INTRODUCTION The polycystic ovary syndrome (PCOS) is an important cause of both

menstrual irregularity and androgen excess in women. When fully expressed, the

manifestations include irregular menstrual cycles, hirsutism, obesity, insulin resistance, and

anovulatory infertility.

The treatment of PCOS will be reviewed here. The epidemiology and pathogenesis, diagnostic

criteria, and clinical manifestations of PCOS are described in detail separately.

(See "Epidemiology and pathogenesis of the polycystic ovary syndrome in

adults" and "Diagnosis of polycystic ovary syndrome in adults" and "Clinical manifestations of

polycystic ovary syndrome in adults".)

OVERVIEW OF APPROACH Women with polycystic ovary syndrome (PCOS) have multiple

abnormalities that require attention, including oligomenorrhea, hyperandrogenism, anovulatory

infertility, and metabolic risk factors such as obesity, insulin resistance, dyslipidemia, and

impaired glucose tolerance. Weight loss, which can restore ovulatory cycles and improve

metabolic risk, is the first-line intervention for most women. Our overall approach is similar to

that described by the 2013 Endocrine Society Clinical Guidelines [1].

Goals The overall goals of therapy of women with PCOS include:

Amelioration of hyperandrogenic symptoms (hirsutism, acne, scalp hair loss)

Management of underlying metabolic abnormalities and reduction of risk factors for type

2 diabetes and cardiovascular disease

Prevention of endometrial hyperplasia and carcinoma, which may occur as a result of

chronic anovulation

Contraception for those not pursuing pregnancy, as women with oligomenorrhea ovulate

intermittently and unwanted pregnancy may occur

Ovulation induction for those pursuing pregnancy

Lifestyle changes We suggest diet and exercise for weight reduction as the first step for

overweight and obese women with PCOS. Available evidence suggests that lifestyle

interventions (diet, exercise, and behavioral interventions) are more effective than minimal

treatment for weight loss and for improving insulin resistance and hyperandrogenism [2].

(See 'Weight reduction' below.)

Oral contraceptives and risk assessment Oral contraceptives (OCs) are the mainstay of

pharmacologic therapy for women with PCOS for managing hyperandrogenism and menstrual

dysfunction and for providing contraception. OCs are associated with an increased risk of

venous thromboembolism (VTE) in all users, but particularly in obese women. There have been

concerns that the presence of PCOS per se may represent an additional independent risk factor

for VTE, but available data do not support this concept. (See "Clinical manifestations of

polycystic ovary syndrome in adults", section on 'Venous thromboembolism'.)

Our approach to the use of OCs in women with PCOS is the same as in women without PCOS.

Risk factors for VTE including obesity, patient age, and family history of VTE should be

assessed. We currently suggest using caution if OCs are prescribed to obese women (body

mass index [BMI] 30 kg/m2) over age 40 years, because these women are at particularly high

risk for VTE. Other relative and absolute contraindications to OC use are outlined in the table

(table 1). Alternatives to oral estrogen-progestin contraceptives include cyclic progestin therapy,

continuous progestin therapy (progestin-only OCs [the minipill]), or a progestin-releasing

intrauterine device (IUD). Cyclic progestin therapy can induce regular withdrawal uterine

bleeding and reduce the risk of endometrial hyperplasia. Both continuous progestin therapy (eg,

a progestin-only OC such as norethindrone 0.35 mg/day) and the progestin-releasing IUD

provide contraception and reduce the risk of endometrial hyperplasia. (See"Risks and side

effects associated with estrogen-progestin contraceptives", section on 'Venous thromboembolic

disease' and 'Endometrial protection' below.)

WOMEN NOT PURSUING PREGNANCY

Menstrual dysfunction

Endometrial protection The chronic anovulation seen in polycystic ovary syndrome (PCOS)

is associated with an increased risk of endometrial hyperplasia and possibly endometrial

cancer. (See "Clinical manifestations of polycystic ovary syndrome in adults", section on

'Endometrial cancer risk' and "Endometrial carcinoma: Epidemiology and risk factors", section

on 'Chronic anovulation'.)

We suggest combined estrogen-progestin contraceptives as first-line therapy for menstrual

dysfunction and endometrial protection.

