AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Stein and Leventhal were first to recognize an association between the presence of polycystic ovaries and signs of hirsutism and amenorrhea (eg, oligomenorrhea, obesity). After women diagnosed with Stein-Leventhal syndrome underwent successful wedge resection of the ovaries, their menstrual cycles became regular, and they were able to conceive. As a consequence, a primary ovarian defect was thought to be the main culprit, and the disorder came to be known as polycystic ovarian disease. Further biochemical, clinical, and endocrinologic studies revealed an array of underlying abnormalities; hence, the condition is now referred to as polycystic ovary syndrome (PCOS), though it may occur in women without ovarian cysts.

Pathophysiology

Women with PCOS have abnormalities in the metabolism of androgens and estrogen and in the control of androgen production. High serum concentrations of androgenic hormones, such as testosterone, androstenedione, and dehydroepiandrosterone sulfate (DHEA-S), may be encountered in these patients. However, individual variation is considerable, and a particular patient might have normal androgen levels.

PCOS is also associated with peripheral insulin resistance and hyperinsulinemia, and obesity amplifies the degree of both abnormalities. Insulin resistance in PCOS can be secondary to a postbinding defect in insulin receptor signaling pathways, and elevated insulin levels may have gonadotropin-augmenting effects on ovarian function.

A proposed mechanism for anovulation and elevated androgen levels suggests that, under the increased stimulatory effect of luteinizing hormone (LH) secreted by the anterior pituitary, stimulation of the ovarian theca cells is increased. In turn, these cells increase the production of androgens (eg, testosterone, androstenedione). Because of a decreased level of follicle-stimulating hormone (FSH) relative to LH, the ovarian granulosa cells cannot aromatize the androgens to estrogens, and this inability leads to decreased estrogen levels and consequent anovulation. Growth hormone (GH) and insulin-like growth factor-1 (IGF-1) may also augmenting effect on ovarian function.

Hyperinsulinemia is also responsible for dyslipidemia and for elevated levels of plasminogen activator inhibitor-1 (PAI-1) in patients with PCOS. An elevated PAI-1 levels is a risk factor for intravascular thrombosis.

Polycystic ovaries are enlarged bilaterally and have a smooth thickened capsule that is avascular. On cut sections, subcapsular follicles in various stages of atresia are seen in the peripheral part of the ovary. The most striking ovarian feature of PCOS is hyperplasia of the theca stromal cells surrounding arrested follicles. On microscopic examination, luteinized theca cells are seen.

Frequency

United States

PCOS is one of the most common endocrine disorders of women in the reproductive age group, with a prevalence of 4-12%.

International

In various European studies, the prevalence of PCOS was 6.5-8%.

Sex

PCOS occurs in women only.

Age

PCOS affects mostly women of reproductive age.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

Patients with PCOS may present with various clinical features.

