section name header

Information

Editors

LaureMorin-Papunen

Polycystic Ovary Syndrome (PCOS)

Essentials

  • Polycystic ovary syndrome is not purely a gynaecological problem.
  • Diagnosis can be made if the patient has at least two of the following: menstrual disorder (infrequent menstrual periods - cycle more than 35 days - or amenorrhoea), hyperandrogenism, polycystic ovaries.
  • Polycystic ovary syndrome is associated with reduced insulin sensitivity which may lead to increased health risks.

Prevalence and consequences

  • The prevalence of PCOS is estimated to be 5-15% in women of reproductive age.
  • PCOS will mean increased morbidity at various stages throughout the woman's life.

Gynaecological problems

  • Patients usually present with menstrual irregularities, hirsutism and infertility problems.
  • Pregnancies appear to be associated with a higher risk of miscarriage, hypertension and diabetes. The increased risk is, however, likely to be associated with obesity rather than with PCOS as such.
  • Long-term oestrogenic activity with simultaneous lack of luteal hormone activity predispose to endometrial hyperplasia and thus increase the risk of cancer of the uterine corpus. It has been reported that the risk of uterine cancer is increased 2-6 -fold in women with PCOS as compared with the general population. However, it is difficult to distinguish between the increased risk caused by obesity and that by PCOS, and large-scale epidemiological studies are needed.
  • There is no evidence of a link with breast or ovarian cancer.

Metabolic disturbances

  • Women with PCOS often have reduced insulin sensitivity which is associated with truncal obesity and disturbances in lipid metabolism.
  • Depending on the population, 20-70% of the women with PCOS are overweight.
  • Insulin resistance and the resulting compensatory increased concentration of insulin are more marked in overweight patients with PCOS than in otherwise overweight controls.
  • Typical findings include low plasma HDL-cholesterol concentration and hypertriglyceridaemia.
  • PCOS appears to increase the risk of developing type 2 diabetes at a considerably early age (the risk is 5-10-fold) and hypertension (the risk is 2-3-fold).
  • The risk of venous thrombosis is 1.5-2-fold and the risk of stroke 2-fold in women with PCOS.
  • The risk of cardiovascular diseases seems to be increased already at young age.
  • The risk of complications associated with cerebrovascular disease and diabetes is increased.

Other disturbances

  • Women with PCOS have additionally an increased risk of many other diseases, such as thyroid diseases (3-fold), asthma (1.5-fold), depression (3-fold), anxiety disorders (1.4-fold) and migraine (2-fold).

Diagnosis

  • Diagnosis is based on the history, clinical findings (menstrual irregularities, male pattern of hair distribution, acne) and, if necessary, on hormone studies.
  • A gynaecological ultrasound examination is used to verify the diagnosis; polycystic morphology of the ovaries is evident.
  • Two of the following criteria must be present for PCOS diagnosis:
    • anovulation characterized by menstrual irregularities (oligomenorrhoea, i.e. cycle duration more than 35 days, or amenorrhoea)
    • clinical (male pattern of hair distribution) or biochemical hyperandrogenism (serum testosterone > 2.7 nmol/l or > 2.3 nmol/l depending on the method and laboratory)
    • polycystic morphology of the ovaries, verified by ultrasound examination (presence of 20 or more follicles in each ovary measuring 2-9 mm in diameter, and/or increased ovarian volume).
  • Exclude thyroid disease, hyperprolactinaemia, androgen-secreting tumours and disturbances in adrenal function.
    • If the patient presents with menstrual irregularities, measure serum TSH and prolactin to exclude other causes. Remember to exclude eating disorders.
    • If the patient presents with hirsutism and/or acne, measure serum testosterone.
    • Serum FSH and LH concentrations should be determined for differential diagnostics of menstrual disorders. Serum oestradiol assay is not usually of diagnostic benefit.
  • Due to the risk of metabolic disturbances the following screening is indicated, particularly in overweight patients:
    • blood glucose, lipids (cholesterol, HDL cholesterol, LDL cholesterol, triglycerides) and blood pressure at regular intervals (for example every one to two years)
    • HbA1c in overweight and obese persons as well as in persons with substantial increase in weight, followed by regular testing (for example every 2-3 years).

