Polycystic ovary syndrome
Encyclopedia
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.
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 female subfertility and the most frequent endocrine problem in women of reproductive age.
The principal features are anovulation
, resulting in irregular menstruation
, amenorrhea, ovulation-related infertility, and polycystic ovaries; excessive amounts or effects of androgen
ic (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.
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.
Most common names for this disease derive from a typical finding on medical images, called a polycystic ovary. A polycystic ovary has an abnormally large number of developing eggs visible near its surface, looking like many small cyst
s or a string of pearls.
NIH
Rotterdam
Other entities are excluded that would cause these.
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.
Androgen Excess PCOS Society
, congenital adrenal hyperplasia
(21-hydroxylase deficiency), Cushing's syndrome
, hyperprolactinemia, androgen secreting neoplasms, and other pituitary or adrenal disorders, should be investigated. PCOS has been reported in other insulin-resistant situations such as acromegaly
.
in monozygotic compared with dizygotic twins and heritability of endocrine and metabolic features of PCOS.
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. 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. The allele
appears to manifest itself at least partially via heightened androgen levels secreted by ovarian follicle
theca
cells from women with the allele. The exact gene affected has not yet been identified.
The clinical severity of PCOS symptoms appears to be largely determined by factors such as obesity.
Alternatively or as well, reduced levels of sex-hormone binding globulin can result in increased free androgens.
The syndrome acquired its most widely used name due to the common sign on ultrasound examination of multiple (poly) ovarian cyst
s. 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.
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, decreased follicular maturation, and decreased SHBG binding; all these steps contribute to the development of PCOS. Insulin resistance is a common finding among patients of normal weight as well as overweight patients.
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.
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).
PCOS may be associated with chronic inflammation, with several investigators correlating inflammatory mediators with anovulation and other PCOS symptoms.
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.
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.
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.
s and sustained regular exercise 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. Vitamin D deficiency may play some role in the development of the metabolic syndrome
, so treatment of any such deficiency is indicated.
, and the newer thiazolidinedione
(glitazones), have been an obvious approach and initial studies seemed to show effectiveness. 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. 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.
or infrequent ovulation is a common cause. Other factors include changed levels of gonadotropin
s, hyperandrogenemia and hyperinsulinemia
. 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 and FSH
are the principal treatments used to promote ovulation. Previously, the anti-diabetes medication metformin
was recommended treatment for anovulation, but it appears less effective than clomiphene.
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 or ovulations after adjuvant treatment with clomiphene or FSH. (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.
effects that block the action of male hormones that are believed to contribute to acne and the growth of unwanted facial and body hair. On the other hand, progestogens such as norgestrel and levonorgestrel should be avoided due to their androgenic effects.
Other drugs with anti-androgen effects include flutamide
and spironolactone
, 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. Medications that reduce acne by indirect hormonal effects also include ergot dopamine agonists such as bromocriptine
. 5-alpha reductase
inhibitors (such as finasteride
and dutasteride
) may also be 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), 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.
can usually be regulated with a contraceptive pill, 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. 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).
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. If menstruation occurs less often or not at all, some form of progestogen replacement is recommended. 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. An alternative is oral progestogen taken at intervals (e.g. every three months) to induce a predictable menstrual bleeding.
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. Inositol has no documented side-effects and is a naturally occurring human metabolite known to be involved in insulin metabolism. 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.
Early diagnosis and treatment may reduce the risk of some of these, such as type 2 diabetes and heart disease.
One study in the United Kingdom concluded that the risk of PCOS development was higher in lesbian women than in heterosexuals. However, two subsequent studies of women with PCOS have not replicated this finding.
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 female subfertility and the most frequent endocrine problem in women of reproductive age.
The principal features are anovulation
Anovulation
An anovulatory cycle is a menstrual cycle during which the ovaries do not release an oocyte. Therefore, ovulation does not take place. However, a woman who does not ovulate at each menstrual cycle is not necessarily going through menopause...
, resulting in irregular menstruation
Menstruation
Menstruation is the shedding of the uterine lining . It occurs on a regular basis in sexually reproductive-age females of certain mammal species. This article focuses on human menstruation.-Overview:...
, amenorrhea, ovulation-related infertility, and polycystic ovaries; excessive amounts or effects of androgen
Androgen
Androgen, also called androgenic hormone or testoid, is the generic term for any natural or synthetic compound, usually a steroid hormone, that stimulates or controls the development and maintenance of male characteristics in vertebrates by binding to androgen receptors...
ic (masculinizing) hormones, resulting in acne
Acne
Acne is a general term used for acneiform eruptions. It is usually used as a synonym for acne vulgaris, but may also refer to:*Acne aestivalis*Acne conglobata*Acne cosmetica*Acne fulminans*Acne keloidalis nuchae*Acne mechanica...
and hirsutism
Hirsutism
Hirsutism or frazonism is the excessive hairiness on women in those parts of the body where terminal hair does not normally occur or is minimal - for example, a beard or chest hair. It refers to a male pattern of body hair and it is therefore primarily of cosmetic and psychological concern...
