Certain lifestyle changes, such as diet and exercise, are considered first-line treatment for

adolescent girls and women with polycystic ovarian syndrome (PCOS). [42] Pharmacologic
treatments are reserved for so-called metabolic derangements, such as anovulation, hirsutism,
and menstrual irregularities. Medications for such conditions include oral contraceptives,
metformin, prednisone, leuprolide, clomiphene, and spironolactone.
Mean platelet volume (MPV) is a marker associated with adverse cardiovascular events, and
women with newly diagnosed PCOS appear to have significantly elevated MPV levels. [48] Kabil
Kucur et al reported that use of ethinyl estradiol/cyproterone acetate or metformin for the
treatment of women with PCOS seemed to have similar beneficial effects in reducing MPV.[48]
Consultation with an endocrinologist is necessary for performing an adrenocorticotropic hormone
(ACTH) stimulation test or for other causes of menstrual irregularity such as thyroid disease or
pituitary adenoma. A reproductive endocrinologist should be consulted if the patient is infertile and
desires pregnancy.[49]
In October 2013, the Endocrine Society released practice guidelines for the diagnosis and
treatment of PCOS. The following were among their conclusions [50] :

Use the Rotterdam criteria for diagnosing PCOS (presence of 2 of the following:
androgen excess, ovulatory dysfunction, or polycystic ovaries).
In adolescents with PCOS, hyperandrogenism is central to the presentation; hormonal
contraceptives and metformin are treatment options in this population.
Postmenopausal women do not have a consistent PCOS phenotype.
Exclude alternate androgen-excess disorders and risk factors for cardiovascular disease,
diabetes, endometrial cancer, mood disorders, and obstructive sleep apnea.
For menstrual abnormalities and hirsutism/acne, hormonal contraceptives are first-line
treatment.
For infertility, clomiphene is first-line treatment.
For metabolic/glycemic abnormalities and for improving menstrual irregularities,
metformin is beneficial.
Metformin is of limited or no benefit for managing hirsutism, acne, or infertility.
Overall, thiazolidinediones have an unfavorable risk-benefit ratio.
More investigation is needed to determine the roles of weight loss and statins in PCOS.

Lifestyle Modifications
The American College of Obstetricians and Gynecologists (ACOG) and the Society of
Obstetricians and Gynaecologists of Canada (SOGC) indicate that lifestyle modifications such as
weight loss and increased exercise in conjunction with a change in diet consistently reduce the
risk of diabetes. This approach has been found to be comparable to or better than treatment with
medication and should therefore be considered first-line treatment in managing women with
polycystic ovarian syndrome (PCOS).[3, 4] These modifications have been effective in restoring
ovulatory cycles and achieving pregnancy in obese women with PCOS. Weight loss in obese
women with PCOS also improves hyperandrogenic features.

DRUG TREATMENT
Medical management of PCOS is aimed at the treatment of metabolic derangements, anovulation,
hirsutism, and menstrual irregularity. The use of insulin-sensitizing drugs to improve insulin
sensitivity is associated with a reduction in circulating androgen levels, as well as improvement in