Treatment

  • The most important treatment form is weight reduction down to the patient's normal weight. Weight reduction may
  • Exercise reduces insulin resistance .
  • Smoking cessation is important due to the increased risk of vascular diseases.

Hormone treatment

Treatment of anovulatory infertility

  • Refer a PCOS patient at an earlier stage than usual to a gynaecologist familiar with infertility treatments.

Metformin

  • Metformin, combined with lifestyle changes, may have beneficial effects on metabolic risk factors and restoration of ovulation Metformin for Polycystic Ovary Syndrome. Not enough evidence is available on whether long-term use of metformin reduces the risk of developing metabolic diseases.
  • Always consult a gynaecologist before prescribing metformin to discuss its use on an individual basis.
    • If there is no urgent need for infertility treatment, metformin may be helpful also in losing weight.
    • Metformin seems to improve fertilization and live birth ratesMetformin for Polycystic Ovary Syndrome.
    • It may be used also in combination with an ovulation induction drugMetformin Combined with Gonadotrophins during Ovulation Induction for Subfertility in Polycystic Ovary Syndrome, if the patient does not ovulate using the maximal dosage.
      • Metformin started 3 months earlier and combined with ovulation induction drug (gonadotropin) improves both pregnancy and live birth rates by up to 15%.
      • For the time being there are no studies on combining metformin and aromatase inhibitor drugs, but such combination therapy is nowadays routinely used (see Other treatments of anovulation).
    • Although metformin may further weight loss, there is not enough evidence on whether metformin is more effective in overweight PCOS women compared with normal-weight PCOS women.
    • Use of metformin during IVF treatment may reduce the risk of hyperstimulation Metformin Treatment Before and during Ivf or Icsi in Women with Polycystic Ovary Syndrome.
    • Metformin does not appear to decrease the risk of miscarriage in women with PCOS.
    • According to current practice, metformin is discontinued when a pregnancy test is positive.
    • If the patient has earlier had gestational diabetes, the further use of metformin during pregnancy should be discussed with an obstetrician with expertise in the topic.
    • Metformin has been presumed to possibly reduce the occurence of gestational complications, such as pre-eclampsia and gestational diabetes, but no significant effect has been verified in adequately large placebo-controlled studies.
    • Use of metformin during pregnancy may reduce the risk of prematurity.

Other treatments of anovulation

  • All other ovulation induction treatment is carried out by a gynaecologist who has expertise in fertility treatment.
  • Aromatase inhibitors (letrozole and the more rarely used anastrozole) are the primary drugs for inducing ovulation in PCOS and they have in Finland completely replaced clomiphene which was used earlier.
  • Aromatase inhibitors are drugs used in breast cancer therapy. They prevent oestrogen production in the ovaries. As a result, the inhibitory effect of oestrogens on gonadotropin secretion decreases and the secretion of gonadotropins increases, which stimulates ovarian follicle growth.
  • The next step is ovarian diathermy (”drilling”) or the use of gonadotropins. Gonadotropin treatment is more problematic than letrozole treatment and it is expensive.
    • Gonadotropins are injected daily, and ovulation induction may take a long time. The treatment requires repeated ultrasound examinations, and still the risk of multiple pregnancy or hyperstimulation remains.
    • Laparoscopic ovarian drilling has recently regained popularity along with the development of new techniques. Treatment costs are considerably lower than those of gonadotropin treatment, and the method has been found to be equally effectiveLaparoscopic ”drilling” for Ovulation Induction in Polycystic Ovary Syndrome and to reduce the risk of multiple pregnancy. The choice between drilling and gonadotropins is made on an individual basis.
  • If conception does not occur with ovulation induction, in vitro fertilization is considered.