; and insulin resistance
Insulin resistance
Insulin resistance is a physiological condition where the natural hormone insulin becomes less effective at lowering blood sugars. The resulting increase in blood glucose may raise levels outside the normal range and cause adverse health effects, depending on dietary conditions. Certain cell types...
, often associated with obesity
Obesity
Obesity is a medical condition in which excess body fat has accumulated to the extent that it may have an adverse effect on health, leading to reduced life expectancy and/or increased health problems...
, Type 2 diabetes, and high cholesterol levels
Hypercholesterolemia
Hypercholesterolemia is the presence of high levels of cholesterol in the blood. It is not a disease but a metabolic derangement that can be caused by many diseases, notably cardiovascular disease...
. The symptoms and severity of the syndrome vary greatly among affected women.
Names
Other names for this syndrome include polycystic ovary disease, functional ovarian hyperandrogenism, ovarian hyperthecosis, sclerocystic ovary syndrome, and Stein-Leventhal syndrome. The eponymousMedical eponyms
Medical eponyms are terms used in medicine which are named after people .New discoveries are often attached to the people who made the discovery because of the nature of the history of medicine...
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
Hirsutism
Hirsutism or frazonism is the excessive hairiness on women in those parts of the body where terminal hair does not normally occur or is minimal - for example, a beard or chest hair. It refers to a male pattern of body hair and it is therefore primarily of cosmetic and psychological concern...
, and enlarged polycystic ovaries.
Most common names for this disease derive from a typical finding on medical images, called a polycystic ovary. A polycystic ovary has an abnormally large number of developing eggs visible near its surface, looking like many small cyst
Cyst
A cyst is a closed sac, having a distinct membrane and division on the nearby tissue. It may contain air, fluids, or semi-solid material. A collection of pus is called an abscess, not a cyst. Once formed, a cyst could go away on its own or may have to be removed through surgery.- Locations :* Acne...
s or a string of pearls.
Definition
Two definitions are commonly used:NIH
- In 1990 a consensus workshop sponsored by the NIH/NICHD suggested that a patient has PCOS if she has all of the following:
- oligoovulation
- signs of androgen excess (clinical or biochemical)
- other entities are excluded that would cause polycystic ovaries
Rotterdam
- In 2003 a consensus workshop sponsored by ESHRE/ASRM in RotterdamRotterdamRotterdam is the second-largest city in the Netherlands and one of the largest ports in the world. Starting as a dam on the Rotte river, Rotterdam has grown into a major international commercial centre...
indicated PCOS to be present if any 2 out of 3 criteria are met- oligoovulation and/or anovulationAnovulationAn anovulatory cycle is a menstrual cycle during which the ovaries do not release an oocyte. Therefore, ovulation does not take place. However, a woman who does not ovulate at each menstrual cycle is not necessarily going through menopause...
- excess androgen activity
- polycystic ovaries (by gynecologic ultrasound)
- oligoovulation and/or anovulation
Other entities are excluded that would cause these.
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.
Androgen Excess PCOS Society
- In 2006 the Androgen Excess PCOS Society suggested a tightening of the diagnostic criteria to all of:
- excess androgen activity
- oligoovulation/anovulation and/or polycystic ovaries
- other entities are excluded that would cause excess androgen activity
Signs and symptoms
Common symptoms of PCOS include:- Menstrual disorderMenstrual disorder-Disorders of ovulation:Infrequent or irregular ovulation -Disorders of ovulation:Infrequent or irregular ovulation -Disorders of ovulation:Infrequent or irregular ovulation (usually defined as cycles of ≥36 days or -Disorders of ovulation:Infrequent or irregular ovulation (usually defined as...
s: PCOS mostly produces oligomenorrheaOligomenorrheaOligomenorrhea is infrequent menstruation. More strictly, it is menstrual periods occurring at intervals of greater than 35 days, with only four to nine periods in a year. Also, menstrual periods should have been regularly established previously before the development of infrequent flow...
(few menstrual periods) or amenorrhea (no menstrual periods), but other types of menstrual disorders may also occur. - InfertilityInfertilityInfertility primarily refers to the biological inability of a person to contribute to conception. Infertility may also refer to the state of a woman who is unable to carry a pregnancy to full term...
: This generally results directly from chronic anovulationAnovulationAn anovulatory cycle is a menstrual cycle during which the ovaries do not release an oocyte. Therefore, ovulation does not take place. However, a woman who does not ovulate at each menstrual cycle is not necessarily going through menopause...
(lack of ovulation). - High levels of masculinizing hormonesHyperandrogenismHyperandrogenism is a medical condition characterized by excessive production and/or secretion of androgens.It is one of the primary symptoms of polycystic ovary syndrome. In such cases, it presents with symptoms such as acne or hyperseborrhea, is frequent in adolescent girls and is often...
