Polycystic ovary syndrome

Polycystic Ovary Syndrome.

Classification and external resources

A polycystic ovary (aka PCO) shown on an ultrasound image. PCO no longer defines PCOS but is a common symptom. As many as 30% or more of women with PCOS do not have PCO as a sign. ICD-10 E28.2 ICD-9 256.4 OMIM 184700 eMedicine med/2173 ped/2155 radio/565 MeSH D011085 Polycystic ovary syndrome (PCOS) is one of the most common female endocrine disorders. PCOS is a complex, heterogeneous disorder of uncertain aetiology, but there is strong evidence that it can to a large degree be classified as a genetic disease.[1][2][3] PCOS produces symptoms in approximately 5% to 10% of women of reproductive age (1245 years old). It is thought to be one of the leading causes of female subfertility[4][5][6] and the most frequent endocrine problem in women of reproductive age.[7] The principal features are anovulation, resulting in irregular menstruation, amenorrhea, ovulation-related infertility, and polycystic ovaries; excessive amounts or effects of androgenic (masculinizing) hormones, resulting in acne and hirsutism; and insulin resistance, often associated with obesity, Type 2 diabetes, and high cholesterol levels. The symptoms and severity of the syndrome vary greatly among affected women.

Contents
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1 Names 2 Definition 3 Signs and symptoms 4 Diagnosis o 4.1 Standard diagnostic assessments o 4.2 Common assessments for associated conditions or risks o 4.3 Differential diagnosis 5 Cause 6 Pathogenesis 7 Management o 7.1 Diet o 7.2 Medications o 7.3 Infertility o 7.4 Hirsutism and acne o 7.5 Menstrual irregularity and endometrial hyperplasia o 7.6 Alternative approaches 8 Prognosis 9 Epidemiology 10 History 11 See also 12 References 13 External links

Names
Other names for this syndrome include polycystic ovary disease, functional ovarian hyperandrogenism, ovarian hyperthecosis, sclerocystic ovary syndrome, and SteinLeventhal 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.[8] Most common names for this disease derive from a typical finding on medical images, called a polycystic ovary.[9] A polycystic ovary has an abnormally large number of developing eggs visible near its surface,[8] looking like many small cysts[10] or a string of pearls.

Definition
Two definitions are commonly used:[citation needed]

NIH In 1990 a consensus workshop sponsored by the NIH/NICHD suggested that a patient has PCOS if she has all of the following:[11] 1. oligoovulation 2. signs of androgen excess (clinical or biochemical) 3. other entities are excluded that would cause polycystic ovaries Rotterdam In 2003 a consensus workshop sponsored by ESHRE/ASRM in Rotterdam indicated PCOS to be present if any 2 out of 3 criteria are met[12] 1. oligoovulation and/or anovulation 2. excess androgen activity 3. polycystic ovaries (by gynecologic ultrasound) Other entities are excluded that would cause these.[7][13] The Rotterdam definition is wider, including many more patients, most notably patients without androgen excess. Critics say that findings obtained from the study of patients with androgen excess cannot necessarily be extrapolated to patients without androgen excess.[14][15] Androgen Excess PCOS Society 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

Signs and symptoms

Common symptoms of PCOS include:

Menstrual disorders: PCOS mostly produces oligomenorrhea (few menstrual periods) or amenorrhea (no menstrual periods), but other types of menstrual disorders may also occur.[7][9] Infertility:[9] This generally results directly from chronic anovulation (lack of ovulation).[7] High levels of masculinizing hormones: The most common signs are acne and hirsutism (male pattern of hair growth), but it may produce hypermenorrhea (very frequent menstrual periods) or other symptoms.[16][7] Approximately three-quarters of patients with PCOS (by the diagnostic criteria of NIH/NICHD 1990) have evidence of hyperandrogenemia.[17]

Metabolic syndrome:[9] This appears as a tendency towards central obesity and other symptoms associated with insulin resistance.[7] Serum insulin, insulin resistance and homocysteine levels are higher in women with PCOS.[18]

Diagnosis
Not all women with PCOS have polycystic ovaries (PCO), nor do all women with ovarian cysts have PCOS; although a pelvic ultrasound is a major diagnostic tool, it is not the only one.[8] The diagnosis is straightforward using the Rotterdam criteria, even when the syndrome is associated with a wide range of symptoms.

