PCOS: Perspectives from a Pediatric Endocrinologist and
a Pediatric Gynecologist
Alvina R. Kansra, MD,a,b,n and Seema Menon, MDa,b
Polycystic ovary syndrome is most common endocrinopathy
recognized in women of childbearing age with a prevalence
of 412%. The prevalence of the disorder in adolescent
Introduction
olycystic ovarian syndrome (PCOS) is a com-
P plex dysfunction that is most commonly
characterized by anovulation and hyperandro-
genism. While this syndrome is well described, it is
poorly understood. The central mechanism leading to
the disruption of ovulation is widely debated; con-
sequently, treatment approaches vary. Much of the
attention PCOS had garnered has focused on the adult
population. Data from adult studies are often extrapo-
lated to the adolescent population; however, subtle
differences in diagnosis and treatment exist between
these two groups. This review seeks to highlight recent
data in an effort to help health care practitioners
develop an efficient guide to diagnose and treat PCOS.
Prevalence and Pathogenesis of PCOS
PCOS is an important condition to understand as
412% of women of reproductive age are affected.1,2
Not only is fertility impaired, a significant association
with endometrial pathology, obesity, insulin resistance
and hyperandrogenemia exists. Consequently, PCOS
has a huge impact on the reproductive, metabolic and
cardiovascular health of affected women.35 Because
From the aDepartment of Pediatrics, Section of Endocrinology &
Diabetes, Medical College of Wisconsin, Milwaukee, WI; and bDepart-
ment of Obstetrics and Gynecology, Medical College of Wisconsin,
Milwaukee, WI.
Corresponding author E-mail: akansra@mcw.edu
Curr Probl Pediatr Adolesc Health Care 2013;43:104-113
1538-5442/$ - see front matter
& 2013 Mosby, Inc. All rights reserved.
http://dx.doi.org/10.1016/j.cppeds.2013.01.002
104
population is poorly defined. The pathogenesis as well as the
management of this disorder is widely debated.
Curr Probl Pediatr Adolesc Health Care 2013;43:104-113
of these associated co-morbidities, the importance of
diagnosing and treating PCOS in adolescents has been
recognized.
The prevalence of PCOS among adolescents has not
been studied. A study conducted in Iranian adolescents
using clinical criteria of menstrual dysfunction and
clinical hyperandrogenism (Hirsutism, severe acne and
androgenic alopecia) without considering biochemical
hyperandrogenemia found a prevalence of three percent.6
The endocrine disruption of PCOS is complex;
clustering of this syndrome in families supports a genetic
association.7,8 The hypothalamicpituitarygonadal axis
(HPG-axis) is a critical part in the development and
regulation of reproduction by controlling the uterine and
ovarian cycles. During childhood there is down regu-
lation of LH and FSH receptor due to the non-pulsatile
release of gonadotropin-releasing hormone (GnRH)
resulting in inactivity of the HPG-axis and low gonado-
tropin levels. HPG-axis gets activated during puberty
when the GnRH secretion becomes pulsatile with the
predominant increase in the frequency and amplitude of
pulsatile LH release in early puberty as compared to
FSH and causes release of estrogen from the ovaries.
During the pubertal progression this gonadotropin secre-
tory pattern changes and LH to FSH ratio normalizes
due to increase in FSH secretion. Disordered gonado-
tropin secretion was the first reported biochemical
feature of PCOS as evidenced by abnormal luteinizing
hormone (LH) to follicle stimulation hormone (FSH)
ratio. Increased LH pulse amplitude and frequency with
normal FSH release has been noted in patients with
PCOS.9,10 Interestingly, the changes seen in gonadotro-
pin release in patients with PCOS are similar to
gonadotropin secretion patterns seen in early puberty.11
In PCOS patients, the abnormal LH secretion pattern
Curr Probl Pediatr Adolesc Health Care, May/June 2013
 Pathogenesis
Obesity Insulin resistance
Hyperandrogenemia
Puberty Genetics
Ethnicity Disordered gonadotropin
Secretion
Fig 1. Pathogenesis.
persists when compared to non-PCOS patients in late
puberty.11,12 Hyperandrogenemia is a prominent finding
in patients with PCOS. The cause of hyperandrogenemia
is multifactorial (Fig 1). Using antiandrogen therapy in
women with PCOS has shown to restore the impaired
LH secretion.13 Again, hyperandrogenemia can be a
normal finding in early puberty secondary to increased
androgen production from the adrenal gland.