: The most common signs are acneAcneAcne is a general term used for acneiform eruptions. It is usually used as a synonym for acne vulgaris, but may also refer to:*Acne aestivalis*Acne conglobata*Acne cosmetica*Acne fulminans*Acne keloidalis nuchae*Acne mechanica...
and hirsutismHirsutismHirsutism or frazonism is the excessive hairiness on women in those parts of the body where terminal hair does not normally occur or is minimal - for example, a beard or chest hair. It refers to a male pattern of body hair and it is therefore primarily of cosmetic and psychological concern...
(male pattern of hair growth), but it may produce hypermenorrhea (very frequent menstrual periods) or other symptoms. Approximately three-quarters of patients with PCOS (by the diagnostic criteria of NIH/NICHD 1990) have evidence of hyperandrogenemia. - Metabolic syndromeMetabolic syndromeMetabolic syndrome is a combination of medical disorders that, when occurring together, increase the risk of developing cardiovascular disease and diabetes. It affects one in five people in the United States and prevalence increases with age...
: This appears as a tendency towards central obesityCentral obesityAbdominal obesity, colloquially known as belly fat or clinically as central obesity, is the accumulation of abdominal fat resulting in an increase in waist size...
and other symptoms associated with insulin resistanceInsulin resistanceInsulin resistance is a physiological condition where the natural hormone insulin becomes less effective at lowering blood sugars. The resulting increase in blood glucose may raise levels outside the normal range and cause adverse health effects, depending on dietary conditions. Certain cell types...
. Serum insulinInsulinInsulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....
, insulin resistance and homocysteineHomocysteineHomocysteine is a non-protein amino acid with the formula HSCH2CH2CHCO2H. It is a homologue of the amino acid cysteine, differing by an additional methylene group. It is biosynthesized from methionine by the removal of its terminal Cε methyl group...
levels are higher in women with PCOS.
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. 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 ruleClinical prediction ruleA clinical prediction rule is type of medical research study in which researchers try to identify the best combination of medical sign, symptoms, and other findings in predicting the probability of a specific disease or outcome....
found that these four questions can diagnose PCOS with a sensitivity of 77.1% (95% confidence intervalConfidence intervalIn statistics, a confidence interval is a particular kind of interval estimate of a population parameter and is used to indicate the reliability of an estimate. It is an observed interval , in principle different from sample to sample, that frequently includes the parameter of interest, if the...
[CI] 62.7%–88.0%) and a specificity of 93.8% (95% CI 82.8%–98.7%). - Gynecologic ultrasonographyGynecologic ultrasonographyGynecologic ultrasonography or Gynecologic sonography refers to the application of medical ultrasonography to the female pelvic organs, specifically the uterus, the ovaries, the Fallopian tubes, as well as the bladder, the adnexa, the Pouch of Douglas, and any findings in the pelvis of relevance...
, 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 cycleMenstrual cycleThe menstrual cycle is the scientific term for the physiological changes that can occur in fertile women for the purpose of sexual reproduction. This article focuses on the human 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 progesteroneProgesteroneProgesterone also known as P4 is a C-21 steroid hormone involved in the female menstrual cycle, pregnancy and embryogenesis of humans and other species...
-producing corpus luteumCorpus luteumThe corpus luteum is a temporary endocrine structure in mammals, involved in production of relatively high levels of progesterone and moderate levels of estradiol and inhibin A...
, 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). According to the Rotterdam criteria, 12 or more small follicles should be seen in an ovary on ultrasound examination. 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. - LaparoscopicLaparoscopic surgeryLaparoscopic surgery, also called minimally invasive surgery , bandaid surgery, or keyhole surgery, is a modern surgical technique in which operations in the abdomen are performed through small incisions as opposed to the larger incisions needed in laparotomy.Keyhole surgery makes use of images...
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.) - Serum (blood) levels of androgenAndrogenAndrogen, also called androgenic hormone or testoid, is the generic term for any natural or synthetic compound, usually a steroid hormone, that stimulates or controls the development and maintenance of male characteristics in vertebrates by binding to androgen receptors...
s (male hormones), including androstenedioneAndrostenedioneAndrostenedione is a 19-carbon steroid hormone produced in the adrenal glands and the gonads as an intermediate step in the biochemical pathway that produces the androgen testosterone and the estrogens estrone and estradiol.-Synthesis:Androstenedione is the common precursor of male and female sex...
and testosteroneTestosteroneTestosterone is a steroid hormone from the androgen group and is found in mammals, reptiles, birds, and other vertebrates. In mammals, testosterone is primarily secreted in the testes of males and the ovaries of females, although small amounts are also secreted by the adrenal glands...
may be elevated. Dehydroepiandrosterone sulfate levels above 700-800mcg/dL are highly suggestive of adrenal dysfunction because DHEA-S is made exclusively by the adrenal glands. The free testosterone level is thought to be the best measure, with ~60% of PCOS patients demonstrating supranormal levels. The Free androgen indexFree androgen indexFree Androgen Index or FAI is a ratio used to determine abnormal androgen status in humans. The ratio is the total testosterone level divided by the sex hormone binding globulin level, and then multiplying by a constant, usually 100. The concentrations of testosterone and SHBG are normally...
of the ratio of testosterone to sex hormone-binding globulin (SHBG) is high 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, possibly because FAI is correlated with the degree of obesity. - Some other blood tests are suggestive but not diagnostic. The ratio of LH (Luteinizing hormoneLuteinizing hormoneLuteinizing hormone is a hormone produced by the anterior pituitary gland. In females, an acute rise of LH called the LH surge triggers ovulation and development of the corpus luteum. In males, where LH had also been called interstitial cell-stimulating hormone , it stimulates Leydig cell...