Standard diagnostic assessments

History-taking, specifically for menstrual pattern, obesity, hirsutism, and the absence of breast development. A clinical prediction rule found that these four questions can diagnose PCOS with a sensitivity of 77.1% (95% confidence interval [CI] 62.7%88.0%) and a specificity of 93.8% (95% CI 82.8%98.7%).
[19]

Gynecologic ultrasonography, specifically looking for small ovarian follicles. These are believed to be the result of disturbed ovarian function with failed ovulation, reflected by the infrequent or absent menstruation that is typical of the condition. In a normal menstrual cycle, one egg is released from a dominant follicle - essentially a cyst that bursts to release the egg. After ovulation the follicle remnant is transformed into a progesterone-producing corpus luteum, which shrinks and disappears after approximately 1214 days. In PCOS, there is a so called "follicular arrest", i.e., several follicles develop to a size of 57 mm, but not further. No single follicle reaches the preovulatory size (16 mm or more). According to the Rotterdam criteria, 12 or more small follicles should be seen in an ovary on ultrasound examination.[11] The follicles may be oriented in the periphery, giving the appearance of a 'string of pearls'. The numerous follicles contribute to the increased size of the ovaries, that is, 1.5 to 3 times larger than normal.[citation needed] Laparoscopic examination may reveal a thickened, smooth, pearl-white outer surface of the ovary. (This would usually be an incidental finding if laparoscopy were performed for some other reason, as it would not be routine to examine the ovaries in this way to confirm a diagnosis of PCOS.)[citation needed] Serum (blood) levels of androgens (male hormones), including androstenedione and testosterone may be elevated.[7] Dehydroepiandrosterone sulfate levels above 700-800mcg/dL are highly suggestive of adrenal dysfunction because DHEA-S is made exclusively by the adrenal glands.[20][21] The free testosterone level is thought to be the best measure,[21][22] with ~60% of PCOS patients demonstrating supranormal levels.[17] The Free androgen index of the ratio of testosterone to sex hormone-binding globulin (SHBG) is high[7][21] and is meant to be a predictor of free testosterone, but is a poor parameter for this and is no better than testosterone alone as a marker for PCOS,[23] possibly because FAI is correlated with the degree of obesity.[24]

Some other blood tests are suggestive but not diagnostic. The ratio of LH (Luteinizing hormone) to FSH (Follicle stimulating hormone) is greater than 1:1 (sometimes more than 3:1),[21] as tested on Day 3 of the menstrual cycle. The pattern is not very specific and was present in less than 50% in one study.[25] There are often low levels of sex hormone binding globulin,[21] particularly among obese or overweight women.[citation needed]

Common assessments for associated conditions or risks

Fasting biochemical screen and lipid profile[21] 2-hour oral glucose tolerance test (GTT) in patients with risk factors (obesity, family history, history of gestational diabetes)[7] may indicate impaired glucose tolerance (insulin resistance) in 15-33% of women with PCOS.[21] Frank diabetes can be seen in 6568% of women with this condition.[citation needed] Insulin resistance can be observed in both normal weight and overweight patients, although it is more common in the latter (and in those matching the stricter NIH criteria for diagnosis); 50-80% of PCOS patients may have insulin resistance at some level.[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 blood sugar and insulin values do not predict who responds to an insulin-lowering medication, lowglycemic diet, and exercise. Many women with normal levels may benefit from combination therapy. A hypoglycemic response in which the two-hour insulin level is higher and the blood sugar lower than fasting is consistent with insulin resistance. A mathematical derivation known as the HOMAI, calculated from the fasting values in glucose and insulin concentrations, allows a direct and moderately accurate measure of insulin sensitivity (glucose-level x insulinlevel/22.5).[citation needed] Glucose tolerance testing (GTT) instead of fasting glucose can increase diagnosis of increased glucose tolerance and frank diabetes among patients with PCOS according to a prospective controlled trial.[26] While fasting glucose levels may remain within normal limits, oral glucose tests revealed that up to 38% of asymptomatic women with PCOS (versus 8.5% in the general population) actually had impaired glucose tolerance, 7.5% of those with frank diabetes according to ADA guidelines.[26]

