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Original Study

Differences in Anthropometric and Ultrasonographic Parameters between


Adolescent Girls with Regular and Irregular Menstrual Cycles: A Case-Study
of 835 Cases
Ubavka D. Radivojevic MSc 1,*, Gordana B. Lazovic PhD 2,3, Tamara K. Kravic-Stevovic PhD 4,
Zarko D. Puzigaca PhD 1, Fadil M. Canovic MD 5, Rajko R. Nikolic PhD 1, Srboljub M. Milicevic PhD 2,3
1
Department of Human Reproduction, Mother and Child Healthcare Institute “Dr Vukan Cupic,” Belgrade, Serbia
2
Institute of Gynecology and Obstetrics, Clinical Centre of Serbia, Belgrade, Serbia
3
School of Medicine, University of Belgrade, Belgrade, Serbia
4
Institute of Histology and Embryology, School of Medicine, University of Belgrade, Belgrade, Serbia
5
Outpatient Gynecological Department Zemun, Belgrade, Serbia

a b s t r a c t
Study Objective: Exploring the relation between the age, time since menarche, anthropometric parameters and the growth of the uterus
and ovaries in postmenarcheal girls.
Design: Cross sectional.
Setting: Department of Human reproduction at a tertiary pediatric referral center.
Participants: Eight hundred thirty-five adolescent girls.
Interventions: Postmenarcheal girls were classified according to the regularity of their menstrual cycles in 2 groups (regular and irregular
cycles) and compared. Anthropometric measurements and ultrasonographic examination of the pelvis was conducted with all participants.
Main Outcome Measures: Anthropometric and ultrasonographic parameters were evaluated.
Results: Results of our study showed that girls with regular and irregular cycles differed in height, weight, body mass index, percentage of
body fat and ovarian volumes. The size of the ovaries decreases in the group of girls with regular cycles (r 5 0.14; P ! .005), while it
increases in girls with irregular cycles (r 5 0.15; P ! .001) with advancing age. Uterine volume in all patients increases gradually with age
reaching consistent values at 16 years (r 5 0.5; P ! .001). Age at menarche, the time elapsed since menarche, the height, weight, body
mass index and percentage of body fat in patients correlated with uterine volume. Ovarian volume correlated with patients' weight, BMI
and percentage of fat.
Conclusion: Uterus continues to grow in postmenarcheal years, with increasing height and weight of girls, regardless of the regularity of
cycles. Postmenarcheal girls with irregular cycles were found to have heavier figures and larger ovaries.
Key Words: Adolescents, Uterus, Ovary, Growth, Anthropometry, Menstrual cycles, Body composition, Ultrasonography

Introduction regularity of menstrual bleeding, regularity of ovulation and


progesterone levels, do not appear to be related to uterine
Adequate pubertal growth of the genital organs is essen- size and growth rate.1
tial for reproductive health of a girl.1 The development of the The imaging technique of choice for studying the pelvic
female reproductive system from birth until menarche is well organs in adolescent girls is real-time ultrasonography (US)
documented.2,3 On the other hand, fewer data are available because it is noninvasive, painless and free of ionizing ra-
on morphologic changes and growth patterns of the uterus diation.1 Transabdominal US is the approach of choice for
and ovaries during the first few years after menarche.1,4 non sexually active adolescents2 and provides an optimal
It has been suggested that after the menarche uterus overview of the anatomy, shape, size, and echogenicity of
continues to grow and gradually reaches the adult size and the pelvic organs.
form.1 This process is thought to be completed by the age of The aim of this study was to explore postmenarcheal
16.4,5 An ovary, in the immediate premenarchal period, en- development of the uterus and ovaries. We studied the
larges rapidly and attains, by menarche, the adult appear- relation between age, time since menarche, antrophometric
ance.5 After menarche, the ovarian/uterine ratio decreases parameters and the volume and size of the uterus and ovaries
with increasing gynecologic age.1 Among the reproductive in a population of girls with regular and irregular menstrual
hormones, estradiol seems to be the main agent stimulating cycles.
uterine growth. Other reproductive parameters, such as the
Methods

The authors indicate no conflicts of interest. Study Design and Participants


* Address correspondence to: Ubavka D. Radivojevic, MSc, Department of Human
Reproduction, Mother and Child Healthcare Institute “Dr Vukan Cupic,” Radoja A cross sectional study on 857 postmenarcheal patients
Dakica 6 St, 11000 Belgrade, Serbia; Phone: þ 381 60 550 30 33; fax: þ 381 11 667
14 81 (postmenarcheal period ranged from 6-72 months) was
E-mail address: radivojevic.ubavka@gmail.com (U.D. Radivojevic). conducted from July 2008 to January 2013.
1083-3188/$ - see front matter Ó 2013 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc.
http://dx.doi.org/10.1016/j.jpag.2013.11.007
2 U.D. Radivojevic et al. / J Pediatr Adolesc Gynecol xxx (2013) 1e5