both the ovulation rate and glucose tolerance. [4] The Endocrine Society has published a clinical
practice guideline on hirsutism evaluation and treatment in premenopausal women. [51]ACOG notes
that eflornithine in conjunction with laser treatment is superior to laser therapy alone in treating
hirsutism.[4]
First-line medical therapy usually consists of an oral contraceptive to induce regular menses. The
contraceptive not only inhibits ovarian androgen production but also increases sex hormonebinding globulin (SHBG) production. ACOG recommends use of combination low-dose hormonal
contraceptive agents for long-term management of menstrual dysfunction. [4] If symptoms such as
hirsutism are not sufficiently alleviated, an androgen-blocking agent may be added. Pregnancy
should be excluded before therapy with oral contraceptives or androgen-blocking agents is
started.
First-line treatment for ovulation induction when fertility is desired is clomiphene citrate. [3, 4,
6]
Second-line strategies may be equally effective in infertile women with clomiphene citrate
resistant PCOS.
A randomized study suggested that combined metformin/letrozole and bilateral ovarian drilling are
similarly effective as second-line treatment in infertile women with clomiphene citrateresistant
PCOS.[52] In this study, 146 patients were given metformin and letrozole, and 73 underwent bilateral
ovarian drilling. There was significant reduction in testosterone, fasting insulin, and ratio of fasting
glucose to fasting insulin in the metformin/letrozole group. There was significant reduction in
follicle-stimulating hormone (FSH), luteinizing hormone (LH), and ratio of LH to FSH in the bilateral
drilling group. There was no significant difference between the patients in the 2 groups regarding
cycle regularity, ovulation, pregnancy rate, and abortion rate. [52]
Another study, a double-blind trial by Legro et al, found that letrozole is more effective than
clomiphene in the treatment of infertility in PCOS. Based on treatment periods of up to five cycles,
the study, which involved 750 anovulatory women with PCOS, found that the birth rates for
letrozole and clomiphene were 27.5% and 19.1%, respectively. The rate of congenital
abnormalities and the risk of pregnancy loss in the letrozole and clomiphene groups were found to
be comparable, although the likelihood of twin births was lower with letrozole. [53, 54]
Metformin
If the patient develops type 2 diabetes mellitus, consider treatment with oral antihyperglycemic
drugs, such as metformin. Metformin can also be considered in other women with PCOS who are
insulin resistant and therefore at risk of developing cardiovascular disease, even women without
type 2 diabetes.
Clinical trials have shown that metformin can effectively reduce androgen levels, improve insulin
sensitivity, and facilitate weight loss in patients with PCOS as early as adolescence. [55, 56, 57, 58] One
study concluded that the use of metformin throughout pregnancy was associated with a 9-fold
decrease in gestational diabetes in women with PCOS. [59] In addition to having the potential to
reduce gestational diabetes in pregnant women with PCOS, metformin may also reduce the risk of
preeclampsia in this population.[60]
A long-term study suggested that metformin continued to improve the metabolic profile of women
with PCOS over a 36-month treatment course, particularly improving circulating high-density
lipoprotein cholesterol (HDL-C), diastolic blood pressure, and body mass index (BMI). [61] However,
data are insufficient as yet to recommend metformin to all women with PCOS.
Other agents

If the patient has concomitant adrenal hyperandrogenism, treatment with low-dose prednisone or
dexamethasone may be considered.
Depot leuprolide acetate (Lupron) is effective in suppressing ovarian hormone production, which
effectively induces menopause; therefore, this drug must be accompanied by hormone
replacement therapy. This treatment approach has not gained widespread favor.
Several medications, including benzoyl peroxide, topical retinoids (Retin-A), and topical and oral
antibiotics, are effective for acne treatment. Systemic isotretinoin is used for severe or refractory
cases.

FDA SAVETY ALERT

Statins
On March 1, 2012, the US Food and Drug Administration (FDA) updated health care professionals
regarding changes to the prescribing information concerning interactions between protease
inhibitors (drugs for management of human immunodeficiency virus [HIV] and hepatitis B infection)
and certain statin drugs. The combination of these drugs may raise the blood levels of statins and
increase the risk for myopathy. Rhabdomyolysis, the most serious form of myopathy, can cause
kidney damage and lead to kidney failure, which is life threatening. [62]
On February 28, 2012, the FDA approved important safety label changes for the class of
cholesterol-lowering drugs known as statins, including removal of routine monitoring of liver
enzymes. Information about the potential for generally nonserious and reversible cognitive side
effects and reports of increased blood glucose and glycosylated hemoglobin (HbA1c) levels was
added to the statin labels. In addition, extensive contraindication and dose-limitation updates were
added to the lovastatin label in situations when this drug is taken with certain medications that can
increase the risk for myopathy.[63]
On June 8, 2011, the FDA notified health care professionals of its recommendations for limiting the
use of the highest approved dose (80 mg) of the cholesterol-lowering medication simvastatin
(Zocor) because of increased risk of muscle damage. The FDA required changes to the
simvastatin label to add new contraindications (should not be used with certain medications) and
dose limitations for using simvastatin with certain medications.[64]

Sibutramine
On October 8, 2010, Abbott Laboratories and the FDA notified health care professionals and
patients about the voluntary withdrawal of the obesity drug sibutramine (Meridia) from the US
market because of clinical trial data indicating an increased risk of heart attack and stroke. [65]

