History

Fact Explanation
History of subfertility [2] Ovulation is an essential factor needed for the fertility. Matured ovum is released with the ovulation which usually occurs nearly 14 days prior to the onset of menstruation. Anovulation or the absence of the ovulation is a major factor contributing to the subfertility. [1,4] Normal ovulation is controlled by the hypothalamo pituitary ovarian axis where the secretion of gonadotrophin releasing hormone by hypothalamus acts on the anterior pituitary to release follicular stimulating hormone and luteinizing hormone. This FSH and LH act on the ovary inducing the follicular maturation and release of oestrogen. [3] Anovulation [1] may be due to the problems at various levels of this axis such as hypothalamus, pituitary and ovary. Commonest cause of anovulation is polycystic ovarian disease [1] which is a heterogenous multifactorial condition. Polycystic ovarian disease is diagnosed with the presence of 2 out of 3 criteria: Amenorrhoea/oligomenorrhoea, hyperandrogenism [1] and polycystic ovaries on ultrasound scan.
History of irregular menstruation Usually ovulatory cycles are associated with regular monthly bleeding. Ovulation may also be indicated by mid cycle pain. Irregular bleeding is a feature of PCOD. There is either oligomenorrhoea [1] (cycle duration more than 35 days ) or amenorrhoea [1] (absence of menstruation).
Polyuria and polydipsia Insulin resistance causing diabetes mellitus [1] is a feature of PCOD which may be due to defect in insulin receptors.
History of hypertension and heart disease PCOD increase the risk of these metabolic complications. [1]
Excessive body hair growth Hirsuitism [1] is a complication due to hyperandrogenism.
History of infection, autoimmune disorders, surgery or radiotherapy related/ affects the ovaries These can cause premature ovarian failure. [3]
Vaginal dryness, night sweats, or hot flushes Vaginal dryness, night sweats, or hot flushes are seen in premature ovarian failure associate with low oestrogen levels. [2]
References
  1. SAM S. Obesity and Polycystic Ovary Syndrome Obes Manag [online] 2007 Apr, 3(2):69-73 [viewed 13 September 2014] Available from: doi:10.1089/obe.2007.0019
  2. SOAVE I, LO MONTE G, MARCI R. POI: Premature Ovarian Insufficiency/Pregnancy or Infertility? N Am J Med Sci [online] 2013 Jan, 5(1):71 [viewed 24 August 2014] Available from: doi:10.4103/1947-2714.106217
  3. PENEFSKY HS. Mechanism of inhibition of mitochondrial adenosine triphosphatase by dicyclohexylcarbodiimide and oligomycin: relationship to ATP synthesis. Proc Natl Acad Sci U S A [online] 1985 Mar, 82(6):1589-1593 [viewed 24 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC397317
  4. RAJASHEKAR L, KRISHNA D, PATIL M. Polycystic ovaries and infertility: Our experience J Hum Reprod Sci [online] 2008, 1(2):65-72 [viewed 13 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2700664

Examination

Fact Explanation
Obesity High body mass index is found in patients with PCOD. [3]
Acne, hirsuitism (excessive body hair) and alopecia Features of hyperandrogenism [2] are due to the hypersecretion of androgens by the theca cells in the ovaries due to the stimulation of LH.
Acanthosis nigricans Insulin resistance [3] is a feature of PCOD which may be due to defect in insulin receptors. Acanthosis negricans is the skin lesions characterized by velvety, brownish-black pigmentation of the skin of the posterior aspect of the neck, axillae, elbows and knees. [4]
Wide carrying angle, shield chest, low hair line, short stature etc. Turner’s syndrome is a recognized cause of ovarian dysfunction. [1]
References
  1. PENEFSKY HS. Mechanism of inhibition of mitochondrial adenosine triphosphatase by dicyclohexylcarbodiimide and oligomycin: relationship to ATP synthesis. Proc Natl Acad Sci U S A [online] 1985 Mar, 82(6):1589-1593 [viewed 24 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC397317
  2. BENTLEY-LEWIS R, SEELY E, DUNAIF A. Ovarian Hypertension: Polycystic Ovary Syndrome Endocrinol Metab Clin North Am [online] 2011 Jun, 40(2):433-x [viewed 24 August 2014] Available from: doi:10.1016/j.ecl.2011.01.009
  3. SAM S. Obesity and Polycystic Ovary Syndrome Obes Manag [online] 2007 Apr, 3(2):69-73 [viewed 13 September 2014] Available from: doi:10.1089/obe.2007.0019
  4. DASSANAYAKE ANURADHA S, KASTURIRATNE ANURADHANI, NIRIELLA MADUNIL A, KALUBOVILA UDAYA, RAJINDRAJITH SHAMAN, DE SILVA ARJUNA P, KATO NORIHIRO, WICKREMASINGHE A RAJITHA, DE SILVA H JANAKA. Prevalence of Acanthosis Nigricans in an urban population in Sri Lanka and its utility to detect metabolic syndrome. Array [online] 2011 December [viewed 13 September 2014] Available from: doi:10.1186/1756-0500-4-25