• Menstrual abnormalities
• • Patients have abnormal menstruation patterns attributed to chronic anovulation.
  • Some women have oligomenorrhea (menstrual bleeding that occurs at intervals of 35 d to 6 mo, with <9 menstrual periods per y) or secondary amenorrhea (an absence of menstrual for 6 mo). Dysfunctional uterine bleeding and infertility are the other consequences of anovulatory menstrual cycles.
  • The menstrual irregularities in PCOS usually manifest around the time of menarche.
• Hyperandrogenism
• • Hyperandrogenism clinically manifests as excess terminal body hair in a male distribution pattern. Hair is commonly seen on the upper lip, chin, around the nipples, and along the linea alba of the lower abdomen.
  • Some patients have acne and/or male-pattern hair loss (androgenic alopecia).
  • A few patients may also have increased muscle mass, deepening voice, and/or clitoromegaly due to excessive androgens.
• Infertility
• • A subset of women with PCOS are infertile.
  • Most women with PCOS ovulate intermittently. Conception may take longer than in other women, or women with PCOS may have fewer children than they had planned.
• Obesity
• • Obesity is present in nearly half of all women with PCOS.
  • A study comparing the body mass index (BMI) in American and Italian women with PCOS showed that American women had a BMI higher than that of their Italian counterparts.
• Diabetes mellitus: Approximately 10% of women with PCOS have type 2 diabetes mellitus, and 30-40% of women with PCOS have impaired glucose tolerance by the age of 40 years.
• Sleep apnea: Many women with PCOS have obstructive sleep apnea syndrome. These patients have excessive daytime somnolence and have apnea/hypopnea episodes during sleep.
• Acanthosis nigricans: Patients with PCOS may have dark, pigmented skin on the nape of their neck, skin folds, knuckles, and/or on elbows.
• Metabolic syndrome
• • In women, metabolic syndrome is characterized by abdominal obesity (waist circumference > 35 in.), dyslipidemia (triglyceride level >150 mg/dL, high-density lipoprotein cholesterol [HDL-C] level < 50 mg/dL), elevated blood pressure, a proinflammatory state characterized by an elevated C-reactive protein level, and a prothrombotic state characterized by elevated PAI-1 and fibrinogen levels.
  • Numerous patients with PCOS have characteristics of metabolic syndrome. A recent study showed a 43% prevalence of metabolic syndrome in women with PCOS.
  • Women with PCOS have increased prevalence of coronary artery calcification and a thickened carotid intima media, which may be responsible for subclinical atherosclerosis.

Physical

Physical examination findings are notable for the findings described below.

• Hirsutism: Patients may have excessive body hair in a male distribution pattern and acne. Some patients have virilizing signs, such as male-pattern balding or alopecia, increased muscle mass, deepening voice, or clitoromegaly; these findings should prompt a search for other causes of hyperandrogenism.
• Obesity: Approximately 50% of women with PCOS have abdominal obesity characterized by a waist circumference of greater than 35 in (>88 cm).
• Acanthosis nigricans: This is a diffuse, velvety thickening and hyperpigmentation of the skin. It may be present at the nape of the neck, axillae, area beneath the breasts, intertriginous areas, and exposed areas (eg, elbows, knuckles). In patients with PCOS, acanthosis nigricans is thought to be the result of insulin resistance.
• Blood pressure: Patients with signs and symptoms of metabolic syndrome may have elevated blood pressure with a systolic blood pressure of 130 mm Hg or higher and diastolic blood pressure of 85 mm of Hg or higher.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Ovarian hyperthecosis
Congenital adrenal hyperplasia (late-onset)
Androgen-producing tumors of the ovary and adrenals
Drugs (eg, danazol, androgenic progestins)