METABOLIC DERANGEMENT
In patients with polycystic ovarian syndrome (PCOS) who are obese, endocrine-metabolic
parameters markedly improve after 4-12 weeks of dietary restriction. Their sex hormonebinding
globulin (SHBG) levels rise, and free testosterone levels fall by 2-fold. [66] Serum insulin and insulinlike growth factor-1 (IGF-1) levels also decrease. In patients with PCOS who are obese, weight
loss is associated with a reduction of hirsutism and a return of ovulatory cycles in 30% of women,
thereby improving pregnancy rates, as well as improving glucose tolerance and lipid levels. [13, 4]

The Androgen Excess and Polycystic Ovary Syndrome Society recommends lifestyle
management as the primary therapy for metabolic complications in overweight and obese women
with PCOS.[67] A moderate amount of daily exercise increases levels of IGF-1 binding protein and
decreases levels of IGF-1 by 20%. Modest weight loss of 2-5% of total body weight can help
restore ovulatory menstrual periods in obese patients with PCOS. A decrease of 500-1000 calories
daily, along with 150 minutes of exercise per week, can cause ovulation.
Metformin, an antidiabetic drug, improves insulin resistance and decreases hyperinsulinemia in
patients with PCOS.[68] This drug also has a small but beneficial effect on metabolic syndrome, as
well as potentially causing a modest reduction in androgen levels (11%). [5] Note that women with a
body mass index (BMI) greater than 37 kg/m2 may not have a good response to metformin.[5] An
Italian study of 33 patients with PCOS demonstrated that metformin affected thyroid hormone by
lowering thyroid-stimulating hormone (TSH) in hypothyroid patients with PCOS, regardless of
whether these individuals received levothyroxine or were untreated. [69]
Ascertain that kidney and liver function are normal and that the patient does not have advanced
congestive heart failure before starting metformin therapy. The usual starting dose is 500 mg given
orally twice a day. Because common adverse effects are nausea, vomiting, and diarrhea,
metformin should be taken with meals. Patients who develop these adverse effects can be
instructed to decrease the dosage to once a day for a week and then gradually increase the
dosage. Also, inform patients that there is a high likelihood that they will have ovulatory cycles
while taking metformin. The US Food and Drug Administration (FDA) has not approved metformin
for this indication.

ANOVULATION
The American College of Obstetricians and Gynecologists (ACOG) and Society of Obstetricians
and Gynaecologists of Canada (SOGC) recommend clomiphene citrate as first-line therapy to
stimulate ovulation when fertility is desired.[3, 4, 6]
Second-line therapy, when clomiphene citrate fails to lead to pregnancy, is either exogenous
gonadotropins or laparoscopic ovarian surgery.[3, 4] If gonadotropins are used, a low-dose regimen
is recommended,[4] and patients must be monitored with ultrasonography and laboratory studies.
[3]
Note that gonadotropin therapy is expensive and is associated with an increased risk of multiple
pregnancy and ovarian hyperstimulation syndrome. [3]
Evidence suggests that metformin frequently, but not universally, improves ovulation rates and
pregnancy rates in women with polycystic ovarian syndrome (PCOS), especially in obese women.
[3, 4, 70]
In addition, pretreatment with metformin has been shown to enhance the efficacy of
clomiphene for inducing ovulation.[71] Consider the combination of metformin and clomiphene in
older women with visceral obesity and clomiphene resistance. [3] However, this combination doesnt
significantly improve the live birth rate relative to clomiphene monotherapy.[3] Whether short-course
metformin pretreatment (less than 4 weeks) is as effective as conventional long-course metformin
remains uncertain.[6, 72]
A study found that N-acetylcysteine may enhance the effect of clomiphene citrate in inducing
ovulation in patients with PCOS.[73]
Patients with PCOS who are infertile but desire pregnancy should be referred to a reproductive
endocrinologist for further evaluation and management of infertility. Morbidly obese women with
PCOS should also be referred for pregnancy risk [3] ; metabolic surgery may be considered in
morbidly obese women with PCOS, because many features of this syndrome are reversible with

successful weight loss.In vitro fertilization (IVF) is reserved for women with PCOS and
unsuccessful gonadotropin therapy or those with other indications for this procedure. [3]

