eMedicine Specialties > Pediatrics: General Medicine > Endocrinology
Polycystic Ovarian Syndrome
Updated: Oct 21, 2009
Introduction
Background
In 1935, Stein and Leventhal first described the association of polycystic ovaries, amenorrhea, hirsutism, and obesity.1 However, the key features necessary for the diagnosis of polycystic ovarian syndrome (PCOS) were not detailed until 1990 at a conference convened by the National Institutes of Health (NIH). These key features included hyperandrogenism, menstrual dysfunction, and exclusion of other causes of hyperandrogenism (eg, congenital adrenal hyperplasia, androgen-secreting tumors, hyperprolactinemia). Probable criteria included insulin resistance, perimenarchal onset, elevated ratio of luteinizing hormone (LH) to follicle stimulating hormone (FSH) ratio, and polycystic ovaries identified using ultrasonography.
The hyperandrogenic effects observed in polycystic ovarian syndrome most commonly include hirsutism, acne, or androgen-dependent alopecia. Obesity is also common. Endocrine abnormalities include elevated serum concentrations of androgens (particularly testosterone and androstenedione), increased LH levels, and normal or decreased FSH levels. Polycystic ovarian syndrome is also associated with insulin resistance and changes in lipid metabolism. A common mnemonic acronym for the clinical association of hyperandrogenism, insulin resistance, and acanthosis nigricans is the HAIRAN syndrome.
Beyond the NIH criteria of hyperandrogenism and menstrual dysfunction, other manifestations vary; polycystic ovarian syndrome is a clinically, histologically, and biochemically heterogeneous condition. For example, many women with the syndrome do not have evidence of polycystic ovaries. Although earlier descriptions of the syndrome were based on ovarian morphology, approximately 20% of regularly ovulating normal women have polycystic ovaries. Therefore, ovarian morphology is no longer an essential requirement for diagnosis.
Pathophysiology
Major features of polycystic ovarian syndrome include menstrual dysfunction, anovulation, and signs of hyperandrogenism.2 Although the exact etiopathophysiology is unclear, polycystic ovarian syndrome can result from abnormal function of the hypothalamic-pituitary-ovarian (HPO) axis. A key characteristic of polycystic ovarian syndrome is inappropriate gonadotropin secretion, which is more likely a result of, rather than a cause of, ovarian dysfunction. LH levels are tonically elevated throughout the menstrual cycle, whereas FSH levels are within the reference range or low. The LH-to-FSH ratio is often more than 3, and pituitary LH release is exaggerated after exogenous gonadotropin-releasing hormone (GnRH) stimulation.
Androgens such as testosterone, free testosterone, and dehydroepiandrosterone sulfate (DHEAS)may or may not be measurably elevated in the peripheral circulation; however, these hormones and their metabolites account for the physical characteristics of the syndrome. The source of androgens may be from the ovaries, adrenals, or both. Other contributing factors to androgen excess in women with polycystic ovarian syndrome (compared with women who do not have polycystic ovarian syndrome) include an elevated serum level of androstenedione (which is converted within adipose tissue to testosterone) and a greater percentage of unbound active testosterone circulating in the peripheral blood.
In the early phase of the menstrual cycle, circulating estradiol levels in women with polycystic ovarian syndrome are equal to those of normal women. However, mid cycle elevations of estrogen and progesterone that normally occur after ovulation are absent. Because of the lack of cyclical progesterone secretion, the action of estradiol on both the hypothalamic-pituitary axis and the endometrium is unopposed. Both progesterone deficiency and acyclic estrogen production contribute to increased LH release. The effects of unopposed estrogen on the endometrium may cause it to become hyperplastic, which may cause intermittent and heavy uterine bleeding and may increase the long-term risk of endometrial cancer. These effects may be compounded by increased levels of estrone converted from androstenedione in adipose tissue, especially in patients who are obese.
Frequency
United States
Polycystic ovarian syndrome affects approximately 5-7% of premenopausal women.
Mortality/Morbidity
Prolonged, unopposed estrogen stimulation of the endometrium increases the risk of endometrial cancer in patients with polycystic ovarian syndrome. Approximately 40% of patients with polycystic ovarian syndrome have insulin resistance that is independent of body weight. These women are at increased risk for type 2 diabetes mellitus and consequent cardiovascular complications compared with healthy women. Women with hyperandrogenism also have elevated serum lipoprotein levels similar to men, which may increase their risk of cardiovascular disease.
Race
A great deal of ethnic variability in hirsutism is observed. For instance, Asian women have less hirsutism given the same serum androgen values as white women. On the other hand, southern Mediterranean women more often are hirsute.
Sex
Polycystic ovarian syndrome affects females of reproductive age. Studies of family members with polycystic ovarian syndrome indicate that an autosomal dominant mode of inheritance with premature male pattern baldness as the male phenotype may occur.
