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Polycystic ovary syndrome
Set of symptoms caused by abnormal hormones in females

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age, characterized by symptoms such as hyperandrogenism, anovulation, insulin resistance, and neuroendocrine disruption. Although named for the cysts sometimes found on the ovaries, these are not present in all cases. Women with PCOS may experience irregular menstrual periods, excess hair, acne, and fertility challenges. The exact cause is unknown, with prevalence estimates ranging from 5% to 18%. Treatment often includes medication to regulate cycles and manage symptoms, alongside lifestyle changes to reduce cardiometabolic risks.

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Signs and symptoms

Signs and symptoms of PCOS include irregular or no menstrual periods, heavy periods, excess body and facial hair, acne, difficulty getting pregnant, and patches of thick, darker, velvety skin,9 ovarian cysts, enlarged ovaries, excess androgens, and weight gain.1011

Associated conditions include type 2 diabetes, obesity, obstructive sleep apnea, heart disease, mood disorders, and endometrial cancer.12

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.13
  • Infertility: This generally results directly from chronic anovulation (lack of ovulation).14
  • High levels of masculinizing hormones: Known as hyperandrogenism, the most common signs are acne and hirsutism (male pattern of hair growth, such as on the chin or chest), but it may produce hypermenorrhea (heavy and prolonged menstrual periods), androgenic alopecia (increased hair thinning or diffuse hair loss), or other symptoms.1516 Approximately three-quarters of women with PCOS (by the diagnostic criteria of NIH/NICHD 1990) have evidence of hyperandrogenemia.17
  • Metabolic syndrome: This appears as a tendency towards central obesity and other symptoms associated with insulin resistance, including low energy levels and food cravings.18 Serum insulin, insulin resistance, and homocysteine levels are higher in women with PCOS.19
  • Acne: A rise in testosterone levels increases the oil production within the sebaceous glands and clogs pores.20 For many women, the emotional impact is great and quality of life can be significantly reduced.21
  • Androgenic alopecia: Estimates suggest that androgenic alopecia affects 22% of PCOS sufferers.22
  • Acanthosis nigricans (AN): A skin condition where dark, thick, and "velvety" patches can form.23 Often forms under the arms, in the groin area, on the back of the neck.24
  • Polycystic ovaries: There are small cysts on one or both ovaries. Ovaries might enlarge and compress follicles surrounding the eggs. As a 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.

Women with PCOS tend to have central obesity. Still, 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.25 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.26

Although 80% of PCOS presents in women with obesity, 20% of women diagnosed with the disease are non-obese or "lean" women.27 However, obese women who have PCOS have a higher risk of adverse outcomes, such as hypertension, insulin resistance, metabolic syndrome, and endometrial hyperplasia.28

Even though most women with PCOS are overweight or obese, 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 are usually diagnosed after struggles to conceive.29 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 for losing weight and healthy dieting.30

Hormone levels

Testosterone levels are usually elevated in women with PCOS.3132 In a 2020 systematic review and meta-analysis of sexual dysfunction related to PCOS which included 5,366 women with PCOS from 21 studies, testosterone levels were analyzed and were found to be 2.34 nmol/L (67 ng/dL) in women with PCOS and 1.57 nmol/L (45 ng/dL) in women without PCOS.33 If testosterone levels are above 100 to 200 ng/dL, per different sources, other possible causes of hyperandrogenism, such as congenital adrenal hyperplasia or an androgen-secreting tumor, may be present and should be excluded.343536

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.37[medical citation needed]

A diagnosis of PCOS suggests an increased risk of the following:

The risk of ovarian cancer and breast cancer is not significantly increased overall, but women with PCOS were about three times more likely to develop endometrial cancer than other women.57

Some medical providers and groups consider PCOS to be an intersex condition because some sex hormones are outside the typical range.58 However, medical consensus, including the Endocrine Society and NIH, defines PCOS as an endocrine/metabolic disorder, not intersex, as it lacks congenital sex characteristic variations.5960 A 2023 study notes two transmasculine individuals self-identified as intersex without medical diagnosis, tying it to identity, not biology.61

Cause

PCOS is a heterogeneous disorder of uncertain cause.6263 There is some 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.646566 There is some evidence that exposure to higher than typical levels of androgens and the anti-Müllerian hormone (AMH) in utero increases the risk of developing PCOS in later life.67

It may be caused by a combination of genetic and environmental factors.686970 Risk factors include obesity, a lack of physical exercise, and a family history of someone with the condition.71 Diagnosis is based on two of the following three findings: anovulation, high androgen levels, and ovarian cysts.72 Other conditions that produce similar symptoms include adrenal hyperplasia, hypothyroidism, and high blood levels of prolactin.73

Genetics

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), the daughter will have the disease to some extent.74757677 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.7879 The phenotype appears to manifest itself at least partially via heightened androgen levels secreted by ovarian follicle theca cells from women with the allele.80 The exact gene affected has not yet been identified.818283 In rare instances, single-gene mutations can give rise to the syndrome phenotype.84 Current understanding of the pathogenesis of the syndrome suggests, however, that it is a complex multigenic disorder.85