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• An expert conference sponsored by National Institute of Child Health and Human Disease (NICHD) of the United States National Institutes of Health (NIH) proposed following criteria for the diagnosis of PCOS:
• • Oligo-ovulation or anovulation manifested by oligomenorrhea or amenorrhea
  • Hyperandrogenism (clinical evidence of androgen excess) or hyperandrogenemia (biochemical evidence of androgen excess)
  • Exclusion of other disorders that can result in menstrual irregularity and hyperandrogenism
• The European Society for Human Reproduction and Embryology (ESHRE) and the American Society for Reproductive Medicine (ASRM) recommended that at least 2 of the following 3 features are required for PCOS to be diagnosed:
• • Oligo-ovulation or anovulation manifested as oligomenorrhea or amenorrhea
  • Hyperandrogenism (clinical evidence of androgen excess) or hyperandrogenemia (biochemical evidence of androgen excess)
  • Polycystic ovaries (as defined on ultrasonography)
• The diagnosis of PCOS requires the exclusion of all disorders that can result in menstrual irregularity and hyperandrogenism. Polycystic ovaries are defined as 12 or more follicles in at least 1 ovary measuring 2-9 mm in diameter or a total ovarian volume of >10 cm³.
• PCOS is a diagnosis of exclusion, and biochemical and/or radiologic studies must be done to ascertain the diagnosis.
• • Androgen excess can be tested by checking for testosterone levels. An elevated free testosterone level is a sensitive indicator of androgen excess.
  • Levels of sex hormone-binding globulin (SHBG) are usually low in patients with PCOS.
  • Other androgens, such as dehydroepiandrosterone-sulfate (DHEA-S), may be normal or slightly above the normal range in patients with PCOS.
• A serum hCG level should be checked to rule out pregnancy in women with oligomenorrhea or amenorrhea.
• Patients with androgen-secreting ovarian or adrenal tumors can present with hirsutism, amenorrhea, and signs of virilization. However, these tumors are rapidly progressive, and patients have high androgen levels. Their testosterone level may be higher than 150 ng/dL, and their DHEA-S level may be greater than 800 mcg/dL.
• Late-onset congenital adrenal hyperplasia due to 21-hydroxylase deficiency can be ruled out by measuring serum 17-hydroxyprogesterone levels after a cosyntropin stimulation test. A 17-hydroxyprogesterone level of less than 1000 ng/dL, as measured 60 minutes after cosyntropin stimulation, rules out late-onset congenital adrenal hyperplasia.
• Cushing syndrome can be ruled out by checking a 24-hour urine sample for free cortisol and creatinine. Levels of urinary free cortisol that are 4-fold the upper limit of normal are diagnostic for Cushing syndrome.
• Hyperprolactinemia can be excluded by checking a fasting serum prolactin concentration.
• Because the prevalence of impaired glucose tolerance and type 2 diabetes mellitus is high in women with PCOS, a 75-g oral glucose-tolerance test (OGTT) can be performed. A 2-hour postload glucose value of less than 140 mg/dL indicates normal glucose tolerance, a value of 140-199 mg/dL indicates impaired glucose tolerance, and a value of 200 mg/dL or higher indicates diabetes mellitus.
• The fasting lipid profile is often abnormal and shows elevated triglyceride and low-density lipoprotein cholesterol (LDL-C) levels and a decreased HDL-C level.
• • Blood work should be done to assess the level of thyroid-stimulating hormone (TSH) to rule out hypothyroidism, and the FSH level should be checked to rule out primary ovarian failure.
  • A serum IGF-1 level should be checked to rule out acromegaly. Serum IGF-1 is a sensitive and specific marker of GH excess. Normal levels rule out GH excess.

Imaging Studies

• Ovarian ultrasonography, preferably accomplished by using a transvaginal approach, can be performed to assess ovarian morphology.
• Polycystic ovaries are defined as 12 or more follicles in at least 1 ovary measuring 2-9 mm in diameter or a total ovarian volume of >10 cm³.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

Medical management is aimed at the treatment of metabolic derangements, anovulation, hirsutism, and menstrual irregularity.