) to FSH (Follicle stimulating hormone) is greater than 1:1 (sometimes more than 3:1), 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. There are often low levels of sex hormone binding globulinSex hormone binding globulinSex hormone-binding globulin or sex steroid-binding globulin is a glycoprotein that binds to sex hormones, to be specific, testosterone and estradiol...
, particularly among obese or overweight women.
Common assessments for associated conditions or risks
- Fasting biochemical screen and lipid profile
- 2-hour oral glucose tolerance testGlucose tolerance testA glucose tolerance test is a medical test in which glucose is given and blood samples taken afterward to determine how quickly it is cleared from the blood. The test is usually used to test for diabetes, insulin resistance, and sometimes reactive hypoglycemia and acromegaly, or rarer disorders of...
(GTT) in patients with risk factors (obesity, family history, history of gestational diabetes) may indicate impaired glucose tolerance (insulin resistance) in 15-33% of women with PCOS. Frank diabetes can be seen in 65–68% of women with this condition. 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. - 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 sugarBlood sugarThe blood sugar concentration or blood glucose level is the amount of glucose present in the blood of a human or animal. Normally in mammals, the body maintains the blood glucose level at a reference range between about 3.6 and 5.8 mM , or 64.8 and 104.4 mg/dL...
and insulin values do not predict who responds to an insulin-lowering medication, low-glycemic 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 insulin-level/22.5). - Glucose tolerance testGlucose tolerance testA glucose tolerance test is a medical test in which glucose is given and blood samples taken afterward to determine how quickly it is cleared from the blood. The test is usually used to test for diabetes, insulin resistance, and sometimes reactive hypoglycemia and acromegaly, or rarer disorders of...
ing (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. 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.
Differential diagnosis
Other causes of irregular or absent menstruation and hirsutism, such as hypothyroidismHypothyroidism
Hypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormone.Iodine deficiency is the most common cause of hypothyroidism worldwide but it can be caused by other causes such as several conditions of the thyroid gland or, less commonly, the pituitary gland or...
, congenital adrenal hyperplasia
Congenital adrenal hyperplasia
Congenital adrenal hyperplasia refers to any of several autosomal recessive diseases resulting from mutations of genes for enzymes mediating the biochemical steps of production of cortisol from cholesterol by the adrenal glands ....
(21-hydroxylase deficiency), Cushing's syndrome
Cushing's syndrome
Cushing's syndrome is a hormone disorder caused by high levels of cortisol in the blood. This can be caused by taking glucocorticoid drugs, or by tumors that produce cortisol or adrenocorticotropic hormone or CRH...
, hyperprolactinemia, androgen secreting neoplasms, and other pituitary or adrenal disorders, should be investigated. PCOS has been reported in other insulin-resistant situations such as acromegaly
Acromegaly
Acromegaly is a syndrome that results when the anterior pituitary gland produces excess growth hormone after epiphyseal plate closure at puberty...
.
Cause
PCOS is a complex, heterogeneous disorder of uncertain aetiology. There is strong evidence that it is a genetic disease. Such evidence includes the familial clustering of cases, greater concordanceConcordance
Concordance can mean:* Concordance , a list of words used in a body of work, with their immediate contexts* Concordance , the presence of the same trait in both members of a pair of twins...
in monozygotic compared with dizygotic twins and heritability of endocrine and metabolic features of PCOS.
The genetic component appears to be inherited in an autosomal dominant fashion with high genetic penetrance but variable expressivity
Expressivity
Expressivity is a term used in genetics to refer to variations in a phenotype among individuals carrying a particular genotype. The term can be used to characterize qualitatively or quantitatively the extent of phenotypic variation given a particular genotype. The term is analogous to the...
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. 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
Baldness
Baldness implies partial or complete lack of hair and can be understood as part of the wider topic of "hair thinning". The degree and pattern of baldness can vary greatly, but its most common cause is male and female pattern baldness, also known as androgenic alopecia, alopecia androgenetica or...
and/or excessive hair) and daughters, who will show signs of PCOS. The allele
Allele
An allele is one of two or more forms of a gene or a genetic locus . "Allel" is an abbreviation of allelomorph. Sometimes, different alleles can result in different observable phenotypic traits, such as different pigmentation...
appears to manifest itself at least partially via heightened androgen levels secreted by ovarian follicle
Ovarian follicle
Ovarian follicles are the basic units of female reproductive biology, each of which is composed of roughly spherical aggregations of cells found in the ovary. They contain a single oocyte . These structures are periodically initiated to grow and develop, culminating in ovulation of usually a single...
theca
Theca
A theca refers to any case, covering, or sheath.In botany, the theca of an angiosperm consists a pair of microsporangia that are adjacent to each other and share a common area of dehiscence called the stomium. Any part of a microsporophyll that bears microsporangia is called an anther. Most...
cells from women with the allele. The exact gene affected has not yet been identified.