Differential diagnosis
Other causes of irregular or absent menstruation and hirsutism, such as hypothyroidism, congenital adrenal hyperplasia (21-hydroxylase deficiency), Cushing's syndrome, hyperprolactinemia, androgen secreting neoplasms, and other pituitary or adrenal disorders, should be investigated.[7][13][21] PCOS has been reported in other insulin-resistant situations such as acromegaly.[citation needed]

Cause

PCOS is a complex, heterogeneous disorder of uncertain aetiology.[1][9][2] There is strong evidence that it is a genetic disease. Such evidence includes the familial clustering of cases, greater concordance in monozygotic compared with dizygotic twins and heritability of endocrine and metabolic features of PCOS.[1][2][3] The genetic component appears to be inherited in an autosomal dominant fashion with high genetic penetrance but variable expressivity in females; this means that each child has a 50% chance of inheriting the predisposing genetic variant(s) from a parent, and if a daughter receives the variant(s), then the daughter will have the disease to some extent.[27] [2][28][29] The genetic variant(s) can be inherited from either the father or the mother, and can be passed along to both sons (who may be asymptomatic carriers or may have symptoms such as early baldness and/or excessive hair) and daughters, who will show signs of PCOS.[29][27] The allele appears to manifest itself at least partially via heightened androgen levels secreted by ovarian follicle theca cells from women with the allele.[28] The exact gene affected has not yet been identified.[2][3][30] The clinical severity of PCOS symptoms appears to be largely determined by factors such as obesity.[3][7]

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[28]):

the release of excessive luteinizing hormone (LH) by the anterior pituitary gland[citation needed] through high levels of insulin in the blood (hyperinsulinaemia) in women whose ovaries are sensitive to this stimulus[9]

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] 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-pituitaryovarian axis that lead to PCOS. Hyperinsulinemia increases GnRH pulse frequency, LH over FSH dominance, increased ovarian androgen production,[9] 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][18] 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).[31] PCOS may be associated with chronic inflammation,[9][32] with several investigators correlating inflammatory mediators with anovulation and other PCOS symptoms.[33][34] 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.[35] 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.[36][37]

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 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.

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. Low-carbohydrate diets and sustained regular exercise[38] may help. Some experts recommend a low GI diet in which a significant part of total carbohydrates are obtained from fruit, vegetables and whole grain sources.[39][9] Vitamin D deficiency may play some role in the development of the metabolic syndrome,[38] so treatment of any such deficiency is indicated.

Medications
Reducing insulin resistance by improving insulin sensitivity through medications such as metformin, and the newer thiazolidinedione (glitazones), have been an obvious approach and initial studies seemed to show effectiveness.[40][9][38] Although metformin is not licensed for use in PCOS, the United Kingdom's National Institute for Health and Clinical Excellence recommended in 2004 that women with PCOS and a body mass index above 25 be given metformin when other therapy has failed to produce results.[41] However subsequent reviews in 2008 and 2009 have noted that randomised control trials have in general not shown the promise suggested by the early observational studies.[42][43]

Infertility
Main article: Infertility in polycystic ovary syndrome 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.[44] 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 clomiphene citrate[38] and FSH are the principal treatments used to promote ovulation.[9] Previously, the anti-diabetes medication metformin was recommended treatment for anovulation,[9] but it appears less effective than clomiphene.[45] For patients who do not respond to clomiphene, diet and lifestyle modification, there are options available including assisted reproductive technology procedures such as controlled ovarian hyperstimulation with follicle-stimulating hormone (FSH) injections followed by 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[38] 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.[38]

