Polycystic Ovary Syndrome.
Classification and external resources

A polycystic ovary (aka PCO) shown on an ultrasound image. PCO is not necessary for diagnosing PCOS, but is a common sign. As many as 30% or more of women with PCOS do not have PCO as a sign.
10 E28.2
9 256.4
OMIM 184700
MedlinePlus 000369
eMedicine med/2173 ped/2155 radio/565
MeSH D011085

Polycystic ovary syndrome (PCOS) is one of the most common female [3]

PCOS produces symptoms in approximately 5% to 10% of women of reproductive age (12–45 years old). It is thought to be one of the leading causes of [7]

The principal features are anovulation, resulting in irregular menstruation, amenorrhea, ovulation-related infertility, and polycystic ovaries; excessive amounts or effects of androgenic hormones, resulting in acne and hirsutism; and insulin resistance, often associated with obesity, Type 2 diabetes, and high cholesterol levels.[8] The symptoms and severity of the syndrome vary greatly among affected women.

[edit] Classification

The corpus luteum, which shrinks and disappears after approximately 12–14 days. In PCOS, there is a so-called “follicular arrest”, i.e., several follicles develop to a size of 5–7 mm, but not further. No single follicle reaches the preovulatory size (16 mm or more).

[edit] Signs and symptoms

PCOS includes a heterogeneous collection of signs and symptoms with varying degree of mildness and severity in affecting the reproductive, endocrine and metabolic functions.[11] The classic triad of the disorder includes hirsutism, menstrual dysfunction, and obesity. Some common symptoms of PCOS include:

Clinical signs and symptoms associated with PCOS[16]
Symptom Frequency
Oligomenorrea 29-52%
Amenorrea 19-51%
Hirsutism 64-69%
Obesity 35-41%
Acne 27-35%
Alopecia 3-6%
Acanthosis nigricans <1-3%
Infertility 20-74%
Elevated Serum LH 40-51%
Elevated testosterone 29-50%

[edit] Diagnosis

In 1990, a consensus workshop sponsored by the NIH/NICHD suggested that a patient has PCOS if she has all of the following:[17]

  1. oligoovulation
  2. signs of androgen excess (clinical or biochemical). Androgen excess can be tested by measuring total and free testosterone levels. Other androgens, such as DHEA-S, may be normal or slightly above the normal range in patients with polycystic ovarian syndrome (PCOS) while levels of sex hormone–binding globulin (SHBG) are usually low in patients with PCOS. Androstenedione levels are also elevated in women with PCOS. This androgen precursor is 60% ovarian and 40% adrenal in derivation.[18]
  3. other entities are excluded that would cause polycystic ovaries

More recently, in 2003, a consensus workshop sponsored by [20]

  1. oligoovulation and/or anovulation
  2. excess androgen activity
  3. polycystic ovaries (by [22]

The initial NIH diagnostic criteria based on oligomenorrhoea/amenorrhoea and clinical or biochemical hyperandrogenism have been broadened in the 2003 Rotterdam diagnostic criteria to include polycystic ovaries (PCO) at ultrasound as a key diagnostic criteria. A total of 25% of young women have PCO on ultrasound and the inclusion of PCO in diagnostic criteria has increased the prevalence of PCOS. Earlier studies conducted in Greece, Spain and USA using the NIH criteria estimated the prevalence of PCOS at 4% to 8%. However, the first community-based prevalence study based on current Rotterdam diagnostic criteria conducted recently has shown the prevalence of PCOS to be 18%.[24]

In 2006, the Androgen Excess & PCOS Society suggested a tightening of the diagnostic criteria to all of:[7]

  1. excess androgen activity
  2. oligoovulation/anovulation and/or polycystic ovaries
  3. other entities are excluded that would cause excess androgen activity

A recent study found that a questionnaire addressing the history of menstrual pattern, obesity and hirsutism can diagnose PCOS, according to a [26]

[edit] Common assessments for associated conditions or risks

  • Fasting biochemical screen and lipid profile[18]
  • 2-hour oral [7]
  • Fasting insulin level or GTT with insulin levels (also called IGTT). Elevated insulin levels have been helpful to predict response to medication and may indicate women who will need higher dosages of metformin or the use of a second medication to significantly lower insulin levels. Elevated citation needed]
  • [27]