The clinical severity of PCOS symptoms appears to be largely determined by factors such as obesity.
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):- the release of excessive luteinizing hormoneLuteinizing hormoneLuteinizing hormone is a hormone produced by the anterior pituitary gland. In females, an acute rise of LH called the LH surge triggers ovulation and development of the corpus luteum. In males, where LH had also been called interstitial cell-stimulating hormone , it stimulates Leydig cell...
(LH) by the anterior pituitary gland - through high levels of insulin in the blood (hyperinsulinaemia) in women whose ovaries are sensitive to this stimulus
Alternatively or as well, reduced levels of sex-hormone binding globulin can result in increased free androgens.
The syndrome acquired its most widely used name due to the common sign on ultrasound examination of multiple (poly) ovarian cyst
Cyst
A cyst is a closed sac, having a distinct membrane and division on the nearby tissue. It may contain air, fluids, or semi-solid material. A collection of pus is called an abscess, not a cyst. Once formed, a cyst could go away on its own or may have to be removed through surgery.- Locations :* Acne...
s. 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.
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, decreased follicular maturation, and decreased SHBG binding; all these steps contribute to the development of PCOS. Insulin resistance is a common finding among patients of normal weight as well as overweight patients.
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.
Adipose tissue possesses aromatase
Aromatase
Aromatase is an enzyme responsible for a key step in the biosynthesis of estrogens. It is a member of the cytochrome P450 superfamily , which are monooxygenases that catalyze many reactions involved in steroidogenesis. In particular, aromatase is responsible for the aromatization of androgens into...
, 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).
PCOS may be associated with chronic inflammation, with several investigators correlating inflammatory mediators with anovulation and other PCOS symptoms.
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.
PCOS has also been associated with a specific FMR1
FMR1
FMR1 is a human gene that codes for a protein called fragile X mental retardation protein, or FMRP. This protein, most commonly found in the brain, is essential for normal cognitive development and female reproductive function...
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.
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 hirsutismHirsutismHirsutism or frazonism is the excessive hairiness on women in those parts of the body where terminal hair does not normally occur or is minimal - for example, a beard or chest hair. It refers to a male pattern of body hair and it is therefore primarily of cosmetic and psychological concern...
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
Sample (statistics)
In statistics, a sample is a subset of a population. Typically, the population is very large, making a census or a complete enumeration of all the values in the population impractical or impossible. The sample represents a subset of manageable size...
tend to be less reliable
Sampling error
-Random sampling:In statistics, sampling error or estimation error is the error caused by observing a sample instead of the whole population. The sampling error can be found by subtracting the value of a parameter from the value of a statistic...
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 dietLow-carbohydrate diet
Low-carbohydrate diets or low-carb diets are dietary programs that restrict carbohydrate consumption usually for weight control or for the treatment of obesity. Foods high in digestible carbohydrates are limited or replaced with foods containing a higher percentage of proteins and fats...
s and sustained regular exercise 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. Vitamin D deficiency may play some role in the development of the metabolic syndrome
Metabolic syndrome
Metabolic syndrome is a combination of medical disorders that, when occurring together, increase the risk of developing cardiovascular disease and diabetes. It affects one in five people in the United States and prevalence increases with age...
, so treatment of any such deficiency is indicated.
Medications
Reducing insulin resistance by improving insulin sensitivity through medications such as metforminMetformin
Metformin is an oral antidiabetic drug in the biguanide class. It is the first-line drug of choice for the treatment of type 2 diabetes, in particular, in overweight and obese people and those with normal kidney function. Its use in gestational diabetes has been limited by safety concerns...
, and the newer thiazolidinedione
Thiazolidinedione
The thiazolidinediones , also known as glitazones, are a class of medications used in the treatment of diabetes mellitus type 2. They were introduced in the late 1990s.- Mechanism of action :...
(glitazones), have been an obvious approach and initial studies seemed to show effectiveness. Although metformin is not licensed
Off-label use
Off-label use is the practice of prescribing pharmaceuticals for an unapproved indication or in an unapproved age group, unapproved dose or unapproved form of administration...
for use in PCOS, the United Kingdom's National Institute for Health and Clinical Excellence
National Institute for Health and Clinical Excellence
The National Institute for Health and Clinical Excellence is a special health authority of the English National Health Service , serving both English NHS and the Welsh NHS...
recommended in 2004 that women with PCOS and a body mass index
Body mass index
The body mass index , or Quetelet index, is a heuristic proxy for human body fat based on an individual's weight and height. BMI does not actually measure the percentage of body fat. It was invented between 1830 and 1850 by the Belgian polymath Adolphe Quetelet during the course of developing...
above 25 be given metformin when other therapy has failed to produce results. 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.