HIRSUTISM
A clear primary treatment for hirsutism in women with polycystic ovarian syndrome (PCOS)
remains lacking.[4] However, short-term, nonpharmacologic treatments of hirsutism include shaving
and the use of chemical depilatories and/or bleaching cream. [74] Plucking or waxing unwanted hair
can result in folliculitis and ingrown hairs. Long-term, more permanent measures for unwanted
hairs include electrolysis and laser treatment.
Adjunctive eflornithine with laser treatment is superior to laser therapy alone in treating hirsutism.
[4]
Eflornithine (Vaniqa) is a topical cream that can be used to slow hair growth. This agent works by
inhibiting ornithine decarboxylase, which is essential for the rapidly dividing cells of hair follicles.
Weight reduction decreases androgen production in women who are obese; therefore, losing
weight can slow hair growth.
Women who do not wish to become pregnant can be effectively treated for hirsutism with oral
contraceptives.[75] Oral contraceptives slow hair growth in 60-100% of women with
hyperandrogenemia. Therapy can be started with a preparation that has a low dose of estrogen
and a nonandrogenic progestin. Preparations that have norgestrel and levonorgestrel should be
avoided because of their androgenic activity. There is also a risk of thrombotic events in obese
women who use oral contraceptives; therefore, the proper precautions should be exercised to
prevent such events. Oral contraceptives containing cyproterone acetate are also very effective in
the treatment of more severe hirsutism[76] ; however, this combination of agents has not been
approved by the FDA for use in the United States.
Antiandrogens, such as spironolactone, are effective for hirsutism. [77]Spironolactone (50-100 mg
twice daily) is an effective primary therapy for hirsutism. Because of the potential teratogenic
effects of spironolactone, patients require an effective form of contraception (eg, an oral
contraceptive). Adverse effects of spironolactone include gastrointestinal discomfort and irregular
menstrual bleeding, which can be managed by adding an oral contraceptive.
Ovulation induction with clomiphene citrate, metformin, or both does not alter hirsutism in infertile
hirsute women with PCOS.[78]

DIET AND ACTIVITY

Patients with polycystic ovarian syndrome (PCOS) who have impaired glucose tolerance should
start a comprehensive program of diet and exercise to reduce their risk of developing diabetes
mellitus. Encourage moderate physical activity, provided the patient has no contraindications.
Discourage smoking because of the increased risk of cardiovascular disease. In addition, obese
women with PCOS can benefit from a low-calorie diet for weight reduction.
A diet patterned after the type 2 diabetes diet has been recommended for PCOS patients. [79] This
diet emphasizes increased fiber; decreased refined carbohydrates, trans fats, and saturated fats;
and increased omega-3 and omega-9 fatty acids. However, in some obese patients with PCOS,
weight loss has improved menstrual regularity.[80] Omega-3 fatty acid supplementation has been
shown to reduce liver fat content and other cardiovascular risk factors in women with PCOS,
including those with hepatic steatosis, although these effects have not yet been proven to
translate into a reduction in cardiometabolic events. [81]

Women with an abnormal lipid profile should be counseled on ways to manage the dyslipidemia.
Such measures include eating a diet low in cholesterol and saturated fats and increasing physical
activity. Guidelines from the Third Report of the National Cholesterol Education Program (NCEP)
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult
Treatment Panel III, or ATP III) (2001) serve as a guide for the treatment of women with PCOS
and dyslipidemia. The NCEP is currently updating the ATP III guidelines; Readers are encouraged
to check the National Health Lung and Blood Institute Web site for the most recent
guidelines:http://www.nhlbi.nih.gov/guidelines/cholesterol/atp4/index.htm.
Accumulating evidence suggests an association of vitamin D deficiency with metabolic syndrome.
One study found insufficient levels of 25-hydroxyvitamin D (< 30 ng/mL) in almost 75% of PCOS
patients, with lower levels in those with metabolic syndrome (17.3 ng/mL) than in those without
metabolic syndrome (25.8 ng/mL).[82]

