History

Fact Explanation
Oligomenorrhoea/ Amenorrhoea Polycystic ovarian syndrome (PCOS) is defined as ovarian dysfunction associated with hyperandrogenism and polycystic ovarian morphology.[1] PCOS is the commonest endocrinopathy among women of the reproductive age group and is characterized by metabolic derangement – hyperinsulinemia, hyperandrogenism and excess LH. The excess luteinizing hormone and insulin cause increased ovarian androgen production. These hormonal changes lead to anovulation and bleeding irregularities. Symptoms onset is usually in the late second and third decades.
Infertility PCOS is major cause of infertility especially in the developed countries. About 75% of patients’ with PCOS may complain of difficulty in conceiving.[2] Anovulatory cycles lead to inadequate oocyte formation.
Recurrent miscarriages PCOS is associated with 3-fold increase in the rate of spontaneous pregnancy loss. PCOS is also considered an important cause for recurrent miscarriage. The specific aetiology for miscarriage is not known. Factors implicated with pregnancy loss include obesity, insulin resistance, hyperandrogenism, polycystic ovaries and placental thrombosis.[3]
Acne/ Excess hair growth / male pattern boldness Due to hyperandrogenism. Excess hair growth (hirsutism) mainly occurring in the face, chest and lower abdomen is a common symptom of PCOS and may in fact be the only symptom. Androgen secretion from the ovary is stimulated by LH and hyperinsulinaemia.
Weight gain The excess fat mass in obese patients increase insulin resistance. The resulting hyperinsulinaemia contributes to weight gain which turn further worsens insulin resistance. This results in a vicious cycle.
Psychological impact Patients may have depressive symptoms and low self-esteem due to subfertility, hyperandrogenic features and irregular bleeding.[4]
Associations/Risk factors The aetiology of PCOS is still unknown. PCOS has a strong genetic predisposition. Obesity, hypertension, insulin resistance and metabolic syndrome are risk factors for the disease.[5] Autoimmune thyroid disease may rarely be associated.
History of hypertension, hyperlipidaemia and diabetes Look for risk factors for disease development.
References
  1. EHRMANN DAVID A.. Polycystic Ovary Syndrome. N Engl J Med [online] 2005 March, 352(12):1223-1236 [viewed 26 July 2014] Available from: doi:10.1056/NEJMra041536
  2. KNOCHENHAUER ES, KEY TJ, KAHSAR-MILLER M, WAGGONER W, BOOTS LR, AZZIZ R. Prevalence of the polycystic ovary syndrome in unselected black and white women of the southeastern United States: a prospective study. J Clin Endocrinol Metab [online] 1998 Sep, 83(9):3078-82 [viewed 26 July 2014] Available from: doi:10.1210/jcem.83.9.5090
  3. ESSAH PA, CHEANG KI, NESTLER JE. The Pathophysiology of Miscarriage in Women with Polycystic Ovary Syndrome. Review and Proposed Hypothesis of Mechanisms Involved. HORMONES, 2004, 3(4), 221-227.
  4. TEEDE H, DEEKS A, MORAN L. Polycystic ovary syndrome: a complex condition with psychological, reproductive and metabolic manifestations that impacts on health across the lifespan. BMC Med [online] 2010 Jun 30:41 [viewed 26 July 2014] Available from: doi:10.1186/1741-7015-8-41
  5. GOODARZI MARK O., DUMESIC DANIEL A., CHAZENBALK GREGORIO, AZZIZ RICARDO. Polycystic ovary syndrome: etiology, pathogenesis and diagnosis. Nat Rev Endocrinol [online] December, 7(4):219-231 [viewed 26 July 2014] Available from: doi:10.1038/nrendo.2010.217

Examination

Fact Explanation
General examination : Body mass index (BMI) / Waist to hip ratio Measurement of the BMI and waist to hip ratio is important. Obese patients require weight reduction interventions.
General examination : Features of hyperandrogenism Inspect for hirsutism, acne and boldness. Thinning of scalp hair may also be noted.
General examination : Acanthosis nigricans A black discoloration and roughening usually observed at the back of the neck, axillae and other flexures. Acanthosis nigricans is associated with hyperinsulinaemia. This may appear before the onset of diabetes mellitus.[1]
Cardiovascular system : Hypertension Hypertension may be found as part of the metabolic syndrome.
Abdominal and vaginal examination Usually normal.
References
  1. GILKISON C, STUART CA. Assessment of patients with acanthosis nigricans skin lesion for hyperinsulinemia, insulin resistance and diabetes risk. Nurse Pract [online] 1992 Feb, 17(2):26, 28, 37 passim [viewed 26 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/1542462