In addition to increased adrenal androgen production
and disordered gonadotropic secretion, insulin resistance
and increased weight gain may be found in adolescents
during early puberty.14 Obesity may play a role in
persistence of disordered gonadotropin secretion and
hyperandrogenemia. Increased weight gain especially
during early childhood and puberty has higher associ-
ation with menstrual disorders.15 The overall frequency
of obesity in woman with anovulation and polycystic
ovaries is reported to be 3540%.16 In general, patients
with PCOS appear to have greater severity of insulin
resistance when compared to the general population,
irrespective of weight.17 In addition, obesity exacerbates
insulin resistance.18,19
Hyperinsulinemia has been shown to disrupt normal
ovarian function as this hormone has gonodotropic
activity and synergizes LH action. Ultimately, hyper-
insulinemia leads to increased androgen production
from the ovary by stimulating theca and granulosa cell
activity.20,21 In addition hyperinsulinemia increases
pituitary sensitivity to gonadotropin-releasing hormone
(GnRH),22 leading to abnormal gonadotropin dynam-
ics.23 Hyperinsulinemia also suppresses hepatic syn-
thesis of sex hormone-binding globulins resulting in
increased levels of free testosterone.
Clinical Presentation
The most common clinical manifestations of PCOS
are menstrual abnormalities and clinical signs of
hyperandrogenemia. The menstrual abnormalities most
Curr Probl PediatrAdolesc Health Care, May/June 2013
commonly seen are amenorrhea, oligomenorrhea, or
dysfunctional uterine bleeding. These abnormal bleed-
ing patterns develop secondary to the chronic anov-
ulation associated with this syndrome. Chronic
anovulation is not only associated with fertility chal-
lenges later in life, but also with an increased risk for
endometrial carcinoma.5
Specific cutaneous features of PCOS include hirsutism,
acne, increased oily skin, androgenic alopecia and acan-
thosis nigricans (AN). The development of these features
is quite complex and a great deal of variability exists
among patients with PCOS. While androgens are likely to
play a role, clinical hyperandrogenemia has been observed
in the absence of biochemical hyperandrogenism.24
Recent studies have shown that the circulating
androgens in patients with PCOS are not only respon-
sible for the classic cutaneous feature described above,
they are also associated with the clinical and biochem-
ical markers of metabolic syndrome.25 Obese adoles-
cent girls with PCOS are at a particularly high risk for
insulin resistance and metabolic syndrome. Therefore,
it is important to discuss the long-term health con-
sequences associated with PCOS once the diagnosis is
established. Additional glucose tolerance and lipid-
profile testing should be considered in this subset of
patients.26Assessing hirsutism has served as a way to
gauge the severity of hyperandrogenemia. A number of
methods have been described in the literature to score
hirsutism. The FerrimanGallwey scale (FGS) is most
commonly used, and is often cited by different stud-
ies.27 This scoring system offers the advantage of cost-
effectiveness and relative ease, as other methods
involve photographic evaluation and microscopic meas-
urement of hair diameter with extensive counting of
shafts. The original FGS method used 11 body areas
(upper lip, chin, chest, upper back, lower back, upper
abdomen, lower abdomen, upper arms, forearms,
thighs, and legs). This method was further modified to
include only 9 body parts. In this modified approach,
assessment of the forearms and legs were excluded.
Hair growth is rated from a score of 0 (no growth of
terminal hair) to 4 (extensive hair growth) in each of the
nine locations, allowing for a minimum score of 0 and a
maximum score of 36. A score of 8 or higher in
Caucasian women is regarded as indicative of androgen
excess. Hair growth can vary between women of different
ethnic backgrounds. Unfortunately, there are no standards
to guide the interpretation of hair growth in patients of
non-Caucasian ethnicity. This should be strongly consid-
ered when making as assessment of hirsutism.
105
 In 2001 this method was further modified to include
an additional 10 regions of the body, bringing the total
number of body sites needing examination to 19. The
additional sites are sideburns, neck, buttocks, inguinal
area, perianal area, forearm, leg, foot, toes and fingers.
