DR. Nedaa Bahkali
2012
Introduction
Definition, DIAGNOSTIC CRITERIA
DIAGNOSTIC APPROACH
Treatment of polycystic ovary syndrome in
adolescents
SUMMARY AND RECOMMENDATIONS
 Menstrual
cycles are often irregular in the
first months after menarche.
 According to a study by WHO :


the median length of the first cycle after
menarche was 34 days,
with 38%of the cycles > 40 days and 7 %
occurring <20 days apart .
World Health Organization multicenter study on menstrual and
ovulatory patterns in adolescent girls, J Adolesc Health Care. 1986
 Menstrual
disorders and abnormal uterine
bleeding (AUB) are among the most frequent
gynecologic complaints of adolescents
account for 50% .


Menstrual disorders in adolescence: pathophysiology and treatment,
Horm Res., 1991,Belgique.
Menstrual disorders during adolescence, Pediatr Endocrinol Rev. 2006,
University of Athens, Greece.

Polycystic ovary syndrome (PCOS) accounts for
the vast majority of anovulatory symptoms and
hyperandrogenism in adolescent .
 PCOS
is the most common endocrine
abnormality of reproductive-aged women in the
United States.

 The
The prevalence and features of the polycystic ovary syndrome in an
unselected population, The University of Alabama at Birmingham, J Clin
Endocrinol Metab. 2004.
diagnosis of PCOS has life-long implications
with increased risk for infertility, metabolic
syndrome, type 2 diabetes mellitus, and
probably cardiovascular disease.
 The
classic syndrome originally was described by
Stein and Leventhal as the association of
amenorrhea with polycystic ovaries, and variably,
hirsutism and obesity.

J Obstet Gynecol 1935
Cutaneous
hyperandr
ogenism
Obesity
and insulin
resistance
PCOS
Polycystic
ovary
Menstrual
irregularity
 controversy
arises from the fact that a
polycystic ovary is often a normal variant and
some asymptomatic ovulatory girls have
subclinical PCOS according to the RotterdamAES criteria .
 None
of these criteria fully addresses some of the
unique problems in diagnosing PCOS in
adolescents. As an example, even in girls without
PCOS, approximately one-half of menstrual cycles
are anovulatory in the first two years after
menarche .

Hyperandrogenism during puberty and adolescence, and its relationship to
reproductive function in the adult female. In: Reproductive Medicine, Raven
Press, 1993.
 Furthermore,
polycystic ovaries may be missed by
the Transabdominal ultrasound technique that is
typically used for virginal adolescents, particularly
if they are obese.

Evaluation for PCOS is recommended in the
following clinical scenarios:

Girls with a sole finding of moderate or severe hirsutism,
or a hirsutism equivalent, including persistent acne , or
pattern alopecia

Girls with mild hirsutism or obesity with any other
feature of PCOS (eg, menstrual abnormality)

Adolescent girls with menstrual irregularity that persists
more than two years or who have severe dysfunctional
uterine bleeding

Adolescent girls with intractable obesity whether or not
hirsutism, hirsutism equivalents, or menstrual
irregularity are present
DIAGNOSTIC
APPROACH
unexplained clinical
and/or biochemical
hyperandrogenism
ovarian dysfunction
Evidence
of
Hyperandrogenism

Menstrual irregularity constitutes evidence
of ovarian dysfunction.
 However,
normal menstrual regularity does
not mean ovulatory function is normal.
A
polycystic ovary is considered evidence of
ovarian dysfunction in the setting of
hyperandrogenism when menses are regular.


The key androgen to measure is serum (or plasma) testosterone.
Serum total and free testosterone:
 best assessed in the early morning.

on days 4 through 10 of the menstrual cycle in regularly cycling
women; norms are standardized for this part of the menstrual cycle.

Oral contraceptive pills interfere with the assessment of androgens.


They suppress gonadotropins, elevate sex hormone binding globulin (SHBG),
and directly inhibit steroidogenic enzymes such as 3ß-hydroxysteroid
dehydrogenase.
After discontinuing oral contraceptive pills, normal women may transiently
have a slightly high total testosterone level but a normal free testosterone
level because SHBG turnover is slower than testosterone turnover.