SURGICAL INTERVENTION
Surgical management of polycystic ovarian syndrome (PCOS) is aimed mainly at restoring
ovulation. Ovarian wedge resection has fallen out of favor because of postoperative adhesion
formation and the successful introduction of ovulation-inducing medications.
Various laparoscopic methods, including electrocautery, laser drilling, and multiple biopsy, have
been used with the goal of creating focal areas of damage in the ovarian cortex and stroma.
According to the Society of Obstetricians and Gynaecologists of Canada (SOGC), laparoscopic
ovarian drilling may be considered in women with clomiphene-resistant PCOS, especially in the
presence of other laparoscopic indications.[3] A small French study also suggested that surgical
management via ovarian drilling with hydrolaparoscopy may be beneficial in cases of PCOS that
are resistant to clomiphene citrate.[83]
Potential complications must be considered as well. These include formation of adhesions and
ovarian atrophy. Multiple pregnancy rates are lower with ovarian drilling than with gonadotropin
treatment (1% vs 16%, respectively), but there are ongoing concerns about the long-term effects
of ovarian drilling on ovarian function.[84]

LONG TERM MONITORING

Polycystic ovarian syndrome (PCOS) is a disease with many long-term complications. Patients
need regular follow-up with their physicians for early detection and management of any untoward
sequelae associated with the syndrome (see Prognosis).
Women with PCOS who conceive are at increased risk for gestational diabetes, preeclampsia,
cesarean delivery, and preterm and postterm delivery. In addition, their newborns are at increased
risk of being large for gestational age, but they are not at increased risk of stillbirth or neonatal
death.[85]
Participation in a peer support group may alleviate distress and improve self-management. [86]

Hypoglycemic Agents
Class Summary
These agents reduce blood glucose levels.

Metformin (Glucophage, Glumetza, Riomet, Fortamet)

Metformin reduces insulin resistance; it is an insulin sensitizer. Hepatic glucose output is
decreased and peripheral, insulin-stimulated uptake is increased. Metformin may also decrease
TSH levels in hypothyroidism patients with polycystic ovarian syndrome (PCOS), regardless of
whether they are treated with thyroxine or not (off-label use).

Insulin (Humulin, Novolin)

Insulin is effective when metformin cannot control hyperglycemia. Several short-acting and longacting dosage forms are available. Insulin must be initiated in conjunction with dietary assessment
and nutritional management by a registered clinical dietitian as part of an overall weightmanagement system. Insulin is seldom indicated as a first-line agent for PCOS, unless a patient
also has a diagnosis of diabetes.

ADULT
Type 2 Diabetes Mellitus
Monotherapy or with sulfonylurea
Immediate-release tablet or solution

Initial: 500 mg PO q12hr or 850 mg PO qDay with meals; increase q2Weeks

Maintenance: 1500-2550 mg/day PO divided q8-12hr with meal
No more than 2550 mg/day
Extended-release
Glucophage XR: 500 mg PO qDay with dinner; titrate by 500 mg/day qWeek; no more
than 2000 mg/day
Fortamet: 500-1000 mg PO qDay; titrate by 500 mg/day qWeek; no more than 2500
mg/day
Glumetza: 1000 mg PO qDay; titrate by 500 mg/day qWeek; no more than 2000 mg/day

Type 2 Diabetes Prevention (Off-label)

850 mg PO qDay
Target dosing: 850 mg PO q12hr

Dosing Modifications
Hepatic impairment: Avoid use; risk of lactic acidosis
Renal impairment

Males: Contraindicated if serum creatinine 1.5 mg/dL

Females: Contraindicated if serum creatinine 1.4 mg/dL

PEDIATRIC
Type 2 Diabetes Mellitus
Immediate-release (10-16 years)

Initial: 500 mg PO q12hr

Maintenance: Titrate qWeek by 500 mg; no more than 2000 mg/day in divided doses

Immediate-release (17 years)

Initial: 500 mg PO q12hr or 850 mg PO qDay with meals; increase q2Weeks

Maintenance: 1500-2550 mg/day PO divided q8-12hr with meal
No more than 2550 mg/day
Extended-release (<17 years)

Safety and efficacy not established

Extended-release (17 years)