Each area has its own specified definition of the four-
point scale.28 Despite the level of detail provided by
the FGS, the greatest limitation is that scoring is
subjective. Studies have found that a great deal of
observer variability exists.29
Diagnostic Criteria
In 1990 National Institute of Health (NIH) proposed
that the criteria for PCOS diagnosis should include the
presence of anovulation and clinical signs of hyper-
androgenism and/or hyperandrogenemia after excluding
other causes of hyperandrogenemia, such as non-
classical adrenal hyperplasia, androgen-secreting
tumors and Cushings syndrome.30 In 2003, a consen-
sus meeting between European Society of Human
Reproduction and Embryology (ESHRE) and American
Society for Reproductive Medicine (ASRM) in Rotter-
dam broadened the diagnostic criteria and suggested
that a diagnosis should include the presence of two of
the following three criteria: anovulation, hyperandroge-
nemia and polycystic ovarian morphology.31 With this,
a new PCOS phenotype was introduced; one that did
not require the presence of hyperandrogenemia. Some
controversy ensued, and ultimately the Androgen
Excess Society (AES) in 2006 offered revised criteria
that re-emphasized the importance of hyperandrogene-
mia.32 AES recommend that a PCOS diagnosis be made
if there is clinical and/or biochemical evidence of
hyperandrogenemia, presence of ovarian dysfunction
as evidenced by oligomenorrhea, amenorrhea or poly-
cystic ovarian morphology, and requires the exclusion
of other causes of hyperandrogenemia. All these
definitions have specifically addressed an adult
population.
There is no adolescent specific definition for PCOS.
Because of the normal biochemical changes that occur
during adolescence, it is theorized that by applying
adult definitions to a younger population, PCOS may
be over diagnosed. Profound functional changes in the
hypothalamicpituitaryovarian axis during puberty
can result in hormonal imbalance mimicking some of
the clinical features of PCOS. In 2006 Sultan and Paris
proposed five criteria to diagnose PCOS in the
106
adolescent population and recommended that the
adolescents girls with PCOS should meet four out
of the five criteria: (1) persistent oligomenorrhea
or amenorrhea 2 years after menarche; (2) clinical
evidence of hyperandrogenemia (acne and severe
hirsutism); (3) biochemical hyperandrogenemia (total
testosterone 4 50 ng/dL (1.75 nmol/L) and LH/FSH
ratio 42); (4) hyperinsulinemia/insulin resistance
manifested as acanthosis nigricans, abdominal obesity,
glucose intolerance; and (5) polycystic and ultrasound
evidence of enlarged ovaries with peripheral micro-
cysts and increased stroma.33 Recently Carmina et al.
published new criteria to diagnose PCOS in adolescents
with the aim of avoiding over-diagnosis of this
condition (Table 1). This guideline recommends that
all three of the following be present to make a definitive
diagnosis: hyperandrogenism, chronic anovulation and
polycystic ovaries. The authors suggest that if only two
of the three criteria are present the adolescent should be
closely followed and re-evaluated for PCOS if the
characteristics do not resolve. This new recommenda-
tion also suggests that a greater emphasis be placed on
biochemical hyperandrogenism (elevated blood andro-
gen levels using sensitive assays) as opposed to clinical
findings, with the exception of worsening hirsutism.
TABLE 1. Diagnostic criteria for polycystic ovary syndrome in adolescents
Criteria Hyperandrogenisma Chronic Polycystic
anovulationb ovariesc
Diagnosis of PCOS
Diagnosis of PCOS
probable but not 
conrmed
Diagnosis of PCOS not
possible during 
adolescence
Diagnosis of PCOS not
possible during 
adolescence
Not PCOS  
Not PCOS  
Not PCOS  
PCOS, polycystic ovary syndrome. Carmina. The diagnosis of PCOS
in adolescents. Am J Obstet Gynecol 2010.
(a) Hyperandrogenemia is primary criterionacne and alopecia are
not considered as evidence for hyperandrogenismhirsutism may
be considered a sign of hyperandrogenism only when it has been
documented to be progressive.
(b) Oligomenorrhea (or documented anovulation) has to be present
for at least 2 years.
(c) Diagnosis of polycystic ovaries by abdominal ultrasound has to
include increased ovarian size (410 cm3).
(Permission granted from American Journal of Obstetrics and
Gynecology Article Title: The diagnosis of polycystic ovary syn-
drome in adolescents. Author(s): Carmina, Enrico; Oberfield,
Sharon E.; Lobo, Rogerio A.).
