Original Study

The Effect of Chromium Supplementation on Polycystic Ovary

Syndrome in Adolescents
Nermine Amr MD, FRCPCH 1,*, Hossam Eldin Abdel-Rahim FRCOG, MD 2
1
Department of Pediatrics, Ain-Shams University, Cairo, Egypt
2
Department of Obstetrics and Gynaecology, Al-Azhar University, Cairo, Egypt

a b s t r a c t
Background: Polycystic ovary syndrome (PCOS) is a common condition. Treatment with chromium has been shown to improve insulin
sensitivity in adults with PCOS. Treatment of adolescents with PCOS remains a challenge.
Objective: To investigate the effect of chromium supplementation on the various components of polycystic ovary syndrome in adolescent girls.
Patients and Methods: Thirty-ve adolescent girls with PCOS were enrolled. History of menstrual irregularities was recorded. All underwent
physical examination for presence of acne, scoring of hirsutism, and calculation of body mass index. Pelvic ultrasonography was done and serum
free testosterone was measured in all subjects. All subjects received 1000 mg chromium picolinate for 6 months followed by re-evaluation.
Results: Mean (SD) age was 15.5 (1) years (range: 14-17 y). No signicant change in BMI standard deviation score (SDS) with chromium
supplementation was noted (1.9 (0.7) SDS vs 2 (0.7) SDS, P 5 .638). The number of patients with oligo/amenorrhea decreased with
treatment (29/35 (83%) versus 11/35 (31%), P ! .001). Signicant reduction in mean ovarian volume (P ! .001), total follicular count (P !
.034), and free testosterone (P! .002) was observed. No signicant improvement in acne or hirsutim was noted.
Conclusion: Supplementation with chromium to adolescents with PCOS is a promising treatment option.
Key Words: Polycystic ovary syndrome, Adolescents, Chromium

Introduction and may further improve insulin sensitivity and ovulation

rates.12 Chromium picolinate consists of trivalent chro-
Polycystic ovary syndrome (PCOS) is a condition charac- mium, a trace element combined with picolinic acid to
terized by hyperandrogenism, menstrual irregularities, and improve its gut absorption. No adverse effects are reported
polycystic ovaries. It affects 6%-8% of women in the repro- with high levels of intake of chromium picolinate.13 The
ductive age.1,2 Its prevalence among adolescents varies be- dose and duration of chromium supplements needed in
tween populations and according to criteria used for this regard remain unknown. The aim of this study is to
denition.3 Prevalence rates of 8%, 18%, and 26% are reported investigate the effect of chromium supplementation on the
from different populations,3e5 PCOS risk is increased among various components of polycystic ovary syndrome in
obese patients. Obesity, particularly with abdominal fat adolescent girls.
distribution, is observed in 50% of women with PCOS.6 Since
obesity starts in early life, obese adolescents are a high risk
Patients and Methods
population for PCOS.6
The etiology of PCOS remains unclear. Studies increas-
Thirty-ve girls were recruited from the Obesity Clinic of
ingly show that epigenetic, genetic, and environmental fac-
Ain-Shams University Hospital, Paediatric Department and
tors interact.7,8 Insulin resistance is implicated in the
from the Gynaecology Clinic of Bab El-Shareya University
pathogenesis of PCOS especially among obese girls,9 and at
Hospital in Cairo during the period from 1st July, 2012 until
the same time PCOS is associated with increased incidence of
25th September, 2013. Inclusion criteria included age less
glucose intolerance,7 and metabolic syndrome5,10 Thus
than eighteen years, menarche for at least 2 years, and
which starts rst is largely unknown. Insulin sensitizers have
established diagnosis of polycystic ovary syndrome accord-
a positive effect on obesity, ovarian morphology, insulin
ing to the revised 2004 Rotterdam Consensus Workshop
sensitivity, and hyperandrogenemia in PCOS, and are used in
Criteria.14 Patients were diagnosed with PCOS if they had 2
its treatment.9
out of 3 of the following criteria:
The role of trace elements in the pathogenesis of many
diseases including PCOS has recently been elucidated.11 1. Oligo/amenorrhea: oligomenorrhea was dened as
Lucidi et al showed that chromium picolinate supple-
menstrual cycles $ 45 days, and amenorrhea was
mentation in adults with PCOS improves glucose tolerance,
dened as absence of menstruation for $ 90 days.15
2. Enlarged polycystic ovary on ultrasonography: dened
The authors indicate no conicts of interest. as one or more ovary with a volume O 10 cm3 or 12 or
* Address correspondence to: Nermine Amr, MD, FRCPCH, Department of Pediat- more follicles between 2 and 9 mm diameter.16
rics, Ain-Shams University, PO Box 12311, 10 El-Zahraa Street, Dokki, Cairo, Egypt;
Phone: 2 0122 770 9226 3. Clinical and/or biochemical hyperandrogenism: Clinical
E-mail address: nerminehamr@hotmail.com (N. Amr). hyperandrogenism (HA) included acne or hirsutism.14
1083-3188/$ - see front matter 2015 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc.
http://dx.doi.org/10.1016/j.jpag.2014.05.005
 N. Amr, H.E. Abdel-Rahim / J Pediatr Adolesc Gynecol 28 (2015) 114e118 115