[edit] Differential diagnosis

Other causes of irregular or absent menstruation and hirsutism, such as citation needed]

[edit] Cause

PCOS is a complex, heterogeneous disorder of uncertain aetiology.[3]

The genetic component appears to be inherited in an [31]

The clinical severity of PCOS symptoms appears to be largely determined by factors such as obesity.[7]

[edit] Pathogenesis

Polycystic ovaries develop when the ovaries are stimulated to produce excessive amounts of male hormones (androgens), particularly testosterone, by either one or a combination of the following (almost certainly combined with genetic susceptibility[29]):

  • the release of excessive citation needed]
  • through high levels of insulin in the blood (hyperinsulinaemia) in women whose ovaries are sensitive to this stimulus[12]

Alternatively or as well, reduced levels of sex-hormone binding globulin can result in increased free androgens.[citation needed]

The syndrome acquired its most widely used name due to the common sign on ultrasound examination of multiple (poly) ovarian cysts. These “cysts” are actually immature follicles, not cysts (“polyfollicular ovary syndrome” would have been a more accurate name). The follicles have developed from primordial follicles, but the development has stopped (“arrested”) at an early antral stage due to the disturbed ovarian function. The follicles may be oriented along the ovarian periphery, appearing as a ‘string of pearls’ on ultrasound examination.[citation needed]

Women with PCOS have higher GnRH, which in turn results in an increase in LH/FSH ratio.[32]

A majority of patients with PCOS have insulin resistance and/or are obese. Their elevated insulin levels contribute to or cause the abnormalities seen in the hypothalamic-pituitary-ovarian axis that lead to PCOS. Hyperinsulinemia increases GnRH pulse frequency, LH over FSH dominance, increased ovarian androgen production,[12] decreased follicular maturation, and decreased SHBG binding; all these steps contribute to the development of PCOS.[citation needed] Insulin resistance is a common finding among patients of normal weight as well as overweight patients.[7][15]

In many cases PCOS is characterised by a complex positive feedback loop of insulin resistance and hyperandrogenism. In most cases it can not be determined which (if any) of those two should be regarded causative. Experimental treatment with either antiandrogens or insulin sensitizing agents improves both hyperandrogenism and insulin resistance.[citation needed]

Adipose tissue possesses aromatase, an enzyme that converts androstenedione to estrone and testosterone to estradiol. The excess of adipose tissue in obese patients creates the paradox of having both excess androgens (which are responsible for hirsutism and virilization) and estrogens (which inhibits FSH via negative feedback).[33]

PCOS may be associated with chronic inflammation,[36]

It has previously been suggested that the excessive androgen production in PCOS could be caused by a decreased serum level of IGFBP-1, in turn increasing the level of free IGF-I which stimulates ovarian androgen production, but recent data concludes this mechanism to be unlikely.[37]

PCOS has also been associated with a specific FMR1 sub-genotype. The research suggests that women who have heterozygous-normal/low FMR1 have polycystic-like symptoms of excessive follicle-activity and hyperactive ovarian function.[38]

[edit] Management

Medical treatment of PCOS is tailored to the patient’s goals. Broadly, these may be considered under four categories:

  • Lowering of insulin levels
  • Restoration of fertility
  • Treatment of hirsutism or acne
  • Restoration of regular menstruation, and prevention of endometrial cancer

In each of these areas, there is considerable debate as to the optimal treatment. One of the major reasons for this is the lack of large scale clinical trials comparing different treatments. less reliable and hence may produce conflicting results.

General interventions that help to reduce weight or insulin resistance can be beneficial for all these aims, because they address what is believed to be the underlying cause.

In addition, as PCOS appears to cause significant emotional distress, it is recommended that clinicians discuss emotional aspects of PCOS with patients and refer for appropriate support where necessary and in accordance with patient preference.[39]

[edit] Diet

Where PCOS is associated with overweight or obesity, successful weight loss is the most effective method of restoring normal ovulation/menstruation, but many women find it very difficult to achieve and sustain significant weight loss. [40] so treatment of any such deficiency is indicated.