• Metabolic derangements
• • Diet and exercise: In patients with PCOS who are obese, endocrine-metabolic parameters markedly improve after 4-12 weeks of dietary restriction. Their SHBG levels rise and free testosterone levels fall by 2-fold. Serum insulin and IGF-1 levels also decrease. Weight loss in patients with PCOS who are obese is associated with a reduction of hirsutism and a return of ovulatory cycles in 30% of women. A moderate amount of daily exercise increases of levels of IGF-1 binding protein and decreases IGF-1 levels by 20%. Modest weight loss of 2-5% of total body weight can help restore ovulatory menstrual periods in obese patients with PCOS. A daily 500-1000 calorie deficit with 150 minutes of exercise per week can cause ovulation.
  • Metformin: This is an antidiabetic drug that improves insulin resistance and decrease hyperinsulinemia in patients with PCOS. Ascertain that kidney and liver function are normal and that the patient does not have advanced congestive heart failure before starting metformin. The usual starting dose is 500 mg given orally twice a day. Common adverse effects are nausea, vomiting, and diarrhea. 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 they have a high likelihood of having ovulatory cycles while taking metformin. of the US Food and Drug Administration has been not approved metformin for this indication; therefore, this use is off label.
• Anovulation
  • Metformin: Metformin therapy resulted in ovulation in 46% of patients compared with placebo. Metformin combined with clomiphene resulted in ovulation in 76% of patients compared with 42% in patients who received clomiphene alone. Metformin also has a small but beneficial effect on metabolic syndrome.
  • Management of infertility: Patients with PCOS who are infertile but who desire pregnancy should be referred to a reproductive endocrinologist for further evaluation and management of infertility.
• Hirsutism
• • Hair removal: Short-term nonpharmacologic treatments of hirsutism include shaving and use of chemical depilatories and/or bleaching cream. Measures like plucking or waxing unwanted hair can be associated with folliculitis and ingrown hairs. Long-term measures include techniques such as electrolysis and laser treatment of unwanted hairs.
  • Weight reduction: Weight reduction decreases androgen production in women who are obese; therefore, losing weight can slow hair growth.
  • Oral contraception: Women who do not wish to become pregnant can be effectively treated for hirsutism with oral contraceptives. 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.
  • Spironolactone: Antiandrogens, such as spironolactone, are effective for hirsutism. Spironolactone 50-100 mg twice daily is an effective primary therapy for hirsutism. Because of its potential teratogenic effects, spironolactone should be prescribed with an oral contraceptive. Adverse effects of spironolactone include GI discomfort, and irregular menstrual bleeding (which can be managed by adding an oral contraceptive).
  • Eflornithine: Eflornithine (Vaniqa) is a topical cream that can be used to slow the hair growth. Eflornithine works by inhibiting ornithine decarboxylase, which is essential for the rapidly dividing cells of hair follicles.
• Menstrual irregularity
  • This is treated with an oral contraceptive, which not only inhibits ovarian androgen production but also increases SHBG production.
  • Pregnancy should be excluded before therapy with oral contraceptives is started.

Surgical Care

Surgical management is aimed mainly at restoring ovulation.

• Ovarian wedge resection: This procedure has fallen out of favor because of postoperative adhesion formation and the introduction of ovulation-inducing medications.
• Laparoscopic surgery: 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. Potential complications include formation of adhesions and ovarian atrophy.

Consultations

• An endocrinologist should be consulted for follow-up evaluations of biochemical and metabolic derangements.
• A reproductive endocrinologist should be consulted if the patient is infertile and desires pregnancy.

Diet

• Women who have impaired glucose tolerance should start a comprehensive program of diet and exercise to reduce their risk of developing diabetes mellitus.
• Obese women with PCOS can benefit from a low-calorie diet for weight reduction.
• Women with abnormal lipid profile need to be counseled on ways to manage the dyslipidemia. Such ways 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.

Activity

• Encourage moderate physical activity in these patients, provided they have no contraindications to vigorous physical activity.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Drugs used in the treatment of PCOS include metformin (off-label use), spironolactone, eflornithine (topical cream to treat hirsutism), and oral contraceptives. Oral contraceptives containing a combination of estrogen and progestin increase SHBG levels and thereby reduce the free testosterone level. LH and FSH levels are also suppressed. This effect restores cyclic exposure of the endometrium to estrogen-progestin, with the resumption of menstrual periods and decreased hirsutism. The use of oral contraceptives may be associated with an increased risk of thrombosis and metabolic abnormalities.

An oral contraceptive containing ethinyl estradiol and a progestin with minimal androgenic activity, such as norgestimate, norethindrone, or desogestrel, should be selected. Ethinyl estradiol combined with drospirenone (Yasmin) has a progestin that acts as an antiandrogen and thus has added antiandrogenic effects.

Withdrawal bleeding can be induced with medroxyprogesterone (Provera) given for 5-10 days before the start of oral contraceptive therapy.

Drug Category: Hypoglycemic agents

These agents reduce blood glucose levels.