Differential Diagnoses

Fact Explanation
Pregnancy [3] Pregnancy should be excluded in people with period of amenorrhoea. [3] They may have other features suggestive of pregnancy such as nausea, vomiting [5] , urinary frequency and faintishness. Urine or serum beta hCG needs to be done in a suspicious conditions.
Use of contraceptive methods Contraceptives that contain oestrogen and progesterone alone or in combination will cause amenorrhoea. [4]
Premature ovarian failure [2] This is a heterogeneous disorder leading to ovarian failure before the age of 40 years and causes secondary amenorrhea. [1] Low Levels of gonadal hormones (estrogens and inhibins) will be low and level of gonadotropins [luteinizing hormone (LH) and Follicle stimulating hormone (FSH)] are usually increased.
References
  1. PENEFSKY HS. Mechanism of inhibition of mitochondrial adenosine triphosphatase by dicyclohexylcarbodiimide and oligomycin: relationship to ATP synthesis. Proc Natl Acad Sci U S A [online] 1985 Mar, 82(6):1589-1593 [viewed 24 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC397317
  2. SOAVE I, LO MONTE G, MARCI R. POI: Premature Ovarian Insufficiency/Pregnancy or Infertility? N Am J Med Sci [online] 2013 Jan, 5(1):71 [viewed 24 August 2014] Available from: doi:10.4103/1947-2714.106217
  3. SAID-AHMED K, MOUSTAFA G, FAWZY M. Incidence and Natural Course of Symptomatic Central Serous Chorioretinopathy in Pregnant Women in a Maternity Hospital in Kuwait Middle East Afr J Ophthalmol [online] 2012, 19(3):273-276 [viewed 13 September 2014] Available from: doi:10.4103/0974-9233.97920
  4. SHEARMAN RP. Post-pill amenorrhoea. Br Med J [online] 1977 Nov 26, 2(6099):1414 [viewed 13 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1632379
  5. LACASSE A, REY E, FERREIRA E, MORIN C, BéRARD A. Epidemiology of nausea and vomiting of pregnancy: prevalence, severity, determinants, and the importance of race/ethnicity BMC Pregnancy Childbirth [online] :26 [viewed 13 September 2014] Available from: doi:10.1186/1471-2393-9-26

Investigations - for Diagnosis

Fact Explanation
LH and FSH levels LH:FSH ratio is usually increaed (LH/FSH ratio >2:1) in polycystic ovarian disease. FSH level is usually > 40 mUI/mL in premature ovarian failure. [2]
Day 21 day progesterone levels This is done on day 21 of menstrual cycle. Usually progesterone are elevated in the luteal phase of the cycle following ovulation. Estradiol (E2)level would be < 40 pg/mL in premature ovarian failure. [4]
Anti- Mullerian hormone (AMH) This is a new diagnostic method for premature ovarian failure. It is produced by antral follicles and secretion is decreased in these patients. [1]
Ultrasound scan [2] For the diagnosis of PCOD, 12 or more antral follicles in one ovary and volume of ovary more than 10 ml is a useful criteria. [3]
References
  1. PENEFSKY HS. Mechanism of inhibition of mitochondrial adenosine triphosphatase by dicyclohexylcarbodiimide and oligomycin: relationship to ATP synthesis. Proc Natl Acad Sci U S A [online] 1985 Mar, 82(6):1589-1593 [viewed 24 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC397317
  2. BENTLEY-LEWIS R, SEELY E, DUNAIF A. Ovarian Hypertension: Polycystic Ovary Syndrome Endocrinol Metab Clin North Am [online] 2011 Jun, 40(2):433-x [viewed 24 August 2014] Available from: doi:10.1016/j.ecl.2011.01.009
  3. SAM S. Obesity and Polycystic Ovary Syndrome Obes Manag [online] 2007 Apr, 3(2):69-73 [viewed 13 September 2014] Available from: doi:10.1089/obe.2007.0019
  4. QUAAS A, DOKRAS A. Diagnosis and Treatment of Unexplained Infertility Rev Obstet Gynecol [online] 2008, 1(2):69-76 [viewed 13 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2505167