Age
Polycystic ovarian syndrome affects premenopausal women, and the age of onset is most often perimenarchal (before bone age reaches 16 y). However, clinical recognition of the syndrome may be delayed by failure of the patient to become concerned by irregular menses, hirsutism, or other symptoms or by the overlap of polycystic ovarian syndrome findings with normal physiologic maturation during the 2 years after menarche.
Clinical
History
- Family history
- Hirsutism
- Adrenal enzyme deficiencies
- Menstrual disorders
- Polycystic ovarian syndrome (PCOS)
- Diabetes
- Infertility
- Menstrual disturbance
- The patient usually has a history of menstrual disturbance dating back to menarche. Irregular menses during the initial 2 years after menarche are most often physiologic, requiring no special evaluation. Persistent clinical symptoms beyond this time, especially in the presence of other signs of polycystic ovarian syndrome, warrant further evaluation.
- Because of anovulation or oligo-ovulation, patients may present with amenorrhea, oligomenorrhea, dysfunctional uterine bleeding, or infertility. Menarche may be delayed, and primary amenorrhea, although uncommon, does occur.
- Hyperandrogenism
- Hyperandrogenism presents as hirsutism, acne, and male pattern alopecia.
- Rapid progression of virilization is characteristic of adrenal or ovarian androgen-producing tumors.
- Other signs of hyperandrogenism (eg, clitoromegaly, increased muscle mass, voice deepening) are more characteristic of an extreme form of polycystic ovarian syndrome termed hyperthecosis. These signs and symptoms could also be consistent with androgen-producing tumors, exogenous androgen administration, or virilizing congenital adrenal hyperplasia.
- Premature adrenarche is a common occurrence and, in some cases, may represent a precursor to polycystic ovarian syndrome. Both hirsutism and obesity may be present in premenarchal adolescent girls with polycystic ovarian syndrome.
- Acanthosis nigricans
- Another cutaneous manifestation is acanthosis nigricans.
- Patients may have a dark and thickened area of skin behind the neck and in skin folds. Acanthosis nigricans is staged according to the scoring system below. Among sites where severity is taken into consideration, the neck showed the highest agreement and the least variation between a pediatric endocrinologist's examination (the gold standard) and individual observers, and between the individual observers themselves. Texture should be noted as smooth, rough, or rugated.
- Staging acanthosis (neck severity)
- Absent (0) - Not detectable on close inspection
- Present (1) - Clearly present on close visual inspection, not visible to the casual observer, extent not measurable
- Mild (2) - Limited to the base of the skull, usually does not extend to the lateral margins of the neck
- Moderate (3) - Extends to lateral margins of neck, but not visible anteriorly
- Severe (4) - Visible anteriorly
- Severe (5) - Circumferential
- Obesity
- Obesity, although common, is not universal.
- Obesity is not usually the presenting complaint.
Physical
- Hirsutism: The modified Ferriman-Gallwey score grades 11 body areas from 0 (no hair) to 4 (frankly virile), including the upper lip, chin, chest, upper and lower abdomen, thighs, upper and lower back, arm, forearm, and buttocks. A total score of 8 or more is considered abnormal for an white adult woman; a score of 44 is the most severe.
- Other cutaneous findings
- Acne
- Acanthosis nigricans (marker for insulin resistance)
- Other possible physical examination findings
- Increased upper body mass
- Obesity (increased body mass index >85%)
- Male pattern baldness
- Clitoromegaly
- Enlarged ovaries (not always present): Evaluate for ovarian mass.
- Elevated prolactin levels and galactorrhea
- Endometrial hyperplasia
Causes
- Enzyme abnormality
- The cause is unknown, although some evidence suggests that patients have a functional abnormality of cytochrome P450c17, the 17-hydroxylase, which is the rate-limiting enzyme in androgen biosynthesis.3
- Cytochrome P450c17 is active in the adrenals and ovaries, and excess activity of this enzyme could explain the increased androgen production from both sources in polycystic ovarian syndrome.
- Genetic causes
- Polycystic ovarian syndrome is, in some cases, a familial disorder, but the genetic basis of the syndrome remains unclear. One study revealed evidence of an autosomal dominant mode of inheritance.4
- Full expression of the syndrome may require an insulin abnormality and a defect in androgen biosynthesis, but no gene (or genes) has been identified.
Differential Diagnoses
| 3-Beta-Hydroxysteroid Dehydrogenase
Deficiency | Gigantism and Acromegaly |
| Adrenal Carcinoma | Hyperthyroidism |
| Amenorrhea | Hypothyroidism |
| Congenital Adrenal Hyperplasia | Obesity |
Other Problems to Be Considered
Patients with menstrual disturbances and signs of hyperandrogenism
Idiopathic hirsutism
Late-onset congenital adrenal hyperplasia
Familial hirsutism
Masculinizing tumors of the adrenal or ovary (rapid onset of signs of virilization)
Cushing syndrome (low K+, striae, central obesity, high cortisol; high androgens in adrenal carcinoma)
Hyperprolactinemia
Exogenous anabolic steroid use
Medications
Stromal hyperthecosis (valproic acid)
Workup
Laboratory Studies
The goal in patients with polycystic ovarian syndrome (PCOS) is to assess the severity and source of androgen excess and to rule out an adrenal or ovarian tumor. A karyotype usually excludes mosaic Turner syndrome as a cause of the primary amenorrhea.
- Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels
- FSH levels are within the reference range or low.
- LH levels are elevated for Tanner stage, gender, and age.
- The LH-to-FSH ratio is usually more than 3.
- Stimulation testing with a long-acting gonadotropin-releasing hormone (GnRH) agonist induces a characteristic rise in ovarian-derived 17-hydroxyprogesterone after 24 hours. This is thought to be a result of excessive 17-hydroxylase activity.
- Prolactin levels: A small percentage of patients have elevated prolactin levels (typically >25 mg/dL).
- Thyroid-stimulating hormone (TSH) and free thyroxine levels
- Thyroid dysfunction may cause amenorrhea and hirsutism.
- Thyroid function tests are within the reference range in patients with polycystic ovarian syndrome.
- Long-standing primary hypothyroidism can be associated with markedly elevated circulating TSH level. Elevated alpha subunit delivery (from one half of the dimeric TSH molecule) can then crossreact with FSH and LH receptors on breast tissue, leading to premature thelarche and, on ovarian tissue, leading to a polycystic ovarian syndrome–like picture. These physical findings of the van Wyk-Grumbach syndrome resolve upon thyroxine replacement therapy.
- Total and free testosterone levels
- Total testosterone is elevated in women with polycystic ovarian syndrome; however, total testosterone levels greater than 200 ng/dL is suggestive of an androgen-producing tumor of the ovary or adrenal gland.
- Free testosterone levels are sensitive for ovarian hyperandrogenism and are elevated in patients with polycystic ovarian syndrome.
- Sex hormone-binding globulin (SHBG) is concomitantly low.
- Dehydroepiandrosterone (DHEAS) levels
- DHEAS is a marker of adrenal androgen production.
- DHEAS levels greater than 700 mcg/dL are suggestive of a tumor. DHEAS is elevated in women with polycystic ovarian syndrome but not at such high levels.
- Androstenedione levels are also elevated. This androgen precursor is 60% ovarian and 40% adrenal in derivation.
- Fasting cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides, insulin, glucose, and hemoglobin A1C levels: Some women with polycystic ovarian syndrome have insulin resistance and an abnormal lipid profile (cholesterol >200 mg/dL; LDL >160 mg/dL). Approximately one third of women with polycystic ovarian syndrome who are overweight have impaired glucose tolerance or type 2 diabetes mellitus by age 30 years.5
- Adrenocorticotropic hormone stimulation test
- In female patients with signs of virilization that include clitoromegaly, premature pubarche, and high serum 17-hydroxyprogesterone (eg, >200 ng/dL in an 8-am sample), suspect late-onset congenital adrenal hyperplasia due to 21-hydroxylase deficiency.
- Further evaluation of adrenal function is required. An adrenocorticotropic hormone (ACTH) stimulation test can be used to check for late-onset congenital adrenal hyperplasia.
- Dexamethasone suppression test: History and physical examination usually exclude Cushing syndrome, but further tests, including 24-hour urine collection for free cortisol and 17-ketosteroids, a dexamethasone suppression test, and corticotropin-releasing hormone (CRH) stimulation tests, may be needed.
Imaging Studies
- Ultrasonography
- Perform ultrasonography if pelvic examination is inadequate, the patient has abdominal pain, or if testosterone levels are unusually high (eg, >200 ng/dL).
- Criteria for polycystic ovaries include bilateral ovarian enlargement (>9 cm in diameter), 10 or more follicles 2-10 mm in diameter per ovary, and increased density of the stroma.
Longitudinal transabdominal ultrasonogram of an ovary. This image reveals multiple peripheral follicles.
- CT scan or MRI: If a tumor is suspected, obtain a CT scan or MRI to visualize the adrenals and ovaries.
Histologic Findings
- Histological changes of the ovary include enlarged, sclerotic, multiple cystic follicles.
Treatment
Medical Care
Medical therapy in patients with polycystic ovarian syndrome (PCOS) is used to treat menstrual dysfunction, manifestations of hyperandrogenism, infertility,6 and insulin resistance. The Endocrine Society published its clinical practice guideline in April 2008.7
- First-line medical therapy usually consists of an oral contraceptive to suppress ovarian androgen production and induce regular menses. If symptoms such as hirsutism are not sufficiently alleviated, an androgen-blocking agent may be added (see Medications).
- Recently, metformin has been successfully used in clinical trials;8 however, data are insufficient as yet to recommend this agent to all women with polycystic ovarian syndrome. A recent study concluded that the use of metformin throughout pregnancy was associated with a 9-fold decrease in gestational diabetes in women with polycystic ovarian syndrome.9
- 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, Retin-A, and topical and oral antibiotics, are effective for acne treatment.