Clinical practice. Hirsutism, N Engl J Med. 2005, Department of Pediatrics and Medicine, University of Chicago,
USA.

Total testosterone :


The normal upper limit for serum total testosterone in women is
approximately 60 ng/dl (2.0 nmol/L) .
Free testosterone :

An elevation in serum (or plasma) free testosterone is the single most
sensitive test to establish the presence of hyperandrogenemia.

The serum free testosterone concentration is about 50 percent more
sensitive for the detection of hyperandrogenemia than the total
testosterone concentration.

This is because elevated insulin levels (a frequent concomitant of
PCOS) and elevated androgen levels both act to inhibit hepatic
production of sex hormone-binding globulin (SHBG), which is the main
determinant of the bioactive portion of serum testosterone, the
fraction that is free or "bioavailable" the latter including the fraction
that is loosely bound to albumin.

International consensus criteria define a
polycystic ovary on the basis of either excessive
size or follicle number (or both), in the absence
of a dominant-size follicle (>1.0 cc) or a corpus
luteum.

Using these criteria, a polycystic ovary can be
identified by ultrasonography in about 75 % of
women with PCOS.

Excessive ovarian size is defined as




an ovary with a volume >10.5 mL in adults
>10.8 mL in adolescents.
An alternate measure of increased volume is a maximal
area >5.5 cm2. Most polycystic ovaries in PCOS are
enlarged.
Excessive follicle number is defined


by vaginal ultrasonography as a total follicle count of ≥12
per ovary.
In adolescents in whom abdominal rather than vaginal
ultrasonography is indicated, it is defined as ≥10 follicles per
maximum plane .

These follicles are typically 2 to 9 mm in diameter.

Asymptomatic volunteers with a polycystic ovary are a functionally distinct but heterogeneous
population, J Clin Endocrinol Metab. 2009, Section of Adult and Pediatric Endocrinology, The
University of Chicago , USA.


The transabdominal ultrasonographic approach that is standard and
appropriate in virginal adolescents may underestimate the
prevalence of polycystic ovaries in comparison with the
transvaginal approach used in adult women .
This difference is modest.

In a prospective study of patients with PCOS in which these criteria
were used , a polycystic ovary was found in 69 percent of
adolescents and 87 percent of adults (p = 0.12, unpublished data).

The advantage of the transabdominal approach is that a screening
for an adrenal mass is facilitated.


Asymptomatic volunteers with a polycystic ovary are a functionally distinct but heterogeneous population,
J Clin Endocrinol Metab. 2009, Section of Adult and Pediatric Endocrinology, The University of Chicago ,
USA.
Gynecologic imaging: comparison of transabdominal and transvaginal sonography, Radiology. 1988,
Department of Radiology, West Penn Hospital, Pittsburgh, PA
 While
a polycystic ovary is a criterion for
ovarian dysfunction in the setting of
hyperandrogenism, in the absence of
hyperandrogenism a polycystic ovary is
usually a normal variant.
 Polycystic ovaries are common in the general
population,found in about 10 % of regularly
menstruating adolescents.

Polycystic ovaries in adolescents and the relationship with menstrual
cycle patterns, luteinizing hormone, androgens, and insulin, Fertil
Steril. 2000, Division of Reproductive Endocrinology and Fertility, Vrije
Universiteit Medical Center, Amsterdam, The Netherlands.
 Once
a diagnosis of PCOS has been
established, identifying abnormal glucose
tolerance or other features of the metabolic
syndrome is important because PCOS is a risk
factor for the early development of type 2
diabetes mellitus, metabolic syndrome, and
their associated risks for sleep-disordered
breathing and cardiovascular risk sequelae .


Polycystic ovary syndrome is associated with obstructive sleep apnea
and daytime sleepiness: role of insulin resistance, J Clin Endocrinol
Metab. 2001, Sleep Research and Treatment Center, Department of
Psychiatry, Penn State University College of Medicine, USA.
Relationships between sleep disordered breathing and glucose
metabolism in polycystic ovary syndrome, J Clin Endocrinol Metab.
2006, Department of Medicine, University of Chicago, Chicago, USA.
 About
a quarter of adolescents with PCOS
meet proposed adolescent criteria for the
metabolic syndrome [17,23,24].
 screening
for abnormal glucose tolerance,
performing an oral glucose tolerance test
(OGTT) in adolescents with obesity or other
risk factors for diabetes mellitus, even if the
fasting blood sugar is normal.