Infertility
Not all women with PCOS have difficulty becoming pregnant. For those who do, anovulationAnovulation
An anovulatory cycle is a menstrual cycle during which the ovaries do not release an oocyte. Therefore, ovulation does not take place. However, a woman who does not ovulate at each menstrual cycle is not necessarily going through menopause...
or infrequent ovulation is a common cause. Other factors include changed levels of gonadotropin
Gonadotropin
Gonadotropins are protein hormones secreted by gonadotrope cells of the pituitary gland of vertebrates. This is a family of proteins, which include the mammalian hormones follitropin , lutropin , placental chorionic gonadotropins hCG and eCG and chorionic gonadotropin , as well as at least two...
s, hyperandrogenemia and hyperinsulinemia
Hyperinsulinemia
Hyperinsulinemia, or hyperinsulinaemiais a condition which there is excess levels of insulin circulating in the blood than expected relative to the level of glucose. While it is often mistaken for diabetes or hypoglycaemia, hyperinsulinemia can result from a variety of metabolic diseases and...
. 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
Weight loss
Weight loss, in the context of medicine, health or physical fitness, is a reduction of the total body mass, due to a mean loss of fluid, body fat or adipose tissue and/or lean mass, namely bone mineral deposits, muscle, tendon and other connective tissue...
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 and FSH
FSH
FSH may refer to:* Follicle-stimulating hormone* Fox Sports Houston, a regional Fox Sports Net affiliate station for the Houston, Texas area* Facioscapulohumeral muscular dystrophy* International Civil Aviation Organisation code for Flash Airlines...
are the principal treatments used to promote ovulation. Previously, the anti-diabetes medication metformin
Metformin
Metformin is an oral antidiabetic drug in the biguanide class. It is the first-line drug of choice for the treatment of type 2 diabetes, in particular, in overweight and obese people and those with normal kidney function. Its use in gestational diabetes has been limited by safety concerns...
was recommended treatment for anovulation, but it appears less effective than clomiphene.
For patients who do not respond to clomiphene, diet and lifestyle modification, there are options available including assisted reproductive technology
Assisted reproductive technology
Assisted reproductive technology is a general term referring to methods used to achieve pregnancy by artificial or partially artificial means. It is reproductive technology used primarily in infertility treatments. Some forms of ART are also used in fertile couples for genetic reasons...
procedures such as controlled ovarian hyperstimulation with follicle-stimulating hormone
Follicle-stimulating hormone
Follicle-stimulating hormone is a hormone found in humans and other animals. It is synthesized and secreted by gonadotrophs of the anterior pituitary gland. FSH regulates the development, growth, pubertal maturation, and reproductive processes of the body. FSH and Luteinizing hormone act...
(FSH) injections followed by in vitro fertilisation
In vitro fertilisation
In vitro fertilisation is a process by which egg cells are fertilised by sperm outside the body: in vitro. IVF is a major treatment in infertility when other methods of assisted reproductive technology have failed...
(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 or ovulations after adjuvant treatment with clomiphene or FSH. (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.
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. 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-androgenAndrogen
Androgen, also called androgenic hormone or testoid, is the generic term for any natural or synthetic compound, usually a steroid hormone, that stimulates or controls the development and maintenance of male characteristics in vertebrates by binding to androgen receptors...
effects that block the action of male hormones that are believed to contribute to acne and the growth of unwanted facial and body hair. On the other hand, progestogens such as norgestrel and levonorgestrel should be avoided due to their androgenic effects.
Other drugs with anti-androgen effects include flutamide
Flutamide
Flutamide is an oral nonsteroidal antiandrogen drug primarily used to treat prostate cancer. It competes with testosterone and its powerful metabolite, dihydrotestosterone for binding to androgen receptors in the prostate gland. By doing so, it prevents them from stimulating the prostate cancer...
and spironolactone
Spironolactone
Spironolactone , commonly referred to as simply spiro, is a diuretic and is used as an antiandrogen.It is a synthetic 17-lactone drug that is a renal competitive aldosterone antagonist in a class of pharmaceuticals called...
, 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
Eflornithine
Eflornithine is a drug found to be effective in the treatment of facial hirsutism as well as in African trypanosomiasis...
(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. Medications that reduce acne by indirect hormonal effects also include ergot dopamine agonists such as bromocriptine
Bromocriptine
Bromocriptine , an ergoline derivative, is a dopamine agonist that is used in the treatment of pituitary tumors, Parkinson's disease , hyperprolactinaemia, neuroleptic malignant syndrome, and type 2 diabetes.- Indications :Amenorrhea, female infertility, galactorrhea, hypogonadism, and acromegaly...
. 5-alpha reductase
5-alpha reductase
5α-reductases, also known as 3-oxo-5α-steroid 4-dehydrogenases, are enzymes involved in steroid metabolism. They participate in 3 metabolic pathways: bile acid biosynthesis, androgen and estrogen metabolism, and prostate cancer....
inhibitors (such as finasteride
Finasteride
Finasteride is a synthetic antiandrogen that inhibits type II 5-alpha reductase, the enzyme that converts testosterone to dihydrotestosterone...
and dutasteride
Dutasteride
Dutasteride is a dual 5-a reductase inhibitor that inhibits conversion of testosterone to dihydrotestosterone ....
