Polycystic ovary syndrome
Polycystic ovary syndrome | |
---|---|
Other names | Hyperandrogenic anovulation (HA),[1]
Stein-Leventhal syndrome anti-androgens[12] |
Frequency | 2% to 20% of women of childbearing age[8][13] |
Polycystic ovary syndrome, or polycystic ovarian syndrome (PCOS), is the most common
People with PCOS may experience irregular
A review of international evidence found that the prevalence of PCOS could be as high as 26% among some populations, though ranges between 4% and 18% are reported for general populations.[18][19][20]
The exact cause of PCOS remains uncertain, and treatment involves management of symptoms using medication.[19]
Definition
Two definitions are commonly used:
- NIH
- In 1990, a consensus workshop sponsored by the NICHD suggested that a person has PCOS if they have all of the following:[21]
- oligoovulation
- signs of androgen excess(clinical or biochemical)
- exclusion of other disorders that can result in menstrual irregularity and hyperandrogenism (e.g.: Congenital Suprarrenal Hyperplasia, androgen producer tumors, hyperprolactinemia).
- Rotterdam
In 2003, a consensus workshop sponsored by
- oligoovulation and/or anovulation
- excess androgen activity
- polycystic ovaries (by gynecologic ultrasound)
The Rotterdam definition is wider, including many more women, the most notable ones being women without androgen excess. Critics say that findings obtained from the study of women with androgen excess cannot necessarily be extrapolated to women without androgen excess.[25][26]
- Androgen Excess PCOS Society
- In 2006, the Androgen Excess PCOS Society suggested a tightening of the diagnostic criteria to all of the following:[22]
- excess androgen activity
- oligoovulation/anovulation and/or polycystic ovaries
- exclusion of other entities that would cause excess androgen activity
Signs and symptoms
Signs and symptoms of PCOS include irregular or no
Associated conditions include
Common signs and symptoms of PCOS include the following:
- Menstrual disorders: PCOS mostly produces oligomenorrhea (fewer than nine menstrual periods in a year) or amenorrhea (no menstrual periods for three or more consecutive months), but other types of menstrual disorders may also occur.[22]
- Infertility: This generally results directly from chronic anovulation (lack of ovulation).[22]
- hyperandrogenemia.[30]
- central obesity and other symptoms associated with insulin resistance, including low energy levels and food cravings.[22] Serum insulin, insulin resistance, and homocysteine levels are higher in women with PCOS.[31]
- Acne: A rise in testosterone levels, increases the oil production within the sebaceous glands and clogs pores.[32] For many people, the emotional impact is great and quality of life can be significantly reduced.[33]
- Acanthosis Nigricans (AN): A skin condition where dark, thick and "velvety" patches can form. (p. 141)[35]
- Polycystic ovaries: PCOS is a complicated disorder characterized by high androgen levels, irregular menstruation, and/or small cysts on one or both ovaries. Ovaries might get enlarged and comprise follicles surrounding the eggs. As result, ovaries might fail to function regularly. This disease is related to the number of follicles per ovary each month growing from the average range of 6-8 to double, triple or more[citation needed]. Women with PCOS have higher risk of multiple diseases including Infertility, type 2 diabetes mellitus (DM-2), cardiovascular risk, metabolic syndrome, obesity, impaired glucose tolerance, depression, obstructive sleep apnea (OSA), endometrial cancer, and nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH).[36]
Women with PCOS tend to have central obesity, but studies are conflicting as to whether visceral and subcutaneous abdominal fat is increased, unchanged, or decreased in women with PCOS relative to non-PCOS women with the same body mass index.[37] In any case, androgens, such as testosterone, androstanolone (dihydrotestosterone), and nandrolone decanoate have been found to increase visceral fat deposition in both female animals and women.[38]
Although 80% of PCOS presents in women with obesity, 20% of women diagnosed with the disease are non-obese or "lean" women.[39] However, obese women that have PCOS have a higher risk of adverse outcomes, such as hypertension, insulin resistance, metabolic syndrome, and endometrial hyperplasia.[40]
Even though most women with PCOS are overweight or obese, it is important to acknowledge that non-overweight women can also be diagnosed with PCOS. Up to 30% of women diagnosed with PCOS maintain a normal weight before and after diagnosis. "Lean" women still face the various symptoms of PCOS with the added challenges of having their symptoms properly addressed and recognized. Lean women often go undiagnosed for years, and usually are diagnosed after struggles to conceive.[41] Lean women are likely to have a missed diagnosis of diabetes and cardiovascular disease. These women also have an increased risk of developing insulin resistance, despite not being overweight. Lean women are often taken less seriously with their diagnosis of PCOS, and also face challenges finding appropriate treatment options. This is because most treatment options are limited to approaches of losing weight and healthy dieting.[42]
Hormone levels
Associated conditions
Warning signs may include a change in appearance. But there are also manifestations of mental health problems, such as anxiety, depression, and eating disorders.[27][medical citation needed]
A diagnosis of PCOS suggests an increased risk of 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.[21][49] It is not clear whether this risk is directly due to the syndrome or from the associated obesity, hyperinsulinemia, and hyperandrogenism.[50][51][52]