Curr Probl Pediatr Adolesc Health Care, May/June 2013
Finally, the new PCOS diagnostic approach for adolescent
patients requires that menstrual irregularities are persis-
tent 2 years post-menarche, and that pelvic ultrasound
findings are consistent with increased ovarian volume
(410 cm3).34
The proposed diagnostic criteria for adolescents are
stricter than the criteria used to diagnose PCOS in
adults in an effort to avoid misdiagnosing normal
adolescent changes as PCOS. On the other hand,
stricter diagnostic criteria may lead to missing a PCOS
diagnosis in a patient with a milder phenotype. While
under-treating PCOS may not have significant clinical
consequences during adolescence, lack of treatment
throughout adulthood can lead to significant co-
morbidities including endometrial pathology and met-
abolic syndrome, as described previously.
Laboratory Evaluation
Although PCOS is primarily a clinical diagnosis,
laboratory evaluation should be performed. Often, the
laboratory tests ordered are tailored to the patients
clinical presentation. Similar to the wide variety in
clinical symptoms, the biochemical findings in PCOS
lack uniformity. This has led to continued controversy
related to the optimal diagnostic tests to identify the
disorder. A definitive endocrine marker for PCOS has
not been identified. A recent study done in women with
PCOS found that a combination of elevated estrone
(450 pg/ml) and free testosterone (43.3 pg/ml)
appeared to differentiate patients with PCOS with a
high grade of sensitivity and specificity from con-
trols.35 Again, due to lack of normative data in the
adolescent population, application of these laboratory
tests may not be of value.
Although the use of LH/FSH42.0 ratio has been
described in the literature, the variability of serum LH
levels during different stages of menstrual cycle is
problematic and has led many experts to discourage
this test. The LH/FSH ratio appears to have a low
specificity as a diagnostic test for PCOS. Interestingly,
studies found no difference in LH/FSH ratios when
comparing obese PCOS patients to a control group.36
While the utility of the LH/FSH ratio is debatable, a
laboratory assessment of FSH alone is appropriate in
patients presenting with primary or secondary amenor-
rhea. Secondary amenorrhea is defined as the absence
of menses for at least 3 months. While the menstrual
pattern most commonly associated with PCOS is
Curr Probl PediatrAdolesc Health Care, May/June 2013
oligomenorrhea, patient with this syndrome can also
present with amenorrhea. Determination of FSH levels
is critical in patients presenting with amenorrhea, as
PCOS must be differentiated from premature ovarian
insufficiency (POI). POI is defined as menopause
before the age of 40, and is associated with elevated
FSH levels. PCOS, on the other hand, is associated
with FSH levels in the normal range. These conditions
must be distinguished from one another as they are
associated with different co-morbidities and require
different treatment approaches.
Serum total and free testosterone in postmenarchal
adolescent girls helps to identify a hyperandrogenemic
state. Hyperandrogenemia can be diagnosed if the total
testosterone level is greater than 2 SD above the mean
for the assay used, or greater than 5558 ng/dL if the
assay is performed after appropriate extraction.37
Defining hyperandrogenemia by a free testosterone
level of 10 ng/dL (35 pmol/L) has been supported by
some studies.38,39
Radiology Evaluation
Requiring that an ultrasound examination be per-
formed to establish a diagnosis of PCOS has been
debated. The classic ultrasound finding describing
polycystic ovaries is multiple sub-centimeter follicles
concentrated around the periphery of the ovary. How-
ever, this ultrasound finding has been shown to have
low specificity as a PCOS diagnostic test on its own.
Studies have shown that ovarian appearance and
volume can vary during adolescence. Ultrasound find-
ings consistent with polycystic ovaries or enlarged
ovaries during the adolescent period have been found
to normalize over time regardless of menstrual
regularity.40,41
Transvaginal ultrasound allows for clear visualiza-
tion of the ovaries and provides an accurate follicle
count when done by an experienced sonographer.
Adolescent patients, particularly those that are not
sexually active, typically do not undergo transvaginal
ultrasonography. Determining an accurate ovarian fol-
licle assessment can be challenging using a transabdo-
minal ultrasound approach. However, this approach can
reliably determine ovarian volume. The new guidelines
pertaining to PCOS diagnosis in adolescents emphasize
ovarian size as opposed to the classic increased follicle
count. The feasibility of performing an ultrasound
routinely for PCOS diagnostic purposes has not been
107
clearly established at this time. If ultrasound is incorpo-
rated into routine practice for the diagnosis of PCOS in
the adolescent population, an effort should be made to
ensure the radiology team is comfortable imaging
ovaries using the Transabdominal approach. It should
also be communicated that the ultrasound is being done
for PCOS evaluation and that an assessment of ovarian
volume is needed.
