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{{Polycystic ovary syndrome}}
{{Polycystic ovary syndrome}}
 
{{CMG}}; {{AE}} {{ADG}}
{{CMG}}


==Overview==
==Overview==
The first step in the management of PCOS is weight loss if the patient is [[obese]], and treatment of [[type 2 diabetes]] with [[metformin]]. In significantly overweight patients, weight loss alone usually effects a cure and should always be vigorously attempted. Diet and exercise are recommended in all women with PCOS. The next step is the initiation of treatment to break the self-perpetuating [[Anovulatory cycle|anovulatory]] cycles, either by stimulating [[ovulation]] or suppressing [[androgenic]] and [[ovarian]] activity. The selection of treatment depends on whether the pregnancy is desired or not. All anti-androgen treatments will take at least 3 months to affect [[hirsutism]]. The drug regimen for PCOS depends upon the desire for the [[fertility]] of the patient.
==Pharmacotherapy==
The first step in the management of PCOS is weight loss if the patient is [[obese]], and treatment of [[type 2 diabetes]] with [[metformin]]. In significantly overweight patients, weight loss alone usually effects a cure and should always be vigorously attempted. Diet and exercise are recommended in all women with PCOS. The next step is the initiation of treatment to break the self-perpetuating [[annovulation|anovulatory cycling]], either by stimulating ovulation or suppressing [[androgenic]] and [[ovarian]] activity. The selection of treatment depends on whether the pregnancy is desired or not. All anti-androgen treatments will take at least 3 months to affect [[hirsutism]].
The goals of treatment are:<ref name="pmid15931331">{{cite journal |vauthors=Sheehan MT |title=Polycystic ovarian syndrome: diagnosis and management |journal=Clin Med Res |volume=2 |issue=1 |pages=13–27 |year=2004 |pmid=15931331 |pmc=1069067 |doi= |url=}}</ref><ref name="pmid20186113">{{cite journal |vauthors=Artini PG, Di Berardino OM, Simi G, Papini F, Ruggiero M, Monteleone P, Cela V |title=Best methods for identification and treatment of PCOS |journal=Minerva Ginecol |volume=62 |issue=1 |pages=33–48 |year=2010 |pmid=20186113 |doi= |url=}}</ref><ref name="pmid17081931">{{cite journal |vauthors=King J |title=Polycystic ovary syndrome |journal=J Midwifery Womens Health |volume=51 |issue=6 |pages=415–22 |year=2006 |pmid=17081931 |doi=10.1016/j.jmwh.2006.01.008 |url=}}</ref><ref name="pmid21339935">{{cite journal |vauthors=Badawy A, Elnashar A |title=Treatment options for polycystic ovary syndrome |journal=Int J Womens Health |volume=3 |issue= |pages=25–35 |year=2011 |pmid=21339935 |pmc=3039006 |doi=10.2147/IJWH.S11304 |url=}}</ref><ref name="pmid28885578">{{cite journal |vauthors=Kataoka J, Tassone EC, Misso M, Joham AE, Stener-Victorin E, Teede H, Moran LJ |title=Weight Management Interventions in Women with and without PCOS: A Systematic Review |journal=Nutrients |volume=9 |issue=9 |pages= |year=2017 |pmid=28885578 |pmc=5622756 |doi=10.3390/nu9090996 |url=}}</ref><ref name="pmid26060208">{{cite journal |vauthors=Naderpoor N, Shorakae S, de Courten B, Misso ML, Moran LJ, Teede HJ |title=Metformin and lifestyle modification in polycystic ovary syndrome: systematic review and meta-analysis |journal=Hum. Reprod. Update |volume=21 |issue=5 |pages=560–74 |year=2015 |pmid=26060208 |doi=10.1093/humupd/dmv025 |url=}}</ref><ref name="pmid21328294">{{cite journal |vauthors=Moran LJ, Hutchison SK, Norman RJ, Teede HJ |title=Lifestyle changes in women with polycystic ovary syndrome |journal=Cochrane Database Syst Rev |volume= |issue=2 |pages=CD007506 |year=2011 |pmid=21328294 |doi=10.1002/14651858.CD007506.pub2 |url=}}</ref><ref name="pmid24627300">{{cite journal |vauthors=Martin A, Saunders DH, Shenkin SD, Sproule J |title=Lifestyle intervention for improving school achievement in overweight or obese children and adolescents |journal=Cochrane Database Syst Rev |volume= |issue=3 |pages=CD009728 |year=2014 |pmid=24627300 |doi=10.1002/14651858.CD009728.pub2 |url=}}</ref>
*Exclude [[androgen]]-secreting [[tumors]], [[Endometrial cancer|endometrial tumors]], and [[endometrial hyperplasia]]
*Reduce [[ovarian]] androgen secretion and/or [[antagonist]] activity at target tissues
*Interrupt the self-sustaining abnormal [[hormonal]] cycle
*Normalize the [[endometrium]]
*Restore fertility by correcting [[anovulation]] (if desired)
*Reduce [[insulin resistance]]