- If the patient develops type 2 diabetes mellitus, consider treatment with oral antihyperglycemic drugs, such as metformin. Clinical trials have recently shown that metformin can effectively reduce androgens, improve insulin sensitivity, and facilitate weight loss in patients with polycystic ovarian syndrome as early as adolescence.10,11
- The patient may desire mechanical removal of excess hair. Options include electrolysis, waxing, bleaching, tweezing, depilatories, shaving, and laser removal.
- Clomiphene citrate is used to stimulate ovulation when fertility is desired. Other approaches use gonadotropin-releasing hormone (GnRH) analogues in combination with pulsatile luteinizing hormone (LH)-releasing hormone (LHRH) treatment.
Surgical Care
- Ovarian wedge resection was formerly considered an effective treatment for polycystic ovarian syndrome. Since the advent of hormonal therapies, this treatment is not often used but may be effective in alleviating ovarian dysfunction. Laparoscopic "ovarian drilling" is now performed.
- If desired, clitoromegaly may be corrected with surgery.
Consultations
- 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.
Diet
- Nutritional counseling that addresses obesity and dyslipidemia is an important aspect of medical management.
- Weight loss may help to decrease insulin resistance and also may decrease adverse long-term cardiovascular effects.
Activity
- Discourage smoking because of increased risk of cardiovascular disease.
Medication
Low-dose combination oral contraceptive pills (OCPs)
OCPs are the mainstay of treatment for women with polycystic ovarian syndrome (PCOS) who are not actively trying to conceive. OCPs suppress LH production, which suppresses ovarian production of androgens and decreases the level of free testosterone by increasing the level of SHBG circulating in the blood. OCPs also decrease adrenal androgen production and 5-alpha-reductase activity. OCPs improve acne and hirsutism. Restoration of regular menstrual cycles prevents endometrial hyperplasia associated with anovulation. Improvements of hyperandrogenic effects are seen in 60-100% of women but usually require a minimum of 6-12 months of use. A pregnancy test should be performed before initiating therapy. If the woman has had no menstrual period for 3 months, withdrawal bleeding should be induced by administration of 5-10 mg of medroxyprogesterone acetate (Provera) daily for 10 days; then, therapy is begun with OCPs.
Ethinyl estradiol with progestins (Demulen, Ortho 1/35)
Use 30-35 mg ethinyl estradiol combined with any form of progesterone.
Restoration of regular menstrual cycles prevents endometrial hyperplasia associated with anovulation. Improvements of hyperandrogenic effects are seen in 60-100% of women but usually require a minimum of 6-12 mo of use. A pregnancy test should be performed before initiating therapy. If the woman has had no menstrual period for 3 mo, withdrawal bleeding should be induced by administration of 5-10 mg of medroxyprogesterone acetate (Provera) daily for 10 d; then, therapy is begun with OCPs.
Dosing
Adult
1 tab PO qd
Pediatric
Not established
Interactions
Decreased effectiveness and breakthrough bleeding are associated with concomitant use with rifampin, barbiturates, phenylbutazone, phenytoin sodium, carbamazepine, griseofulvin, ampicillin, tetracycline, anticonvulsants, or warfarin
Contraindications
Deep vein thrombosis, thrombophlebitis, thromboembolic disorders, cerebral vascular or coronary vascular disease, breast carcinoma, hepatic carcinomas or adenomas, pregnancy, cholestatic jaundice of pregnancy or jaundice with prior estrogen use, carcinoma of the endometrium or other estrogen-dependent neoplasias
Precautions
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Caution in women >35 y who smoke or have undiagnosed vaginal bleeding or breast mass
Antiandrogens
These agents block active androgen production. Cyproterone acetate is a progestin with antiandrogen activity used to treat hirsutism but has not been approved for use in the United States. In Europe, it is offered as the progestin component of an OCP.
Spironolactone (Aldactone)
Antiandrogen that is a nonspecific androgen receptor blocker. May be used in conjunction with OCPs to treat hirsutism by reducing hair diameter. Begin OCPs 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). Is also used as a potassium-sparing diuretic.
Dosing
Adult
50-100 mg PO bid
Pediatric
0.5-1.5 mg/kg PO bid
Interactions
Use with potassium-sparing diuretics, ACE inhibitors, or NSAIDs is associated with severe hyperkalemia; increases half-life of digoxin; potentiates orthostatic hypotension when taken with alcohol, opioid analgesics, benzodiazepines, or barbiturates; reduces clearance of lithium
Contraindications
Documented hypersensitivity; hyperkalemia, hyponatremia, and severe renal impairment; Addison disease
Precautions
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
May cause fluid and electrolyte imbalance; low-potassium diet recommended
Leuprolide (Lupron)
Suppresses ovarian and testicular steroidogenesis by decreasing LH and FSH levels. GnRH analogs with OCPs are an option to consider for women with hirsutism that fail to respond to combined therapy with spironolactone and OCPs. Anatomic effects of androgens (eg, clitoromegaly and deepening of the voice) are not responsive to GnRH analogs.