Combined estrogen-progestin contraceptives provide a number of benefits in women with

PCOS, including:

Daily exposure to progestin, which antagonizes the endometrial proliferative effect of

estrogen

Contraception in those not pursuing pregnancy, as women with oligomenorrhea ovulate

intermittently and unwanted pregnancy may occur

Cutaneous benefits for hyperandrogenic symptoms (see 'Androgen excess' below)

OCs affect insulin sensitivity, carbohydrate metabolism, and lipid metabolism; the effects

depend upon the estrogen dose and androgenicity of the progestin. However, there is no

evidence that women with PCOS are at greater risk for either metabolic adverse effects or

cardiovascular complications of OCs. (See 'Metabolic effects of OCs in PCOS' below and "Risks

and side effects associated with estrogen-progestin contraceptives" and "Clinical manifestations

of polycystic ovary syndrome in adults", section on 'Venous thromboembolism'.)

Absence of pregnancy should be documented before OCs are begun.

An approach to starting OCs in women with PCOS is described below (see 'Choice of oral

contraceptive' below). Risks and side effects of OCs (including breakthrough bleeding) are

similar to those for women without PCOS. Breakthrough bleeding and an overview of estrogen-

progestin OCs are reviewed in detail separately. (See"Risks and side effects associated with

estrogen-progestin contraceptives" and "Overview of the use of estrogen-progestin

contraceptives".)

For women with PCOS who choose not to or cannot take OCs, alternative treatments for

endometrial protection are intermittent or continuous progestin therapy, or a progestin-releasing

intrauterine device (IUD) [3]. In this setting, we recommend medroxyprogesterone acetate (5 to

10 mg) for 10 to 14 days every one to two months. An alternative, but one that has been less

well studied, is natural micronized progesterone 200 mg (given for the same duration every one

to two months). Patients should be made aware that progestin therapy alone will not reduce the

symptoms of acne or hirsutism, nor will it provide contraception. However, continuous progestin

therapy with norethindrone 0.35 mg daily provides both contraception and endometrial

protection. This is a progestin-only OC that is also referred to as the minipill. An alternative

progestin option that provides both endometrial protection and contraception are the

levonorgestrel-releasing IUDs. (See "Intrauterine contraception (IUD): Overview", section on

'Levonorgestrel-releasing IUDs'.)

Metformin is a potential alternative to restore menstrual cyclicity, as it restores ovulatory menses

in approximately 30 to 50 percent of women with PCOS [4,5]. Its ability to provide endometrial

protection is less well established, and we therefore consider it to be second-line therapy [6,7].

(See "Metformin for treatment of the polycystic ovary syndrome".)

When metformin is used, we suggest monitoring to confirm that ovulatory cycles have been

established. This can be done with luteal phase serum progesterone measurements or

transvaginal ultrasound. (See "Evaluation of the menstrual cycle and timing of ovulation",

section on 'Detection of ovulation' and "Metformin for treatment of the polycystic ovary

syndrome", section on 'Oligomenorrhea'.)

Androgen excess

Hirsutism Our approach to the management of hirsutism is consistent with the 2008

Endocrine Society Clinical Practice Guidelines on Hirsutism, which suggest an estrogen-

progestin contraceptive as first-line pharmacologic therapy for most women [8]. In addition, the

2013 Endocrine Society Clinical Practice Guidelines on the Diagnosis and Treatment of

Polycystic Ovary Syndrome also suggest OCs as first-line therapy for menstrual irregularities

and hirsutism [1]. An antiandrogen is then added after six months if the cosmetic response is

suboptimal (see "Treatment of hirsutism" and "Use of combination estrogen-progestin

contraceptives in the treatment of hyperandrogenism and hirsutism"). OCs and an antiandrogen

may sometimes be started simultaneously at the outset, particularly when the cutaneous

manifestations are particularly bothersome to the patient.

For women with hirsutism and contraindications to OCs, we sometimes

use spironolactone alone, but an alternative form of contraception is essential because, if

pregnancy occurs, an antiandrogen such as spironolactone could prevent development of

normal external genitalia in a male fetus. Spironolactone alone does not regularize menstrual

cycles, and in fact, is sometimes associated with menstrual irregularities. Therefore, in women

using spironolactone as monotherapy for hyperandrogenism, progestin therapy is often needed.