Drug Category: Antihypertensive agents

Spironolactone has been used to treat hirsutism.

Drug Category: Topical hair-removal agents

Eflornithine cream can be used to treat androgen excess.

Drug Category: Oral contraceptives

These agents reduce the secretion of LH and FSH from the pituitary by decreasing amount of gonadotropin-releasing hormones. 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 SHBG and, therefore, reduce free testosterone. Evidence indicates that high doses of contraceptive progestins may inhibit 5-reductase. Oral contraceptives also decrease production of adrenal androgens, particularly 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 have high SHBG are associated with high total testosterone levels.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Outpatient Care

• Patients need regular follow-up to prevent complications that may result from untreated PCOS.

Complications

• Cardiovascular and cerebrovascular disease: Evidence suggest that these women might be at increased for cardiovascular disease and cerebrovascular disease.
• Type 2 diabetes mellitus: Patients with PCOS have an increased risk of developing diabetes mellitus. Patients who are obese should be screened for glucose intolerance with OGTT with a 75-g glucose load. Measures to prevent diabetes should be adopted if patients are found to have impaired glucose tolerance.
• Endometrial carcinoma: Patients with PCOS are at an increased risk for endometrial hyperplasia and carcinoma. The chronic anovulation in PCOS leads to constant endometrial stimulation with estrogen and without progesterone and increases the risk of endometrial hyperplasia and carcinoma.

Patient Education

• 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 PCOS.
• For excellent patient education resources, visit eMedicine's Women's Health Center. Also, see eMedicine's patient education article Ovarian Cysts, Amenorrhea, and Female Sexual Problems.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Failure to diagnose the PCOS in a timely fashion can jeopardize the patient's health and expose her to complications such as increased morbidity and mortality from diabetes mellitus, endometrial carcinoma, and cardiovascular disease.