Dosing
Adult
Suggested dosing: 3.5-7.5 mg/mo IM; not to exceed 6 mo without adding low-dose estrogen and progestin therapy
Pediatric
Not established
Interactions
None reported
Contraindications
Documented hypersensitivity; pregnancy; may cause malformations of the genital tract in the male fetus
Precautions
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Urinary tract obstruction, tumor flare, and bone pain may occur; monitor patients for weakness and paresthesias
Finasteride (Proscar, Propecia)
5-alpha-reductase inhibitor approved for use in benign prostatic hypertrophy and in male-patterned alopecia. Blocks conversion of testosterone to its more active metabolite, dihydrotestosterone. More effective when used in combination with OCPs.
Dosing
Adult
1 mg PO qd
Pediatric
Not established
Interactions
None reported
Contraindications
Documented hypersensitivity; pregnancy
Precautions
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Pregnant women should not handle broken or crushed tab because the drug can be absorbed through the skin; not FDA-approved for use in women; caution in hepatic impairment; may cause a large residual urinary volume; avoid use in patients with severely diminished urinary flow
Progesterones
These agents are used to treat secondary amenorrhea.
Medroxyprogesterone (Provera)
Has no effect on androgen production. Progestins stop endometrial cell proliferation, allowing organized sloughing of cells after withdrawal.
Dosing
Adult
10 mg PO qd for 10 d q2-3mo in amenorrhea or oligomenorrhea
Pediatric
Not established
Interactions
Aminoglutethimide may decrease effects by increasing hepatic metabolism of medroxyprogesterone
Contraindications
Documented hypersensitivity; cerebral apoplexy, undiagnosed vaginal bleeding, thrombophlebitis, and liver dysfunction
Precautions
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Caution in asthma, depression, renal or cardiac dysfunction, or thromboembolic disorders
Antidiabetic agents
These agents are used to treat insulin resistance and overt diabetes mellitus.
Metformin (Glucophage, Glucophage XR)
Improves hepatic insulin sensitivity. Available in 500-mg, 850-mg, or 1000-mg tab. The XR form provides 500 mg or 750 mg for once daily administration.
Dosing
Adult
500 mg PO qd initially, may titrate upward, not to exceed 1000 mg PO bid
Pediatric
<5 years: Not established
>5 years: Not established; limited experience suggests that doses up to 2000 mg/d can be safely tolerated
Interactions
Diuretics, thyroid products, OCPs, phenytoin, calcium channel blocking drugs, phenothiazines may decrease effects of metformin; cimetidine may increase metformin levels
Contraindications
Documented hypersensitivity; acute myocardial infarction, septicemia, renal disease
Precautions
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in renal or hepatic insufficiency; discontinue therapy before performing any surgical procedures
Insulin (Humulin)
Effective when metformin cannot control hyperglycemia. Several short-acting and long-acting dosage forms are available. Must be initiated in conjunction with dietary assessment and nutritional management by a registered clinical dietitian as part of an overall weight management system. Seldom indicated as a first-line agent for PCOS.
Dosing
Adult
0.5-1 U/kg/d SC in divided doses; higher dosage requirement may be needed during pregnancy or with obesity
Pediatric
Daily requirements for a prepubertal child with PCOS (not type 1 diabetes) typically range from 0.5-1 U/kg SC
Daily requirements for a pubertal adolescent with PCOS (not type 1 diabetes) typically range from 0.75-1.2 U/kg SC
Interactions
Medications that may decrease hypoglycemic effects of insulin include acetazolamide, AIDS antivirals, asparaginase, phenytoin, nicotine, isoniazid, diltiazem, diuretics, corticosteroids, thiazide diuretics, thyroid hormone, estrogens, ethacrynic acid, calcitonin, OCPs, diazoxide, dobutamine, phenothiazines, cyclophosphamide, dextrothyroxine, lithium carbonate, epinephrine, morphine sulfate, and niacin
Medications that may increase hypoglycemic effects of insulin include calcium, ACE inhibitors, alcohol, tetracyclines, beta blockers, lithium carbonate, anabolic steroids, pyridoxine, salicylates, MAO inhibitors, mebendazole, sulfonamides, phenylbutazone, chloroquine, clofibrate, fenfluramine, guanethidine, octreotide, pentamidine, and sulfinpyrazone
Contraindications
Documented hypersensitivity; hypoglycemia
Precautions
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Hyperthyroidism may increase renal clearance of insulin and may need more insulin to treat hyperkalemia; hypothyroidism may delay insulin turnover, requiring less insulin to treat hyperkalemia; monitor glucose carefully; dose adjustments of insulin may be necessary in patients diagnosed with renal and hepatic dysfunction
Follow-up
Further Inpatient Care
- The only indication for inpatient care in patients with polycystic ovarian syndrome (PCOS) is menorrhagia with severe anemia.