==Medical Therapy==
==If Pregnancy is not desired==
 
*Preferred regimen (1): Combined [[Oral contraceptive|oral contraceptive pills]] (OCP) one tablet of formulations containing 30 to 35 μg [[estrogen]] orally daily for 21 days.
===Pharmacotherapy===
*Preferred regimen (2): [[Progesterone]]-only contraceptive pills (eg, [[norethindrone]], [[norgestrel]] ) are the treatment of choice if combined [[Oral contraceptive|oral contraceptive pills]] are contraindicated.
 
*Alternative regimen (1): [[Medroxyprogesterone]] may be used, although it is not approved by the U.S. Food and Drug Administration (FDA) for this indication.
Medical treatment of PCOS is tailored to the patient's goals. Broadly, these may be considered under three categories:
*Alternative regimen (2): [[Glucocorticoids]] (eg, [[hydrocortisone]], [[cortisone]], [[dexamethasone]] ) may be used to suppress [[adrenal]] [[androgen]] production, although they are not approved by the [[FDA]] for this indication.
* Restoration of fertility
*Alternative regimen (3): [[Spironolactone]] and [[flutamide]] are [[androgen]] receptor antagonists that may be added to the [[oral contraceptive pill]], but they are not approved by the [[FDA]] for this indication; [[flutamide]] is not usually recommended because of its unproven efficacy and associated risk of [[hepatic]] impairment.
* Treatment of hirsutism or acne
* Restoration of regular menstruation, and prevention of endometrial hyperplasia and 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. Smaller trials tend to be 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 of the syndrome. Where PCOS is associated with overweight or obesity, successful weight loss is probably the most effective method of restoring normal ovulation/menstruation, but many women find it very difficult to achieve and sustain significant weight loss. [[Low-carbohydrate diet]]s and sustained regular exercise may help, and some experts recommend a [[Glycemic index|low-GI]] diet in which a significant part of the total carbohydrates are obtained from fruit, vegetables and wholegrain sources.
 
Many women find [http://www.ivf.com/pcostreat.html insulin-lowering medications] such as [[metformin]] hydrochloride (Glucophage®), [[pioglitazone]] hydrochloride (Actos®), and [[rosiglitazone]] maleate (Avandia®) helpful, and ovulation may resume when they use these agents. Many women report that [[metformin]] use is associated with upset stomach, diarrhea, and weight-loss. Such side effects usually resolve within 2&ndash;3 weeks.  Starting with a lower dosage and gradually increasing the dosage over 2&ndash;3 weeks and taking the medication toward the end of a meal may reduce side effects. It may take up to six months to see results, but when combined with exercise and a [[Glycemic index|low glycemic index diet]] up to 85% will improve menstrual cycle regularity and ovulation.  


