UNIVERSA MEDICINA Serum estradiol levels and bone mineral density in postmenopausal women Martiem Mawi* ABSTRACT
Postmenopausal women are at high risk of disease, such as coronary heart disease,
stroke, malignancies, dementia and osteoporosis. This is due to decreased levels
of estrogen/estradiol, produced mainly in the ovaries, leading to reduced bonemineral density (BMD), which is the gold standard for diagnosis of osteoporosis. Correspondence
The purpose of the present study was to determine the relationship between
serum estradiol levels and BMD in postmenopausal women. The study, which
was of cross-sectional design, involved 184 postmenopausal women meeting
the inclusion criteria, viz. healthy postmenopausal women aged between 47 and
Trisakti UniversityJl. Kyai Tapa No.260 Grogol
60 years having taken no hormonal medications in the previous 3 years. The
subjects were assessed for anthropometric and biochemical characteristics,
including BMD and serum estradiol levels. BMD was measured at the lumbarspine, right femoral neck and at the distal radius by the dual-energy X-ray
absorptiometry (DXA) instrument. The mean serum estradiol concentration was7.54 ± 4.65 pg/ml, while in 49.5% of the subjects the estradiol concentrationwas ≤ 5 pg/ml. In postmenopausal women with estradiol concentrations of > 5pg/ml, a significant positive relationship was found between BMD and the T-scores for the femoral neck. Thus the higher the serum estradiol levels, the higherthe BMD values for femoral neck region. In conclusion, the results of this studypoint to estradiol levels as a major factor in determining the BMD values inpostmenopausal women. Keywords: Postmenopausal, estradiol, bone mineral density, femoral neck INTRODUCTION
be around 60–70 million.(1) Postmenopausalwomen are at high risk of disease, such as
osteoporosis, hypertension, coronary heart
concomitant increase in the numbers of the
disease, and stroke.(2) The menopause is the 12-
elderly, particularly postmenopausal women,
month period after cessation of menstruation,
in developed as well as developing countries.
while the postmenopausal is the period after
menopause onwards.(1) In the postmenopausal
postmenopausal women in the year 2025 will
estradiol are no longer functional, leading to
decreased levels of estradiol.(3,4) In the
Unmodifiable risk factors for osteoporosis
postmenopausal period there is degeneration
are gender (women are of lesser weight and
of the ovaries, resulting in cessation of
have smaller bones than men), advanced age,
estradiol production by these organs. The
family history of osteoporosis, race (Asian and
remaining sources of estradiol are the adrenals,
osteoporosis than African women), body build
aromatization of androstenedione.(5-7) Estradiol
(thin and small women are at higher risk of
is synthesized in osteoblasts and chondrocytes
in osseous tissue from circulatory androgens,
(anorexia, diabetes, chronic diarrhea, renal and
hepatic disorders). Modifiable risk factors are
dehydroepiandrosterone and androtenedione.(5)
smoking, alcohol consumption, low calcium
The reduction in bone mass is significantly
intake, lack of exercise, underweight and use
associated with decreased androgen levels in
of medications (steroids, phenobarbital and
perimenopausal and postmenopausal women.(8)
phenytoin).(10) The objective of this study was
Testosterone level is positively associated with
to determine serum estradiol levels and their
important role in maintaining estrogen levels
formation and absorption are closelyassociated to one another. After the age of 30
Research design
years there is a gradual diminution of bone
mass, which is most clearly seen in women,
design in order to determine serum estradiol
who experience a significant decrease in bone
levels and their relationship with BMD values
mass. This is associated with lowered estrogen
production several years prior to the onset ofthe menopause and continues for a period of
Study subjects
up to 5 years, followed by a slow decrease in
The study subjects were randomly selected
bone mass for the remaining life span of the
postmenopausal women aged 47 up to 60 years
women.(10) Osteoporosis is a condition of
from four villages (kelurahan) in the Mampang
Prapatan subdistrict, South Jakarta, namely the
architecture up to the fracture threshold
villages of Kuningan Barat, Mampang Prapatan,
without clinical signs or symptoms.(12) In this
absorption is increased. Bone loss occurs more
menopause of more than one year, age 47 up
frequently in trabecular bone, such as in the
to 60 years, willing to participate in the study
vertebrae, femoral neck and distal radius.(11)
and sign informed consent, able to actively
The rate of bone loss is 2-2.5% in the first 5
communicate, and actively mobile (requiring
post-menopausal years, 39% in the age range
of 70-79 years and 70% at age 80+ years.(12)