Further Outpatient Care
- Monitor oral contraceptive pill (OCP) use.
- Monitor for adverse effects of medications.
- Monitor for insulin resistance and development of diabetes.
- Monitor lipid profile.
- Encourage exercise and a healthy diet.
Complications
- Type 2 diabetes mellitus
- Cardiovascular disease
- Endometrial carcinoma
- Infertility
Prognosis
- Prognosis is good.
Patient Education
- Encourage a sensible exercise program, a healthy diet, and maintenance of ideal body weight.
- Discourage cigarette smoking.
- When prescribing OCPs for sexually active women, stress condom use for protection against sexually transmitted diseases.
- Make patients aware of the possible long-term complications of polycystic ovarian syndrome and encourage the necessity of medical follow-up care.
- Internet sites for patients include the following:
- Polycystic Ovarian Syndrome Association
- The Cysterhood - Putting Faces to PCOS
- For excellent patient education resources, visit eMedicine's Women's Health Center. Also, see eMedicine's patient education articles Ovarian Cysts, Amenorrhea, and Female Sexual Problems.
- Also, see patient education articles and find a local endocrinologist via The Hormone Foundation.
Multimedia
Media file 1: Longitudinal transabdominal ultrasonogram of an ovary. This image reveals multiple peripheral follicles.
References
Stein IF, Leventhal ML. Amenorrhea associated with bilateral polycystic ovaries. Am J Obstet Gynecol. 1935;29:181-91.
Azziz R, Carmina E, Dewailly D, et al. The Androgen Excess and PCOS Society criteria for the polycystic ovary syndrome: the complete task force report. Fertil Steril. Feb 2009;91(2):456-88. [Medline].
Rosenfield RL, Barnes RB, Cara JF, Lucky AW. Dysregulation of cytochrome P450c 17 alpha as the cause of polycystic ovarian syndrome. Fertil Steril. 1990;53:785-91. [Medline].
Govind A, Obhrai MS, Clayton RN. Polycystic ovaries are inherited as an autosomal dominant trait. J Clin Endocrinol Metab. 1961;21:1440.
Nur MM, Newman IM, Siqueira LM. Glucose Metabolism in Overweight Hispanic Adolescents With and Without Polycystic Ovary Syndrome. Pediatrics. Aug 24 2009;[Medline].
Thessaloniki ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Consensus on infertility treatment related to polycystic ovary syndrome. Fertil Steril. Mar 2008;89:505-22. [Medline].
[Guideline] Martin KA, Chang RJ, Ehrmann DA, Ibanez L, Lobo RA, Rosenfield RL, et al. Evaluation and treatment of hirsutism in premenopausal women: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2008;93:1105-20. [Medline].
[Best Evidence] Otta CF, Wior M, Iraci GS, et al. Clinical, metabolic, and endocrine parameters in response to metformin and lifestyle intervention in women with polycystic ovary syndrome: A randomized, double-blind, and placebo control trial. Gynecol Endocrinol. Aug 2009;1-6. [Medline].
[Best Evidence] Begum MR, Khanam NN, Quadir E, et al. Prevention of gestational diabetes mellitus by continuing metformin therapy throughout pregnancy in women with polycystic ovary syndrome. J Obstet Gynaecol Res. Apr 2009;35:282-6. [Medline].
Allen HF, Mazzoni C, Heptulla RA, et al. Randomized controlled trial evaluating response to metformin versus standard therapy in the treatment of adolescents with polycystic ovary syndrome. J Pediatr Endocrinol Metab. 2005;18:761-768. [Medline].
Moghetti P, Castello R, Negri C, et al. Metformin effects on clinical features, endocrine and metabolic profiles, and insulin sensitivity in polycystic ovary syndrome: a randomized, double-blind, placebo-controlled 6-month trial, followed by open, long-term clinical evaluation. J Clin Endocrinol Metab. 2000;85:139-46. [Medline]. [Full Text].
Arslanian SA. Clamp techniques in paediatrics: what have we learned?. Horm Res. 2005;64:16-24. [Medline].
Barbieri RL, Ryan KJ. Hyperandrogenism, insulin resistance, and acanthosis nigricans syndrome: a common endocrinopathy with distinct pathophysiologic features. Am J Obstet Gynecol. Sep 1 1983;147(1):90-101. [Medline].
Burke JP, Duggirala R, Hale DE, et al. Genetic basis of acanthosis nigricans in Mexican Americans and its association with phenotypes related to type 2 diabetes. Hum Genet. 2000;106:467-472. [Medline].
Burke JP, Hale DE, Hazuda HP, Stern MP. A quantitative scale of acanthosis nigricans. Diabetes Care. 1999;22:1655-1699. [Medline]. [Full Text].