Glucophage XR: 500 mg PO qDay with dinner; titrate by 500 mg/day qWeek; not to
exceed 2000 mg/day
Fortamet: 500-1000 mg PO qDay; titrate by 500 mg/day qWeek; not to exceed 2500
mg/day

Polycystic Ovary Syndrome (Orphan)

Orphan designation for treatment of pediatric polycystic ovary syndrome
Sponsor

EffRx Pharmaceuticals SA; Wolleraustrass 41 B; 8807 Freienbach (SZ); SWITZERLAND

GERIATRIC
Elderly patients are more likely to have decreased renal function; contraindicated in patients with
renal impairment, carefully monitor renal function in the elderly and use with caution as age
increases
Not for use in patients >80 years unless normal renal function establishedInitial and maintenance
dosing of metformin should be conservative in patients with advanced age due to the potential for
decreased renal function in this population
Controlled clinical studies of metformin did not include sufficient numbers of elderly patients to
determine whether they respond differently from younger patients

Antiandrogens
Class Summary
Antiandrogen agents block androgen receptors, thereby inhibiting the effects of male sex
hormones. These agents may be used to treat hirsutism in women with PCOS.

Spironolactone (Aldactone)
Spironolactone is an antiandrogen agent that is a nonspecific androgen-receptor blocker. It may
be used in conjunction with oral contraceptive pills to treat hirsutism by reducing hair diameter.
Initiate oral contraceptive pills first to avoid worsening of menstrual irregularities and to prevent
pregnancy, because spironolactone may have feminizing effects on the male fetus. Periodically
assess adverse effects (eg, fluid and electrolyte abnormalities). Spironolactone is also used as a
potassium-sparing diuretic.
ADULT

Primary Hyperaldosteronism
As a diagnostic agent

Long test: 400 mg PO qDay for 3-4 weeks

Short test: 400 mg PO qDay for 4 days
Short-term perioperative treatment for adrenalectomy
Initial: 100-400 mg PO qDay in preparation for surgery
Maintenance: Lowest effective dose individualized for patient

Edematous Conditions
Cirrhosis of the liver with edema and/or ascites; nephrotic syndrome
Initial: 100 mg qDay or divided q12hr for 5 days; if no clinical response, add second diuretic with
more specific mechanism of action
Range: 25-200 mg PO qDay or divided q12hr

Essential Hypertension
Initial: 25-100 mg PO qDay or divided q12hr for >2 weeks; adjust to patient response

Congestive Heart Failure

Indicated for NYHA class II/IV heart failure (provided CrCl >30 mL/min and serum K <5 mEq/dL)
Initial: 25 mg PO qDay
Range: 12.5-25 mg/day PO; may increase to 50 mg/day if needed; if 25 mg/day not tolerated,
reduce to 25 mg every other day
ACC/AHA guidelines recommend aldosterone antagonist to be added to an ACEI or ARB, plus a
beta blocker; patient conditions may also require additional medications (eg, loop diuretics,
hydralazine, nitrates, digoxin)

Hypokalemia
Range: 25-100 mg PO qDay

Hirsutism (Off-label)
Women with hirsutism
50-200 mg PO qDay or divided q12hr

Acne (Off-label)
Females with hormonal acne
50-200 mg PO qDay or divided q12hr

Dosing Modifications
Renal impairment

CrCl 50 mL/min/1.73 m: 12.5-25 mg qDay; use maintenance dose of 25 mg qDay or

q12hr after 4 weeks of treatment with potassium 5 mEq/L
CrCl 30-49 mL/min/1.73 m: 12.5 mg qDay or every other day; use maintenance dose of
12.5-25 mg qDay after 4 weeks of treatment with potassium 5 mEq/L

CrCl <30 mL/min/1.73 m: Avoid use

Overdose Management
May use normal saline for volume replacement
May use dopamine or norepinephrine to treat hypotension
Treat hyperkalemia with IV glucose (dextrose 25% in water), concurrently with rapid-acting insulin
and IV sodium bicarbonate; oral/rectal solutions of Kayexalate in sorbitol can be used if needed
If dysrhythmia due to decreased K+ or Mg+ suspected, replace aggressively
Discontinue treatment if no symptoms after 6 hr

Leuprolide (Lupron, Eligard)

Leuprolide is not a first-line agent in PCOS and therefore is not used often for this syndrome. This
agent suppresses ovarian and testicular steroidogenesis by decreasing luteinizing hormone (LH)
and follicle-stimulating hormone (FSH) levels. Gonadotropin-releasing hormone (GnRH) analogs
with oral contraceptive pills are an option to consider for hirsutism in women who fail to respond to
combined therapy with spironolactone and oral contraceptive pills. Anatomic effects of androgens
(eg, clitoromegaly and deepening of the voice) are not responsive to GnRH analogs.