[edit] Medications

Reducing insulin resistance by improving insulin sensitivity through medications such as [45]

[edit] Infertility

Not all women with PCOS have difficulty becoming pregnant. For those who do, anovulation or infrequent ovulation is a common cause. Other factors include changed levels of gonadotropins, hyperandrogenemia and hyperinsulinemia.[46] Like women without PCOS, women with PCOS who are ovulating may be infertile due to other causes, such as tubal blockages due to a history of sexually transmitted diseases.

For overweight, anovulatory women with PCOS, weight loss and diet adjustments, especially to reduce the intake of simple carbohydrates, are associated with resumption of natural ovulation.

For those who after weight loss still are anovulatory or for anovulatory lean women, then the ovulation-inducing medications [47]

For patients who do not respond to clomiphene, diet and lifestyle modification, there are options available including in vitro fertilisation (IVF).

Though surgery is not commonly performed, the polycystic ovaries can be treated with a laparoscopic procedure called “ovarian drilling” (puncture of 4–10 small follicles with electrocautery, laser, or biopsy needles), which often results in either resumption of spontaneous ovulations[40] or ovulations after adjuvant treatment with clomiphene or FSH.[citation needed] (Ovarian wedge resection is no longer used as much due to complications such as adhesions and the presence of frequently effective medications.) There are, however, concerns about the long-term effects of ovarian drilling on ovarian function.[40]

[edit] Hirsutism and acne

When appropriate (e.g. in women of child-bearing age who require contraception), a standard contraceptive pill is frequently effective in reducing hirsutism.[12][40] A common choice of contraceptive pill is one that contains cyproterone acetate; in the UK the available brands are Dianette/Diane. Cyproterone acetate is a progestogen with anti-androgen effects that block the action of male hormones that are believed to contribute to acne and the growth of unwanted facial and body hair.[citation needed] On the other hand, progestogens such as norgestrel and levonorgestrel should be avoided due to their androgenic effects.[40]

Other drugs with anti-androgen effects include flutamide[48] and spironolactone,[12][40] which can give some improvement in hirsutism. Spironolactone is probably the most-commonly used drug in the US. Metformin can reduce hirsutism, perhaps by reducing insulin resistance, and is often used if there are other features such as insulin resistance, diabetes or obesity that should also benefit from metformin. Eflornithine (Vaniqa) is a drug which is applied to the skin in cream form, and acts directly on the hair follicles to inhibit hair growth. It is usually applied to the face.[40] Medications that reduce acne by indirect hormonal effects also include ergot dopamine agonists such as bromocriptine.[citation needed] 5-alpha reductase inhibitors (such as finasteride and dutasteride) may also be used;[49] they work by blocking the conversion of testosterone to dihydrotestosterone (the latter of which is responsible for most hair growth alterations and androgenic acne).

Although these agents have shown significant efficacy in clinical trials (for oral contraceptives, in 60–100% of individuals[40]), the reduction in hair growth may not be enough to eliminate the social embarrassment of hirsutism, or the inconvenience of plucking or shaving. Individuals vary in their response to different therapies. It is usually worth trying other drug treatments if one does not work, but drug treatments do not work well for all individuals. For removal of facial hairs, electrolysis or laser treatments are – at least for some – faster and more efficient alternatives than the above mentioned medical therapies.[citation needed]

[edit] Menstrual irregularity and endometrial hyperplasia

If fertility is not the primary aim, then menstruation can usually be regulated with a contraceptive pill.[12][40] The purpose of regulating menstruation is essentially for the woman’s convenience, and perhaps her sense of well-being; there is no medical requirement for regular periods, so long as they occur sufficiently often (see below).[citation needed]

If a regular menstrual cycle is not desired, then therapy for an irregular cycle is not necessarily required – most experts consider that if a menstrual bleed occurs at least every three months, then the endometrium (womb lining) is being shed sufficiently often to prevent an increased risk of endometrial abnormalities or cancer.[50] If menstruation occurs less often or not at all, some form of progestogen replacement is recommended.[49] Some women prefer a uterine progestogen device such as the intrauterine system (Mirena) or the progestin implant (Nexplanon), which provides simultaneous contraception and endometrial protection for years.[citation needed] An alternative is oral progestogen taken at intervals (e.g. every three months) to induce a predictable menstrual bleeding.[12]