(See "Treatment of hirsutism", section on 'Antiandrogen therapy' and 'Endometrial

protection' above.)

Choice of oral contraceptive We typically start with an OC containing 20 mcg of ethinyl

estradiol combined with a progestin with minimal androgenicity (such as norgestimate). Other

progestins with minimal androgenicity or antiandrogenic properties include desogestrel and

drospirenone, but both have been associated with a possible higher risk of venous

thromboembolism (VTE) (table 2). OCs containing one of the original progestins, norethindrone

or norethindrone acetate, are also good options; while they are not as low in androgenicity, they

have not been associated with excess VTE risk. (See "Risks and side effects associated with

estrogen-progestin contraceptives", section on 'Type of progestin'.)

Higher doses of ethinyl estradiol (30 to 35 mcg) are needed in some women for optimal

suppression of ovarian androgens and management of hyperandrogenic symptoms. Although

transdermal or vaginal ring preparations are potential options, they have not been well studied

for the management of hirsutism and there are concerns about an excess risk of VTE with both

regimens. (See "Transdermal contraceptive patch", section on 'Risk of thrombotic

events' and "Contraceptive vaginal ring", section on 'Cardiovascular events'.)

Antiandrogens After six months, if the patient is not satisfied with the clinical response to

OC monotherapy (for hyperandrogenic symptoms), we typically addspironolactone 50 to 100

mg twice daily. (See "Treatment of hirsutism", section on 'Antiandrogen therapy'.)

Other antiandrogens that are effective include finasteride and cyproterone

acetate (cyproterone is available in most countries, but not the United States). Flutamide is also

effective, but we recommend not using it because of its potential hepatotoxicity.

(See "Treatment of hirsutism", section on 'Antiandrogen therapy' and "Overview of the use of

estrogen-progestin contraceptives".)

Other Gonadotropin-releasing hormone (GnRH) agonists are also sometimes used to

suppress ovarian androgen production; add-back estrogen-progestin therapy is necessary to

avoid bone loss and estrogen deficiency symptoms. Although this approach is effective, it is

limited by its complexity and cost. (See "Treatment of hirsutism", section on 'GnRH agonist'.)

Although some clinicians use metformin to treat hirsutism, the Endocrine Society Clinical

Practice Guidelines suggest against its routine use as it is associated with minimal or no benefit

and is less effective than treatment with OCs and/or antiandrogens [8]. (See "Metformin for

treatment of the polycystic ovary syndrome", section on 'Hirsutism'.)

Hirsutism can also be treated by removal of hair by mechanical means such as shaving,

waxing, depilatories, electrolysis, or laser treatment. In addition, Vaniqa

(eflornithine hydrochloride cream 13.9%) is a topical drug that inhibits hair growth. It is not a

depilatory and must be used indefinitely to prevent regrowth. (See "Removal of unwanted

hair" and "Treatment of hirsutism", section on 'Nonpharmacologic methods'.)

Acne and androgenetic alopecia The management of acne and scalp hair loss

(androgenetic alopecia) in women with PCOS are reviewed in detail separately.

(See "Treatment of acne vulgaris", section on 'Hormonal therapy' and "Treatment of

androgenetic alopecia in men".)

Metabolic abnormalities

Obesity Weight loss, which can restore ovulatory cycles and improve metabolic risk, is the

first-line intervention for most women. The approach to obesity management is the same as that

for patients without PCOS, starting with lifestyle changes (diet and exercise) [9], followed by

pharmacotherapy, and when necessary, bariatric surgery [10]. (See 'Weight reduction' below

and "Obesity in adults: Overview of management" and "Short-term medical outcomes following

bariatric surgery", section on 'Polycystic ovary syndrome'.)

Weight reduction We suggest weight loss strategies using calorie restricted diets combined

with exercise for women with PCOS and obesity. Although there are no large randomized trials

of exercise-specific interventions, a systematic review of exercise therapy in PCOS concluded

that there may be modest weight loss, and improvements in ovulation and insulin sensitivity

[11]. (See "Obesity in adults: Role of physical activity and exercise", section on 'Exercise plus

diet' and "Obesity in adults: Dietary therapy".)