This is the recommendations made by the Rotterdam workshop ,the
American Association of Clinical Endocrinologists, and the Androgen
Excess and PCOS Society in adult women with PCOS.
The prevalence of diabetes was reported to be 2
% based on the fasting blood sugar in one series,
 and 8 % when based on OGTT criteria in another
series of adolescents.
 In both series, almost all of the adolescents had
no symptoms of diabetes.


Relationship of adolescent polycystic ovary syndrome to parental metabolic
syndrome, J Clin Endocrinol Metab. 2006, University of Chicago Comer
Children's Hospital, Section of Pediatric Endocrinology, USA.

Adolescent girls with polycystic ovary syndrome have an increased risk of the
metabolic syndrome associated with increasing androgen levels independent
of obesity and insulin resistance, J Clin Endocrinol Metab. 2006, Division of
Endocrinology, Metabolism, and Molecular Medicine, Northwestern University
Feinberg School of Medicine, Chicago, USA

In patients with PCOS:

Glucose tolerance should be monitored regularly because a
substantial number will experience deterioration in glucose
tolerance.

As an example, among 25 adolescent and young women followed
for a mean of 34 months, the two hour blood glucose deteriorated
at an average of 9 mg/dL (0.5 mmol/L) per year .

Among the 14 women with PCOS and normal glucose tolerance at
baseline, 55 percent experienced deterioration of glucose
tolerance when they were retested with an OGTT.

Among the 14 women with PCOS and impaired glucose tolerance at
baseline, 29 percent progressed to diabetes.

Prevalence of impaired glucose tolerance and diabetes in women with
polycystic ovary syndrome, Diabetes Care. 1999, Department of
Medicine, University of Chicago, Illinois, USA.
 PCOS
is a risk factor for endometrial carcinoma.
 The basis of the risk is multifactorial:


arise from the combined effects of unopposed
estrogens on the endometrium, caused by chronic
oligo-anovulation
and progesterone resistance, obesity,
hyperinsulinemia, and hyperandrogenism.

Polycystic ovary syndrome and endometrial cancer, Semin Reprod Med. 2008, University
Department of Obstetrics and Gynaecology, Royal Free and University College Medical
School, University College London, London, United Kingdom.

Polycystic ovary syndrome increases the risk of endometrial cancer in women aged less
than 50 years: an Australian case-control study, Cancer Causes Control. 2010, School of
Population Health, The University of Queensland, Herston Road, Herston, QLD 4006,
Australia.

Progesterone Resistance in PCOS Endometrium: A Microarray Analysis in Clomiphene
Citrate-Treated and Artificial Menstrual Cycles, J Clin Endocrinol Metab. 2011,
Department of Obstetrics and Gynecology, Greenville Hospital System, Greenville, South
Carolina .

There is a high frequency of PCOS and
metabolic syndrome among immediate relatives
of individuals with PCOS.
 According


to one study,
approximately one-half of sisters of PCOS have an
elevated serum testosterone level,
and half of these in turn have menstrual irregularity
and thus meet NIH criteria for PCOS .

Evidence for a genetic basis for hyperandrogenemia in polycystic ovary
syndrome, Proc Natl Acad Sci U S A. 1998 Department of Obstetrics and
Gynecology, Pennsylvania State University College of Medicine, Hershey, PA
17033, USA.
 In

another study,
¼ of sisters met Rotterdam criteria for PCOS,
having hyperandrogenism and a polycystic ovary,
although menses were ovulatory .

Ovarian morphology is a marker of heritable biochemical traits in
sisters with polycystic ovaries, J Clin Endocrinol Metab. 2008, Institute
of Reproductive and Developmental Biology, Imperial College
London,UK.
 Treatment
for PCOS in adolescents is
directed at the following clinical
manifestations:

Menstrual irregularity

Cutaneous hyperandrogenism, primarily hirsutism
and acne .

