Polycystic Ovarian Syndrome (PCOS) – Causes, Symptoms, Diagnosis, Treatment and Ongoing care
- Polycystic ovary syndrome (PCOS) is the most common endocrine disorder of unknown etiology.
- PCOS is a complex disorder characterized by a state of chronic oligoovulation or anovulation, associated with functional androgen excess, and manifesting most commonly as oligomenorrhea or amenorrhea.
- System(s) affected: Reproductive; Endocrine/Metabolic; Skin/Exocrine
- Synonym(s): Stein-Leventhal syndrome; polycystic ovary disease
- Condition may begin at puberty.
- Pregnancy does not resolve the syndrome.
- Predisposes to and associated with obesity, hypertension, diabetes, metabolic syndrome, hyperlipidemia, infertility, insulin-resistance syndrome
- Polycystic ovary syndrome (PCOS) affects 6.6–6.8% of women of reproductive age (1).
- Much higher in olgiomenorrheic women
- Predominant age: Reproductive age
- Predominant sex: Females only
See “Commonly Associated Conditions”; cause and effect are difficult to disentangle in this disorder.
- Increased prevalence in 1st-degree relatives of affected individuals suggests genetic factors.
- Ultimate expression is likely a combination of polygenic and environmental factors.
- No single gene has been identified as the susceptibility gene for PCOS.
- Efforts are ongoing to dissect the variants of genes from multiple logical pathways, which are involved in pathophysiology of PCOS.
- None known; focus on early diagnosis and treatment to prevent long-term complications.
- Valproic acid use is associated with development of PCOS.
- Incompletely defined and possibly heterogeneous
- Recent evidence points to a primary role for insulin resistance with hyperinsulinemia, as well as a genetic predisposition to excess androgen production (2).
- Insulin resistance causes elevated insulin levels.
- Elevated insulin directly and indirectly stimulates ovarian androgen production in a genetically primed ovary.
- Abnormal insulin and androgen balance alter gonadotropin (follicle-stimulating hormone [FSH] and luteinizing hormone [LH]) release (disrupted hypothalamic–pituitary–ovarian axis).
- Insulin lowers hepatic sex hormone–binding globulin (SHBG) production, increasing serum free testosterone.
- Insulin resistance may cause the frequently associated metabolic syndrome and frank diabetes mellitus (DM).
Commonly Associated Conditions
- Obstructive sleep apnea
- Diabetes mellitus
- Breast carcinoma
- Endometrial hyperplasia and/or carcinoma
- Hyperandrogenism, insulin resistance, acanthosis nigricans (HAIRAN) syndrome
- Take a complete patient history, especially as it relates to contraceptive and reproductive goals.
- History should include a detailed menstrual history, as well as information about weight gain, hirsutism, acne, fertility, gestational diabetes, lipid levels.
- Vital signs: Body mass index (BMI), high BP
- General appearance: Central obesity, deepened voice, hirsutism, acne
- Skin: Hair pattern and growth, acne, seborrhea, acanthosis nigricans
- Genitalia: Clitoromegaly
Look specifically for signs of virilization such as hair pattern, deepened voice, and clitoromegaly.
Diagnostic Tests & Interpretation
- Diagnostic criteria (Rotterdam criteria, 2 of 3):
- Oligo- or anovulation
- Clinical and/or biochemical signs of hyperandrogenism
- Transvaginal ultrasonographic polycystic ovaries and exclusion of other etiologies; therefore, consider exclusion of Cushing disease, congenital adrenal hyperplasia, and androgen-secreting tumors.
- More recent criteria also focus on similar criteria while acknowledging that there may be forms of PCOS without overt evidence of hyperandrogenism (3).
Initial lab tests
- Screening workup should include human chorionic gonadotropin (hCG), TSH, prolactin, and FSH (exclude premature ovarian failure).
- LH determination may be ordered but is not usually necessary.
- Hirsute women should have a testosterone or free testosterone determination and a DHEAS determination.
- Consider 17-OH progesterone if congenital adrenal hyperplasia is a possibility.
- LH/FSH level ≥2.5–3.0/L in ∼50% of women with PCOS, but LH testing is not generally necessary.