Differential Diagnoses

Fact Explanation
Exclude conditions which may present similar to PCOS with hyperandrogenic features and menstrual irregularities For the diagnosis of PCOS conditions such as thyroid dysfunction, hyperprolactinemia, Cushing’s syndrome, acromegaly and adrenal tumors need to be excluded. These conditions present similar to PCOS with oligomenorrhoea/ amenorrhoea / infertility and features of hyperandrogenism.
Cushing’s syndrome Cushing’s syndrome is the chronic exposure to excess glucocorticoid which may result from various causes. Prolonged administration of excess exogenous glucocorticoid treatment is the commonest cause. Other causes are tumors which secrete ACTH and ectopic tumors which secrete glucocorticoids. Clinical features of the condition are hirsutism, acne, hair thinning, easy bruising, central obesity and striae. In females menstrual irregularities may be noted. The patient may also develop complications such as peptic ulcers, osteoporosis, myopathies, menstrual disturbances and psychosis. Diagnosis is a two step process where the first step is to confirm Cushing’s syndrome by dexamethasone suppression test or 24h urinary cortisol measurement. Investigations are planned accordingly from here-on to find the aetiology.[1]
Thyroid dysfunction Changes in serum thyroxin level is associated with systemic effects. Patients with hyperthyroidism present with weight loss, heat intolerance, palpations, diarrhea, excessive sweating and oligomenorrhoea.[2] Important findings in physical examination : tachycardia, sweaty palms, temors lid lag & lid retraction. Graves disease presents with characteristic eye features and pretibial myxedema. A prominent nodular goiter is present in multinodular goiter. In comparison hypothyroidism presents with letharginess, cold intolerance, constipation and weight gain. Females may develop menorrhagia. Puffy facies, hoarse voice, loss of eyebrows, bradycardia and slow relaxing reflexes are characteristic features. Auto-immune destruction of the gland is the commonest aetiology. Diagnosis is by measurement of TSH and free T4/T3 levels.
Hyperprolactinemia Excess secretion of the anterior pituitary hormone prolactin, commonly present with menstrual symptoms (oligomenorrhoea/ amenorrhoea) and infertility. Galctorrhea, excess production of milk is due to increased stimulation of the breasts by the excess hormone. The commonest cause for hyperprolactinemia is pituitary tumors - pituitary lactotroph adenomas. Various drugs, hypothyroidism and ectopic production by tumors are rare causes of hyperprolactinemia. The tumor may give rise to headache and visual field defects. Diagnosis is by serum prolactin level measurement. MRI of the brain is a sensitive test to identify prolactinomas. Dopamine is used to inhibit the excess activity of prolactin while specific therapy for the aetiological agent is initiated - surgery for prolactinoma.[3]
References
  1. PRAGUE J. K., MAY S., WHITELAW B. C.. Cushing's syndrome. BMJ [online] December, 346(mar27 3):f945-f945 [viewed 26 July 2014] Available from: doi:10.1136/bmj.f945
  2. KOUTRAS DA. Disturbances of menstruation in thyroid disease. Ann N Y Acad Sci [online] 1997 Jun 17:280-4 [viewed 26 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/9238278
  3. SERRI O, CHIK CL, UR E, EZZAT S. Diagnosis and management of hyperprolactinemia. CMAJ, September 2003, 169(6), 575-581.

Investigations - for Diagnosis

Fact Explanation
Diagnosis depends on both clinical information and investigations Rotterdam criteria is used for diagnosis of PCOS. Two or more out of the following three criteria is required to diagnose PCOS. 1. A history of irregular bleeding due to anovulation – oligomenorrhoea, amenorrhoea, 2. Clinical or biochemical evidence of hyperandrogenism, 3. Ultrasonic features of polycystic ovaries.[1]
Pelvic ultrasound scan – transvaginal scan. Polycystic ovaries are defined as 12 or more subcapsular follicles of <10mm diameter in an ovary or ovarian volume > 10ml.[2]
LH, FSH levels The normal 1:1 ratio between concentrations of LH and FSH is lost in PCOS. In PCOS the LH concentration is usually elevated with a ratio of LH to FSH of 2:1 or 3:1. Assessment LH, FSH ratio is not essential for diagnosis.
Testosterone, androstenedione, Sex hormone binding globulin (SHBG) The concentration of androgens is usually elevated. The level of SHBG will be reduced.
Thyroid function test Rule out thyroid dysfunction which may present with menstrual irregularities and hyperandrogenism.
Serum prolactin level Screen for hyperprolactinemia
References
  1. ROE AH, DOKRAS A. The Diagnosis of Polycystic Ovary Syndrome in Adolescents Rev Obstet Gynecol [online] 2011, 4(2):45-51 [viewed 26 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3218544
  2. BALEN A. H., LAVEN J. S. E., TAN S.-L., DEWAILLY D.. Ultrasound assessment of the polycystic ovary: international consensus definitions. Human Reproduction Update [online] 2003 November, 9(6):505-514 [viewed 26 July 2014] Available from: doi:10.1093/humupd/dmg044