Investigations - Fitness for Management

Fact Explanation
Fasting blood sugar/HbA1c To check the glycaemic state as there can be associated diabetes mellitus in PCOD. [1]
References
  1. BENTLEY-LEWIS R, SEELY E, DUNAIF A. Ovarian Hypertension: Polycystic Ovary Syndrome Endocrinol Metab Clin North Am [online] 2011 Jun, 40(2):433-x [viewed 24 August 2014] Available from: doi:10.1016/j.ecl.2011.01.009

Investigations - Followup

Fact Explanation
Ultrasound scan For the follow up of PCOD, and in people with subfertility.[1]
Androgen levels: dyhydroepiandrosterone sulfate, androstendione and sex hormone binding globulin To evaluate the hyperandrogenism. [3]
Serum prolactin level May be needed in hyperprolacinaemia. [2]
References
  1. BENTLEY-LEWIS R, SEELY E, DUNAIF A. Ovarian Hypertension: Polycystic Ovary Syndrome Endocrinol Metab Clin North Am [online] 2011 Jun, 40(2):433-x [viewed 24 August 2014] Available from: doi:10.1016/j.ecl.2011.01.009
  2. SEPPăLă M, HIBROVEN E, RANTA T, VIRKKUNEN P, LEPPăLUOTO J. Raised serum prolactin levels in amenorrhoea. Br Med J [online] 1975 May 10, 2(5966):305-306 [viewed 13 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1681912
  3. SAM S. Obesity and Polycystic Ovary Syndrome Obes Manag [online] 2007 Apr, 3(2):69-73 [viewed 13 September 2014] Available from: doi:10.1089/obe.2007.0019

Investigations - Screening/Staging

Fact Explanation
Androgen levels: dyhydroepiandrosterone sulfate, androstendione and sex hormone binding globulin [2] To evaluate the hyperandrogenism. [2]
Serum prolactin level Elevated prolactin is seen in hyperprolacinaemia. [3]
Anti-adrenal, anti-ovarian and anti-thyroid autoantibodies Important to diagnose the immune system deficiency leading to premature ovarian failure. [1]
Karyotyping Important to exclude major genetic causes. [1]
Thyroid stimulating hormone-TSH Hypothyroidism may be a cause for the anovulation. [3]
References
  1. PENEFSKY HS. Mechanism of inhibition of mitochondrial adenosine triphosphatase by dicyclohexylcarbodiimide and oligomycin: relationship to ATP synthesis. Proc Natl Acad Sci U S A [online] 1985 Mar, 82(6):1589-1593 [viewed 24 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC397317
  2. SAM S. Obesity and Polycystic Ovary Syndrome Obes Manag [online] 2007 Apr, 3(2):69-73 [viewed 13 September 2014] Available from: doi:10.1089/obe.2007.0019
  3. SEPPăLă M, HIBROVEN E, RANTA T, VIRKKUNEN P, LEPPăLUOTO J. Raised serum prolactin levels in amenorrhoea. Br Med J [online] 1975 May 10, 2(5966):305-306 [viewed 13 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1681912

Management - General Measures

Fact Explanation
Management of PCOD with weight reduction First step is weight reduction which itself may be a factor for improving the fertility. Other complications such as menstrual irregularities, subfertility, insulin resistance, [3] hyperandrogenism and other metabolic disorders need specific management. [2]
Psychological support [1] Patients may be suffering from problems such as subfertllity, that may need psuchological support. [1]
References
  1. PENEFSKY HS. Mechanism of inhibition of mitochondrial adenosine triphosphatase by dicyclohexylcarbodiimide and oligomycin: relationship to ATP synthesis. Proc Natl Acad Sci U S A [online] 1985 Mar, 82(6):1589-1593 [viewed 24 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC397317
  2. NDEFO UA, EATON A, GREEN MR. Polycystic Ovary Syndrome: A Review of Treatment Options With a Focus on Pharmacological Approaches P T [online] 2013 Jun, 38(6):336-355 [viewed 24 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3737989
  3. SAM S. Obesity and Polycystic Ovary Syndrome Obes Manag [online] 2007 Apr, 3(2):69-73 [viewed 13 September 2014] Available from: doi:10.1089/obe.2007.0019