Obesity and insulin resistance.
 Menstrual
irregularity should be treated in
adolescents with PCOS:

chronic anovulation increases the risk of
developing endometrial hyperplasia, which is
associated with endometrial carcinoma.

Anemia can result from dysfunctional uterine
bleeding or menorrhagia.
 the
first-line treatment.
 OCPs
induce regular menstrual periods with a
higher degree of reliability than other forms
of treatment.
Progestin
• Inhibits endometrial
hyperplasia.
proliferation
,
preventing
Estrogen
• inhibits the activity of the hypothalamic-pituitarygonadal axis,
• reducing ovarian androgen production as well as
increasing (SHBG) levels.
• decreased concentrations of unbound testosterone.
• OCP will normalize androgen levels within 18 - 21
days

Norgestimate:



a potent progestin with low androgenic effect and is
combined with ethinyl estradiol: 35 mcg (in Ortho-TriCyclen®).
It is especially useful for patients with associated
acne vulgaris, for which it has received (FDA)
approval.
There is variable absorption of this medication, and
adjustment of dose may be necessary.
•
Ethynodiol diacetate:



a progestin of low androgenic potential,
is combined with ethinyl estradiol: 35 or 50 mcg (in
Zovia® 1/35-28 or 1/50-28, respectively).
The 1/50 preparation is useful for patients who require
a large dose of estrogen, such as those with obesity or
dysfunctional uterine bleeding.

After three months,

the efficacy of treatment is assessed by evaluating
clinical symptoms and androgen levels.

If the treatment is effective, as a general rule, OCPs
should be continued until the patient is gynecologically
mature (five years postmenarcheal) or has lost a
substantial amount of excess weight.

At that point, withholding treatment for a few months
to allow recovery of suppression of pituitary-gonadal
function and to ascertain whether the menstrual
abnormality is persistent is advisable.

In doing so, however, one must keep in mind that the
anovulatory cycles of PCOS lead to relative infertility,
not absolute infertility.
 If
treatment is not successful in reducing
androgen levels,
the patient either has an unusually prominent
component of functional adrenal
hyperandrogenism to the PCOS,
OR
 the diagnosis of PCOS should be questioned.

Limitations :
The role of OCPs in the management of PCOS in
adolescents may be limited for several reasons:

may make weight loss more difficult to attain because it
promotes salt and water retention.
 OCPs do not permit conception if and when it is desired.
 In perimenarcheal girls with short stature who have open
epiphyses, OCPs are contraindicated because OCPs contain
growth-inhibitory amounts of estrogen.
 Concerns have been raised that the incompletely mature
adolescent neuroendocrine system may have heightened risk
for post-pill amenorrhea and infertility [6]. However, this
hypothetical concern is based on observations in other patient
groups undergoing treatment with high-dose estrogens during
adolescence, and its relevance to girls with PCOS is unclear.


Oestrogen treatment to reduce the adult height of tall girls: long-term effects on fertility,
Lancet. 2004, Menzies Research Institute, University of Tasmania, Private Bag 23, Hobart
7001, Australia
 Other
risks of OCPs are similar in adolescents
with PCOS to those without PCOS.
 There is a risk of venous thromboembolism
with use of OCPs that is primarily related to
the dose and duration of estrogen use,
although third generation progestins such as
drospirenone confer about a twofold
independent risk for first-time users .


Risk of non-fatal venous thromboembolism in women using oral
contraceptives containing drospirenone compared with women using
oral contraceptives containing levonorgestrel: case-control study using
United States claims data, BMJ. 2011, Boston Collaborative Drug
Surveillance Program, Boston University , USA.
Hormonal contraception and risk of venous thromboembolism: national
follow-up study, BMJ. 2009, Gynaecological Clinic, Rigshospitalet,
Copenhagen University, Denmark.
Menstrual irregularities in sexually mature
adolescents often can be controlled with
cyclic progestin alone.
 Transient reduction in androgen levels is
variably achieved during cyclic therapy, but
this is insufficient to expect improvement in
hirsutism or hirsutism equivalents .