Adolescents were selected based on the following crite- Table 1


Baseline Data: Age, Age at Menarche, Time Elapsed Since Menarche and a Summary
rion: the ultrasonographic presence of the uterus and both of Anthropometric Characteristics and Ultrasonographic Findings
ovaries. The exclusion criteria were: endocrinopathies (hypo/
Adolescents Adolescents Total P
hyperthireoidism, hyperprolactinemia, diabetes mellitus); with with
evidence of congenital adrenal hyperplasia or androgen- Irregular Regular
secreting tumors; cardiovascular or other systemic diseases; Cycles Cycles

chromosomopathies; ovarian cysts and tumors; suspicion of N 5 428 N 5 407 N 5 835


ovarian torsion; malformations of the internal genital organs; Mean SD Mean SD Mean SD
nutrition disorders and current use of medications known to Age (years) 15.77 2.18 15.58 2.08 15.68 2.14 NS
alter reproductive hormones (hormonal contraceptives, Time elapsed since 2.94 1.77 2.86 1.76 2.89 1.76 NS
progesterone therapy, insulin sensitizers and antihyperten- menarche (years)
Age at menarche (years) 12.81 1.30 12.70 1.29 12.76 1.29 NS
sive medications). Height (m) 1.65 0.07 1.66 0.07 1.65 0.07 !.05
Menstrual cycles were defined as either (1) regular, if Weight (kg) 57.85 11.36 54.92 8.27 56.43 10.08 !.001
their length was 22-35 days, or (2) irregular, when they were BMI (kg/m2) 21.28 3.83 19.88 2.44 20.61 3.31 !.001
Fat (%) 23.91 4.96 22.10 3.38 23.04 4.36 !.001
less than 22 or more than 35 days long.6 Uterus volume (cm3) 49.54 20.47 48.67 22.72 49.10 21.61 NS
The study protocol was approved by the Ethic Committee Right ovary volume (cm3) 8.57 4.11 6.35 2.58 7.42 3.57 !.001
Left ovary volume (cm3) 8.28 3.82 6.74 4.64 7.48 4.33 !.001
of the Mother and Child Healthcare Institute. Signed in-
Mean ovarian volume (cm3) 8.44 3.61 6.52 2.99 7.46 3.45 !0.001
formed consent was obtained from all participants and/or
P, Statistical differences between parameters in the group of adolescents with
their parent or legal guardian before participation in the irregular and regular cycles; NS, Not significant.
study.

Procedures between the 3rd and the 97th percentiles compared with a
sex- and age-matched normal population. Body fat per-
At the examination each subject had a protocol consist- centage (fat %) was estimated from BMI, using Deurenberg's
ing of anthropometric measurements and ultrasonographic prediction formulas.7
evaluation of the ovaries and uterus.
Postmenarcheal patients were grouped into 2 distinct Statistical Analysis
groups. First group consisted of patients with menstrual
irregularities (IC) and the second group comprised of pa- Statistical analysis was performed with SPSS for Win-
tients with regular cycles (RC). Data distribution regarding dows software, version 15.0 (SPSS, Chicago, IL). Most of the
age and time since menarchae did not show statistically results are expressed as the mean and SD. The scatter plot
significant differences, thus our groups had homogenous was used to compare the volumes of uterus, ovaries and
distribution. ovarian/uterine ratio, and construction of estimation curves
using cubic and linear models was done. The inflection
Ultrasonographic Examination point of the cubic estimated curve was determined as a
point at which second derivative changed sign. Pearson's
Transabdominal ultrasonographic examination of the correlation was employed to assess the correlations be-
ovaries and uterus was performed during the early follicular tween considered parameters. A P value of ! .05 was
phase of the cycle (day 1-6), or on a random day of a cycle (at considered statistically significant. Finally, graphic displays
least 3 months of amenorrhea) for the amenorrheic pa- of uterine volume, mean ovarian volume and ovarian/
tients. The examinations were conducted by 1 sonographer uterine volume ratio versus age were generated.
in all cases, using MyLab 50 Xvision scanner equipped with
CA631 convex probe (8-1 MHz). Transabdominal US was Results
performed in all the cases, with a patient in dorsal decubitus
and with a full urinary bladder. The uterine and ovarian Data are available for 835 patients. Baseline data in-
volumes were calculated using the formula for ellipsoid cluding the age at the time of the study, the age at menarche,
bodies (volume equals to 0.523  length  width  height the time elapsed since menarche and a summary of ultra-
of the organ), and expressed in cubic centimeters. The study sonographic findings and anthropometric characteristics are
included 835 out of 857 patients in whom uterus and both reported in Table 1. There are no differences between RC and
ovaries were identified. In remaining 22 cases only 1 ovary IC group of girls regarding the age at the time of the study
was visualized, and we excluded those patients from data and the age at menarche. However, the girls with RC are
analysis. taller, with lower weight, lower BMI, and lower percentage
of fat than the girls with IC. Uterine measurements did not
Anthropometric Measurements differ significantly between the 2 groups. Girls with IC have
bigger left, right and mean ovarian volumes. The mean
Patients had a height measurement (in meters) to within ovarian volume was used for further analysis since the vol-
 0.005 m, and weight (in kilograms) was measured  0.1 kg umes of the right and the left ovary did not differ signifi-
with minimal clothing on. Body mass index, defined as the cantly in each individual subject.
individual's body mass divided by the square of their height, The best curve estimation of uterine volume, according
was calculated. All patients had height and weight and BMI to age for all the patients, was achieved with cubic model. In
U.D. Radivojevic et al. / J Pediatr Adolesc Gynecol xxx (2013) 1e5 3