====Treatment of Infertility====
==If Pregnancy is desired==
 
*Preferred regimen (1): [[Clomiphene]], alone or in combination with [[glucocorticoids]], is the first-choice treatment.
[[Clomiphene citrate]] and [[metformin]] are the principal treatments used to help infertility.  Both have been shown to be effective, but in the largest trial to date clomiphene appeared to be most effective. <ref>{{cite journal |author=Legro RS, Barnhart HX, Schlaff WD |title=Clomiphene, Metformin, or Both for Infertility in the Polycystic Ovary Syndrome|journal=N Engl J Med|volume=356 |issue=6 |pages=551-566 |year=2007 |pmid=17287476 |doi=}}</ref>  In this trial, 626 women were randomized to three groups: metformin alone, clomiphene alone, or both.  The live birth rates after 6 months were 7.2% (metformin), 22.5% (clomiphene), and 26.8% (both).  The major complication of clomiphene was multiple pregancy, affecting 0%, 6% and 3.1% of women respectively.  The overall success rates for live birth remained disappointing, even in women receiving combined therapy, but it is important to consider that the women in this trial had already been attempting to conceive for an average of 3.5 years, and over half had received previous treatment for infertility.  Thus, these were women with significant fertility problems, and the live birth rates are probably not representative of the 'average' PCOS woman.
*Preferred regimen (2): [[FSH|Follicle-stimulating hormone]] may be administered in conjunction with timed [[HCG|human chorionic gonadotropin]] for [[ovulation]] induction.
 
*Preferred regimen (3): [[Metformin]]
However, many specialists continue to recommend metformin which has, separately, been shown to increase ovulation rates <ref>{{cite web | title = Efficacy of metformin for ovulation induction in polycystic ovary syndrome | url = http://www.endocrine-abstracts.org/ea/0003/ea0003p228.htm | publisher = Endocrine Abstracts}}</ref> and reduce miscarriage rates.<ref>{{cite web | title = Diabetes Drug Helps Prevent Miscarriage | url = http://www.webmd.com/infertility-and-reproduction/news/20020301/diabetes-drug-helps-prevent-miscarriage | publisher = WebMD }}</ref>.  Metformin may be a rational choice in women in whom significant insulin resistance is diagnosed or suspected, as clomiphene works through a different mechanism and does not affect insulin resistance.
 
Diet adjustments and weight loss also increase rates of pregnancy. The most drastic increase in ovulation rate occurs with a combination of diet modification, weight loss, and treatment with metformin and clomiphene citrate<ref>{{cite web | title = Do insulin-sensitizing drugs increase ovulation rates for women with PCOS? | url = http://findarticles.com/p/articles/mi_m0689/is_2_54/ai_n10299300 | publisher = Find Articles }}</ref>.  It is currently unknown if diet change and weight loss alone have an effect on live birth rates comparable to those reported with clomiphene and metformin.
 
Though the use of [[basal body temperature]] or BBT charts is sometimes advised to predict ovulation, clinical trials have not supported a useful role.
 
For patients who do not respond to clomiphene, metformin, other insulin-sensitizing agents, diet and lifestyle modification, there are options available including [[assisted reproductive technology]] procedures such as controlled ovarian hyperstimulation and [[in vitro fertilisation]].  Ovarian stimulation has an associated risk of ovarian hyperstimulation in women with PCOS &mdash; a dangerous condition with morbidity and rare mortality.  Thus recent developments have allowed the oocytes present in the multiple follicles to extracted in natural, unstimulated cycles and then matured ''in vitro'', prior to IVF. This technique is known as IVM (in-vitro-maturation)
 
Though surgery is usually the treatment option of last resort, the polycystic ovaries can be treated with surgical procedures such as
* laparoscopy electrocauterization or laser cauterization
* ovarian wedge resection (rarely done now because it is more invasive and has a 30% risk of adhesions, sometimes very severe, which can impair fertility) was an older therapy
* ovarian drilling


==Symptomatic Medical Therapy==
====Treatment of Hirsutism and Acne====
====Treatment of Hirsutism and Acne====
 
*[[Cyproterone acetate]] is an anti-[[androgen]], which blocks the action of male hormones that are believed to contribute to [[Acne vulgaris|acne]] and the growth of unwanted facial and body hair.
[[Cyproterone acetate]] is an anti-[[androgen]], which blocks the action of male hormones that are believed to contribute to acne and the growth of unwanted facial and body hair. Cyproterone acetate is also contained in the contraceptive pill Dianette®. [[Spironolactone]] also has some benefits, again through anti-androgen activity, and metformin can also help. [[Eflornithine]] is a drug which is applied to the skin in cream form (Vaniqa®), and acts directly on the hair follicles to inhibit hair growth. It is usually applied to the face.
* [[Cyproterone acetate]] is also contained in the contraceptive pill Dianette®.  
 