Burkman RT Jr. The role of oral contraceptives in the treatment of hyperandrogenic disorders. Am J Med. Jan 16 1995;98(1A):130S-136S. [Medline].
Carmina E, Koyama T, Chang L, et al. Does ethnicity influence the prevalence of adrenal hyperandrogenism and insulin resistance in polycystic ovary syndrome?. Am J Obstet Gynecol. 1992;167:1807-12. [Medline].
Castelo-Branco C, Martinez de Osaba MJ, Pons F, Fortuny A. Gonadotropin-releasing hormone analog plus an oral contraceptive containing desogestrel in women with severe hirsutism: effects on hair, bone, and hormone profile after 1-year use. Metabolism. Apr 1997;46(4):437-40. [Medline].
Cruz ML, Shaibi GQ, Weigensberg MJ, et al. Pediatric obesity and insulin resistance: chronic disease risk and implications for treatment and prevention beyond body weight modification. Annu Rev Nutr. 2005;25:435-468. [Medline].
Cumming DC, Yang JC, Rebar RW, Yen SS. Treatment of hirsutism with spironolactone. JAMA. Mar 1982;247:1295-8. [Medline].
Denburg MR, Silfen ME, Manibo AM, et al. Insulin sensitivity and the insulin-like growth factor system in prepubertal boys with premature adrenarche. J Clin Endocrinol Metab. 2002;87:5604-5609. [Medline]. [Full Text].
Ehrmann DA. Relation of functional ovarian hyperandrogenism to non-insulin dependent diabetes mellitus. Baillieres Clin Obstet Gynaecol. Jun 1997;11(2):335-47. [Medline].
Ehrmann DA, Barnes RB, Rosenfield RL. Polycystic ovary syndrome as a form of functional ovarian hyperandrogenism due to dysregulation of androgen secretion. Endocr Rev. Jun 1995;16(3):322-53. [Medline]. [Full Text].
Elkind-Hirsch KE, Anania C, Mack M, Malinak R. Combination gonadotropin-releasing hormone agonist and oral contraceptive therapy improves treatment of hirsute women with ovarian hyperandrogenism. Fertil Steril. May 1995;63(5):970-8. [Medline].
Ferriman D, Gallwey JD. Clinical assessment of body hair growth in women. J Clin Endocrinol Metab. 1961;21:1440.
Franks S. Polycystic ovary syndrome [published erratum appears in N Engl J Med 1995;333:1435]. N Engl J Med. 1995;333:853-61. [Medline].
Glueck CJ, Goldenberg N, Pranikoff J, et al. Height, weight, and motor-social development during the first 18 months of life in 126 infants born to 109 mothers with polycystic ovary syndrome who conceived on and continued metformin through pregnancy. Hum Reprod. 2004;19:1323-1330. [Medline]. [Full Text].
Goldfarb A. Menstrual dysfunction. In: Coupey S, ed. Coupey's Primary Care of Adolescent Girls. Hanley and Belfus, Inc; 2000:258.
Gubitosi-Klug RA, Martinez A, Mericq V, Palmert MR. Drugs and hormones used to treat pediatric and adolescent reproductive endocrine disorders. Pediatr Endocrinol Rev. 2004;2:93-107. [Medline].
Holmes KW, Kwiterovich PO Jr. Treatment of dyslipidemia in children and adolescents. Curr Cardiol Rep. 2005;7:445-456. [Medline].
Ibanez L, Valls C, Marcos MV, et al. Insulin sensitization for girls with precocious pubarche and with risk for polycystic ovary syndrome: effects of prepubertal initiation and postpubertal discontinuation of metformin treatment. J Clin Endocrinol Metab. 2004;89:4331-4337. [Medline]. [Full Text].
Leibel NI, Baumann EE, Kocherginsky M, Rosenfield RL. Relationship of adolescent polycystic ovary syndrome to parental metabolic syndrome. J Clin Endocrinol Metab. 2006;91:1275-1283. [Medline].
McClamrock H, Adashi EY. Polycystic ovarian syndrome and associated hirsutism in the adolescent. Adolesc Pediatr Gynecol. 1992;5:231-41.
Musso C, Cochran E, Javor E. The long-term effect of recombinant methionyl human leptin therapy on hyperandrogenism and menstrual function in female and pituitary function in male and female hypoleptinemic lipodystrophic patients. Metabolism. 2005;54:255-263.
Musso C, Cochran E, Moran SA, et al. Clinical course of genetic diseases of the insulin receptor (type A and Rabson-Mendenhall syndromes): a 30-year prospective. Medicine (Baltimore). 2004;83:209-222. [Medline].
Myers ER, Silva SG, Hafley G, et al. Estimating live birth rates after ovulation induction in polycystic ovary syndrome: sample size calculations for the pregnancy in polycystic ovary syndrome trial. Contemp Clin Trials. 2005;26:271-80. [Medline].
Polson DW, Adams J, Wadsworth J, Franks S. Polycystic ovaries--a common finding in normal women. Lancet. 1988;1(8590):870-2. [Medline].
