fat ratio.
Discussion
This is the first large, prospective study with a control
comparison group to evaluate long-term weight change in
women using DMPA for contraception. Furthermore, it is the
only study to include measures of body composition and fat
distribution. Our data demonstrate that, over 30 months,
women using DMPA have a substantial increase in weight.
This weight gain is comprised entirely of increased fat mass,
not lean mass. These observations of significantly greater
weight gain, increased fat mass, and increase in the central

Figure 1 Change in mean weight (upper section), lean mass (middle section), and fat mass (lower section) over 30 months in DMPA users () and women using
no hormonal method of contraception (J). Shaded lines represent the modeled changes for DMPA users (light gray) and controls (dark gray). The observed
changes and standard error are represented by the solid black lines and dashed lines, respectively. The observed change in measures of fatness included data from up
to 12 visits for DMPA users and 11 visits for controls. Total n for DMPA users at visit 112 was 178, 165, 152, 134, 115, 103, 90, 80, 73, 61, 43, 31. Total n at visits
111 for controls was 145, 139, 125, 110, 101, 88, 79, 69, 57, 40, 27.

International Journal of Obesity

 Fat and DMPA
MK Clark et al
1256

Figure 2 Change in mean fat ratio over 30 months for women using DMPA for contraception () and women using no hormonal method of contraception (J).
Shaded lines represent the modeled changes for DMPA users (light gray) and controls (dark gray). The observed changes and standard error are represented by the
solid black lines and dashed lines, respectively. The observed change in fat ratio included data from up to 12 visits for DMPA users and 11 visits for controls. Total n
for DMPA users at visit 112 was 178, 165, 152, 134, 115, 103, 90, 80, 73, 61, 43, 31. Total n at visits 111 for controls was 145, 139, 125, 110, 101, 88, 79, 69, 57,
40, 27.

deposition of fat among women using DMPA compared to
controls demonstrate that changes in weight and fatness are
unique to DMPA users and not just typical of all women, as
some suggest.20
Our observation that DMPA users had a significant
increase in the central distribution of body fat has potential
metabolic and vascular implications if not reversed following
DMPA discontinuation. This central fat distribution pattern
is a component of the metabolic syndrome and may
predispose directly to the development of insulin resis-
tance21 and the generation of proinflamatory cytokines.22
Visceral fat accumulation is an important determinant of
plasminogen-activating inhibitor-1 (PAI-1) levels in young,
nonobese men and women and contributes to vascular
dysfunction.23,24 Although not studied extensively, there is
evidence of decreased vascular function in women using
DMPA for contraception.25
The mechanism(s) by which DMPA could increase weight
and fat mass while also altering fat distribution is unknown
and cannot be discerned from our current study. However,
the effects of DMPA or progesterone in humans and
experimental animals raise interesting mechanistic possibi-
lities. DMPA induces hypoestrogenemia26 which has been
linked to visceral fat accumulation and weight gain in both
animal models27,28 and in humans.29,30 Alternatively, MPA
can activate the glucocorticoid signaling receptor31 and, in
higher doses, has been associated with glucocorticoid-like
changes in fat mass in humans,32 which include increased
visceral fat.33 DMPA could also alter neurohumeral regula-
tion of appetite and energy expenditure at the level of the
hypothalamus as has been suggested in rodent models.34
These mechanisms will need to be formally evaluated in
other prospective studies.
Our study demonstrates that higher levels of physical
activity offered some protection against gains in fat mass and
fat ratio, and this suggests a behavioral means of offsetting
some of the DMPA-related increase in fat mass. It is not
surprising that physical activity did not predict change in
weight since physical activity is typically associated with
increases in heavier lean mass. The role of physical activity in
the prevention and treatment of obesity in general is well
known. There is some evidence that physical activity reduces
visceral fat mass in obese children and older men and
women;35,36 however, the effect of activity on fat distribu-
tion has not been well studied.
While this study compares longitudinal changes in body
composition in a large cohort of young adult DMPA users
and controls, there are limitations. This is not a clinical trial
with random assignment to DMPA therapy. In addition,
because the main focus of the study was on changes in BMD,

International Journal of Obesity

 Fat and DMPA
MK Clark et al
1257
Table 2 Predictors of change in measures of fatness over 30 months and do not necessarily represent the official views of the NIH
or the Department of Veterans Administration.
Variable b s.e. P-value

Change in weight
DMPA use 0.6183 0.3426 0.07
Time in study (months) 0.0036 0.0282 0.90
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