Even modest weight loss (5 to 10 percent reduction in body weight) in women with PCOS may

result in restoration of normal ovulatory cycles [12-14] and improved pregnancy rates [15] in

short-term studies. However, the response to weight loss is variable; not all individuals have

restoration of ovulation or menses despite similar weight reduction [9,10,16]. In addition, there

are no randomized trials and no long-term data on reproductive or metabolic outcomes with

weight loss.

Weight loss results in a decrease in serum androgen concentrations, and in some instances,

improvements in hirsutism. However, data demonstrating an improvement in hirsutism are

limited [2,9].

There is no good evidence that one type of diet is superior to another for women with PCOS.

Low-carbohydrate diets have become very popular for women with PCOS, based upon the

notion that less carbohydrate leads to less hyperinsulinemia and therefore less insulin

resistance. However, a 12-week study of a high protein/lowcarbohydrate diet (30 percent

protein, 40 percent carbohydrate, 30 percent fat) and a low protein/high carbohydrate diet (15

percent protein, 55 percent carbohydrate, 30 percent fat) were equally effective for weight loss,

improvements in menstrual cyclicity, insulin resistance, dyslipidemia, and abdominal fat in one

study of 28 overweight women with PCOS [17]. It is not known if an extremely low carbohydrate

diet would be any more effective for these endpoints. (See "Obesity in adults: Dietary therapy",

section on 'Low-carbohydrate diets'.)

Bariatric surgery Bariatric surgery is another strategy for weight loss in women with PCOS.

In one study of 17 obese women with PCOS with a mean body mass index (BMI) of

50.7 kg/m2, bariatric surgery was associated with a mean weight loss after 12 months of 41 9

kg, restoration of ovulatory cycles, and improvements in insulin resistance, hyperandrogenemia,

and hirsutism scores [10]. (See "Bariatric operations for management of obesity: Indications and

preoperative preparation" and "Short-term medical outcomes following bariatric surgery",

section on 'Polycystic ovary syndrome'.)

Insulin resistance/type 2 diabetes Several drugs, including biguanides (metformin) and

thiazolidinediones (pioglitazone, rosiglitazone), can reduce insulin levels in women with PCOS.

These drugs may also reduce ovarian androgen production (and serum free testosterone

concentrations) and restore normal menstrual cyclicity [18-21]. (See "Metformin for treatment of

the polycystic ovary syndrome" and "Thiazolidinediones in the treatment of diabetes mellitus".)

Although there had been widespread enthusiasm and use of metformin for a number of

indications in PCOS, clinical data no longer support this approach. A detailed discussion of

metformin use in PCOS is found elsewhere. (See "Metformin for treatment of the polycystic

ovary syndrome".)

Strategies recommended by the American Diabetes Association for prevention of type 2

diabetes are discussed separately. The approach in women with PCOS is the same as for

women without PCOS. (See "Prevention of type 2 diabetes mellitus".)

Thiazolidinediones have been less well studied than metformin, but they appear to improve

insulin sensitivity and hyperandrogenemia [18-24]. However, because of limited clinical data,

potential weight gain, and a possible association with cardiovascular adverse events, we do not

recommend the use of thiazolidinediones in women with PCOS who do not have diabetes.

(See "Thiazolidinediones in the treatment of diabetes mellitus".)

Metabolic effects of OCs in PCOS In healthy women, OC use decreases insulin sensitivity,

but in general, this decrease is not clinically significant [25]. It has been assumed that OC use

would also worsen insulin sensitivity in women with PCOS, although data are conflicting, with

studies showing an improvement [26], worsening [27], or no change [28] in insulin sensitivity.

When compared with metformin, OCs may be less beneficial for insulin sensitivity, but better for

androgen suppression and menstrual cycle control [29]. This topic is reviewed separately.

(See "Metformin for treatment of the polycystic ovary syndrome", section on 'Metabolic effects'.)

There are also theoretical concerns that women with PCOS may be at particular risk for

cardiovascular complications with OCs, given their other underlying cardiovascular risk factors.

However, there are no OC risk data specific to women with PCOS. (See "Risks and side effects

associated with estrogen-progestin contraceptives", section on 'Coronary heart disease'.)

The effects of combination OC-metformin therapy are reviewed elsewhere. (See "Metformin for

treatment of the polycystic ovary syndrome", section on 'Metformin plus oral contraceptives'.)