References

  • Pierpoint T, McKeigue PM, Isaacs AJ, Wild SH, Jacobs HS. Mortality of women with polycystic ovary syndrome at long-term follow-up. J Clin Epidemiol 1998 Jul;51(7):581-6. [PubMed]
  • Hardiman P, Pillay OC, Atiomo W. Polycystic ovary syndrome and endometrial carcinoma. Lancet 2003 May 24;361(9371):1810-2. [PubMed]
  • The Rotterdam ESHRE/ASRM-Sponsored PCOS consensus workshop group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod 2004 Jan;19(1):41-7. [PubMed]
  • Teede HJ, Misso ML, Costello MF et al. Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome. Fertil Steril 2018;110(3):364-379.[PubMed]
  • Practice Committee of the American Society for Reproductive Medicine. Electronic address: ASRM@asrm.org., Practice Committee of the American Society for Reproductive Medicine.. Role of metformin for ovulation induction in infertile patients with polycystic ovary syndrome (PCOS): a guideline. Fertil Steril 2017;108(3):426-441.[PubMed]
  • Glueck CJ, Goldenberg N, Wang P, Loftspring M, Sherman A. Metformin during pregnancy reduces insulin, insulin resistance, insulin secretion, weight, testosterone and development of gestational diabetes: prospective longitudinal assessment of women with polycystic ovary syndrome from preconception throughout pregnancy. Hum Reprod 2004 Mar;19(3):510-21. [PubMed]
  • Morin-Papunen L, Rantala AS, Unkila-Kallio L et al. Metformin improves pregnancy and live-birth rates in women with polycystic ovary syndrome (PCOS): a multicenter, double-blind, placebo-controlled randomized trial. J Clin Endocrinol Metab 2012;97(5):1492-500. [PubMed]
  • Kjøtrød SB, Carlsen SM, Rasmussen PE et al. Use of metformin before and during assisted reproductive technology in non-obese young infertile women with polycystic ovary syndrome: a prospective, randomized, double-blind, multi-centre study. Hum Reprod 2011;26(8):2045-53. [PubMed]
  • Vanky E, Stridsklev S, Heimstad R et al. Metformin versus placebo from first trimester to delivery in polycystic ovary syndrome: a randomized, controlled multicenter study. J Clin Endocrinol Metab 2010;95(12):E448-55. [PubMed]
  • Pavone ME, Bulun SE. Clinical review: The use of aromatase inhibitors for ovulation induction and superovulation. J Clin Endocrinol Metab 2013;98(5):1838-44. [PubMed]
  • Goodman NF, Cobin RH, Futterweit W et al. American Association of Clinical Endocrinologists, American College of Endocrinology, and Androgen Excess and PCOS Society disease state clinical review: Guide to the best practices in the evaluation and treatment of polycystic ovary syndrome - Part 1. Endocr Pract 2015;21(11):1291-300. [PubMed]
  • Legro RS, Brzyski RG, Diamond MP et al. Letrozole versus clomiphene for infertility in the polycystic ovary syndrome. N Engl J Med 2014;371(2):119-29. [PubMed]
  • Barry JA, Azizia MM, Hardiman PJ. Risk of endometrial, ovarian and breast cancer in women with polycystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod Update 2014;20(5):748-58. [PubMed]
  • Glintborg D, Hass Rubin K, Nybo M et al. Morbidity and medicine prescriptions in a nationwide Danish population of patients diagnosed with polycystic ovary syndrome. Eur J Endocrinol 2015;172(5):627-38. [PubMed]
  • Amsterdam ESHRE/ASRM-Sponsored 3rd PCOS Consensus Workshop Group.. Consensus on women's health aspects of polycystic ovary syndrome (PCOS). Hum Reprod 2012;27(1):14-24. [PubMed]
  • Sharpe A, Morley LC, Tang T et al. Metformin for ovulation induction (excluding gonadotrophins) in women with polycystic ovary syndrome. Cochrane Database Syst Rev 2019;12():CD013505. [PubMed]
  • Tso LO, Costello MF, Albuquerque LET et al. Metformin treatment before and during IVF or ICSI in women with polycystic ovary syndrome. Cochrane Database Syst Rev 2020;12():CD006105. [PubMed]
  • Cao Q, Hu Y, Fu J et al. Gestational metformin administration in women with polycystic ovary syndrome: A systematic review and meta-analysis of randomized control studies. J Obstet Gynaecol Res 2021;47(12):4148-4157. [PubMed]