Hirsutism and acne

For more details on this topic, see Hirsutism. When appropriate (e.g. in women of child-bearing age who require contraception), a standard contraceptive pill is frequently effective in reducing hirsutism.[9][38] 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 antiandrogen 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.[38] Other drugs with anti-androgen effects include flutamide[46] and spironolactone,[9][38] which can give some improvement in hirsutism. Spironolactone is probably the mostcommonly 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.[38] 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 [47] used; 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[38]), 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]

Menstrual irregularity and endometrial hyperplasia

If fertility is not the primary aim, then menstruation can usually be regulated with a contraceptive pill,[9][38] though the effects are caused by substituted hormones that can easily cause more problems if the pill is taken for a long period of time.[citation needed] 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.[48] If menstruation occurs less often or not at all, some form of progestogen replacement is recommended.[47] Some women prefer a uterine progestogen device such as the intrauterine system (Mirena) or the progestin implant (Implanon), 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.[9]

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.[49][50][51] Inositol has no documented side-effects and is a naturally occurring human metabolite known to be involved in insulin metabolism.[52] 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]

Prognosis
Women with PCOS are at risk for the following:

Endometrial hyperplasia and endometrial cancer (cancer of the uterine lining) are possible, due to overaccumulation of uterine lining, and also lack of progesterone resulting in prolonged stimulation of uterine cells by estrogen.[9][11] It is not clear if this risk is directly due to the syndrome or from the associated obesity, hyperinsulinemia, and hyperandrogenism.[53][54][55][56] Insulin resistance/Type II diabetes.[9] A review published in 2010 concluded that women with PCOS had an elevated prevalence of insulin resistance and type II diabetes, even when controlling for body mass index (BMI).[57][11] PCOS also makes a woman, particularly if obese, prone to gestational diabetes.[9] High blood pressure, particularly if obese and/or during pregnancy[9] Depression/Depression with Anxiety[58][7] Dyslipidemia[9] - disorders of lipid metabolism cholesterol and triglycerides. PCOS patients show decreased removal of atherosclerosis-inducing remnants, seemingly independent of insulin resistance/Type II diabetes.[59] Cardiovascular disease,[9][11] with a meta-analysis estimating a 2-fold risk of arterial disease for women with PCOS relative to women without PCOS, independent of BMI.[60] Strokes[11] Weight gain[9]

Miscarriage[4][5] Sleep apnea, particularly if obesity is present[9] Non-alcoholic fatty liver disease, again particularly if obesity is present[9] Acanthosis nigricans (patches of darkened skin under the arms, in the groin area, on the back of the neck)[11] Autoimmune thyroiditis[61]

Early diagnosis and treatment may reduce the risk of some of these, such as type 2 diabetes and heart disease.[9]

What Is Polycystic Ovary Syndrome?

Polycystic (pronounced: pol-ee-sis-tik) ovary syndrome is a common health problem that can affect teenage girls and women. Although no one really knows what causes PCOS, it seems to be related to an imbalance in a girl's hormones.

Both girls and guys produce sex hormones, but in different amounts. In girls, the ovaries produce the hormones estrogen and progesterone, and also androgens. These hormones regulate a girl's menstrual cycle and ovulationovulation, when the egg is released. Even though androgens are sometimes referred to as "male hormones," every female produces them. In girls with PCOS, the ovaries produce higher than normal amounts of androgens, and this can interfere with egg development and release. Sometimes instead of the eggs maturing, cysts, which are little sacs filled with liquid, develop. Instead of an egg being released during ovulation, like during a normal menstrual cycle, the cysts build up in the ovaries and may become enlarged. Because girls with PCOS are not ovulating or releasing an egg each month, it's common for them to have irregular or missed periods. Although PCOS (which used to be called Stein-Leventhal syndrome) was first recognized in the 1930s, doctors can't say for sure what causes it. Research has suggested that PCOS may be related to increased insulin production in the body. Women with PCOS may produce too much insulin, which signals their ovaries to release extra male hormones.