Investigations - Screening/Staging

Fact Explanation
Blood glucose test To identify the presence of diabetes. Patients with PCOS have a 5-10 fold risk of developing type 2 diabetes in future.
References
  1. OVALLE F, AZZIZ R. Insulin resistance, polycystic ovary syndrome, and type 2 diabetes mellitus. Fertil Steril [online] 2002 Jun, 77(6):1095-105 [viewed 26 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/12057712

Management - General Measures

Fact Explanation
Patient education The patient should be provided information regarding the natural course of the disease, aetiology, complication and treatment options available. It is important to address the patients’ main concerns.
Weight reduction Weight reduction is associated with significant improvement in menstrual symptoms.[1] Life style modifications, dietary changes and regular exercise help reduce weight.
Dietary modifications Dietary modifications should be made to reduce weight. Weight reduction improves menstrual irregularities and reduced the risk of diabetes and cardiovascular disease.
Regular exercise Encourage aerobic exercises to reduce the weight.
Management of existing diabetes, hypertension and hyperlipidaemia Optimize pharmacological therapy for Diabetes, hypertension and hyperlipidaemia.
Psychological support Management of PCOS is difficult and the symptoms may cause significant distress to the patient.[2] Patients should be managed sensitively and motivation should be provided continuously. Specialist psychological support may be required.
References
  1. MORAN LISA J, LOMBARD CATHERINE B, LIM SIEW, NOAKES MANNY, TEEDE HELENA J. Polycystic ovary syndrome and weight management. Women's Health [online] 2010 March, 6(2):271-283 [viewed 26 July 2014] Available from: doi:10.2217/whe.09.89
  2. HIMELEIN MJ, THATCHER SS. Polycystic ovary syndrome and mental health: A review. Obstet Gynecol Surv [online] 2006 Nov, 61(11):723-32 [viewed 26 July 2014] Available from: doi:10.1097/01.ogx.0000243772.33357.84

Management - Specific Treatments

Fact Explanation
Managing menstrual dysfunction Combined oral contraceptive pill and cyclical progesterone is used to regulate menstruation. Contraceptive pills with anti-androgen effects (cyproterone acetate/co-cyprindiol- dianette) are used to control both menstrual irregularities and features of hyperandrogenism.[1] Weight loss also improves regularity of menstruation.
Treatment for hyperinsulinaemia Lifestyle modification with dietary changes and regular exercise is the most effective measure to control the effects of hyperinsulinaemia. Metformin is increasingly being used for management of PCOS patients with metabolic syndrome. Metformin has beneficial effects on regularizing the menstruation. Even though widely used, the evidence on the benefits of metformin is limited and controversial.[2]
Management of subfertility Weight loss alone may improve spontaneous ovulation. Ovulation induction can be carried out with clomiphene. Use of Gonadotrophins is another management option if anti-estrogens fail. Metformin is currently not recommended for management of subfertility.[3] In vitro fertilization may be required in patients who fail to conceive after medical therapy.
Management of hyperandrogenic features Hirsutism can be managed with topical therapy with Eflornithine cream or with oral therapy with Cyproterone acetate and metformin. GnRH analogues with low dose HRT, Finasteride and Spironolactone can be used in patients with severe symptoms. Cosmetic hair removal by shaving, depilatory cream, laser or electrolysis can also be carried out.[4]
Surgical treatment Laparoscopic ovarian drilling can be tried to improve ovulation and chances of fertility.
References
  1. EHRMANN DAVID A.. Polycystic Ovary Syndrome. N Engl J Med [online] 2005 March, 352(12):1223-1236 [viewed 26 July 2014] Available from: doi:10.1056/NEJMra041536
  2. BARBIERI RL. Metformin for the treatment of polycystic ovary syndrome. Obstet Gynecol [online] 2003 Apr, 101(4):785-93 [viewed 26 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/12681887
  3. MATHUR R, ALEXANDER CJ, YANO J, TRIVAX B, AZZIZ R. Use of metformin in polycystic ovary syndrome. Am J Obstet Gynecol [online] 2008 Dec, 199(6):596-609 [viewed 26 July 2014] Available from: doi:10.1016/j.ajog.2008.09.010
  4. AZZIZ R. The evaluation and management of hirsutism. Obstet Gynecol [online] 2003 May, 101(5 Pt 1):995-1007 [viewed 26 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/12738163