* [[Spironolactone]] also has some benefits, again through anti-androgen activity, and [[metformin]] can also help.  
Although all of these agents have shown some efficacy in clinical trials, the average reduction in hair growth is generally in the region of 25%, which may not be enough to eliminate the social embarrassment of hirsutism, or the inconvenience of plucking/shaving.  Individuals may vary in their response to different therapies, and it is usually worth trying other drug treatments if one does not work, but drug treatments do not work well for all individuals. Alternatives include electrolysis and various forms of laser therapy.
* [[Eflornithine]] is a drug which is applied to the skin in cream form (Vaniqa®), and acts directly on the hair follicles to inhibit hair growth.
 
* The average reduction in hair growth is generally in the region of 25%, which may not be enough to eliminate the social embarrassment of [[hirsutism]] or the inconvenience of plucking/shaving.   
* Individuals may vary in their response to different therapies, and it is recommended to try other medications if one is not effective although, drug treatments is not effective for all individuals.  
* Alternatives include [[electrolysis]] and various forms of laser therapy.
====Treatment of Menstrual Irregularity and Prevention of Endometrial Hyperplasia/Cancer====
====Treatment of Menstrual Irregularity and Prevention of Endometrial Hyperplasia/Cancer====
* [[Menstruation]] can be regulated with a contraceptive pill.
* Most brands of contraceptive pill result in a withdrawal menstrual bleeding every 28 days.
* Dianette® (a contraceptive pill containing [[cyproterone acetate]]) is also beneficial for hirsutism and is therefore often prescribed in PCOS.
* If a regular menstrual cycle is not desired, then a standard contraceptive pill is not appropriate.
* Women who are having irregular menses do not necessarily require any therapy; 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.
* If [[menstruation]] occurs less often or not at all, some form of [[progesterone]] replacement is recommended.  Some women prefer a uterine [[progesterone]] implant such as the [[intrauterine system|Mirena®]] coil, which provides simultaneous [[contraception]] and [[endometrial]] protection for years, though often with unpredictable minor bleeding.
*  An alternative is an oral [[progesterone]] taken at intervals (e.g. every three months) to induce a predictable menstrual bleed.


If fertility is not the primary aim, then menstruation can usually be regulated with a contraceptive pill.  Most brands of contraceptive pill result in a withdrawal bleed every 28 days.  Dianette® (a contraceptive pill containing [[cyproterone acetate]]) is also beneficial for hirsutism, and is therefore often  prescribed in PCOS.
==References==
{{Reflist|2}}


If a regular menstrual cycle is not desired, then a standard contraceptive pill is not appropriate.  Women who are having irregular menses do not necessarily require any therapy; 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.  If menstruation occurs less often or not at all, some form of progestogen replacement is recommended.  Some women prefer a uterine progestogen implant such as the [[intrauterine system|Mirena®]] coil, which provides simultaneous contraception and endometrial protection for years, though often with unpredictable minor bleeding.  An alternative is oral progestogen taken at intervals (e.g. every three months) to induce a predictable menstrual bleed.
[[Category:Endocrinology]]
[[Category:Gynecology]]
[[Category:Obstetrics]]


==References==
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{{Reflist|2}}
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Latest revision as of 14:19, 2 November 2017

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2]

Overview

The first step in the management of PCOS is weight loss if the patient is obese, and treatment of type 2 diabetes with metformin. In significantly overweight patients, weight loss alone usually effects a cure and should always be vigorously attempted. Diet and exercise are recommended in all women with PCOS. The next step is the initiation of treatment to break the self-perpetuating anovulatory cycles, either by stimulating ovulation or suppressing androgenic and ovarian activity. The selection of treatment depends on whether the pregnancy is desired or not. All anti-androgen treatments will take at least 3 months to affect hirsutism. The drug regimen for PCOS depends upon the desire for the fertility of the patient.