Special Concerns

• All other conditions that mimic PCOS should be ruled out before the diagnosis of PCOS is confirmed.
• Pregnancy must be ruled out before oral contraceptive therapy is started.
• Women starting metformin therapy should be informed that such treatment results in ovulatory menstrual cycles and increases the probability of pregnancy. The indications, contraindications, and adverse effects of metformin therapy should be carefully reviewed with the patient before therapy is begun.
• Patients who are having difficulty conceiving should receive an adequate workup to rule out both male and female factors that might contribute to infertility.
• Women taking spironolactone should be given an oral contraceptive. If oral contraception is contraindicated, they should practice another form of contraception.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• ADA. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. Jan 2005;28 Suppl 1:S37-42. [Medline].
• Apridonidze T, Essah PA, Iuorno MJ, Nestler JE. Prevalence and characteristics of the metabolic syndrome in women with polycystic ovary syndrome. J Clin Endocrinol Metab. Apr 2005;90(4):1929-35.
• Asuncion M, Calvo RM, San Millan JL, et al. A prospective study of the prevalence of the polycystic ovary syndrome in unselected Caucasian women from Spain. J Clin Endocrinol Metab. Jul 2000;85(7):2434-8. [Medline].
• Azziz R, Woods KS, Reyna R, et al. The prevalence and features of the polycystic ovary syndrome in an unselectedpopulation. J Clin Endocrinol Metab. Jun 2004;89(6):2745-9.
• Azziz R. The evaluation and management of hirsutism. Obstet Gynecol. May 2003;101(5 Pt 1):995-1007. [Medline].
• Balen AH, Conway GS, Kaltsas G, et al. Polycystic ovary syndrome: the spectrum of the disorder in 1741 patients. Hum Reprod. Aug 1995;10(8):2107-11. [Medline].
• Carmina E, Legro RS, Stamets K, et al. Difference in body weight between American and Italian women with polycystic ovary syndrome: influence of the diet. Hum Reprod. Nov 2003;18(11):2289-93. [Medline].
• Christian RC, Dumesic DA, Behrenbeck T, et al. Prevalence and predictors of coronary artery calcification in women with polycystic ovary syndrome. J Clin Endocrinol Metab. Jun 2003;88(6):2562-8.
• Conway GS, Agrawal R, Betteridge DJ, Jacobs HS. Risk factors for coronary artery disease in lean and obese women with the polycystic ovary syndrome. Clin Endocrinol (Oxf). Aug 1992;37(2):119-25. [Medline].
• Coulam CB, Annegers JF, Kranz JS. Chronic anovulation syndrome and associated neoplasia. Obstet Gynecol. Apr 1983;61(4):403-7. [Medline].
• Cumming DC, Yang JC, Rebar RW, Yen SS. Treatment of hirsutism with spironolactone. JAMA. Mar 5 1982;247(9):1295-8. [Medline].
• Derksen J, Nagesser SK, Meinders AE. Identification of virilizing adrenal tumors in hirsute women. N Engl J Med. Oct 13 1994;331(15):968-73. [Medline].
• Diamanti-Kandarakis E, Kouli CR, Bergiele AT, et al. A survey of the polycystic ovary syndrome in the Greek island of Lesbos: hormonal and metabolic profile. J Clin Endocrinol Metab. Nov 1999;84(11):4006-11. [Medline].
• Donesky BW, Adashi EY. Surgically induced ovulation in the polycystic ovary syndrome: wedge resection revisited in the age of laparoscopy. Fertil Steril. Mar 1995;63(3):439-63. [Medline].
• Dunaif A, Wu X, Lee A, Diamanti-Kandarakis E. Defects in insulin receptor signaling in vivo in the polycystic ovary syndrome(PCOS). Am J Physiol Endocrinol Metab. Aug 2001;281(2):E392-9. [Medline].
• Ehrmann DA, Barnes RB, Rosenfield RL, et al. Prevalence of impaired glucose tolerance and diabetes in women with polycystic ovary syndrome. Diabetes Care. Jan 1999;22(1):141-6. [Medline].
• Farah L, Lazenby AJ, Boots LR, Azziz R. Prevalence of polycystic ovary syndrome in women seeking treatment from community electrologists. Alabama Professional Electrology Association Study Group. J Reprod Med. Oct 1999;44(10):870-4.
• Gopal M, Duntley S, Uhles M, Attarian H. The role of obesity in the increased prevalence of obstructive sleep apnea syndrome in patients with polycystic ovarian syndrome. Sleep Med. Sep 2002;3(5):401-4. [Medline].
• Grundy SM, Brewer HB, Cleeman JI, et al. Definition of metabolic syndrome: Report of the National Heart, Lung, and Blood Institute/American Heart Association conference on scientific issues related to definition. Circulation. Jan 27 2004;109(3):433-8.