[edit] Complementary or alternative approaches

At least two inositol isomers – D-chiro-inositol and myo-inositol have shown considerable promise in improving PCOS. They are generally very well tolerated and have been evaluated by several small-scale trials.[51][52][53] Inositol has no documented side-effects and is a naturally occurring human metabolite known to be involved in insulin metabolism.[54] DCI is regulated as a dietary supplement in the United States. Myo-inositol is naturally present in many foods although not readily digestible from most of them.[citation needed]

[edit] Prognosis

Women with PCOS are at risk for the following:

Early diagnosis and treatment may reduce the risk of some of these, such as type 2 diabetes and heart disease.[12]

[edit] Epidemiology

The prevalence of PCOS depends on the choice of diagnostic criteria. One community-based prevalence study using the Rotterdam criteria found that about 18% of women had PCOS, and that 70% of them were previously undiagnosed.[7]

One study in the United Kingdom concluded that the risk of PCOS development was higher in lesbian women than in heterosexuals.[66]

[edit] History

The condition was first described in 1935 by American gynecologists Irving F. Stein, Sr. and Michael L. Leventhal, from whom its original name of Stein-Leventhal syndrome is taken.[68]

[edit] Names

Other names for this syndrome include polycystic ovary disease, functional ovarian hyperandrogenism, ovarian hyperthecosis, sclerocystic ovary syndrome, and Stein-Leventhal syndrome. The eponymous last option is the original name; it is now used, if at all, only for the subset of patients with all the symptoms of amenorrhea with infertility, hirsutism, and enlarged polycystic ovaries.[22]

Most common names for this disease derive from a typical finding on medical images, called a polycystic ovary.string of pearls.