Dyslipidemia The approach to treatment of dyslipidemia in women with PCOS is the same

as for other patients with dyslipidemia. Exercise and weight loss are the first line approach,

followed by pharmacotherapy, if needed. (See "Statins: Actions, side effects, and

administration".)

Statins Statins are effective for dyslipidemia in women with PCOS, but do not appear to

have other clinically important metabolic or endocrine effects. In a meta-analysis of four trials in

244 women randomly assigned to a statin (simvastatin or atorvastatin) or placebo for 6 to 12

months, statin therapy decreased serum low-density lipoprotein (LDL) and triglycerides, but had

no effect on high-density lipoprotein (HDL), fasting insulin, or C-reactive protein. A small

decrease in serum testosterone was observed, but there were no improvements in menstrual

cycle regularity, ovulation, acne, hirsutism, or BMI [30].

Obstructive sleep apnea Sleep apnea, a common disorder in women with PCOS, is an

important determinant of insulin resistance, glucose intolerance, and type 2 diabetes

(see "Clinical manifestations of polycystic ovary syndrome in adults"). In one report of women

with PCOS and obstructive sleep apnea, treatment with continuous positive airway pressure

(CPAP) improved insulin sensitivity and reduced diastolic blood pressure [31].

Nonalcoholic steatohepatitis The prevalence of nonalcoholic steatohepatitis (NASH)

appears to be increased in women with PCOS. Both weight loss andmetformin use appear to

improve metabolic and hepatic function in these women [32,33]. (See "Clinical manifestations of

polycystic ovary syndrome in adults", section on 'Nonalcoholic fatty liver disease'.)

WOMEN PURSUING PREGNANCY

Ovulation induction It is important to complete a basic evaluation of the couple before

initiating therapy in an infertile woman, including a semen analysis of the male. Weight loss

should always be attempted prior to initiating ovulation induction because ovulation can be

restored with a modest amount of weight loss. If unsuccessful, a multistep approach to ovulation

induction is then undertaken (table 3). (See "Ovulation induction with clomiphene

citrate" and "Strategies for improving the efficacy of clomiphene induction of

ovulation" and "Overview of ovulation induction".)

Weight loss In many overweight and obese women with polycystic ovary syndrome (PCOS),

weight loss alone is often associated with a reduction in serum testosterone concentration,

resumption of ovulation, and pregnancy [12,34,35]. As an example, in one series of 18 obese

women with PCOS treated with a hypocaloric diet, mean weight fell from 77 to 57 kg and mean

plasma testosterone concentration fell from 0.75 to 0.39 ng/mL [34]. Moreover, many women

resumed ovulation after the weight loss.

Another study placed 20 women with PCOS and mean body mass index (BMI) of

32 kg/m2, amenorrhea for greater than three months, and increased plasma concentrations of

androstenedione, testosterone, or dehydroepiandrosterone sulfate on a hypocaloric diet (1000

to 1500 kcal/day) [34]. After weight loss ranging from 4.8 to 15.2 kg (mean 9.7 kg), significant

reductions in the concentration of luteinizing hormone (LH) (45 percent decrease), fasting

insulin (40 percent decrease), and testosterone (35 percent decrease) were observed; most of

the women ovulated, and many of the infertile women became pregnant. Similar results were

reported in a small randomized study [35].

Medications

Clomiphene citrate We suggest clomiphene citrate as first-line therapy for ovulation

induction in non-obese women with PCOS (BMI

Although women with PCOS are not likely gonadotropin-releasing hormone (GnRH)

deficient, pulsatile GnRH is moderately effective for ovulation induction. It is currently

available in Europe but not in the United States. In one study of 41 patients

undergoing 114 ovulation induction cycles, 56 percent of women ovulated, and 40

percent of ovulatory patients achieved pregnancy [42]. Ovulatory cycles were

associated with lower BMI and fasting insulin, and higher baseline serum follicle-

stimulating hormone (FSH) concentrations. Thus, pulsatile GnRH may be a

reasonable option, particularly for lean women with PCOS.