Evaluation of the Patient in Different
Clinical Settings
Due to heterogeneous nature of this disorder, ado-
lescents are seen in different clinical settings. In our
experience, the bothersome symptom is what deter-
mines which specialist the patient sees, and ultimately
affects the work-up that is done. Typically, patients
with menstrual irregularities present to the adolescent
gynecology clinic, and with hirsutism, obesity, and/or
abnormal lipid profile present to the endocrine clinic.
Laboratory tests done in the gynecology clinic are
mainly focused on the oligomenorrhea or amenorrhea
menstrual pattern and mostly include FSH, prolactin,
thyroid function, free testosterone, hcg, and 17 hydrox-
yprogesterone testing. Although, a HbA1c test is also
done, the use of this as a screening test in adolescents
has not been established. Patients presenting to the
endocrine clinic are worked up more extensively from
a hyperandrogenemia and metabolic syndrome stand-
point. The following laboratory tests are routinely
ordered in addition to the ones above: androgens
(DHEAS, 17 hydroxyprogesterone and androstene-
dione) if a patient has excessive hirsuitism to exclude
the other causes, and metabolic work-up (HbA1c, lipid
panel, OGTT) if the patient is significantly overweight.
In addition, an ultrasound evaluation is commonly
done in patients presenting to the Adolescent clinic as
compared to Endocrine clinic.
Treatment
Treating PCOS in adolescents requires bridging
patient expectations of improving symptoms with
health practitioner goals of preventing the development
of co-morbid conditions. Patients, especially adoles-
cents, are extremely bothered by irregular menses, acne
and hirsutism, and typically seek care to treat these
symptoms. Health care providers, while wanting to
improve the quality of patients lives, are focused on
108
reducing the risk of developing endometrial cancer/
hyperplasia, diabetes, and cardiovascular disease. Ulti-
mately, the treatment must focus on the core dysfunc-
tion of PCOS: anovulation, hyperandrogenism,
obesity, and insulin resistance. Successful treatment
of these leads to both improvements of the bothersome
symptoms as well as the prevention of co-morbid
conditions.
A large focus of PCOS treatment in the adult
population is on fertility. While practitioners will rarely
encounter an adolescent requesting fertility treatment, a
discussion concerning future reproductive function
should be held. Adolescent patients are typically not
interested in immediate fertility, but may be anxious
about their future reproductive health. Therefore,
fertility should be included in the conversation. First,
patients should be counseled that although menses are
irregular, spontaneous and unpredictable ovulation can
occur, making pregnancy possible. If the patient is
sexually active and pregnancy is not desired, contra-
ception must be discussed. Second, reassurance should
be given to patients and their families that if menstrual
irregularities persist and fertility challenges present in
the future, medical therapy is relatively successful at
achieving pregnancy and live births.42
Restoring Menses
A priority of PCOS treatment in adolescents is
menstrual regulation. Menstrual regularity is depend-
ent on ovulation. After the dominant follicle releases
the ova, it transforms into the progestin-secreting
corpus luteum. If no pregnancy occurs, the corpus
luteum regresses, progestin level falls and menses
ensues. Progestin is important in the transformation
of the endometrial lining from proliferative to secre-
tory; progestins ability to regulate endometrial growth
is so profound that it is actually protective against
endometrial hyperplasia and cancer. Although the
association between PCOS and endometrial pathology
is well accepted, data supporting this finding are
limited.43,44 Regardless; treatment with progestins is
the cornerstone to PCOS management not only for
menstrual regulation, but also for endometrial cancer
prevention.43
Combination oral contraceptive pills (COC) are an
effective way to deliver progestin therapy. Progestin is
the dominant component in COC, therefore, menstrual
regulation and prevention of endometrial pathology
Curr Probl Pediatr Adolesc Health Care, May/June 2013
should be achieved. All oral contraceptives contain
ethinyl estradiol (EE); however, the dose may vary
between 10 mcg and 50 mcg. The dose of EE in
low-dose pills ranges from 10 mcg to 35 mcg. Low-
dose COCs are preferred to the high-dose 50 mcg Levonorgestrel
containing COC secondary to thromboembolic event
concerns.45 While an optimal COC has not been
established for the treatment of PCOS, there are some
limited data guiding the selection in adolescents. There
are limited data supporting the use of a 30 or 35 mcg
EE containing pill secondary to irregular bleeding
associated with the lower doses.46 In addition, the
lower doses of EE have been associated with a
reduction in bone density accrual during the adolescent
years as compared to placebo treatment.47
While all COC only contain one type of estrogen, the
progestins vary widely. The vast majority of progestins
used in COC are derived from 19-nortestosterone.45
Not surprisingly, the progestin component may have
some androgenic activity. Progestins are divided into
four generations; the second generation has been found
to have more androgenic activity than the other
generations. Drospirenone, a fourth generation proges-
tin, is derived from spironolactone and has been found
to have anti-androgenic activity.45 Multiple small
studies have been performed comparing third and
fourth generation progestins in women with PCOS.