hysterectomy or bilateral oophorectomy, acute
infections, diabetes mellitus, diseases of the
women in the US to be 14% at age 50-59 years,
kidneys, lungs and liver, malignancies, and
22% at 60-69 years, 39% at age 70-79 years
those consuming hormonal medications in the
last 3 years. The respondents were interviewed
Mawi Serum estradiol levels and bone mineral density
osteopenia the BMD value is more than 1 SD
center cadres, using a questionnaire that
osteoporosis the BMD is 2.5 SD or more below
menopause. All participating women signed an
the reference mean.(16) Expressed as T-scores:
normal if T-score > -1; osteopenia if -2.5 < T-score < -1; osteoporosis if T-score < -2.5.(15)
Assessment of physical characteristics
(BMI). Height was measured to the nearest 0.1
Research Ethics Commission of the Medical
cm with the subjects in the upright position
without shoes. Body weight was determinedto the nearest 0.1 kg with the subjects wearing
Data analysis
calculated as weight (kg)/ height (m)2. BMI is
data, data entry was performed using Statistical
classified into the following categories:
Package for Social Science (SPSS) version 15for Windows. Initially a test of normality was
underweight (< 18.5 kg/m2), normal (18.5-22.9
kg/m2), overweight (23.0-27.5 kg/m2), and
distributed, correlation analysis was performedby calculating Spearman’s rho in order to
Biochemical measurements
determine correlations between BMI and serum
estradiol levels. The level of statistical
significance was set at p < 0.05.
after a fast of 12-14 hours. Subsequently theserum was separated and stored at –700C until
concentration (coefficient of variation = 3.2%)
(31/125 = 0.25%) did not meet the inclusion
was performed at Prodia Laboratories, Jakarta,
biochemical testing revealed to have diabetes
mellitus and 11 did not show up for laboratory
determinations was 5.00 - 4300.00 pg/ml.
inclusion criteria participated in this study. Mean age of the subjects was 53.58 ± 3.53
BMD measurements
years, with age range of 47 – 60 years. Mean
BMI was 26.75 ± 4.68 kg/m2. The majority of
lumbar vertebrae), the right femoral neck, and
the distal left radius was determined by dual-
energy X-ray absorptiometry (DXA), using a
category. Mean estradiol concentration was
7.54 ± 4.65 pg/ml, while 46.5% of women were
in the low estradiol category (≤ 5 pg/ml). Mean
lumbar T-score was –1.63 ± 1.04, mean femoral
neck T-score was –0.99 ± 0.96, and mean distal
categories suggested by a WHO study group
radial T-score was –1.95 ± 1.17. Mean duration
in 1994, the normal category has a BMD within
of menopause was 4.47 ± 2.24 years, with a
1 SD of the reference mean (young adults). In
Table 1. Mean values for age, BMI, lumbar,
of the femoral neck (r=0.021;p=0.042) (Table
femoral and radial T-scores, estradiol level
3). Thus the higher the serum estradiol levels,
and duration of menopause in postmenopausal
the higher the BMD values for the femoral neck
General characteristics Mean ± SD DISCUSSION
concentrations of < 5 pg/ml. In postmenopausal
estradiol concentration was > 5 pg/ml, this study
showed a significant positive relationship
between estradiol levels and T-scores for the
femoral neck region. Essentially similar resultswere found by Bagur et al. in postmenopausal
women < 65 years of age, who had estradiollevels of > 10 pg/ml and higher BMD values inall skeletal sites examined, in comparison with
women whose estradiol levels were < 10 pg/
osteopenia was for the lumbar vertebrae (50%),
ml.(5) A study involving 370 postmenopausal
women aged between 55 and 85 years found a
highest in the left distal radius (35.3%) (Table
significant positive relationship between serum
estradiol levels and BMD values for the lumbar
normality showed that serum estradiol was not
normally distributed. Nonparametric correlation
according to Spearman rho showed a positive
degeneration resulting in diminished estradiol
correlation between serum estradiol and BMD
Table 2. Distribution of osteopenia and osteoporosis by BMD site
Osteopenia (n,%) Osteoporosis (n,%)
Table 3. Correlation between serum estradiol and bone mineral density in postmenopausal
women with estradiol concentrations of > 5 pg/ml (n=93)
Lumbar spine Femoral neck Distal radius Mawi Serum estradiol levels and bone mineral density
osteoporosis. Extragonadal sources of estradiol
postmenopausal women, the most frequently
are the adrenals, adipose tissue, liver, kidney
affected by osteoporosis are the trabecular
and muscle, where estradiol is synthesized
bones (spongious bones).(1)As is well-known,
through aromatization of andrestenedione.(7)
two risk factors for osteoporosis are age and
homeostasis is widely recognized, and one of
increased resorption of old bone in comparison
its consequences is the loss of bone occurring
weaken and fracture easily at the slightest
function ceases.(17) Extragonadal aromatization
is affected by age, gender, and body weight.