) may also be used; they work by blocking the conversion of testosterone
Testosterone
Testosterone is a steroid hormone from the androgen group and is found in mammals, reptiles, birds, and other vertebrates. In mammals, testosterone is primarily secreted in the testes of males and the ovaries of females, although small amounts are also secreted by the adrenal glands...
to dihydrotestosterone
Dihydrotestosterone
Dihydrotestosterone is an androgen or male sex hormone. The enzyme 5α-reductase synthesises DHT in the prostate, testes, hair follicles, and adrenal glands...
(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), 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.
Menstrual irregularity and endometrial hyperplasia
If fertility is not the primary aim, then menstruationMenstruation
Menstruation is the shedding of the uterine lining . It occurs on a regular basis in sexually reproductive-age females of certain mammal species. This article focuses on human menstruation.-Overview:...
can usually be regulated with a contraceptive pill, 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. 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).
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. If menstruation occurs less often or not at all, some form of progestogen replacement is recommended. Some women prefer a uterine progestogen device such as the intrauterine system
IntraUterine System
The IUD with progestogen, intrauterine system , or IntraUterine Contraceptive is a long-acting reversible hormonal contraceptive device that is placed in the uterus. An IUS has a hormone cylinder that releases a progestin called levonorgestrel...
(Mirena) or the progestin implant (Implanon
Implanon
Implanon, made by Organon International, is a single-rod long acting reversible hormonal contraceptive subdermal implant that is inserted just under the skin of a woman's upper arm. The 4 cm by 2 mm Implanon rod contains 68 milligrams of etonogestrel which is released over a three year...
), which provides simultaneous contraception and endometrial protection for years. An alternative is oral progestogen taken at intervals (e.g. every three months) to induce a predictable menstrual bleeding.
Alternative approaches
At least two inositolInositol
Inositol or cyclohexane-1,2,3,4,5,6-hexol is a chemical compound with formula 6126 or 6, a sixfold alcohol of cyclohexane. It exists in nine possible stereoisomers, of which the most prominent form, widely occurring in nature, is cis-1,2,3,5-trans-4,6-cyclohexanehexol, or myo-inositol...
isomers - D-chiro-inositol
D-chiro-inositol
D-chiro-Inositol is a member of a family of related substances often referred to collectively as "inositol," although that term encompasses several isomers of questionable biological relevance...
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. Inositol has no documented side-effects and is a naturally occurring human metabolite known to be involved in insulin metabolism. DCI is regulated as a dietary supplement
Dietary supplement
A dietary supplement, also known as food supplement or nutritional supplement, is a preparation intended to supplement the diet and provide nutrients, such as vitamins, minerals, fiber, fatty acids, or amino acids, that may be missing or may not be consumed in sufficient quantities in a person's diet...
in the United States. Myo-inositol is naturally present in many foods although not readily digestible from most of them.
Prognosis
Women with PCOS are at risk for the following:- Endometrial hyperplasiaEndometrial hyperplasiaEndometrial hyperplasia is a condition of excessive proliferation of the cells of the endometrium, or inner lining of the uterus.Most cases of endometrial hyperplasia result from high levels of estrogens, combined with insufficient levels of the progesterone-like hormones which ordinarily...
and endometrial cancerEndometrial cancerEndometrial cancer refers to several types of malignancies that arise from the endometrium, or lining, of the uterus. Endometrial cancers are the most common gynecologic cancers in the United States, with over 35,000 women diagnosed each year. The incidence is on a slow rise secondary to the...
(cancer of the uterine lining) are possible, due to overaccumulation of uterine lining, and also lack of progesteroneProgesteroneProgesterone also known as P4 is a C-21 steroid hormone involved in the female menstrual cycle, pregnancy and embryogenesis of humans and other species...
resulting in prolonged stimulation of uterine cells by estrogen. It is not clear if this risk is directly due to the syndrome or from the associated obesity, hyperinsulinemiaHyperinsulinemiaHyperinsulinemia, or hyperinsulinaemiais a condition which there is excess levels of insulin circulating in the blood than expected relative to the level of glucose. While it is often mistaken for diabetes or hypoglycaemia, hyperinsulinemia can result from a variety of metabolic diseases and...
, and hyperandrogenismHyperandrogenismHyperandrogenism is a medical condition characterized by excessive production and/or secretion of androgens.It is one of the primary symptoms of polycystic ovary syndrome. In such cases, it presents with symptoms such as acne or hyperseborrhea, is frequent in adolescent girls and is often...
. - Insulin resistanceInsulin resistanceInsulin resistance is a physiological condition where the natural hormone insulin becomes less effective at lowering blood sugars. The resulting increase in blood glucose may raise levels outside the normal range and cause adverse health effects, depending on dietary conditions. Certain cell types...