- Testosterone increased but <200 ng/dL (6.94 nmol/L)
- Typical findings in PCOS include mild elevation in DHEAS but <800 µg/dL (20.8 µmol/L), mild increase in 17-OH progesterone level, increased estrogen level, decreased SHBG.
- Drugs that may alter lab results:
- Oral contraceptives (OCs)
Follow-Up & Special Considerations
- Consider fasting serum glucose, insulin level, and plasminogen activator inhibitor-1 determinations to establish presence of insulin resistance and glucose intolerance, especially if diagnosis in doubt.
- Overnight dexamethasone suppression test (Decadron 1 mg p.o. at 11:00 p.m. and fasting serum cortisol at 8:00 a.m. the next morning) to rule out Cushing syndrome in the appropriate setting.
- Endometrial biopsy to rule out hyperplasia and/or carcinoma if indicated
- If the syndrome is diagnosed, determination of fasting glucose and fasting lipid levels should be performed, and formal glucose tolerance test considered.
- Transvaginal US (positive if enlarged ovaries with ≥8 small follicular cysts) may be performed if diagnosis is in doubt, but nonspecific.
- Some research being done into use of MRI as diagnostic technique
- Ovary usually enlarged with a smooth white glistening capsule
- Ovarian cortex lined with follicles in all stages of development but most atretic
- Thecal cell proliferation with an increase in the stromal compartment
- Cushing syndrome
- HAIRAN syndrome
- Testosterone-producing ovarian or adrenal tumor
- Prolactin-producing pituitary adenoma
- Adult-onset adrenal hyperplasia
- Partial congenital adrenal hyperplasia (21-hydroxylase deficiency)
- Endometrial hyperplasia
- Endometrial carcinoma
- 11β-hydroxylase deficiency
- 17β-hydroxysteroid dehydrogenase deficiency
- Drug-induced hirsutism, oligoovulation (e.g., danazol, steroids, valproic acid)
- Thyroid disease
Drug costs related to this condition are high.
- If pregnancy not desired:
- Low-dose OCs (30–35 µg); newer formulations containing progestins with lower androgenicity (e.g., norethindrone, desogestrel, norgestimate, drospirenone) may be particularly beneficial, but all OCs increase SHBG and decrease excess androgen and estrogen.
- Cyclic withdrawal bleeding with medroxyprogesterone (Provera) 10 mg p.o. × 10 days given every 1–2 months
- Metformin may help to correct metabolic abnormalities in women who are shown to be insulin-resistant. Initial dose is 500 mg at dinner time × 1 week, increasing by 500 mg/week to a total of 1,500–2000 mg/d divided b.i.d.; take with food.
- Overall, data support the usefulness of metformin on both cardiometabolic risk and reproduction assistance in PCOS women (1).
- Thiazolidinediones may increase likelihood of ovulation and treat insulin resistance.
- If pregnancy desired:
- Ovulation induction with clomiphene (Clomid, Serophene) and/or exogenous gonadotropins: see “Infertility.” Birth rate with Clomid is 22.5%, 7.2% with Metformin, and 26.8% in women who use both medications (4).
- Metformin (Glucophage): 500–2,000 mg p.o. divided b.i.d. has been shown to improve hyperandrogenism and restore ovulation. Many times the drug is continued throughout the 1st trimester or the entire pregnancy if there is a history of spontaneous abortion or glucose intolerance. It does improve clinical pregnancy rates, but does not improve live birth rates alone or in combination with clomiphene when used for ovulation induction (5).
- Has been demonstrated that metformin reduces the incidence of gestational diabetes
- Refer to a perinatologist for opinion in high-risk patient.
- Spironolactone for androgen-excess hirsutism not addressed by OC therapy
- Dexamethasone or prednisone for congenital adrenal syndromes or for nonobese women with functional adrenal androgen excess (high 17-ketosteroids) not suppressed by OC
- Eflornithine hydrochloride cream 13% to inhibit hair growth
- No ideal treatment exists.
- Therapy must be individualized according to the needs and desires of each patient.
- Weight loss in overweight women results in biochemical and symptomatic improvement in most.
Issues for Referral
- To reproductive endocrinologist for all women who cannot achieve pregnancy with Clomid
- To endocrinologist if Cushing syndrome, congenital adrenal hyperplasia, or adrenal or ovarian tumors are found during the workup
Complementary and Alternative Medicine
Initial trials with acupuncture to assist with cycle normalization and weight loss are promising (6).