PCOS seems to run in families, too, so if someone in your family has it, you might be more likely to develop it. If PCOS is not treated properly, it can put a girl at risk for lots of problems. Girls with PCOS are more likely to have infertility, excessive hair growth, acne, obesity, diabetes, heart disease, high blood pressure, abnormal bleeding from the uterus, and cancer. The good news is that, although there's no cure for PCOS, it can be treated. The most important step is diagnosing the condition, because getting treatment for PCOS reduces a girl's chances of having serious side effects.

What Are the Signs and Symptoms?

A key sign of PCOS is irregular or missed periods because the effects of the condition on the ovaries can make a girl stop ovulating. However, because it can take up to 2 years after her first period for a girl's menstrual cycle to become regular, it can be hard to recognize missed periods as a sign of PCOS in teen girls. Imbalanced hormone levels can cause changes in a girl's entire body, not just her ovaries. So doctors also look for these other signs that might indicate PCOS:

very heavy periods or irregular periods weight gain, obesity, or difficulty maintaining a normal weight, especially when the extra weight is concentrated around the waist a condition called hirsutism (pronounced: her-suh-tiz-um), where a girl grows extra hair on her face, chest, abdomen, nipple area, or back (a little of this is normal for most girls, though) thinning hair on the head (doctors call this alopecia) acne and clogged pores darkened, thickened skin around the neck, armpits, or breasts (this is called acanthosis nigricans) high blood pressure, high cholesterol, or diabetes mellitus (high levels of sugar in your blood)

Girls who show certain signs of puberty early such as girls who develop underarm or pubic hair before the age of 8 may be at greater risk of having PCOS later on.

How Is Polycystic Ovary Syndrome Diagnosed?

If you've taken your concerns about your body to your doctor, you're on the right track. Your doctor may refer you to a gynecologistgynecologist or an endocrinologistendocrinologist for a diagnosis. The gynecologist or endocrinologist will ask you about any concerns and symptoms you have, your past health, your family's health, any medications you're taking, any allergies

you may have, and other issues. He or she will also ask you lots of questions specifically about your period and its regularity. This is called the medical history. In addition to your medical history, your doctor will do a physical examination, which includes checking your weight, and checking especially for physical signs such as acne, hair growth, and darkened skin. The doctor may perform a gynecologic examination to rule out other possible causes of your symptoms, but this is not always necessary for diagnosis. A doctor may also perform blood tests to diagnose PCOS or other conditions, such as thyroid or other ovarian or gland problems. Blood tests allow doctors to measure androgen, insulin, and other hormone levels. The results of these tests can help doctors to determine the type of treatment a girl will receive. Your doctor also might order an ultrasound to look at your ovaries and to determine if you have cysts or other abnormalities of the ovaries. Because cysts are not always visible, this test is not always used. Early diagnosis and treatment for PCOS are important because the condition can put girls at risk for long-term problems. Getting treated for PCOS is also a good idea if you want to have a baby someday PCOS often causes infertility if it's not treated. But when PCOS is treated properly, many women with the condition have healthy babies. Also, many girls with PCOS can get pregnant. If you are sexually active, you need to use condoms every time you have sex in order to avoid getting pregnant or getting a sexually transmitted disease (STD). This is important whether or not you have PCOS.