Fig. 1. Scatter plot showing the distribution of uterine volume according to age. The Fig. 3. Scatter plot showing the distribution of mean ovarian volume in the group of
curves represent the 5th, 50th, and 95th percentiles. The intersection between the patients with regular cycles according to age. The curves represent the 5th, 50th, and
mean uterine volume and the cubic model curve estimation is presented. 95th percentiles.

the cubic equation y 5 ax3þ bx2 þ cx þ d, y stands for Ovarian volume all patients 5 0. 05 age þ 6. 63 (r 5 0. 03; P
uterine volume, x stands for age in years; and a, b, c, and !. 001);
d are constants calculated using the SPSS software for each Ovarian volumeirregular cycles 5 0. 2463 age þ 4. 5028
of the variables. The following equation was calculated for (r 5 0. 15; P !. 001);
all patients: Ovarian volumeregular cycles 5 -0. 1979 age þ 9. 4936
Uterine volume all patients 5 0. 1303 age3þ6. 5226 age2- (r 5 0. 14; P ! . 005);
101. 84 ageþ542. 68 (r 5 0. 5; P ! . 001); The linear equation reveals the decrease in mean ovarian
The cubic equation reveals a gradual increase in uterine volume with advancing age (Fig. 2). Mean ovarian volume in
volume with age (Fig. 1). Further mathematical analysis of the RC and IC group of patients showed differences pre-
the cubic equation for uterine volume, reveals a falling in- sented in Fig. 3 and Fig. 4, respectively. In the RC group of
flection point which corresponds to the point of intersec- patients decrease in mean ovarian volume with age was
tion between the mean uterine volume and the cubic model noticed, while in the IC group of girls, the increase of mean
curve estimation. This point of intersection corresponds to ovarian volume was seen.
the age in which uterine volume reached consistent values, Correlations between uterine volume, mean ovarian
and this age is calculated to be 16.69 years. volume and the age at menarche with age, the time elapsed
The best curve estimation of ovarian volume, according since menarche, height, weight, body mass index, and
to age, was achieved with linear models. In the linear percentage of body fat are illustrated in Table 2. Uterine
equation y 5 ax þ b, y stands for ovarian volume, x stands volume correlated with all examined parameters except
for age in years while a and b are calculated constants for BMI. Ovarian volume correlated with weight, BMI, and
each of the variables. Following equations were calculated: percentage of fat.

Fig. 4. Scatter plot showing the distribution of mean ovarian volume in the group of
Fig. 2. Scatter plot showing the distribution of mean ovarian volume according to age. patients with irregular cycles according to age. The curves represent the 5th, 50th, and
The curves represent the 5th, 50th, and 95th percentiles. 95th percentiles.
4 U.D. Radivojevic et al. / J Pediatr Adolesc Gynecol xxx (2013) 1e5