Finasteride (Proscar, Propecia)

Finasteride is a 5-alpha-reductase inhibitor that is approved for use in benign prostatic
hypertrophy and in male-pattern alopecia. This agent blocks conversion of testosterone to its more
active metabolite, dihydrotestosterone. Finasteride tends to be a second-line agent for hirsutism in
PCOS, when hirsutism persists despite the use of first-line agents (ie, oral contraceptives). This
agent is more effective when used in combination with oral contraceptive pills. Due to the potential
for teratogenic effects (eg, risk of genital ambiguity in male fetuses), finasteride therapy must be
used in conjunction with a reliable form of contraception in sexually active women.

Topical Hair-Removal Agents

Class Summary
Eflornithine cream can be used to treat androgen excess.

Eflornithine (Veniqa)
Eflornithine is indicated for the reduction of unwanted facial hair in women. It interferes with
ornithine decarboxylase (needed for hair growth) in skin hair follicles. Eflornithine does not have a
depilatory action; instead, it appears to retard hair growth and improve appearance where applied.
Improvement may be seen in as short a period as 4-8 weeks, although 6 months of treatment may
be required. Keep in mind that in clinical studies, hair returned to its previous condition 8 weeks
after discontinuation of eflornithine (ie, hirsutism may return following discontinuation of
eflornithine).
Note: The use of eflornithine has been studied only on the face and adjacent involved areas under
the chin of individuals with hypertrichosis; therefore, limit use of this drug to these areas. Patients
will likely need other hair-removal methods in conjunction with eflornithine therapy.

ORAL CONTRACEPTIVE

agents reduce the secretion of luteinizing hormone (LH) and

follicle-stimulating hormone (FSH) from the pituitary gland by decreasing the amount of
gonadotropin-releasing hormone (GnRH). All oral contraceptives decrease ovarian androgen
production. By inhibiting gonadotropin secretion and, therefore, tertiary follicle development,
ovarian secretion of testosterone and androstenedione is decreased. All oral contraceptives
increase sex hormone-binding globulin (SHBG) and, therefore, reduce free testosterone. Evidence
indicates that high doses of contraceptive progestins may inhibit 5-alpha reductase. Oral
contraceptives also decrease the production of adrenal androgens, particularly
dehydroepiandrosterone sulfate (DHEA-S).
Different contraceptive preparations have different effects on ovarian androgen production and
SHBG. However, they all reduce levels of free testosterone equally (by approximately 50%). Free
testosterone levels achieved with oral contraceptive preparations are unrelated to the increased
levels of SHBG. Preparations that result in higher SHBG levels also result in higher total
testosterone levels. That is, a decrease in free testosterone level is the same for all oral
contraceptives and, although some of these preparations increase SHBG levels more than others,
this is off-set by a concomitant increase in total testosterone level.
Restoration of regular menstrual cycles prevents endometrial hyperplasia associated with
anovulation. Oral contraceptives also improve acne and hirsutism.

Ethinyl estradiol
Ethinyl estradiol reduces the secretion of LH and FSH from the pituitary by decreasing the amount
of GnRH. Use ethinyl estradiol 30-35 mg combined with any form of progesterone. Restoration of
the regular menstrual cycles prevents endometrial hyperplasia associated with anovulation.
Improvement of hyperandrogenic effects are seen in 60-100% of women, but usually, at least 6-12
months of use are required. Perform a pregnancy test before therapy. If the patient has had no
menstrual period for 3 months, induce withdrawal bleeding with medroxyprogesterone acetate
(Provera) 5-10 mg/day for 10 days; then, begin therapy with oral contraceptives.