Rebar R, Judd HL, Yen SS, et al. Characterization of the inappropriate gonadotropin secretion in polycystic ovary syndrome. J Clin Invest. 1976;57:1320-9. [Medline]. [Full Text].
Siow Y, Kives S, Hertweck P, et al. Serum Mullerian-inhibiting substance levels in adolescent girls with normal menstrual cycles or with polycystic ovary syndrome. Fertil Steril. 2005;84:938-944. [Medline].
Styne DM. Review of the 2nd Annual World Congress on the Insulin Resistance Syndrome. J Pediatr Endocrinol Metab. 2005;18:723-726. [Medline].
Ten S, Maclaren N. Insulin resistance syndrome in children. J Clin Endocrinol Metab. 2004;89:2526-2539. [Medline]. [Full Text].
Trent ME, Rich M, Austin SB, Gordon CM. Fertility concerns and sexual behavior in adolescent girls with polycystic ovary syndrome: implications for quality of life. J Pediatr Adolesc Gynecol. Feb 2003;16(1):33-7. [Medline].
Wong IL, Morris RS, Chang L, et al. A prospective randomized trial comparing finasteride to spironolactone in the treatment of hirsute women. J Clin Endocrinol Metab. 1995;80:233-8. [Medline].
Yoo RY, Dewan A, Basu R, et al. Increased luteinizing hormone pulse frequency in obese oligomenorrheic girls with no evidence of hyperandrogenism. Fertil Steril. 2006;85:1049-1056. [Medline].
Zukauskaite S, Seibokaite A, Lasas L, et al. Serum hormone levels and anthropometric characteristics in girls with hyperandrogenism. Medicina (Kaunas). 2005;41:305-312. [Medline].
Keywords
polycystic ovarian syndrome, PCOS, Stein-Leventhal syndrome, hyperandrogenism, functional ovarian hyperandrogenism, sclerocystic disease of the ovary, insulin resistance, perimenarchal onset, amenorrhea, obesity, menstrual dysfunction, HAIR-AN syndrome, treatment, diagnosis
Contributor Information and Disclosures
Author
Robert J Ferry Jr, MD,, Chief, Division of Pediatric Endocrinology and Metabolism, Le Bonheur Children's Medical Center, University of Tennessee Health Science Center at Memphis, and St. Jude Children's Research Hospital; Brigade Surgeon, 36th Sustainment Brigade, 13th Expeditionary Sustainment Command, U.S. Army
Robert J Ferry Jr, MD, is a member of the following medical societies: American Academy of Pediatrics, American Diabetes Association, American Medical Association, Endocrine Society, Lawson-Wilkins Pediatric Endocrine Society, Society for Pediatric Research, and Texas Pediatric Society
Disclosure: Nutropin Speakers Bureau Honoraria Speaking and teaching; Genotropin Speakers Bureau Honoraria Speaking and teaching; Eli Lilly & Co. Grant/research funds Independent contractor; MacroGenics, Inc. Grant/research funds Independent contractor; Ipsen, S.A. (formerly Tercica, Inc.) Grant/research funds Independent contractor
Medical Editor
Phyllis W Speiser, MD, Chief of Pediatric Endocrinology, Schneider Children's Hospital; Professor of Pediatrics, New York University School of Medicine
Phyllis W Speiser, MD is a member of the following medical societies: American Association of Clinical Endocrinologists, Endocrine Society, Lawson-Wilkins Pediatric Endocrine Society, and Society for Pediatric Research
Disclosure: Nothing to disclose.
Pharmacy Editor
Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner
Managing Editor
Lynne Lipton Levitsky, MD, Chief, Pediatric Endocrine Unit, Massachusetts General Hospital; Associate Professor, Department of Pediatrics, Harvard University Medical School
Lynne Lipton Levitsky, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Diabetes Association, American Pediatric Society, Endocrine Society, Lawson-Wilkins Pediatric Endocrine Society, and Society for Pediatric Research
Disclosure: Pfizer Grant/research funds P.I.; Tercica Grant/research funds PI, also occasional consultant
CME Editor
Merrily P M Poth, MD, Professor, Department of Pediatrics and Neuroscience, Uniformed Services University of the Health Sciences
Merrily P M Poth, MD is a member of the following medical societies: American Academy of Pediatrics, Endocrine Society, and Lawson-Wilkins Pediatric Endocrine Society
Disclosure: Nothing to disclose.
Chief Editor
Stephen Kemp, MD, PhD, Professor, Department of Pediatrics, Section of Pediatric Endocrinology, University of Arkansas and Arkansas Children's Hospital
Stephen Kemp, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Association of Clinical Endocrinologists, American Pediatric Society, Endocrine Society, Phi Beta Kappa, Southern Medical Association, and Southern Society for Pediatric Research
Disclosure: Genentech, Inc. Honoraria Speaking and teaching; Pfizer, Inc. Honoraria Consulting