- Insulin resistance/type 2 diabetes. A review published in 2010 concluded that women with PCOS have an elevated prevalence of insulin resistance and type 2 diabetes, even when controlling for body mass index (BMI).[21][53] PCOS is also associated with higher risk for diabetes.[54]
- High blood pressure, in particular if obese or during pregnancy[55]
- Dyslipidemia – disorders of lipid metabolism – cholesterol and triglycerides. Women with PCOS show a decreased removal of atherosclerosis-inducing remnants, seemingly independent of insulin resistance/type 2 diabetes.[57]
- Cardiovascular disease,[21] with a meta-analysis estimating a 2-fold risk of arterial disease for women with PCOS relative to women without PCOS, independent of BMI.[58]
- Strokes[21]
- Weight gain
- Miscarriage[59][60]
- Sleep apnea, particularly if obesity is present
- Non-alcoholic fatty liver disease, particularly if obesity is present
- Acanthosis nigricans (patches of darkened skin under the arms, in the groin area, on the back of the neck)[21]
- Autoimmune thyroiditis[citation needed]
- Iron deficiency[61]
The risk of ovarian cancer and breast cancer is not significantly increased overall.[49]
Cause
PCOS is a
It may be caused by a combination of genetic and environmental factors.
Genetics
The genetic component appears to be inherited in an
Due to the scarcity of large-scale screening studies, the prevalence of endometrial abnormalities in PCOS remains unknown, though women with the condition may be at increased risk for endometrial hyperplasia and carcinoma as well as menstrual dysfunction and infertility.
The severity of PCOS symptoms appears to be largely determined by factors such as obesity.[7][22][72] PCOS has some aspects of a metabolic disorder, since its symptoms are partly reversible. Even though considered as a gynecological problem, PCOS consists of 28 clinical symptoms.[73]
Even though the name suggests that the ovaries are central to disease pathology, cysts are a symptom instead of the cause of the disease. Some symptoms of PCOS will persist even if both ovaries are removed; the disease can appear even if cysts are absent. Since its first description by Stein and Leventhal in 1935, the criteria of diagnosis, symptoms, and causative factors are subject to debate. Gynecologists often see it as a gynecological problem, with the ovaries being the primary organ affected. However, recent insights show a multisystem disorder, with the primary problem lies in hormonal regulation in the hypothalamus, with the involvement of many organs. The term PCOS is used due to the fact that there is a wide spectrum of symptoms possible. It is common to have polycystic ovaries without having PCOS; approximately 20% of European women have polycystic ovaries, but most of those women do not have PCOS.[15]
Environment
PCOS may be related to or worsened by exposures[
Pathogenesis
Polycystic ovaries develop when the ovaries are stimulated to produce excessive amounts of androgenic hormones, in particular testosterone, by either one or a combination of the following (almost certainly combined with genetic susceptibility):[67]
- the release of excessive luteinizing hormone (LH) by the anterior pituitary gland
- through high levels of insulin in the blood (hyperinsulinaemia) in women whose ovaries are sensitive to this stimulus
A majority of women with PCOS have
Adipose (fat) tissue possesses aromatase, an enzyme that converts androstenedione to estrone and testosterone to estradiol. The excess of adipose tissue in obese women creates the paradox of having both excess androgens (which are responsible for hirsutism and virilization) and excess estrogens (which inhibit FSH via negative feedback).[84]
The syndrome acquired its most widely used name due to the common sign on ultrasound examination of multiple (poly) ovarian
PCOS may be associated with
Diagnosis
Not every person with PCOS has polycystic ovaries (PCO), nor does everyone with
-
Transvaginal ultrasound scan of polycystic ovary
-
Polycystic ovary as seen on sonography
Differential diagnosis
Other causes of irregular or absent menstruation and hirsutism, such as
Assessment and testing
Standard assessment
- History-taking, specifically for menstrual pattern, obesity, hirsutism and acne. A specificity of 93.8% (95% CI 82.8%–98.7%).[93]
- 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 – in essence, 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 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, which are widely used for diagnosis of PCOS,[10] 12 or more small follicles should be seen in a suspect ovary on ultrasound examination.[21] More recent research suggests that there should be at least 25 follicles in an ovary to designate it as having polycystic ovarian morphology (PCOM) in women aged 18–35 years.[94] The follicles may be oriented in the periphery, giving the appearance of a 'string of pearls'.[95] If a high-resolution transvaginal ultrasonography machine is not available, an ovarian volume of at least 10 ml is regarded as an acceptable definition of having polycystic ovarian morphology. rather than follicle count.[94]
- 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.)[96]
- Serum (blood) levels of
Some other blood tests are suggestive but not diagnostic. The ratio of LH (
Glucose tolerance testing