The findings support the fourth generation progestins
ability to suppress androgens and increase sex
hormone-binding globulin to a greater degree than
third generation progestins.48 It has also been shown
that patients maintain regular monthly cycles for
6 months following treatment with fourth generation
progestins compared to third generation progestins.49
Certainly, these data are limited and should not be
interpreted to mean that fourth generation progestins
must be used in PCOS treatment. Complicating mat-
ters, drospirenone, the fourth generation progestin
available in the US, has been identified as carrying a
higher risk of deep venous thrombosis events when
compared to COCs with different progesterone for-
mulations. While the clinical significance of this find-
ing is debated, the actual benefit of drospirenone in
patients with PCOS remains largely theoretical (Table 2).
COC are one of many available methods to administer
progestin therapy. Contraceptive progesterone-only
pills, cyclic oral progesterone pills, depot medroxypro-
gesterone acetate, the transdermal contraceptive patch,
the transvaginal contraceptive ring, the subdermal con-
traceptive implant and the levonorgestrel-containing
Curr Probl PediatrAdolesc Health Care, May/June 2013
TABLE 2
Common Progestins Generation
Norethindrone First-generation
Norethisterone Second-generation
Second-generation
Norgestrel Second-generation
Gestodene Third-generation
Desogestrel Third-generation
Norgestimate Third-generation
Drosperinone Fourth-generation
intrauterine device are all effective at delivering
progestin therapy, and therefore can regulate cycles
and prevent endometrial hyperplasia. The method that
most effectively prevents endometrial pathology is
unknown.42 Health care practitioners should be aware
of all the available options as COCs often present
compliance challenges to adolescents. In addition,
secondary to the risk of thromboembolic events, some
patients may actually have a contraindication to sys-
temic estrogen therapy making the progestin-only
option necessary.
As opposed to COC which override ovarian function,
other therapies have been shown to restore menses by
inducing ovulation. Common pharmacologic ovulation
induction agents include clomiphene citrate, insulin-
sensitizing agents and injectable gonadotropin hor-
mones. Clomiphene citrate has been well accepted to
be first-line therapy in treating ovulation dysfunction in
women with PCOS desiring fertility based on the
findings of several large randomized control trials.42,50
Letrazole, an aromatase inhibitor, is used with more
frequency, but is not FDA approved for this indication.42
While ovulation induction therapy is not routinely
appropriate for an adolescent, the ovulation induction
ability of other therapies such as insulin sensitizers,
antiandrogens, and weight loss have been evaluated.
Limited data exist to support the benefit of anti-
androgen medications such as flutamide and finasteride
on restoring ovulation or regulating cycles.51 Insulin-
sensitizing medications have been shown to regulate
menses in adult women compared to placebo, however,
are not as effective in cycle regulation as COC.51
Additionally, data supporting the use of these medi-
cations to regulate menses in the adolescent population
is limited.52 Weight loss has been shown to be
effective in restoring menstrual cycles. Lifestyle mod-
ification leading to a loss of 27% of body weight has
been found to improve ovulatory function in women
with PCOS. While lifestyle modification is important
for maintaining healthy body weight, there are no data
109
that support this approach to be more effective than
COC in regulating menses.42,51
Treating Hirsutism and Acne
A common complaint among patients with PCOS is
acne. Combination oral contraceptive pills are effective in
treating this bothersome symptom. This medication has
been shown to reduce the amount of androgen produced
from the ovary as well as increase sex hormone-binding
globulin leading to decreased free testosterone levels.