Hirsutism was dened by a Ferriman-Gallwey (FG) score
of $8.17 Acne was assessed according to severity.18
Biochemical HA was dened by elevated levels of free
testosterone (FT).14
Menstrual irregularities were ascertained by recalling
menstrual pattern in the preceding year. All subjects un-
derwent physical examination including assessment for the
presence of acne and hirsutism, measurement of weight,
height, and calculation of body mass index (BMI). Over-
weight was dened as BMI $85th percentile for age and sex,
and obesity was dened as BMI $95th percentile for age and
sex. BMI Standard deviation scores (SDS) were calculated.19
Conditions including congenital adrenal hyperplasia, ad-
renal tumors, Cushing syndrome, thyroid gland dysfunction,
hyperprolactinemia were excluded. Patients on multivita-
mins, food supplements, and insulin sensitizers were
excluded. All patients and their families signed an informed
consent prior to participation in the study. The study pro-
tocol was approved by the local ethics committee of Ain-
Shams and Al-Azhar University Hospitals.
Ultrasonographic Evaluation
All subjects underwent transabdominal pelvic ultraso-
nography as part of their PCOS diagnostic workup in the early
follicular phase (Days 2-4 of their menstrual cycle). The im-
ages were obtained using a General Electric LOGIQ Pro P5
ultrasonography machine with a curved 5 mHz transducer.
Ultrasonographic examination was performed by a senior
gynecologist. Ovarian volume was calculated using the
prolate ellipsoid formula: volume 5 length  width 
thickness  p/6.
Biochemical Evaluation
Venous samples were withdrawn for determination of free
testosterone, thyroid function, prolactin level, and 17 hydroxy
progesterone. Serum free testosterone level was measured by
a commercially available kit (EIA-2924, DRG International,
Springeld, NJ) using the principle of competitive immu-
noenzymatic colorimetric assay; normal values were at a
range of 0.2-4.2 pg/ml.
Chromium Supplementation
All subjects received a supply of 200 mg chromium pi-
colinate capsules. Each patient was instructed to ingest 1
capsule 5 times daily for 6 months, and all were instructed
to complete a diary for the intake. Patients were asked to
report adverse effects such as watery diarrhea, vertigo,
headache, and urticaria.
for assessment of acne and scoring of hirsutism was per-
formed. Body mass index was recalculated according to
weight and height measurements. Ultrasonographic exam-
ination for polycystic ovarian morphology was repeated, and
serum free testosterone level was re-measured.
Statistical Analysis
The data were analyzed by SPSS statistical software
(version 17.0, SPSS Inc, Chicago, IL). Descriptive statistics are
expressed as mean, standard deviation (SD). Paired Student
t tests were performed for comparison between the mean
values for parametric data. McNemar test was used for
comparison of paired proportions. For all tests a probability
P less than .05 was considered signicant while P 5 .01 and
.001 were highly signicant.
Results
Mean (SD) age of patients at time of presentation was 15.5
(1) years (min-max: 14-17 y). Twenty-two patients (63%)
were obese, 8 (23%) were overweight, and 5 (14%) were of
normal weight. Mean (SD) BMI at presentation was 1.9 (0.7)
SDS. No signicant change in BMI SDS was noted after 6
months of treatment with chromium (mean (SD) BMI: 2 (0.7)
SDS, P 5 .638). See Table 1. All patients were compliant on
treatment and none of them reported adverse effects.
Six patients (17%) had regular periods at presentation.
Twenty-three patients (66%) had oligomenorrhea before
treatment of whom 7 patients (7/23, 30%) remained with
oligomenorrhea after treatment, and 16 had regular periods
(16/23, 70%). Amenorrhea was reported by 6 patients (17%)
before treatment, 2 of which had regular periods after 6
months of treatment (2/6, 33%), and 4 patients became oli-
gomenorheic (4/6, 67%). Total number of patients with regular
periods signicantly increased with treatment (P ! .001). See
Table 1.
No improvement in acne or hirsutism was noted with
treatment (Table 1). F-G score of $8 was observed in 18 pa-
tients (51%) before treatment and in 17 patients (49%) after
chromium intake.
Mean ovarian volume was O10 cm3 in 19 patients (54%)
before treatment and in 12 patients (34%) after treatment.
Ovarian volume decreased to 10 cm3 or less in 10 patients
(10/19, 53%) who originally had ovaries O 10 cm3. The
change in mean ovarian volume with treatment was highly
Table 1
Clinical, Ultrasonographic, and Biochemical Parameters before and after Treatment
with Chromium
Before After P Value
Chromium Chromium