Effect of oral micronized progesterone on androgen levels in women
with polycystic ovary syndrome, Fertil Steril. 2002, Department of
Obstetrics and Gynecology The University of Alabama at Birmingham,
USA.
 Micronized
progesterone (Prometrium®, 100
to 200 mg given orally at bedtime) or
 medroxyprogesterone acetate (Provera®, 10
mg given orally at bedtime) can be used for 7
to 10 days out of each month or cycle.
There is considerable controversy about the
efficacy and safety of glucocorticoid therapy
for PCOS .
 Glucocorticoid therapy does not result in
consistent ovulation in patients with PCOS,
even in those with a prominent component
of functional adrenal hyperandrogenism .


Ovulation after glucocorticoid suppression of adrenal androgens in the
polycystic ovary syndrome is not predicted by the basal
dehydroepiandrosterone sulfate level, J Clin Endocrinol Metab. 1999,
Department of Obstetrics/Gynecology, The University of Alabama at
Birmingham, USA

used rarely in lieu of OCPs to regulate
menstrual cyclicity or suppress ovarian
function in the unusual patient who cannot
tolerate OCPs and for whom progestins do
not suffice.
 GnRH
therapy is generally not recommended
in adolescents younger than 16 years of age
because of concerns regarding bone mineral
accrual.
 Patients
who receive GnRH agonist therapy
also should be treated with low-dose
physiologic estradiol and cyclic progestin
add-back therapy (eg, 100 mcg estradiol
transdermal patch) to maintain vaginal
lubrication and to ensure bone mineral
accrual if used during adolescence.
 Bone mineral density should be monitored
during therapy.

Hyperandrogenism is clinically manifested in
2/3 of cases by hirsutism or equivalent
cutaneous findings including acne vulgaris,
pattern alopecia, seborrhea, hyperhidrosis,
and hidradenitis suppurativa.
 Hirsutism
can be treated by cosmetic and
dermatologic measures, and/or by medical
endocrinologic therapy.
 Shaving
 Eflornithine
hydrochloride cream (Vaniqa®)
 is a topical agent that is FDA approved for the removal
of unwanted facial hair in women.
 Laser
therapy
 removes hair permanently by thermal destruction of the

dermal papilla.
FDA-approved devices will permanently reduce hair
density by 30 % or more with three to four treatments of
a site.
The goal of endocrinologic therapy is to
decrease the effect of excess androgens by:
Reducing their production
 Reducing serum free androgen levels by
increasing androgen binding to plasma-binding
proteins
 Blocking androgen action at the level of target
organs (eg, hair follicle)


effective in typical PCOS patients in whom functional ovarian
hyperandrogenism is the predominant source of androgen excess.

The 2008 Endocrine Society Guidelines suggest oral
contraceptives (OCP) as the first-line drug for pharmacologic
therapy.

OCPs lower serum free testosterone levels mainly by decreasing
ovarian production via suppression of serum gonadotropin levels
and increasing sex hormone binding globulin (SHBG) levels.

They also modestly lower dehydroepiandrosterone (DHEA) sulfate
levels.

The use of OCPs prevents further transformation of vellus to
terminal hairs that occurs with androgen exposure.
 In
most patients with PCOS, treatment with
OCPs can be expected to arrest progression
of hirsutism, reduce the need for shaving by
about half, and improve acne within 3 M.
 It
is reasonable to check androgen levels
after three months of therapy to determine
that androgen levels are lowered, as
expected in typical PCOS.

The OCP preparation selected should have
minimal androgenic activity.

the combination of norgestimate/ethinyl
estradiol has FDA approval for the treatment of
acne vulgaris.

A comparison of controlled trials for the
treatment of acne suggested drospirenone and
norgestimate (ethynodiol diacetate was not
included) were beneficial in the treatment of
severe facial acne.

Selecting an oral contraceptive agent for the treatment of acne in women,
Am J Clin Dermatol. 2004, Department of Dermatology, University Medical
Center , The Netherlands.

Antiandrogenic therapy, inhibits binding of androgen
to its receptor, required if there is to be substantial
improvement of hirsutism.