• Guido M, Romualdi D, Giuliani M, et al. Drospirenone for the treatment of hirsute women with polycystic ovary syndrome:a clinical, endocrinological, metabolic pilot study. J Clin Endocrinol Metab. Jun 2004;89(6):2817-23.
• Hardiman P, Pillay OC, Atiomo W. Polycystic ovary syndrome and endometrial carcinoma. Lancet. May 24 2003;361(9371):1810-2. [Medline].
• Hoeger K. Obesity and weight loss in polycystic ovary syndrome. Obstet Gynecol Clin North Am. Mar 2001;28(1):85-97, vi-vii. [Medline].
• Hoeger KM, Kochman L, Wixom N, et al. A randomized, 48-week, placebo-controlled trial of intensive lifestyle modification and/or metformin therapy in overweight women with polycystic ovary syndrome: a pilot study. Fertil Steril. Aug 2004;82(2):421-9.
• Huber-Buchholz MM, Carey DG, Norman RJ. Restoration of reproductive potential by lifestyle modification in obese polycysticovary syndrome: role of insulin sensitivity and luteinizing hormone. J Clin Endocrinol Metab. Apr 1999;84(4):1470-4. [Medline].
• Kiddy DS, Hamilton-Fairley D, Bush A, et al. Improvement in endocrine and ovarian function during dietary treatment of obese women with polycystic ovary syndrome. Clin Endocrinol (Oxf). Jan 1992;36(1):105-11. [Medline].
• Knochenhauer ES, Key TJ, Kahsar-Miller M, et al. Prevalence of the polycystic ovary syndrome in unselected black and white womenof the southeastern United States: a prospective study. J Clin Endocrinol Metab. Sep 1998;83(9):3078-82. [Medline].
• Knowler WC, Barrett-Connor E, Fowler SE, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. Feb 7 2002;346(6):393-403. [Medline].
• Legro RS, Kunselman AR, Dodson WC, Dunaif A. Prevalence and predictors of risk for type 2 diabetes mellitus and impaired glucose tolerance in polycystic ovary syndrome: a prospective, controlled study in 254 affected women. J Clin Endocrinol Metab. Jan 1999;84(1):165-9. [Medline].
• Lord JM, Flight IH, Norman RJ. Metformin in polycystic ovary syndrome: systematic review and meta-analysis. BMJ. Oct 25 2003;327(7421):951-3. [Medline].
• Michelmore KF, Balen AH, Dunger DB, Vessey MP. Polycystic ovaries and associated clinical and biochemical features in young women. Clinical Endocrinology. Dec 1999;51(6):779-86.
• NCEP. 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) final report. Circulation. Dec 17 2002;106(25):3143-421.
• Nestler JE, Jakubowicz DJ, Evans WS, Pasquali R. Effects of metformin on spontaneous and clomiphene-induced ovulation in the polycystic ovary syndrome. N Engl J Med. Jun 25 1998;338(26):1876-80. [Medline].
• Nieman LK. Diagnostic tests for Cushing''s syndrome. Ann N Y Acad Sci. Sep 2002;970:112-8. [Medline].
• PCOS Consensus Workshop Group. Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril. Jan 2004;81(1):19-25. [Medline].
• Rittmaster RS. Hirsutism. Lancet. Jan 18 1997;349(9046):191-5. [Medline].
• Stein I, Leventhal M. Amenorrhea associated with bilateralpolycystic ovaries. Am J Obstet Gynecol. 1935;29:181.
• Stein IF. Duration of infertility following ovarian wedge resection. West J Surg. 1964;72:237.
• Stumvoll M, Nurjhan N, Perriello G, et al. Metabolic effects of metformin in non-insulin-dependent diabetes mellitus. N Engl J Med. Aug 31 1995;333(9):550-4. [Medline].
• The Medical Letter. Eflornithine cream for facial hair reduction. Med Lett Drugs Ther. Oct 2 2000;42(1089):96. [Medline].
• Velazquez EM, Mendoza S, Hamer T, et al. Metformin therapy in polycystic ovary syndrome reduces hyperinsulinemia, insulin resistance, hyperandrogenemia, and systolic blood pressure, while facilitating normal menses and pregnancy. Metabolism. May 1994;43(5):647-54. [Medline].
• Vgontzas AN, Legro RS, Bixler EO, et al. Polycystic ovary syndrome is associated with obstructive sleep apnea and daytimesleepiness: role of insulin resistance. J Clin Endocrinol Metab. Feb 2001;86(2):517-20. [Medline].
• Vryonidou A, Papatheodorou A, Tavridou A, et al. Association of hyperandrogenemic and metabolic phenotype with carotid intima-media thickness in young women with polycystic ovary syndrome. J Clin Endocrinol Metab. May 2005;90(5):2740-6.
• Zawadzki JK, Dunaif A. Diagnostic criteria for polycystic ovary syndrome: Towards a rational approach. In Dunaif A, Givens JR, Haseltine FP et al, eds. Current issues in Endocrinolgy and Metabolism. Oxford, UK: Blackwell Scientific; 1992:. 377.

Article Last Updated: Jun 27, 2006