Re-evaluation BMI SDS, mean  SD 1.9  0.7 2  0.7 .638

Acne, n (%) 25/35 (71.4) 20/35 (57.1) .063
Ferriman-Galwey score, mean  SD 8.1  2.4 7.9  2.3 .107
All subjects were invited for re-evaluation after 6 months Oligo/amenorrhea, n (%) 29/35 (82.9) 11/35 (31.4) !.001
or sooner if they had any unusual symptoms that could be Mean ovarian volume, cm3, 10.6  1.3 9.8  1.2 !.001
mean  SD
considered as side effects. The intake diary was reviewed to Total follicle number 2-9 mm, 20.7  3.4 19.5  3.9 .034
check compliance. Menstrual pattern was re-assessed using mean  SD
a calendar that all participants were asked to ll during the 6 Free testosterone, pg/mL, mean  SD 6.9  1.4 6.3  1.3 .002

months of treatment with chromium. Physical examination BMI, body mass index; SD, standard deviation; SDS, standard deviation score.
116 N. Amr, H.E. Abdel-Rahim / J Pediatr Adolesc Gynecol 28 (2015) 114e118
signicant (P ! .001). A signicant change was also noted in
mean total follicular count with chromium intake (P 5
.034). See Table 1.
Free testosterone levels decreased from 6.9  1.4 pg/mL
to 6.3  1.3 pg/mL, and this drop was statistically highly
signicant (P 5 .002). See Table 1.
Discussion
Polycystic ovary syndrome continues to be a challenge to
endocrinologists and gynecologists. As much as the patho-
genesis is still not clear, so is the perfect way of treating this
disease.20 Many medications are currently being used to treat
PCOS, yet none of them is considered ideal.5,20,21 So, the quest
for a drug with better results and less side effects is still open.
The combined oral contraceptive (COC) pill is considered
a cornerstone in treatment of PCOS when fertility is not the
main target of treatment.22,23 However, in conservative
cultures like our middle-eastern culture, convincing young
adolescent girls (and their parents) that COC is a good op-
tion for treatment is an almost impossible job. This is
observed from our personal experiences. Even for sexually
active women, the use of COC for contraception is not the
most popular method in some of those cultures for many
reasons, and in some countries natural methods are
preferred to hormonal methods.24 Metformin, which is
among the good treatment options for PCOS,25 has a poor
compliance record because of its many and distressing side
effects, mainly in the form of nausea and diarrhea.26 Met-
formin improves menstrual cyclicity, ovulation, and
androgen levels through its effect on insulin sensitivity. To
produce the desired therapeutic effect, it is usually intro-
duced in small doses with gradual increment until a dose
between 1500-2550 mg/day is reached.27 This leaves the
opportunity for exploring new treatment modalities open.
Chromium is a trace element that is not yet a well studied
medication in PCOS, and not all its effects on the body have
been demonstrated. There are several reports on its effect
on glucose and lipid metabolism in humans and animals.28
Its favorable effect on glucose metabolism in type 2 diabetes
patients and patients with impaired glucose tolerance has
been a controversial issue for many years.29e33
Chromium has been shown to reduce triglycerides levels
in humans.28 In rats, chromium increased HDL cholesterol
and reduced LDL cholesterol,32 and improved platelet
hyperaggregability.34 It was also shown to affect nucleic
acid and RNA synthesis.35 Its benecial effect further
extended to preventing inammation, impaired angiogen-
esis, and oxidative damage in myocardial infarction.36 This
wide spectrum of metabolic effects shows that there is
indeed a potential of using chromium in many pathologies.
It was suggested that chromium could improve the
symptoms of PCOS in adult patients,12,37 because of its ability
to improve insulin sensitivity that was previously shown in
some studies.38e41 However, its effect on adolescent patients
with PCOS has not been explored yet to the best of our
knowledge.
Our study has shown a signicant improvement of some
symptoms and signs in this vulnerable group of patients.
We have shown that the regularity of menstrual periods
was achieved in many patients who had this distressing
symptom. By achieving this improvement, those patients
have actually fallen outside the strict denition of PCOS.
Furthermore, we expect that this improvement could be an