Laparoscopic surgery In the past, wedge resection of the ovaries was a standard treatment

for infertility in women with PCOS. However, this approach has been abandoned, both because

of the efficacy of clomiphene and because of the high incidence of pelvic adhesions seen with

wedge resection. A substitute for wedge resection, laparoscopic ovarian laser electrocautery,

may be effective in some women with PCOS. However, given the other pharmacologic options

for ovulation induction, surgery is not often indicated. The use of laparoscopic surgery for

ovulation induction in PCOS is discussed in detail elsewhere. (See "Laparoscopic surgery for

ovulation induction in polycystic ovary syndrome".)

In vitro fertilization If weight loss, ovulation induction with medications, and/or laparoscopic

ovarian laser electrocautery are unsuccessful, the next step is in vitro fertilization (see "In vitro

fertilization"). Women with PCOS are at increased risk for both multiple gestation and

OHSS. Metformin administration may help to reduce the risk of OHSS in these women.

(See "Metformin for treatment of the polycystic ovary syndrome", section on 'IVF pretreatment'.)

INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials,

The Basics and Beyond the Basics. The Basics patient education pieces are written in plain

language, at the 5th to 6th grade reading level, and they answer the four or five key questions a

patient might have about a given condition. These articles are best for patients who want a

general overview and who prefer short, easy-to-read materials. Beyond the Basics patient

education pieces are longer, more sophisticated, and more detailed. These articles are written

at the 10th to 12th grade reading level and are best for patients who want in-depth information

and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print

or e-mail these topics to your patients. (You can also locate patient education articles on a

variety of subjects by searching on patient info and the keyword(s) of interest.)

Basics topics (see "Patient information: Polycystic ovary syndrome (The Basics)")

Beyond the Basics topics (see "Patient information: Polycystic ovary syndrome (PCOS)

(Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS Regardless of the diagnostic criteria used, the

management of polycystic ovary syndrome (PCOS) includes treatment of individual components

of the syndrome (hirsutism, oligomenorrhea, infertility, obesity, and glucose intolerance),

depending upon the patient's goals.

Weight loss, which can restore ovulatory cycles and improve metabolic risk, is the first-

line intervention for most women. (See 'Overview of approach' above.)

Oral contraceptives (OCs) are the mainstay of pharmacologic therapy for women with

PCOS for managing hyperandrogenism and menstrual dysfunction and for providing

contraception.

Our approach to the use of OCs in women with PCOS is the same as that for women

without PCOS. Risk factors for venous thromboembolism (VTE) including obesity, patient

age, and family history of VTE should be assessed (table 1).

We suggest caution when prescribing OCs in obese women (body mass index [BMI]

30 kg/m2) over age 40 years because of their greater risk of VTE (Grade 2B). Other

relative and absolute contraindications to OC use are outlined in the table (table 1).

(See 'Oral contraceptives and risk assessment' above.)

For hirsutism or other androgenic symptoms, we suggest an OC as the treatment of

choice (Grade 2B). (See 'Androgen excess' above.)

We typically start with a preparation containing 20 mcg of ethinyl estradiol combined with

a progestin with minimal androgenicity (such as norethindrone, norgestimate, desogestrel,

and drospirenone). Higher doses of ethinyl estradiol are needed in some women for

optimal management of hyperandrogenic symptoms. Concerns about VTE risk with newer

progestins and with drospirenone are reviewed separately. (See "Overview of the use of

estrogen-progestin contraceptives"and "Risks and side effects associated with estrogen-

progestin contraceptives", section on 'Type of progestin'.)

If the patient is not satisfied with the clinical response to six months of OC monotherapy

(for hyperandrogenic symptoms), we suggest adding spironolactone(Grade 2B)

(see 'Androgen excess' above). Other options for treating hirsutism are reviewed in detail

elsewhere. (See "Treatment of hirsutism".)

For prevention of endometrial hyperplasia and possibly cancer, we suggest OC therapy

(Grade 2C). (See 'Menstrual dysfunction' above.)

For women with PCOS who choose not to or cannot take OCs, we suggest intermittent

progestin therapy (Grade 2B). (See 'Menstrual dysfunction' above.)

For women with PCOS who desire pregnancy, we first recommend weight loss if the

woman is overweight or obese (Grade 1B). If they are unable to lose weight or modest

weight loss does not restore ovulatory cycles, we suggest initiating ovulation induction

with clomiphene citrate for women with a BMI