Pharmacotherapy

The first step in the management of PCOS is weight loss if the patient is obese, and treatment of type 2 diabetes with metformin. In significantly overweight patients, weight loss alone usually effects a cure and should always be vigorously attempted. Diet and exercise are recommended in all women with PCOS. The next step is the initiation of treatment to break the self-perpetuating anovulatory cycling, either by stimulating ovulation or suppressing androgenic and ovarian activity. The selection of treatment depends on whether the pregnancy is desired or not. All anti-androgen treatments will take at least 3 months to affect hirsutism. The goals of treatment are:[1][2][3][4][5][6][7][8]

If Pregnancy is not desired

If Pregnancy is desired

Symptomatic Medical Therapy

Treatment of Hirsutism and Acne

  • Cyproterone acetate is an anti-androgen, which blocks the action of male hormones that are believed to contribute to acne and the growth of unwanted facial and body hair.
  • Cyproterone acetate is also contained in the contraceptive pill Dianette®.
  • Spironolactone also has some benefits, again through anti-androgen activity, and metformin can also help.
  • Eflornithine is a drug which is applied to the skin in cream form (Vaniqa®), and acts directly on the hair follicles to inhibit hair growth.
  • The average reduction in hair growth is generally in the region of 25%, which may not be enough to eliminate the social embarrassment of hirsutism or the inconvenience of plucking/shaving.
  • Individuals may vary in their response to different therapies, and it is recommended to try other medications if one is not effective although, drug treatments is not effective for all individuals.
  • Alternatives include electrolysis and various forms of laser therapy.

Treatment of Menstrual Irregularity and Prevention of Endometrial Hyperplasia/Cancer

  • Menstruation can be regulated with a contraceptive pill.
  • Most brands of contraceptive pill result in a withdrawal menstrual bleeding every 28 days.
  • Dianette® (a contraceptive pill containing cyproterone acetate) is also beneficial for hirsutism and is therefore often prescribed in PCOS.
  • If a regular menstrual cycle is not desired, then a standard contraceptive pill is not appropriate.
  • Women who are having irregular menses do not necessarily require any therapy; 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.
  • If menstruation occurs less often or not at all, some form of progesterone replacement is recommended. Some women prefer a uterine progesterone implant such as the Mirena® coil, which provides simultaneous contraception and endometrial protection for years, though often with unpredictable minor bleeding.
  • An alternative is an oral progesterone taken at intervals (e.g. every three months) to induce a predictable menstrual bleed.

References

  1. ↑ Sheehan MT (2004). "Polycystic ovarian syndrome: diagnosis and management". Clin Med Res. 2 (1): 13–27. PMC 1069067. PMID 15931331.
  2. ↑ Artini PG, Di Berardino OM, Simi G, Papini F, Ruggiero M, Monteleone P, Cela V (2010). "Best methods for identification and treatment of PCOS". Minerva Ginecol. 62 (1): 33–48. PMID 20186113.
  3. ↑ King J (2006). "Polycystic ovary syndrome". J Midwifery Womens Health. 51 (6): 415–22. doi:10.1016/j.jmwh.2006.01.008. PMID 17081931.
  4. ↑ Badawy A, Elnashar A (2011). "Treatment options for polycystic ovary syndrome". Int J Womens Health. 3: 25–35. doi:10.2147/IJWH.S11304. PMC 3039006. PMID 21339935.
  5. ↑ Kataoka J, Tassone EC, Misso M, Joham AE, Stener-Victorin E, Teede H, Moran LJ (2017). "Weight Management Interventions in Women with and without PCOS: A Systematic Review". Nutrients. 9 (9). doi:10.3390/nu9090996. PMC 5622756. PMID 28885578.
  6. ↑ Naderpoor N, Shorakae S, de Courten B, Misso ML, Moran LJ, Teede HJ (2015). "Metformin and lifestyle modification in polycystic ovary syndrome: systematic review and meta-analysis". Hum. Reprod. Update. 21 (5): 560–74. doi:10.1093/humupd/dmv025. PMID 26060208.
  7. ↑ Moran LJ, Hutchison SK, Norman RJ, Teede HJ (2011). "Lifestyle changes in women with polycystic ovary syndrome". Cochrane Database Syst Rev (2): CD007506. doi:10.1002/14651858.CD007506.pub2. PMID 21328294.
  8. ↑ Martin A, Saunders DH, Shenkin SD, Sproule J (2014). "Lifestyle intervention for improving school achievement in overweight or obese children and adolescents". Cochrane Database Syst Rev (3): CD009728. doi:10.1002/14651858.CD009728.pub2. PMID 24627300.


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