Management - Specific Treatments

Fact Explanation
Management of subfertility Ovulation can be induced with various methods. Clomiphine citrate, FSH, and ovarian drilling are the some methods used for ovulation induction. Clomiphine usually starts with a dose of 5omg from day 2-6 of menstrual cycle, after that day 12 scan is performed to see the size of the matured follicle. HCG injection is later given. FSH can be used further for a improved response. Human menopausal gonadotropin (HMG) [6] and FSH can be used to induce ovulation if clomiphene and/or metformin therapy fails. Drilling is a procedure done laparoscopically. Intrauterine insemination (IUI) cycles, and in vitro fertilization (IVF) [6] cycles are particularly useful in people with ovarian failure. [3]
Menstrual regulation Usually ovulatory cycles are associated with regular monthly bleeding. Ovulation may also be indicated by mid cycle pain. Irregular bleeding is a feature of PCOD. There is either oligomenorrhoea [5] (cycle duration more than 35 days ) or amenorrhoea [5] (absence of menstruation).
Management of hyperandrogenism [3] Hyperandrogenism needs treatment with cyprone acetate, Spironolactone , flutamide and finasteride are antiandrogens that decreasing androgen levels. [3]
Medroxyprogesterone acetate [3] Dosage regimen medroxyprogesterone acetate [3] is 5 to 10 mg/day for 10 to 14 days each month. This is used to treat amenorrhea or dysfunctional uterine bleeding in women with PCOS.
Aromatase inhibitors Letrozole is an aromatase inhibitor usually used for the hormone-responsive breast cancer. It is also useful in treating induction of ovulation in PCOS. [3]
Antidiabetic agents Antidiabetic drugs are used to improve fertility, decrease insulin resistance, and reduce circulating androgen levels. [3]
The hormone replacement therapy (HRT) This is used for the management for premature ovarian failure patients. Estrogen replacement decrease the risk of osteoporosis and cardiovascular disease. [1]
Management of hyperprolactinaemia [2] This is done using prolactin sparing agents like olanzapine, quetiapine, aripiprazole, or clozapine is important in patients taking antipsychotics. Bromocriptine [4] , cabergoline, quinagolide, and amantadine are some common dopamine agonist that correct the prolactin level.
References
  1. PENEFSKY HS. Mechanism of inhibition of mitochondrial adenosine triphosphatase by dicyclohexylcarbodiimide and oligomycin: relationship to ATP synthesis. Proc Natl Acad Sci U S A [online] 1985 Mar, 82(6):1589-1593 [viewed 24 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC397317
  2. BARGIOTA SI, BONOTIS KS, MESSINIS IE, ANGELOPOULOS NV. The Effects of Antipsychotics on Prolactin Levels and Women's Menstruation Schizophr Res Treatment [online] 2013:502697 [viewed 24 August 2014] Available from: doi:10.1155/2013/502697
  3. NDEFO UA, EATON A, GREEN MR. Polycystic Ovary Syndrome: A Review of Treatment Options With a Focus on Pharmacological Approaches P T [online] 2013 Jun, 38(6):336-355 [viewed 24 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3737989
  4. SEPPăLă M, HIBROVEN E, RANTA T, VIRKKUNEN P, LEPPăLUOTO J. Raised serum prolactin levels in amenorrhoea. Br Med J [online] 1975 May 10, 2(5966):305-306 [viewed 13 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1681912
  5. SAM S. Obesity and Polycystic Ovary Syndrome Obes Manag [online] 2007 Apr, 3(2):69-73 [viewed 13 September 2014] Available from: doi:10.1089/obe.2007.0019
  6. QUAAS A, DOKRAS A. Diagnosis and Treatment of Unexplained Infertility Rev Obstet Gynecol [online] 2008, 1(2):69-76 [viewed 13 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2505167