Table 2 The relation between anthropometric parameters and


Correlations between Age and Time Elapsed since Menarche, Ultrasonographic, and
Anthropometric Parameters
sonographic findings of the pelvis was further studied.
Ovarian volume in our study correlated with weight, BMI
Uterine Ovarian Age at Menarche (y)
Volume (cm3) Volume (cm3)
and percentage of fat of postmenarcheal girls. Although we
did not find differences in uterine measures between the
Age (y) r 5 0.005*
Time elapsed since r 5 0.597* studied groups, postmenarcheal girls with irregular cycles
menarche (years) had higher ovarian volume. This finding is consistent with
r 5 0.176* r 5 0.104z
Weight (kg)
previously published data.1
Height (m) r 5 0.309* r 5 0.269*
BMI r 5 0.132y r 5 0.096y We noticed that with age, in the group of girls with
y
%fat r 5 0.084 r 5 0.134y r 5 0.088y regular cycles, the size of ovaries decreases, while in girls
Statistically significant P for all correlations is reported. with irregular cycles it increases. Ovaries of healthy girls in
* P ! .001. the premenarcheal period enlarge rapidly and attain, by
y
P ! .01.
z
P ! .05.
menarche, the adult appearance.5 From that time on, the
volume of ovaries gradually decreases.1 Porcu stated that
girls with irregular cycles have a mean volume significantly
When we analyzed the same correlations in the RC and IC higher than that of regular ovulatory adolescents.1 This may
groups of girls, we found certain differences. Ovarian vol- be related to the possible development of PCOS later in
ume inversely correlated with age (r 5 -0. 143, P ! .05) and adult life in girls with irregular cycles, implying that PCOS
the time elapsed since menarche (r 5 -0. 142, P ! . 05) in RC may emerge at or soon after puberty.18 Polycystic ovary
patients, while in the IC group those correlations were syndrome is characterized by a great diversity in its clinical
positive (r 5 0. 147, P ! . 05; r 5 0. 055, P O .05). presentation and an elevated BMI (O30) is found in 20%-
Although BMI correlated with ovarian volume and the 69% of patients, depending on the studied population,19 but
age at menarche in all patients, it did not correlate with women who are lean can also have PCOS.20 In the studied
those parameters in the RC and IC groups of girls, presum- group of girls, BMI was within normal range in all patients,
ably because of the homogeneity of these 2 groups. The but the girls with IC had significantly higher BMI than the
same was noticed when the percentage of body fat was RC girls. We propose that increasing ovarian volume and
analyzed. Percentage of body fat correlated with uterine heavier figure in adolescence could be a finding that may
and ovarian volume and the age at menarche in all exam- raise suspicion towards the possible development of PCOS
ined patients, but it did not correlate with those parameters or irregular cycles in adulthood.
in the RC and IC groups of girls. The process of uterine growth continues during post-
menarcheal period and it is thought to be completed by the
Discussion age of 16.4,5 In postmenarchal girls, in our study, uterine
volume increases gradually with age, reaching consistent
Menarche is an important landmark in the process of values at 16.7 years. No differences in uterine volume were
growth and maturation of girls.8 Menarche occurs between found in between groups of girls with regular and irregular
12 and 13 years of age in most developed countries.9,10 The cycles, implying that cycle regularity does not influence
mean age at menarche in girls examined in our study was uterine growth. These findings are in agreement with the
12.76 years, which is in accordance with the previously previously published data.1 Porcu stated that height and
published data.9,10 weight correlate with uterine volume before menarche but
Previous studies suggested that maturation of the not afterwards, explaining that at this age they have nearly
hypothalamic-pituitary-ovarian axis takes up to ~5 years exhausted the developmental changes.1 Our results differ
after menarche to be completed.11,12 The period of time from previous findings1 and demonstrate that postmen-
elapsed since menarche in girls included in our study varied archeal growth of uterus correlates with height, weight, and
from 6 months till 6 years. It has been proposed that irreg- percentage body fat. We propose that the regularity of
ular menstrual cycles in the first 5 years after menarche are the menstrual cycles is not related to the uterine growth
physiological, so no clinical or endocrine evaluation13 is and that uterine volume correlates with growth after the
needed. However, in the peri-menarcheal period the first menarchae.
symptoms of ovarian dysfunction appear and in the first In conclusion, studies investigating anthropometric fea-
years after menarche the clinical picture of polycystic ovary tures and the growth of the uterus and ovaries in post-
syndrome (PCOS) may evolve or already be complete.14 Van menarchal girls are scarce, thus, the results of our study add
Hooff et al concluded that the menstrual cycle pattern in the to the medical knowledge regarding this specific age group.
first years after menarche is a better predictor for ovulatory Our study shows that uterus continues to grow in post-
dysfunction in adulthood than androgen or LH concen- menarcheal years, with increasing height and weight of
trations.15 girls, regardless of the cycle regularity, reaching consistent
There are only a few studies investigating anthropo- volume between 16 and 17 years of age. Postmenarcheal
metric features in postmenarchal girls.16,17 From the result girls with irregular cycles in our study were found to have
of our research, the postmenarcheal girls with regular cycles heavier figures and larger ovaries, finding that may raise
showed taller and slimmer figures than girls with irregular suspicion towards developing PCOS or irregular cycles in
cycles. The girls with regular cycles also showed lower BMI adulthood. These patients could benefit from further med-
and lower percentage of body fat. ical evaluation and weight reduction.
U.D. Radivojevic et al. / J Pediatr Adolesc Gynecol xxx (2013) 1e5 5

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menstrual cycles. J Pediatr Adolesc Gynecol 2005; 18:193
13. Gardner J: Adolescent menstrual characteristics as predictors of gynaecological
health. Ann Hum Biol 1983; 10:31
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