vertebrae and wrist.(20) The reduction in bone
mineral mass of the radius in men occurs after
the age of 60 years. However, in women bone
Lack of estrogen also causes osteoporosis,
loss commences around the age of 50 years, is
most rapid 3 or 4 years after menopause, and
menstruation is delayed, resulting in less than
on average continues at a greater rate from the
normal estrogen levels. One in three women
age of 67 years upwards.(19,20) In approximately
half of white postmenopausal women the radial
particularly after the age of 50 years.
Osteoporosis may occur at age under 45 years
association was found between estradiol and
bone density at all body sites examined.(21) In
another study, it was found that increased age
was associated with decreased estradiol and
age, creating a worldwide health problem, as
the aged tend to suffer from bone fractures
concentrations increased bone turnover, which
from mild injury or even without injury. These
is a risk factor for fractures.(16) Zarrabeitia et
fractures increase the morbidity and mortality
al. revealed a significant correlation of serum
rates, and health funding, and reduce the
estradiol concentration with BMD of the spine
quality of life of the patients.(10,18) In the study
in postmenopausal women. In addition, the
investigators also found in subjects with high
decreased with advancing age, whereas BMD
was proportional to BMI.(19) In the present
study, it is unclear whether the extremely low
estradiol level (<5 pg/ml) in the majority of
the respondents was caused by lack of dietary
limitations. First, as this was a cross-sectional
cholesterol (fat), since estrogen is synthesized
community-based study, no conclusions can be
in the liver and some is of dietary origin.
drawn as regards the cause-effect relationship
calcium, low vitamin D and lack of exercise,
longitudinal studies will be necessary to
which affects bone density. It is reported that
confirm our conclusions. Secondly, the women
osteoporosis in Asia is intimately associated
in this study were aged between 47 and 60
with low calcium and lack of vitamin D.
years, for whom no BMD data were available.
Around 35% of postmenopausal women in Asia
Thirdly, no measured values of free estrogen
CONCLUSIONS
Tana L. Pencegahan osteoporosis. Media LitbangKesehatan 2005;15:50-7.
Sowers MR, Jannausch M, Mc Connell D, Little
R, Greendale GA, Filkelstein JS, et al. Hormone
years 49.5% had serum estradiol levels of ≤ 5
predictors of bone mineral density changes during
pg/ml. There was a significant correlation
the menopausal transition. J Clin Endocrinol
Ninghua L, Pinzhong O, Harmin Z, Dingzhuo Y,Pinru Z. Prevalence rate of osteoporosis in the
mid-aged and elderly in selected parts of China. Clind Med J 2002;115:773-5. ACKNOWLEDGEMENTS
World Health Organization. Appropiate bodymass index for Asian populations and its
implications for policy and intervention strategies. The Lancet 2004;363:157-63.
to the Medical Faculty, Trisakti University, for
the funding of this study. And also thanks the
fracture risk and its application to screening for
respondents who were willing to participate in
postmenopausal osteoporosis. WHO technical
report series 843. Geneva: World HealthOrganization;1994.
van Geel TACM, Geusens PP, Winkens B, Sels
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You should mind the fol owing issues, when measuring your blood pressureTake place at a table and rest for about 3-5 minutes before starting the measurement. Normal y the blood pressure on your left arm is higher than on your right arm, therefore take the measurement on your right arm. If the blood pressure on your right arm is higher, take the measurement there. Do not speak during the measure