[edit] See also

[edit] References

  1. ^ edit
  2. ^ 12215335.
  3. ^ 17185788.
  4. ^ 18277353.
  5. ^ 18181085.
  6. 15181052.
  7. ^ http://www.biomedcentral.com/1741-7015/8/41. Retrieved 14 November 2011.
  8. ^ “Polycystic ovary syndrome”. http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001408/.
  9. http://books.google.com/books?id=fgMYVxmPDnMC&pg=PA243. Retrieved 5 September 2012.
  10. ^ Wafaa M Aboul Enien; Nadia A Barghash, Fayrouz S Mohamed Ali (24). “Clinical, ultrasonographic and endocrine predictors of ovarian response to clomiphene citrate in normogonadotropic anovulatory infertility”. Middle East Fertility Society Journal. 3 9: 242–250. http://www.bioline.org.br/request?mf04045. Retrieved 10 October 2012.
  11. http://books.google.com/books?id=S6Ngka-rhakC&pg=PA517. Retrieved 5 September 2012.
  12. ^ http://www.mayoclinic.com/health/polycystic-ovary-syndrome/DS00423/METHOD=print&DSECTION=all. Retrieved 15 November 2011.
  13. ^ Christine Cortet-Rudelli, Didier Dewailly (Sep 21 2006). “Diagnosis of Hyperandrogenism in Female Adolescents”. Hyperandrogenism in Adolescent Girls. Armenian Health Network, Health.am. http://www.health.am/gyneco/more/diagnosis-of-hyperandrogenism-in-female/. Retrieved 2006-11-21.
  14. 19249030. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2859983/.
  15. ^ 19171332.
  16. http://books.google.com/books?id=LN_cu0A0uSAC&pg=PT44. Retrieved 5 September 2012.
  17. ^ a b c d e f g Richard Scott Lucidi (25 October 2011). “Polycystic Ovarian Syndrome”. eMedicine. http://emedicine.medscape.com/article/256806-overview#showall. Retrieved 19 November 2011.
  18. ^ a b c d e “Polycystic Ovarian Syndrome Workup”. eMedicine. 25 October 2011. http://emedicine.medscape.com/article/256806-workup#showall. Retrieved 19 November 2011.
  19. ^ http://humrep.oxfordjournals.org/content/19/1/41.long. Retrieved 14 November 2011.
  20. 16418211.
  21. ^ “Ultrasound assessment of the polycystic ovary: international consensus definitions”. Human Reproduction Update 9 (6): 505–514. 2003. http://humupd.oxfordjournals.org/content/9/6/505.full.pdf. Retrieved 10 October 2012.
  22. ^ a b c d Marrinan, Greg (20 April 2011). “Imaging in Polycystic Ovary Disease”. In Lin, Eugene C. eMedicine. eMedicine. http://emedicine.medscape.com/article/404754-overview. Retrieved 19 November 2011.
  23. 14973405.
  24. 15380140.
  25. Table 5 Clinical tool for diagnosis of polycystic ovary syndrome
  26. 14737959.
  27. ^ http://jcem.endojournals.org/cgi/pmidlookup?view=long&pmid=9920077.
  28. ^ 11212071.
  29. ^ 14644808.
  30. ^ a b Ada Hamosh (12 September 2011). “POLYCYSTIC OVARY SYNDROME 1; PCOS1″. OMIM. McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine. http://omim.org/entry/184700. Retrieved 15 November 2011.
  31. 15380142.
  32. ^ http://www.ncbi.nlm.nih.gov/pubmed/21528473
  33. ^ Kumar Cotran Robbins: Basic Pathology 6th ed. / Saunders 1996
  34. http://www.hindawi.com/journals/mi/2010/758656/.
  35. 1291559.
  36. 16249279.
  37. edit
  38. ^ Gleicher N, Weghofer A, Lee IH, Barad DH (2010). Mailund, Thomas. ed. “FMR1 Genotype with Autoimmunity-Associated Polycystic Ovary-Like Phenotype and Decreased Pregnancy Chance”. PLoS ONE 5 (12): e15303. doi:10.1371/journal.pone.0015303.
  39. edit
  40. ^ a b c d e f g h i j k l “Polycystic Ovarian Syndrome Treatment & Management”. eMedicine. 25 October 2011. http://emedicine.medscape.com/article/256806-treatment#showall. Retrieved 19 November 2011.
  41. http://journals.cambridge.org/abstract_S0007114505001674.
  42. http://www.bmj.com/cgi/content/full/327/7421/951.
  43. ^ National Institute for Health and Clinical Excellence. 11 Clinical guideline 11 : Fertility: assessment and treatment for people with fertility problems . London, 2004.
  44. ^ Balen A (December 2008). “Metformin therapy for the management of infertility in women with polycystic ovary syndrome” (PDF). Scientific Advisory Committee Opinion Paper 13. Royal College of Obstetricians and Gynaecologists. http://www.rcog.org.uk/files/rcog-corp/uploaded-files/SAC13metformin-minorrevision.pdf. Retrieved 2009-12-13.
  45. 19697191.
  46. edit
  47. 17287476.
  48. http://www.nhs.uk/Conditions/Polycystic-ovarian-syndrome/Pages/Treatment.aspx. Retrieved 19 November 2011.
  49. ^ http://emedicine.medscape.com/article/256806-medication#showall. Retrieved 19 November 2011.
  50. http://www.verity-pcos.org.uk/guide_to_pcos/what_is_pcos/health_risks. Retrieved 21 November 2011.
  51. 10219066.
  52. 15251831.
  53. edit
  54. 11900279. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2478565/.
  55. 8323173.
  56. 12781553.
  57. 10632431.
  58. 18854802.
  59. 20159883.
  60. 21725075.
  61. 19765700.
  62. edit
  63. ^ Troischt MJ, Mehlman TR, and Nield LS (November 1, 2008). “Polycystic Ovary Syndrome: An Intriguing Diagnosis”. Consultant for Pediatricians. http://www.consultantlive.com/consultant-for-pediatricians/article/1145470/1404582.
  64. 15533359.
  65. 18765011.
  66. 21310628.
  67. http://books.google.com/books?id=bpn1u9hziVgC&pg=PA4. Retrieved 4 September 2012.
  68. http://books.google.com/books?id=EWhf7ST19SEC&pg=PA2. Retrieved 4 September 2012.
  69. http://www.verity-pcos.org.uk/guide_to_pcos/what_is_pcos. Retrieved 21 November 2011.

[edit] External links

This article uses material from the Wikipedia article Polycystic Ovarian Syndrome, which is released under the Creative Commons Attribution-Share-Alike License 3.0.