How Is It Treated?
Although there's no cure for PCOS, there are several ways that the condition can be treated and managed. If a girl is overweight or obese, a doctor will recommend that she lose weight. Weight loss can be very effective in lessening many of the health conditions associated with PCOS, such as high blood pressure and diabetes. Sometimes weight loss alone can restore hormone levels to normal, causing many of the symptoms to disappear or become less severe. Your doctor or a registered dietitian can look at your food intake and your exercise and activity to tailor a weight-loss program for you. Exercise is a great way to help combat the weight gain that often accompanies PCOS as well as a way to reduce bloating, another symptom girls with PCOS sometimes experience. Sometimes doctors prescribe medications to treat PCOS. A doctor might first have a girl try birth control pills or another hormone pill called progesterone to help control hormone

levels in her body and regulate her menstrual cycle. Birth control pills may help control acne and excessive hair growth in some girls, but they don't work for everyone. Other medications used to treat PCOS include antiandrogens, which counter the effects of excess androgens on a girl's body. Antiandrogens can help clear up skin and hair growth problems in girls with PCOS. Another medication, metformin, which is used to treat diabetes, can lower insulin levels. In some girls with PCOS, it can help control ovulation and androgen levels. This can make a girl's menstrual cycles more regular. Some girls and women treated with metformin have also experienced weight loss and lowering of high blood pressure.

Coping With Polycystic Ovary Syndrome

Having PCOS can be hard on a girl's self-esteem because some of the symptoms, such as skin and hair problems and weight gain, can be noticeable. Fortunately, there are things you can do to reduce the physical symptoms and take care of the emotional side of living with PCOS. Although the medications used to treat PCOS will slow down or stop excessive hair growth for many girls, different types of products are available to help a girl get rid of hair where she doesn't want it. Depilatory creams can gently remove facial hair on the upper lip or chin. Be sure to follow the instructions carefully so you don't develop a rash or allergic reaction. Tweezing and waxing are other things you can do (at home or at a salon) to manage hair growth. A girl can also visit a dermatologist (a doctor who specializes in skin problems) or qualified hair removal specialist for electrolysis and laser surgery treatments. These procedures offer longer term removal of unwanted hair, but they are more expensive. If you have severe acne as a symptom of PCOS, it may improve if part of your treatment includes birth control pills or antiandrogens. If it doesn't, your doctor may refer you to a dermatologist for further acne treatment. A dermatologist may also be able to recommend medications to help reduce skin darkening or discoloration, and to prevent hair growth. Some girls with PCOS may become depressed, in which case it may help to talk to a therapist or other mental health professional. Talking with other teens and women with PCOS is a great way to share information about treatment and get support. Your doctor may be able to recommend a local support group. If you can't find a local group, the Polycystic Ovarian Syndrome Association offers a "Big Cyster" program for teen girls as well as online message boards. If you join, you'll be hooked up with other women or teen girls with PCOS to whom you can turn for advice, support, or just a listening ear.

Polycystic ovary syndrome is characterised by irregular periods starting within two years of puberty usually leading to very scanty or even absent periods. In 50 per cent of cases there will also be weight gain and unwanted body hair, and as you already know, infertility is a possible problem. It is caused by an imbalance of hormones released by the pituitary gland, which sits at the base of the brain. Ovulation fails to occur, there is a high level of circulating oestrogen in the bloodstream and a relative increase in the male-type hormone, testosterone. Tests to assess the severity of your PCOS and to see whether you are ovulating and therefore fertile include a simple blood test, an ultrasound scan of your ovaries and possibly a laparoscopy procedure where a narrow telescope is inserted just below the belly button to look directly at the ovaries from the inside. It would be very helpful if you could be referred to a gynaecology clinic sooner rather than later to see if any measures can be taken now to maximise your chance of having children in the future. Treatments would include the medication clomiphene to stimulate ovulation, a hormone known as LH-RH, the oral contraceptive pill and surgical removal of a small wedge of ovarian tissue to restore ovarian function.

How does it work?