- Two-hour oral glucose tolerance test (GTT) in women with risk factors (obesity, family history, history of gestational diabetes)[22] may indicate impaired glucose tolerance (insulin resistance) in 15–33% of women with PCOS.[92] Frank diabetes can be seen in 65–68% of women with this condition.[104] Insulin resistance can be observed in both normal weight and overweight people, although it is more common in the latter (and in those matching the stricter NIH criteria for diagnosis); 50–80% of people with PCOS may have insulin resistance at some level.[22]
- 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 needing higher doses 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, 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).[105]
Management
PCOS has no cure.[5] Treatment may involve lifestyle changes such as weight loss and exercise.[10][11]
Recent research suggests that daily exercise including both aerobic and strength activities can improve hormone imbalances.[106]
Certain cosmetic procedures may also help alleviate symptoms in some cases. For example, the use of laser hair removal, electrolysis, or general waxing, plucking and shaving are all effective methods for reducing hirsutism.[35] The primary treatments for PCOS include lifestyle changes and use of medications.[108]
Goals of treatment may be considered under four categories:[citation needed]
- Lowering of insulin resistance
- Reducing androgen and testosterone 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 factors underlying the debate is the lack of large-scale clinical trials comparing different treatments.
Diet
Where PCOS is associated with being overweight or obesity, successful weight loss is the most effective method of restoring normal ovulation/menstruation. The
Reducing intake of food groups that cause inflammation, such as dairy, sugars and simple carbohydrates, can be beneficial.[35]
A mediterranean diet is often very effective due to its anti-inflammatory and anti-oxidative properties.[106]
Medications
Medications for PCOS include
Metformin is a medication commonly used in
It can be difficult to become pregnant with PCOS because it causes irregular
Infertility
Not all people with PCOS have difficulty becoming pregnant. But some individuals with PCOS may have difficulty getting pregnant since their body does not produce the hormones necessary for regular ovulation.[129] PCOS might also increase the risk of miscarriage or premature delivery. However, it is possible to have a normal pregnancy. Including medical care and a healthy lifestyle to follow.[citation needed]
For those that do,
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.[133] Digital health interventions have been shown to be particularly effective in providing combined therapy to manage PCOS through both lifestyle changes and medication.[134]
Femara is an alternative medicine that raises FSH levels and promote the development of the follicle.[35]
For those women that after weight loss still are anovulatory or for anovulatory lean women, then
Previously, the anti-diabetes medication metformin was recommended treatment for anovulation, but it appears less effective than letrozole or clomiphene.[138][139]
For women not responsive to letrozole or clomiphene and 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).[140]
Though surgery is not commonly performed, the polycystic ovaries can be treated with a laparoscopic procedure called "
Mental Health
Although women with PCOS are far more likely to have depression than women without, the evidence for anti-depressant use in women with PCOS remains inconclusive.[142] However, the pathophysiology of depression and mental stress during PCOS is linked to various changes including psychological changes such as high activity of pro-inflammatory markers and immune system during stress.[143]
PCOS is associated with other mental health related conditions besides depression such as anxiety, bipolar disorder, and obsessive–compulsive disorder.[33]
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.[113] Progestogens such as norgestrel and levonorgestrel should be avoided due to their androgenic effects.[113] Metformin combined with an oral contraceptive may be more effective than either metformin or the oral contraceptive on its own.[144]
In the case of taking medication for acne, Kelly Morrow-Baez PHD, in her exposition titled Thriving with PCOS, informs that it "takes time for medications to adjust hormone levels, and once those hormone levels are adjusted, it takes more time still for pores to be unclogged of overproduced oil and for any bacterial infections under the skin to clear up before you will see discernible results." (p. 138) [35]
Other medications with anti-androgen effects include
Although these agents have shown significant efficacy in clinical trials (for oral contraceptives, in 60–100% of individuals[113]), 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 medications if one does not work, but medications do not work well for all individuals.[147]
Menstrual irregularity
If fertility is not the primary aim, then menstruation can usually be regulated with a contraceptive pill.[113] The purpose of regulating menstruation, in essence, is for the patient's convenience, and perhaps their sense of well-being; there is no medical requirement for regular periods, as long as they occur sufficiently often.[148]
If a regular menstrual cycle is not desired, then therapy for an irregular cycle is not necessarily required. Most experts say 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.[149] If menstruation occurs less often or not at all, some form of progestogen replacement is recommended.[146]
Alternative medicine
A 2017 review concluded that while both myo-inositol and D-chiro-inositols may regulate menstrual cycles and improve ovulation, there is a lack of evidence regarding effects on the probability of pregnancy.