/Type II diabetesDiabetes mellitus type 2Diabetes mellitus type 2formerly non-insulin-dependent diabetes mellitus or adult-onset diabetesis a metabolic disorder that is characterized by high blood glucose in the context of insulin resistance and relative insulin deficiency. Diabetes is often initially managed by increasing exercise and...
. 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 indexBody mass indexThe body mass index , or Quetelet index, is a heuristic proxy for human body fat based on an individual's weight and height. BMI does not actually measure the percentage of body fat. It was invented between 1830 and 1850 by the Belgian polymath Adolphe Quetelet during the course of developing...
(BMI). PCOS also makes a woman, particularly if obese, prone to gestational diabetesGestational diabetesGestational diabetes is a condition in which women without previously diagnosed diabetes exhibit high blood glucose levels during pregnancy . It is widely accepted as a disease only in the United States, there is some question whether the condition is natural during pregnancy...
. - High blood pressure, particularly if obese and/or during pregnancy
- DepressionDepression (mood)Depression is a state of low mood and aversion to activity that can affect a person's thoughts, behaviour, feelings and physical well-being. Depressed people may feel sad, anxious, empty, hopeless, helpless, worthless, guilty, irritable, or restless...
/Depression with AnxietyAnxietyAnxiety is a psychological and physiological state characterized by somatic, emotional, cognitive, and behavioral components. The root meaning of the word anxiety is 'to vex or trouble'; in either presence or absence of psychological stress, anxiety can create feelings of fear, worry, uneasiness,... - DyslipidemiaDyslipidemiaDyslipidemia or dyslipidaemia is an abnormal amount of lipids in the blood. In developed countries, most dyslipidemias are hyperlipidemias; that is, an elevation of lipids in the blood, often due to diet and lifestyle. The prolonged elevation of insulin levels can lead to dyslipidemia...
- disorders of lipid metabolism — cholesterol and triglycerides. PCOS patients show decreased removal of atherosclerosisAtherosclerosisAtherosclerosis is a condition in which an artery wall thickens as a result of the accumulation of fatty materials such as cholesterol...
-inducing remnants, seemingly independent of insulin resistance/Type II diabetes. - Cardiovascular diseaseCardiovascular diseaseHeart disease or cardiovascular disease are the class of diseases that involve the heart or blood vessels . While the term technically refers to any disease that affects the cardiovascular system , it is usually used to refer to those related to atherosclerosis...
, with a meta-analysis estimating a 2-fold risk of arterial disease for women with PCOS relative to women without PCOS, independent of BMI. - StrokeStrokeA stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...
s - Weight gainWeight gainWeight gain is an increase in body weight. This can be either an increase in muscle mass, fat deposits, or excess fluids such as water.-Description:...
- MiscarriageMiscarriageMiscarriage or spontaneous abortion is the spontaneous end of a pregnancy at a stage where the embryo or fetus is incapable of surviving independently, generally defined in humans at prior to 20 weeks of gestation...
- Sleep apneaSleep apneaSleep apnea is a sleep disorder characterized by abnormal pauses in breathing or instances of abnormally low breathing, during sleep. Each pause in breathing, called an apnea, can last from a few seconds to minutes, and may occur 5 to 30 times or more an hour. Similarly, each abnormally low...
, particularly if obesity is present - Non-alcoholic fatty liver diseaseNon-alcoholic fatty liver diseaseNon-alcoholic fatty liver disease is one cause of a fatty liver, occurring when fat is deposited in the liver not due to excessive alcohol use. It is related to insulin resistance and the metabolic syndrome and may respond to treatments originally developed for other insulin-resistant states...
, again particularly if obesity is present - Acanthosis nigricansAcanthosis nigricansAcanthosis nigricans is a brown to black, poorly defined, velvety hyperpigmentation of the skin. It is usually found in body folds, such as the posterior and lateral folds of the neck, the axilla, groin, umbilicus, forehead, and other areas.-Causes:...
(patches of darkened skin under the arms, in the groin area, on the back of the neck) - Autoimmune thyroiditisAutoimmune thyroiditisAutoimmune thyroiditis is a form of thyroiditis associated with an autoimmune disease where the body treats the thyroid gland and sometimes the hormones it produces as foreign bodies, therefore rejecting and attacking both.-Treatment:...
Early diagnosis and treatment may reduce the risk of some of these, such as type 2 diabetes and heart disease.
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.One study in the United Kingdom concluded that the risk of PCOS development was higher in lesbian women than in heterosexuals. However, two subsequent studies of women with PCOS have not replicated this finding.
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.See also
- Androgen-dependent syndromesAndrogen-dependent syndromesAndrogen-dependent syndromes are caused by the excessive production of adrenal or gonadal androgens by adrenal adenomas, carcinomas, or hyperplasia, Leydig cell tumors in men, and arrhenoblastomas and polycystic ovarian syndrome in women....
- PCOS ChallengePCOS ChallengePCOS Challenge is a reality television series produced to bring greater awareness about polycystic ovary syndrome and support to women living with PCOS. The show addresses common PCOS symptoms and related conditions including infertility, diabetes, obesity, heart disease, anxiety and depression,...
(reality television series)