- Ovarian wedge resection and laparoscopic laser drilling are controversial and rarely used today.
- Mechanical means of hair removal including electrolysis, waxing, and depilatory may improve cosmesis.
Follow-up at 6-month intervals to evaluate response to therapy and to monitor weight as well as medication side effects
- Counsel patient about the risk of endometrial and breast carcinoma, insulin resistance, and diabetes, as well as obesity and its role in infertility.
- See patient frequently throughout the menstrual cycle, depending on which drug combination is used to induce ovulation.
In overweight patients, weight loss is the most successful therapy because it improves cardiovascular risk, insulin sensitivity, and menstrual patterns.
- Provide patient with information about PCOS such as from http://www.acog.org.
- Discuss risks and benefits of medications used for treatment as well as side effects.
- Discuss the chronic nature of this condition.
- Remind patients who do not wish to become pregnant that contraception remains necessary despite oligoovulation.
- Review the importance of weight loss if applicable. Modest weight loss of 5% to 10% of initial body weight has been demonstrated to improve many of the features of PCOS. Provide patient with resources.
- Prognosis for fertility is excellent depending on other fertility factors; assisted reproductive technologies may be necessary.
- Proper treatment and follow-up of chronic anovulation can prevent endometrial hyperplasia or carcinoma.
- Reproductive: Infertility, hyperandrogenism, hirsutism
- Metabolic: Insulin resistance, impaired glucose tolerance, type 2 diabetes mellitus, adverse cardiovascular risk profiles
- Psychological: Increased anxiety, depression, and worsened quality of life
1. Diamanti-Kandarakis E, Economou F, Palimeri S, et al. Metformin in polycystic ovary syndrome. Ann N Y Acad Sci. 2010;1205:192–8.
2. Moran LJ, Misso ML, Wild RA, Norman RJ et al. Impaired glucose tolerance, type 2 diabetes and metabolic syndrome in polycystic ovary syndrome: a systematic review and meta-analysis. Hum. Reprod. Update. 2010;16:347–63.
3. 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. 2008.
4. Legro RS, Barnhart HX, Schlaff WD, et al. Clomiphene, metformin, or both for infertility in the polycystic ovary syndrome. N Engl J Med. 2007;356:551–66.
5. Tang et al. Insulin-sensitising drugs (metformin, rosiglitazone, pioglitazone, D-chiro-inositol) for women with polycystic ovary syndrome, oligo amenorrhoea and subfertility. Cochrane Database of Systematic Reviews. 5, 2010.
6. Lim CE, Wong WS et al. Current evidence of acupuncture on polycystic ovarian syndrome. Gynecol. Endocrinol. 2010;26:473–8.
Carmina E, Oberfield SE, Lobo RA et al. The diagnosis of polycystic ovary syndrome in adolescents. Am J Obstet Gynecol. 2010;203:201.e1–5.
Chang RJ. A practical approach to the diagnosis of polycystic ovary syndrome. Am J Obstet Gynecol. 2004;191:713–7.
Cibula D, et al. The effect of combination therapy with metformin and combined oral contraceptives (COC) versus COC alone on insulin sensitivity, hyperandrogenaemia, SHBG and lipids in PCOS patients. Human Reprod. 2005;20(1):180–4.
Hirschberg AL et al. Polycystic ovary syndrome, obesity and reproductive implications. Womens Health (Lond Engl). 2009;5.
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. 2004;81:19–25.
Tasali E, VanCauter E, Ehrman DA. PCOS & OBstructive sleep apnea. Sleep Med Clin. 2008;3(1):37–46.
Vink JM, et al. Heritability of polycystic ovary syndrome in a Dutch twin-family study. J Clin Endocrinol Metabol. 2006;91(6):2100–4.
See Also (Topic, Algorithm, Electronic Media Element)
256.4 Polycystic ovaries
69878008 polycystic ovaries (disorder)
- In the US, 40% of women with PCOS are not obese.
- Oligomenorrhea should be treated because chronic estrogen stimulation in the absence of progesterone (as occurs in PCOS anovulation) causes endometrial hyperplasia, a precursor of endometrial carcinoma.