Medroxyprogesterone (Depo-Provera, Provera)

Medroxyprogesterone has no effect on androgen production. Progestins stop the proliferation of
endometrial cells, allowing organized sloughing of cells after withdrawal.
SELECTIVE ESTROGEN RESEPTOR MODULATOR
Clomiphene citrate, a selective estrogen receptor modulator, binds to estrogen receptors, inducing
ovulation by increasing the output of pituitary gonadotropins.

Clomiphene citrate (Clomid, Serophene)

Clomiphene acts directly by producing a surge of luteinizing hormone and could cause ovulation
within days.

ADULT
Treatment of Ovulatory Failure
50 mg PO qDay initially for 5 days
If no ovulation, treatment can be repeated as early as 30 days after previous therapy
Dosage can be increased to 100 mg only in patients who do not respond to first course

Monitor
Reassess diagnosis after 3 courses if ovulation has not occurred or if menses does not occur
following ovulatory response

Acne Agents, Topical

Class Summary
Various topical over-the-counter (OTC) and prescription agents are available to treat acne
occurring with polycystic ovarian syndrome (PCOS).

Benzoyl peroxide (Benzac AC Gel, Desquam-X, Benzac AC Wash, BenzEFoam, BPO

Creamy Wash Complete Pack, BPO Foaming Cloth, BPO Gel, Clean and Clear
Advantage 3-in-1 Exfoliating Cleanser, Clean and Clear Continuous Control
Acne Cleanser, Clean and Clear Gel, Clearasil Vanishing Acne Treatment
Cream, Lavoclen-4 Creamy Wash, Lavoclen-8 Creamy Wash, NeoBenz Micro,
NeoBenz Micro SD, NeoBenz Micro Wash, Neutrogena Benzoyl Peroxide
Lotion, Neutrogena Clear Pore Acne Treatment, Neutrogena On-The-Spot Acne
Treatment, Neutrogena Clear Pore Daily Scrub, PanOxyl Acne Cleansing Bar,
PanOxyl Acne Creamy Wash, PanOxyl Acne Foaming Wash, Proactiv, Proactiv
Advanced Blemish Treatment, Proactiv Renewing Cleanser, Proactiv Repairing,
Zapzyt Acne Treatment Gel)
Benzoyl peroxide elicits action by releasing active oxygen; this agent is effective in vitro against
Propionibacterium acnes, an anaerobe found in sebaceous follicles and comedones. Benzoyl
peroxide also elicits a keratolytic and desquamative effect, which may also contribute to its
efficacy.

Tretinoin topical cream 0.020.1%; topical gel 0.010.1%; topical solution 0.05% (Retin
A, Renova, Atralin, Avita, Refissa, Retin-A Micro, Tretin-X)
The exact mechanism of tretinoin is unknown. It appears to decrease cohesiveness of follicular
epithelial cells with a decrease microcomedo formation. This agent also increases turnover of
follicular cells to cause extrusion of comedones.

Adapalene topical cream 0.1%; gel 0.1 and 0.3%; lotion 0.1% (Differin)
Adapalene binds to specific retinoic acid nuclear receptors and modulates cellular differentiation,
keratinization, and inflammatory processes. Its exact mechanism of action for treatment of acne is
unknown.

Erythromycin topical 2% (AkneMycin, Ery)

Although its exact mechanism of action is unknown, erythromycin inhibits protein synthesis in
susceptible organisms by reversibly binding to 50S ribosomal subunits, thereby inhibiting
translocation of aminoacyl transfer-RNA and inhibiting polypeptide synthesis.

Clindamycin topical 1% (Cleocin T, ClindaReach, ClindaDerm, Clindagel, ClindaMax,

Clindets, Evoclin)
Clindamycin is an antibacterial agent that binds to the 50S ribosomal subunits of susceptible
bacteria and prevents elongation of peptide chains by interfering with peptidyl transfer, thereby
suppressing protein synthesis. This agent reduces surface fatty acids on the skin; however, its
exact mechanism of action in treating acne is unknown.

Sodium Sulfacetamide topical 10% (Klaron)

Sodium sulfacetamide is a para-aminobenzoic acid (PABA) inhibitor. This agent restricts folic acid
synthesis that is required for bacterial growth.