The severity of PCOS symptoms appears to be largely determined by factors such as obesity.868788 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.89

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 have been 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 lying in hormonal regulation in the hypothalamus, with the involvement of many organs. The term PCOS is used because 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.90

Environment

PCOS may be related to or worsened by exposures during the prenatal period,919293 epigenetic factors, environmental impacts (especially industrial endocrine disruptors, such as bisphenol A and certain drugs)949596 and the increasing rates of obesity.97

Endocrine disruptors are defined as chemicals that can interfere with the endocrine system by mimicking hormones such as estrogen. According to the NIH (National Institute of Health), examples of endocrine disruptors can include dioxins and triclosan. Endocrine disruptors can cause adverse health impacts in animals.98 Additional research is needed to assess the role that endocrine disruptors may play in disrupting reproductive health in women and possibly triggering or exacerbating PCOS and its related symptoms.99

The study of epigenetic changes in PCOS in utero or after birth has become an emerging area of research. While extensive research is not currently available, some studies are looking into the connection between abnormal DNA methylation changes in various tissues and the development of PCOS.100  Environmental exposure to endocrine disruptors such as phthalates could alter DNA methylation patterns, particularly in the ovaries, granulosa cells, and adipose tissue.101

One study observed early embryonic development of mice subjected to di--(2-ethylhexyl) phthalate (DEHP) and the results showed abnormal methylation patterns in the Stra8 gene involved in meiosis initiation.102 The gene for transcription factor Lhx8, involved in early follicular changes, was also impacted by DEHP when the neonatal mouse ovaries were analyzed. Together, these results showed DEHP induced epigenetic changes via DNA methylation to interfere with folliculogenesis, symptomatic of PCOS.103 Although DNA methylation in human embryonic development is not fully characterized, the animal model studies on epigenetic changes provide information to suggest that PCOS may have fetal origins.

Androgen excess is a central feature in the PCOS phenotype, and exposure in utero has shown PCOS-like features in adulthood. A study from 2014 induced DNA hypomethylation in the ovarian tissue of zebrafish exposed to androgens early in development.104 Glucose homeostasis alterations were also observed. Furthermore, these effects were carried into the next generation, suggesting that epigenetic changes caused by excess androgens in the fetus could be transgenerational.105

Mechanism

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):106

A majority of women with PCOS have insulin resistance and/or are obese, which is a strong risk factor for insulin resistance, although insulin resistance is a common finding among women with PCOS in normal-weight women as well.107108109 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,110 which in turn results in an increase in the LH/FSH ratio111112 increased ovarian androgen production; decreased follicular maturation; and decreased SHBG binding.113 Furthermore, excessive insulin increases the activity of 17α-hydroxylase, which catalyzes the conversion of progesterone to androstenedione, which is in turn converted to testosterone. The combined effects of hyperinsulinemia contribute to an increased risk of PCOS.114

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).115

The syndrome acquired its most widely used name due to the common sign on ultrasound examination of multiple (poly) ovarian cysts. These "cysts" are in fact immature ovarian follicles. The follicles have developed from primordial follicles, but this development has stopped ("arrested") at an early 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.116

PCOS may be associated with chronic inflammation,117 with several investigators correlating inflammatory mediators with anovulation and other PCOS symptoms.118119 Similarly, there seems to be a relation between PCOS and an increased level of oxidative stress.120

Diagnosis

Not every person with PCOS has polycystic ovaries (PCO), nor does everyone with ovarian cysts have PCOS; although a pelvic ultrasound is a major diagnostic tool, it is not the only one.121 The diagnosis is fairly straightforward using the Rotterdam criteria, even when the syndrome is associated with a wide range of symptoms.122

Diagnostic criteria

There are different criteria for PCOS; the 2023 International Evidence-based Guidelines for Assessment and Management of PCOS recommend the revised Rotterdam criteria for diagnosing PCOS. That is, PCOS is present in adults when two out of these three criteria are met:123124

  1. Signs of androgen excess (clinical or biochemical). Androgens are "male" hormones, which can for instance cause facial hair.125
  2. Ovulatory dysfunction with irregular or absent menstrual cycles
  3. Polycystic ovaries on ultrasound or elevated anti-mullerian hormone (AMH) levels

Other causes of these issues need to be excluded. In adolescents, both androgen excess and ovulatory dysfunction are required, as AMH and ultrasounds are not specific in this population.126 Adolescents that only meet one criterion are considered 'at risk', to be reassessed when they are adults.127 Older criteria are the 1990 NIH criteria and the 2006 Androgen Excess Society criteria.128 The Androgen Excess criteria were never adopted widely. The old NIH criteria are stricter than the Rotterdam criteria, as both oligoovulation and signs of androgen excess need to be present:129

  1. Oligoovulation
  2. Signs of androgen excess (clinical or biochemical)
  3. Exclusion of other disorders that can result in the above