excellent motive for those young girls to continue treatment
and improve their weight status, which could further
improve the pathology. Weight loss is a huge challenge that
needs a lot of determination, but achieving regular periods
for those young girls remains an integral aspect of suc-
cessful treatment.42
Nearly 86% of our patients were obese and overweight.
Similar rates were previously reported.43 Overweight and
obesity are common associations with PCOS in adolescents.
Obesity is observed in 30%-60% of PCOS patients.27,44
We could not detect a signicant change in BMI with
chromium therapy. We believe this was due to the short
duration of the study. Patients were not included in any
structured program for weight loss to avoid any confounding
effects with chromium, as weight loss per se would increase
insulin sensitivity, hyperandrogenism, and ovulation
rates.27,45 In addition, the effect of chromium on body
composition remains controversial.46e49
As regards signs, ovarian volume has decreased signi-
cantly in our cohort of patients. Also, the number of follicles
between 2-9 mm has decreased signicantly. Most impor-
tantly, levels of free testosterone have been shown clearly to
be less after the course of treatment with chromium. Ovarian
dysmorphology and biochemical hyperandrogenism are
both diagnostic criteria for PCOS.14 By signicantly
improving ovarian morphology and reducing free testos-
terone, chromium picolinate therapy would have a direct
positive effect on 2 of the 3 major criteria of PCOS, an effect
that would very likely be clinically reected in the form of
improvement of the menstrual cycle regularity. We believe
that oligo/amenorrhea and hyperandrogenism are bothering
symptoms to many young ladies. One would have expected
that this fall in testosterone level would be reected on the
clinical signs of hyperandrogenism including hirsutism and
acne. In our study, there was no signicant improvement in
acne nor in the F-G score. This is most likely explained by the
fact that the life cycle of the hair follicles is relatively long,50
so we expect that this could improve when we follow our
patients for a longer period. The life cycle of the hair follicles
is relatively long as hair grows in cycles.50 The anagen
(growth) phase varies between body parts and takes an
average of 4 months for facial hair. Androgens normally in-
crease hair growth and changes vellus to terminal hair, and
reduction of free testosterone levels is expected to slow the
growth of terminal hair and reduce new hair growth. Given
such facts, it would require more than 6 months of therapy to
produce a signicant improvement in F-G score in patients.51
Acne is on the other hand a common nding in this age
group with or without the presence of PCOS, to the extent
that the Androgen Excess Society does not accept acne as a
genuine marker for hirsutism in PCOS.15 It is not clear if
the prevalence of acne that is reported in PCOS patients is
signicant compared to the general population (15%-25%).2
Some authors suggest that only severe acne such as come-
dones in pre-pubertal girls, or acne not responsive to
treatment should be considered as manifestation of clinical
 N. Amr, H.E. Abdel-Rahim / J Pediatr Adolesc Gynecol 28 (2015) 114e118
hyperandrogenism in PCOS.2,52 For the aforementioned
reasons, we believe that the lack of improvement in acne
found in our study is of limited clinical signicance in this
age group and that it should not be regarded as a sign of lack
in improvement in clinical hyperandrogenism. We do not
know if a signicant improvement might be observed over
an extended study period.
The observed effects of chromium on ovarian morphology,
menstrual cycles, and androgen levels in our study might be
due to the effect of chromium on insulin sensitivity, or due to
an otherwise unknown mechanism, or it may also be due to
rectied pre-existing chromium deciency.11
The pathway by which chromium has achieved these
effects is not yet clear. To the best of our knowledge, this is
the rst study of ovarian morphologic changes in PCOS
adolescents taking chromium picolinate. Further, the sig-
nicant improvement in menstrual regularity and free
testosterone levels remains a novel nding. As no particular
pattern of side effects were reported in our study and all