Limited data supports using a COC containing 30 mcg of
EE as these have been shown to be superior in stimulat-
ing sex hormone-binding globulin, and may inhibit
adrenal androgen production as compared to pills con-
taining lower EE doses.45 While third generation proges-
tins are less androgenic compared to second generation
progestins, no significant difference is seen in the treat-
ment of hirsutism when comparing COCs containing
these different progestins.53 On the other hand, limited
data do support the use of COCs containing fourth
generation progestins as opposed to third generation
progestins in the treatment of hirsutism.51
Medical treatment of hirsutism is more challenging
than acne. Studies evaluating treatment of hirsutism
have been criticized for small sample size, and impre-
cise reporting of results making evidence-based prac-
tice difficult. Hirsutism is reduced after treatment with
both COCs and antiandrogen therapy.54 Comparisons
between COC containing a fourth generation progestin
and antiandrogen therapy showed no difference in
hirsutism reduction.51 The three FDA-approved anti-
androgen medications are spironolactone, flutamide,
and finasteride. Flutamide acts by blocking androgen
activity at the receptor level. This therapy has been
associated with significant hepatotoxicity which has led
many experts to discourage this as first-line therapy.54
Finasteride inhibits 5-alpha reductase preventing the
conversion of testosterone to dihydrotestosterone. Spi-
ronolactone decreases androgen production from the
adrenal gland and also competitively binds androgen
receptors in target tissues. This therapy can be rarely
associated with hyperkalemia, and postural hypoten-
sion. Hyperkalemia is more likely to occur if patients
are taking other medications that potentiate this effect
(angiotensin-converting enzyme inhibitors, angiotensin
receptor blockers, and non-steroidal anti-inflammatory
drugs). This medication is contraindicated in patients
with severe renal excretory impairment, new onset
110
renal insufficiency, or known hyperkalemia. Compar-
isons between these medications reveal that no one
antiandrogen treatment is superior to the others in the
treatment of hirsutism.51,54
While data do not support using one method over
another, most experts recommend initially starting
with COC monotherapy.54,55 Antiandrogen mono-
therapy is cautioned against as these medications
can lead to significant teratogenicity if pregnancy
occurs. In addition, both spironolactone and flutamide
can lead to bothersome menstrual irregularities when
used alone. Data regarding efficacy of hirsutism
treatment with insulin-sensitizing medications are
conflicting. Some studies have shown a positive
impact on hirsutism, whereas others have found no
benefit.51,54 Although treatment with insulin-
sensitizing medications may decrease ovarian andro-
gen production, they should not be used for hirsutism
treatment.54 No data have documented improvement
of hirsutism in patients undergoing weight loss.51
Direct hair removal should be discussed with patients
desiring effective hirsutism treatment. The benefit of
photoepilation and electrolysis has been investigated.
Again, data are neither robust nor complete, but both
have been shown to be effective in hair reduction. Limited
data support that photoepilation therapy leads to greater
hair reduction in a shorter amount of time, and is less
painful than electrolysis. However, this method has
classically been most effective in women with light skin
and dark hair. New laser technology is showing promise in
treating dark-skinned women and women with light hair.
Eflornithine reduces the rate of hair growth. The benefit of
adding this to direct hair removal techniques is unclear.
Developing an evidence-based approach to the treat-
ment of hirsutism in patients with PCOS is difficult
secondary to a relative dearth of data. Relying on the
opinions of expert societies is a reasonable approach.
Discussing comestic hair removal is an integral part of
effective hirsutism therapy.54,55 Therapy with a COC
should be the first medical option; a COC containing a
fourth generation progestin can be considered after the
risks of thromboembolic events are reviewed. Addition
of an antiandrogen medication can be considered in
6 months if treatment is not satisfactory.54
Treatment of Obesity
Obesity management has become a major challenge
to health-care practitioners. Many expert societies
Curr Probl Pediatr Adolesc Health Care, May/June 2013
favor weight reduction as first-line therapy for PCOS.