The 2008 Endocrine Society Clinical Guidelines on
hirsutism suggest adding an antiandrogen in patients
taking OCPs who feel that their cosmetic response is
suboptimal after six months.

Although there is considerable individual variation,
antiandrogenic therapy reduces hirsutism by onethird, on average.

Antiandrogens act by inhibiting the androgeninduced transformation of vellus to terminal hairs
 Antiandrogens
should be prescribed with an
OCP because they may cause menstrual
disturbance and their potential teratogenic
feminization of the male fetus.
 Antiandrogens have only a modest effect on
the metabolic abnormalities associated with
PCOS.

Treatment of hirsutism, hyperandrogenism, oligomenorrhea,
dyslipidemia, and hyperinsulinism in nonobese, adolescent girls, J Clin
Endocrinol Metab. 2000, Endocrinology Unit, Hospital Sant Joan de Déu,
University of Barcelona, Spain

The antiandrogens include the following:

Spironolactone :






probably is the safest and most potent antiandrogen available in the
United States .
the recommended choice for antiandrogen therapy.
It lowers hirsutism by approximately 1/3, which is demonstrated by a
decrease in the hirsutism score using the Ferriman-Gallwey system .
starting with 100 mg twice a day until maximal effect has been achieved
and then reducing the dose to 50 mg twice a day for maintenance
therapy as tolerated.
Administered in these doses, spironolactone usually is well tolerated,
but fatigue and hyperkalemia may limit its usefulness.
Laboratory testing of electrolytes and liver function tests should be
performed one to two weeks after initiation of spironolactone therapy.

A prospective randomized trial comparing finasteride to spironolactone in the treatment of hirsute
women., J Clin Endocrinol Metab. 1995, Department of Obstetrics and Gynecology, University of Southern
California , USA.

Cyproterone acetate:
is a progestin with antiandrogenic activity that is effective for the treatment of hirsutism.

Iavailable as a combination OCP containing ethinyl estradiol and low-dose
cyproterone acetate (5 mg) (Diane®).


Flutamide:
is a more specific antiandrogen with efficacy similar to that of cyproterone.
 Its use has been limited by the risk of fatal hepatocellular toxicity.

The 2008 Endocrine Society Guidelines suggest against the routine use of flutamide because
of its potential hepatotoxicity, expense, and the availability of other effective antiandrogens.


Finasteride:


interferes with androgen action by competitively inhibiting 5α-reductase, type
1.
It has seemed slightly less effective than spironolactone in some studies on the
treatment of women with hirsutism. However, metaanalysis of the limited
available data has not shown a significant difference in efficacy between these
treatments .

Clinical review: Antiandrogens for the treatment of hirsutism: a systematic review and metaanalyses of randomized
controlled trials., J Clin Endocrinol Metab. 2008, Knowledge and Encounter Research Unit, Mayo Clinic College of
Medicine, USA

The treatment of obesity improves ovulation,
acanthosis nigricans, androgen excess, and
cardiovascular risk in patients with PCOS.

Weight reduction is indicated in obese patients
with PCOS as part of a program to reduce
cardiovascular risk factors .

Diet and exercise are the first-line treatment
for obese adolescents with PCOS as for obese
individuals without PCOS.


Polycystic ovary syndrome in adolescence, Endocrinol Metab Clin North Am.
2005, Department of Pediatrics, The University of Chicago Pritzker School of
Medicine, USA
Assessment of cardiovascular risk and prevention of cardiovascular disease in
women with the polycystic ovary syndrome, J Clin Endocrinol Metab. 2010,
Oklahoma University Health Sciences Center, Oklahoma City, USA.
Obesity is of major importance in the
insulin resistance of PCOS,
 Insulin-resistant hyperinsulinism is an
important extrinsic factor in the
pathogenesis of PCOS and its complications.
 As a result, lowering the insulin levels in
adolescents with PCOS may be beneficial.


The main known biochemical action of metformin is to
reduce insulin levels primarily by directly inhibiting
hepatic glucose output.

It tends to suppress appetite and enhance weight loss.

In adolescents with PCOS, metformin is used as an
adjunct to management of obesity and the related
insulin-resistant metabolic abnormalities.