patients had excellent compliance to continue their treat-
ment for the whole duration of follow-up, we expect that
this medication could have an excellent potential among
the medications used to treat PCOS.
A limited number of research papers looked into the ef-
fects of chromium in PCOS. Lydic et al37 found a signicant
improvement in glucose disposal rate in 5 subjects with
PCOS using the euglycemic hyperinsulinemic clamp tech-
nique. This was not associated with signicant reduction in
testosterone levels. Further, neither ovulation nor change in
ovarian morphology or hirsutism were reported. Although
they used similar doses of chromium (1000 mg/day), pa-
tients were reassessed after 2 months only. This could affect
the results and explain the lack of reduction in androgen
levels observed in their study contrary to ours. No consis-
tent change in body composition or weight reduction were
observed in their group of patientsdin agreement with our
results.37 Lucidi et al12 also failed to demonstrate signicant
change in ovulation, insulin sensitivity, or lipid prole with
chromium use in PCOS patients despite a signicant change
in glucose levels when comparing chromium to placebo,
suggesting the favorable effect of chromium use in PCOS.
The lack of signicant results could be due to their small
sample size, small dose (400 mg/day), or short study dura-
tion (4 months) as they explained. On this basis they rec-
ommended that future studies should be carried out with
larger doses and for longer duration.12
We did not assess insulin sensitivity because that was not
the main aim of this study. Previous reports have shown the
presence of impaired insulin sensitivity in both lean and
obese individuals with PCOS,27 to the extent that impaired
insulin sensitivity was questioned as a possible intrinsic
property of PCOS.53,54 For this reason, insulin sensitizers
such as metformin were established as a treatment for PCOS.
However, large doses might be needed to induce ovulation
and reduce hyperandrogenism.27 The main aim of our study
was to explore the effect of other yet uncommon therapeutic
options such as chromium picolinate in PCOS. In particular,
its effect on ovulation as reected by menstrual regularity.
When 200 mg/day chromium was compared with 1500
mg/day metformin in a recent study, both drugs were
117
comparable in their effects on ovulation, pregnancy, BMI,
and insulin sensitivity. Although a reduction in serum
testosterone was noted in their chromium group, it failed to
reach statistical signicance compared to metformin. This
might perhaps be due to the small dose used as compared to
ours and to the dose of metformin used in their study, and
also to their short study duration (3 months). Furthermore,
chromium was better tolerated compared to metformin.55
Metformin use for 3 months' period was associated with
higher incidence of abdominal discomfort, nausea, vomit-
ing, diarrhea, and indigestion.55
This study has some limitations. The rst is the relatively
small sample size. We believe that further studies should be
carried out on larger samples. Chromium picolinate is a
relatively new agent among the therapeutic options of PCOS
and that is why it was quite difcult to recruit a large number
of young adolescents. Second, the short duration of the study
could be the reason that no signicant change was observed
in clinical hyperandrogenism. However, our intention is to
follow up our subjects for another year to observe the long
term effects of chromium especially on clinical hyper-
androgenism and evidence of ovulation.
In conclusion, using chromium picolinate in a daily dose
of 1000 mg in adolescent girls diagnosed with PCOS for 6
months signicantly improves the regularity of their men-
strual cycles, decreases their ovarian volume as noted on
ultrasonography, decreases the number of ovarian follicles
between 2-9 mm, and decreases free testosterone levels.
Patient compliance is excellent, and side effects have not
been reported to us, making this mode of treatment a very
promising one. In view of the aforementioned ndings, we
recommend that this modality of treatment be compared
with the established therapeutic agents available such as
metformin and COC in clinical trials.
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