Clomid tablets contain the active ingredient clomifene citrate (previously spelt clomiphene in the UK). (NB. Clomifene is also available without a brand name, ie as the generic medicine.) Clomifene works by causing an increase in the levels of hormones in the female body which control the development and release of an egg. These hormones are released from the pituitary gland in the brain and are known as follicle stimulating hormone (FSH) and luteinising hormone (LH). FSH stimulates the ovaries and LH causes the release of an egg from the ovaries (ovulation). Oestrogen normally causes the brain to stop releasing FSH and LH following ovulation, as part of the normal menstrual cycle. It does this by acting on receptors in a part of the brain called the hypothalamus, which sends messages to the pituitary gland. Clomifene works by blocking the oestrogen receptors in the hypothalamus. This stops oestrogen from acting on these receptors, and therefore stops the message being sent to the pituitary gland. This results in the release of more FSH and LH from the pituitary gland. The increase in these hormones increases the chances of egg development and ovulation.

Clomifene is used to stimulate ovulation in women whose infertility is due to problems with ovulation.

Clomid
What is it used for?

Infertility in women caused by failure of ovulation

Warning!

Women should have a pregnancy test to make sure they are not pregnant before each course of clomifene therapy. Women should be evaluated for the presence of ovarian cysts before each course of treatment. Inform your doctor if you experience weight gain, pelvic pain or abdominal pain, discomfort or swelling after taking this medicine. Fertility treatment with this medicine carries an increased risk of multiple pregnancies, eg twins, triplets etc, and pregnancies outside the womb (ectopic pregnancy).Your doctor should discuss this with you before you start treatment. This medicine should not be used for more than 6 cycles of therapy, as prolonged use may increase the risk of ovarian cancer. This medicine may cause blurred vision or other visual symptoms during or shortly after taking the medicine. This may make it hazardous to drive or operate machinery, particularly under conditions of variable lighting. If you get visual symptoms you should tell your doctor. Your treatment will need to be stopped and you should have an eye examination.

Use with caution in

Polycystic ovary syndrome Fibroids of the uterus Endometriosis History of seizures

Not to be used in

Pregnancy Liver disease History of decreased liver function

Certain types of cancer that are dependent on hormones for growth, eg endometrial cancer Abnormal bleeding from the uterus of unknown cause Ovarian cysts

This medicine should not be used if you are allergic to one or any of its ingredients. Please inform your doctor or pharmacist if you have previously experienced such an allergy. If you feel you have experienced an allergic reaction, stop using this medicine and inform your doctor or pharmacist immediately.

Pregnancy and Breastfeeding

Certain medicines should not be used during pregnancy or breastfeeding. However, other medicines may be safely used in pregnancy or breastfeeding providing the benefits to the mother outweigh the risks to the unborn baby. Always inform your doctor if you are pregnant or planning a pregnancy, before using any medicine.

This medicine should not be used in pregnancy. Women should have a pregnancy test to make sure they are not pregnant before each course of clomifene therapy. Seek medical advice from your doctor. It is not known whether this medicine passes into breast milk. It may suppress the production of milk. Seek medical advice from your doctor.

Side effects
Medicines and their possible side effects can affect individual people in different ways. The following are some of the side effects that are known to be associated with this medicine. Because a side effect is stated here, it does not mean that all people using this medicine will experience that or any side effect.

Enlargement of the ovaries Pain in the lower abdomen in the middle of the menstrual cycle (mittelschmerz) Over stimulation of the ovaries causing production of many eggs Hot flushes Abdominal discomfort (swelling or bloating) Nausea and vomiting Breast discomfort Visual disturbances Headache Spotting of blood between menstrual periods Heavy or painful menstrual periods Endometriosis Dizziness

Nervous tension Insomnia Fatigue Skin reactions such as rash and itch Loss of contact with reality (psychosis) Stroke (cerebrovascular accident) Depression Seizures (convulsions)

The side effects listed above may not include all of the side effects reported by the drug's manufacturer. For more information about any other possible risks associated with this medicine, please read the information provided with the medicine or consult your doctor or pharmacist.

How can this medicine affect other medicines?

There are no significant interactions reported with this medicine.

Other medicines containing the same active ingredient

Clomifene tablets are also available without a brand name, ie as the generic medicine.