Epidemiology
PCOS is the most common
The prevalence of PCOS depends on the choice of diagnostic criteria. The World Health Organization estimates that it affects 116 million women worldwide as of 2010 (3.4% of women).[159] Another estimate indicates that 7% of women of reproductive age are affected.[160] Another study using the Rotterdam criteria found that about 18% of women had PCOS, and that 70% of them were previously undiagnosed.[22] Prevalence also varies across countries due to lack of large-scale scientific studies; India, for example, has a purported rate of 1 in 5 women having PCOS.[161]
There are few studies that have investigated the racial differences in cardiometabolic factors in women with PCOS. There is also limited data on the racial differences in the risk of metabolic syndrome and cardiovascular disease in adolescents and young adults with PCOS.[162] The first study to comprehensively examine racial differences discovered notable racial differences in risk factors for cardiovascular disease. African American women were found to be significantly more obese, with a significantly higher prevalence of metabolic syndrome compared to white adult women with PCOS.[163] It is important for the further research of racial differences among women with PCOS, to ensure that every woman that is affected by PCOS has the available resources for management.[164][165]
Ultrasonographic findings of polycystic ovaries are found in 8–25% of women non-affected by the syndrome.[166][167][168][169] 14% women on oral contraceptives are found to have polycystic ovaries.[167] Ovarian cysts are also a common side effect of levonorgestrel-releasing intrauterine devices (IUDs).[170]
There are few studies that have investigated the racial differences in cardiometabolic factors in women with PCOS.[171]
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.[90][21] Stein and Leventhal first described PCOS as an endocrine disorder in the United States, and since then, it has become recognized as one of the most common causes of oligo ovulatory infertility among women.[49]
The earliest published description of a person with what is now recognized as PCOS was in 1721 in Italy.[158] Cyst-related changes to the ovaries were described in 1844.[158]
Etymology
Other names for this syndrome include polycystic ovarian syndrome, polycystic ovary disease, functional ovarian hyperandrogenism, ovarian
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 cysts.[90]
Society and culture
In 2005, 4 million cases of PCOS were reported in the US, costing $4.36 billion in healthcare costs.[172] In 2016 out of the National Institute Health's research budget of $32.3 billion for that year, 0.1% was spent on PCOS research.[173] Among those aged between 14 and 44, PCOS is conservatively estimated to cost $4.37 billion per year.[23]
As opposed to women in the general population, women with PCOS experience higher rates of depression and anxiety. International guidelines and Indian guidelines suggest psychosocial factors should be considered in women with PCOS, as well as screenings for depression and anxiety.[174] Globally, this aspect has been increasingly focused on because it reflects the true impact of PCOS on the lives of patients. Research shows that PCOS adversely impacts a patient's quality of life.[174]
Public figures
A number of celebrities and public figures have spoken about their experiences with PCOS, including:
- Victoria Beckham[175]
- Maci Bookout[176]
- Frankie Bridge[177]
- Harnaam Kaur[178]
- Jaime King[179]
- Chrisette Michele[180]
- Lea Michele[181]
- Keke Palmer[182]
- Sasha Pieterse[183][184]
- Daisy Ridley[185]
- Romee Strijd[186]
- Lee Tilghman[187]
See also
- Androgen-dependent syndromes
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Diagnosis and treatment. The first diagnostic test [of PCOS] is measurement of total testosterone and free testosterone by radioimmunoassay. If total testosterone is between 50 ng/dL and 200 ng/dL above normal (<2.5 ng/dL) PCOS is present. If >200 ng/dL then serum DHEA-S should be measured. If total testosterone or DHEA-S >700 μg/dL then rule out an ovarian or adrenal tumor. These tests should be followed by tests for hypothyroidism, hyperprolactinemia, and adrenal hyperplasia.
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Further reading
- Bremer AA (October 2010). "Polycystic ovary syndrome in the pediatric population". Metabolic Syndrome and Related Disorders. 8 (5): 375–394. PMID 20939704.
- "Polycystic Ovary Syndrome (PCOS)". Eunice Kennedy Shriver National Institute of Child Health and Human Development. 31 January 2017.
External links
- Media related to Polycystic ovary syndrome at Wikimedia Commons