Its effectiveness is minimized in the absence of weight
control , which may be why insulin levels are
inconsistently lowered in treated patients .

Effects of metformin on insulin secretion, insulin action, and ovarian
steroidogenesis in women with polycystic ovary syndrome, J Clin Endocrinol Metab.
1997, Department of Medicine, University of Chicago,USA.
 Thiazolidinediones
increase insulin sensitivity
primarily by promoting lipid mobilization
from the bloodstream via activation of
peroxisome-proliferator-related receptors .

Thiazolidinediones, N Engl J Med. 2004, Division of Diabetes,
Department of Medicine, University of Helsinki, Finland
 Troglitazone,:

the initial thiazolidinedione, decreased androgen
levels in women with PCOS but has been
withdrawn from the market in the United States
and the United Kingdom because of the risk of
hepatotoxicity.

Pioglitazone:
is the safest of the newest generation of
thiazolidinediones that are FDA approved for
treatment of type 2 diabetes mellitus.
 In small, randomized trials, this class of drugs
appears to increase ovulation and decrease androgen
levels.
 Unfortunately, these drugs also increase weight gain.
Although pioglitazone is less toxic than troglitazone, a
few cases have been reported of pioglitazone-induced
reversible hepatic toxicity.
 Pioglitazone has been withdrawn from the market in
France and Germany because of an association with
bladder cancer.

 Polycystic
ovary syndrome is the most
common cause of anovulatory symptoms and
hyperandrogenism in women and can present
during adolescence.
 Recognizing
and treating PCOS in adolescents
is important beyond management of the
presenting symptoms because PCOS increases
the risk of developing infertility, endometrial
hyperplasia and carcinoma, type 2 diabetes
mellitus, metabolic syndrome, and possibly
cardiovascular disease.

PCOS is currently defined as otherwise
unexplained hyperandrogenism (eg, hirsutism,
persistent acne, pattern alopecia), and ovarian
dysfunction manifest as either menstrual
irregularity (eg, oligo- or amenorrhea, irregular
bleeding) or polycystic ovaries.

In adolescents, we suggest using the NIH
diagnostic criteria: otherwise unexplained
hyperandrogenism (eg, hirsutism, persistent
acne, pattern alopecia) and menstrual
irregularity (eg, oligo- or amenorrhea, irregular
bleeding).
 Once
a diagnosis of PCOS has been
established, it is important to identify and
monitor for abnormal glucose tolerance and
other features of the metabolic syndrome
because PCOS is a risk factor for the early
development of type 2 diabetes mellitus and
metabolic syndrome, and their associated
morbidity.
 Immediate family members are also at risk
for these metabolic dysfunctions.
 Several
treatment options are available for
adolescents with PCOS .

The choice of therapy depends on the
individual adolescent's symptoms, her goal
for treatment, and preferences .
 We
suggest the use of combination oral
contraceptives as first-line treatment for
adolescents who suffer the menstrual and
cutaneous symptoms of PCOS (Grade 2B).
 If
the adolescent patient is unable or
unwilling to take combination OCP, other
therapeutic options for menstrual
irregularities include progestin alone, lowdose glucocorticoid therapy, and
gonadotropin releasing (GnRH) agonist
therapy with add-back estrogen.
 We suggest that hirsutism initially be treated
by cosmetic and physical measures (Grade
2B).

We suggest that OCPs be the initial
pharmacologic agents used in treating patients
with hirsutism who fail to respond adequately to
cosmetic and dermatologic measures (Grade 2C).

For substantial improvement, we suggest adding
spironolactone, which should only be used in
combination with OCPs (Grade 2B).

Weight loss in obese adolescents with PCOS
improves ovulation, acanthosis nigricans, and
hyperandrogenemia.
 Insulin-lowering
agents improve ovulation in
about half of cases, and modestly reduce
androgen levels .
 They are not as effective as OCPs in
controlling menstrual cyclicity or hirsutism.
 Metformin is the only one of these agents
that we use in adolescents with PCOS, and is
used as an adjunct to weight-control
measures and to treat co-existent insulinresistant metabolic abnormalities.