Family-based lifestyle intervention programs have
served as the basis for adolescent obesity treatment
programs.56 Programs providing an active lifestyle
component to counseling and education have superior
outcomes when compared to counseling alone. Part-
nering with parents has also been identified as a key
component in successful lifestyle modification pro-
grams.57 While several clinical practice guidelines
exist, no one program has been shown to be superior.56
The US preventive task force makes a basic recommen-
dation that overweight and obese children receive
specialty treatment of moderate to high intensity (25 h
of contact over 6 months) that involves counseling and
other interventions to target diet and physical activity.57,58
Medical therapy for the treatment of obesity in
adolescents is limited. Sibutramine and orlistat have
been shown to reduce body mass index compared to
placebo in adolescents in past studies.59 Sibutramine is
no longer FDA approved after an association with
heart disease and stroke was found in adults. Orlistat
was FDA approved for children of 12 years of age and
over; now only an over the counter reduced strength
version is available approved for those of 18 years of
age and older. This medication acts by inhibiting
pancreatic lipase thereby reducing fat absorption.
While this medication has been recommended as
adjunctive therapy especially for those having diffi-
culty maintaining a low-fat diet, bothersome side
effects such as oily spotting, liquid stools, fecal
urgency, and flatulence, along with decreased absorp-
tion of fat soluble vitamins need to be considered.
Metformin is not FDA approved for the treatment of
obesity. This medication inhibits gluconeogenesis and
lipid biosynthesis, and may inhibit appetite. Limited
data available in the pediatric population support an
association between metformin and weight loss, but the
studies conducted were small and short term.60
Although data are supportive, it is limited; the Endo-
crine Society and the American Academy of Pediatrics
advocate that lifestyle modification should be the first
approach when treating obesity.
Surgical treatment for obesity in the adolescent
population is a relatively nascent concept. Currently,
expert societies are debating appropriate guidelines for
bariatric surgery in the adolescent population.58 The
optimal surgical approach is also debated. While data
supporting bariatric surgery in adults is robust, expe-
rience in the adolescent population is limited, but
promising.61 Certainly, surgical treatment of obesity
Curr Probl PediatrAdolesc Health Care, May/June 2013
in adolescent should not be considered before an
intensive lifestyle modification program is completed.
Surgical treatment may be an appropriate treatment
option for certain patients; health care practitioners
should at least be aware of this approach.
Treating Insulin Resistance
Insulin resistance is found in the majority of women
with PCOS.50,52 Although not consistent, data have
shown that treatment with insulin-sensitizing agents is
associated with menstrual cycle regulation, decreased
androgen levels, can serve as a weight-loss aid.
Secondary to this, some experts have advocated treat-
ing all patients with PCOS for insulin resistance.50
Metformin use in adolescents has been established to
be safe in the treatment of type 2 diabetes mellitus.
Data supporting metformins ability to restore regular
cycles in adolescents are limited, as is longitudinal data
supporting improvement in cardiovascular outcomes.
Evidence does not support the treatment of insulin
resistance in all adolescent with PCOS.52 However, if
glucose intolerance or diabetes is diagnosed, treatment
with metformin is an integral part of PCOS therapy.
Preventing Cardiovascular Disease
The association between PCOS and cardiovascular
disease is well accepted. Evidence is growing regard-
ing optimal treatment options for the prevention of
cardiovascular disease in adolescents with PCOS.
COCs have been shown to increase total cholesterol,
C-reactive protein, triglycerides, and leptin.42,62 A
COC containing drospirenone was found to worsen
cardiometabolic profile in a small study.62 However,
the long-term consequences of these findings are not
well understood as COCs also increase HDL levels,
and their use is not associated with increased cardio-
vascular disease in the general population or in women
with PCOS.42,45 The insulin-sensitizing agent, rosigli-
tazone was found to improve triglyceride levels in a
small study; however, other study findings have
associated insulin-sensitizing agents with increased
cardiovascular events.54,62 Investigation into the safety
and long-term impact statin therapy may have in
adolescents with PCOS is ongoing. Given the limited
data available currently, most expert societies recom-
mend lifestyle modification involving exercise and
111
dietary changes as the most effective and safe method
to reduce the risk of cardiovascular disease.42,63
Conclusion
Developing evidence-based approach to the diagnosis
and treatment of PCOS in the adolescent population is
difficult. Highlighting this are the sometimes conflicting
clinical guidelines that the various PCOS expert soci-
eties recommend. Health care practitioners caring for
adolescents with PCOS should be comfortable manag-
ing irregular menses, hirsutism, and obesity. In addition,
it is important to be aware of new diagnostic tests and
therapies that are emerging as research in this field
grows. Diagnosing and treating PCOS, though wrought
with challenges, is extremely important as the risk of
developing cardiovascular disease, diabetes mellitus,
and endometrial pathology can be ultimately reduced.
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