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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.
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.
===Alternative approaches===
[[D-chiro-inositol]] (DCI) offers a well-tolerated and effective alternative treatment for PCOS. It has been evaluated in two peer-reviewed, double-blind studies and found to help both lean and obese women with PCOS; diminishing many of the primary clinical presentations of PCOS.<ref>{{cite journal
| author= Nestler J E, Jakubowicz D J, Reamer P, Gunn R D, Allan G
| title= Ovulatory and metabolic effects of D-chiro-inositol in the polycystic ovary syndrome
| journal= N Engl J Med
| year= 1999
| volume= 340
| issue= 17
| pages= 1314&ndash;1320
| id=PMID 10219066 }}</ref> <ref>{{cite journal
| author= Iuorno M J, Jakubowicz D J, Baillargeon J P, Dillon P, Gunn R D, Allan G, Nestler J E
| title= Effects of d-chiro-inositol in lean women with the polycystic ovary syndrome
| journal= Endocr Pract
| year= 2002
| volume= 8
| issue= 6
| pages= 417&ndash;423
| id=PMID 15251831 }}</ref> It has no known side-effects and is a naturally occurring human metabolite known to be involved in insulin metabolism.<ref>{{cite journal
| author= Larner J
| title= D-chiro-inositol--its functional role in insulin action and its deficit in insulin resistance
| journal= Int J Exp Diabetes Res
| year= 2002
| volume= 3
| issue= 1
| pages= 47&ndash;60
| id=PMID 11900279 }}</ref> Contrary to common &mdash; but false &mdash; claims, DCI is not a drug but rather a nutrient (as defined by the [[DSHEA]]) and is commercially available as a nutritional supplement in the USA.
Ian Stoakes, a UK-based scientist has recently claimed some success in treating PCOS through tailored diets, believing that there is a strong link between PCOS, diabetes (and associated diseases) and inflammation caused by the failure of the blood to absorb specific foods. Blood samples are tested to see how they react to different food types to provide the patient with a list of foods she can eat and foods to avoid.  Weight loss, alleviation of symptoms and successful pregnancies are claimed for this approach. It remains a totally unproven approach with no research papers listed in [[PubMed]] by Stoakes concerning PCOS.


==References==
==References==

Revision as of 12:24, 27 August 2012

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Synonyms and keywords: Stein-Leventhal syndrome; PCOS; polycystic ovary disease; PCOD; syndrome O; functional ovarian hyperandrogenism; hyperandrogenic chronic anovulation; ovarian dysmetabolic syndrome

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Polycystic ovary syndrome from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Treatment

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

  • Restoration of fertility
  • 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 diets and sustained regular exercise may help, and some experts recommend a low-GI diet in which a significant part of the total carbohydrates are obtained from fruit, vegetables and wholegrain sources.

Many women find 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 2–3 weeks. Starting with a lower dosage and gradually increasing the dosage over 2–3 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 low glycemic index diet up to 85% will improve menstrual cycle regularity and ovulation.

Treatment of Infertility

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. [1] 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.

However, many specialists continue to recommend metformin which has, separately, been shown to increase ovulation rates [2] and reduce miscarriage rates.[3]. 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[4]. 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 — 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

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. It is usually applied to the face.

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.

Treatment of Menstrual Irregularity and Prevention of Endometrial Hyperplasia/Cancer

If fertility is not the primary aim, then menstruation can usually be regularised 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.

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 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.

References

  • Ehrmann DA. Polycystic ovary syndrome. N Engl J Med 2005;352:1223-36. PMID 15788499.
  • (UK) Royal College of Obstetricians and Gynaecologists. Guideline No. 33 - Long-term Consequences of Polycystic Ovary Syndrome (PDF). Unknown parameter |origmonth= ignored (help)

Footnotes

  1. Legro RS, Barnhart HX, Schlaff WD (2007). "Clomiphene, Metformin, or Both for Infertility in the Polycystic Ovary Syndrome". N Engl J Med. 356 (6): 551–566. PMID 17287476.
  2. "Efficacy of metformin for ovulation induction in polycystic ovary syndrome". Endocrine Abstracts.
  3. "Diabetes Drug Helps Prevent Miscarriage". WebMD.
  4. "Do insulin-sensitizing drugs increase ovulation rates for women with PCOS?". Find Articles.

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