Assessment and testing

There is a three-step algorithm for diagnosis PCOS. In the first step, clinical androgen excess and irregular menstrual cycles are assessed. If someone has both and other causes are excluded, PCOS is diagnosed. In step 2, those with only irregular cycles undergo a laboratory test for excess androgens in the blood. If that shows excess male hormones, again excluding other causes of systems, PCOS is diagnosed. In the third step, for those with either irregular cycles or excess androgens, an ultrasound is performed or a AMH test, but not both to prevent overdiagnosis. If this test shows polycystic ovaries or elevated AMH levels, PCOS is diagnosed.130

Clinical androgen excess in adults can result in acne, hirsutism (male pattern of hair growth, such as on the chin or chest) and in female pattern hair loss. Hirsutism can be assessed using the standardised Ferriman–Gallwey visual scoring system, with a score above 4 to 6 indicating clinical significance.131 The recommended cut-off score depends on ethnicity, with a lower cut-off for Asian women, and a higher cut-off for Hispanic and Middle Eastern women.132 Assessment may be complicated by self-treatment.133 Hair loss can be assessed with the Ludwig visual score. In adolescents, androgen excess shows as severe acne and hirsutism.134

For individuals who had their first menstrual cycle more than three years ago, menstrual cycles are considered irregular if they occur less than 21 days apart or more than 35 days apart. For those whose first menstrual cycle was between one and three years ago, the cycle is considered irregular if it is less than 21 days apart or more than 45 days apart. Finally, for anyone whose first cycle was over a year ago, a single cycle lasting over 90 days is considered irregular.135

Biochemical androgen excess in PCOS is assessed using total and free testosterone. Accurate measurement requires tandem mass spectometry assays, as direct free testosterone tests are not reliable. Interpretation is based on laboratory reference ranges. Hormonal contraception can interfere with hormone levels, so a withdrawal period of at least three months with alternative contraception may be needed. Markedly elevated androgen levels may indicate other conditions.136

Gynecologic ultrasonography first looks for small ovarian follicles.137 To count as polycystic ovaries, at least 20 follicles need to be present smaller than 9 mm. This used to be 12 in older diagnostic criteria.138 A less clear marker of PCOS is enlarged ovaries.139 Ovary need to be at least 10 cm3 to count.140 For sexually active individuals or those that agree, a transvaginal ultrasound approach is preferred. Alternatively, AMH levels can be tested in the blood.141 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.142

Differential diagnosis

To diagnose PCOS, other conditions must first be ruled out. These include thyroid disease (assessed via thyroid stimulating hormone), hyperprolactinemia (assessed via prolactin), and non-classic congenital adrenal hyperplasia (tested via 17-hydroxy progesterone). For those without any periods whatsoever or more severe signs or symptoms, further tests are recommended to exclude hypogonadotropic hypogonadism, any androgen producing tumors or Cushing's disease. Overt virilisation (development of male sex characteristics) is not characteristic of PCOS and indicates that another underlying condition may be responsible.143

Management

PCOS has no cure.144 Treatment may involve lifestyle changes such as weight loss and exercise.145146 Recent research suggests that daily exercise including both aerobic and strength activities can improve hormone imbalances.147

Birth control pills may help with improving the regularity of periods, excess hair growth, and acne.148 Combined oral contraceptives are especially effective and used as the first line of treatment to reduce acne and hirsutism and regulate the menstrual cycle. This is especially the case in adolescents.149

Metformin, GLP-1, and anti-androgens may also help.150 Other typical acne treatments and hair removal techniques may be used.151 Efforts to improve fertility include weight loss, metformin, and ovulation induction using clomiphene or letrozole.152 In vitro fertilization is used by some in whom other measures are not effective.153

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.154 The primary treatments for PCOS include lifestyle changes and the use of medications.155

Goals of treatment may be considered under these categories:

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. 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.156 As PCOS appears to cause significant emotional distress, appropriate support may also be useful.157

Diet

Where PCOS is associated with being overweight or obese, successful weight loss is the most effective method of restoring normal ovulation/menstruation. The American Association of Clinical Endocrinologists guidelines recommend a goal of achieving 10–15% weight loss or more, which improves insulin resistance and all hormonal disorders.158 Still, many women find it very difficult to achieve and sustain significant weight loss. Insulin resistance itself can cause increased food cravings and lower energy levels, which can make it difficult to lose weight on a regular weight-loss diet. A scientific review in 2013 found similar improvements in weight, body composition and pregnancy rate, menstrual regularity, ovulation, hyperandrogenism, insulin resistance, lipids, and quality of life to occur with weight loss, independent of diet composition.159 Still, a low GI diet, in which a significant portion of total carbohydrates is obtained from fruit, vegetables, and whole-grain sources, has resulted in greater menstrual regularity than a macronutrient-matched healthy diet.160

Reducing the intake of food groups that cause inflammation, such as dairy, sugars, and simple carbohydrates, can be beneficial.161

A mediterranean diet is often very effective due to its anti-inflammatory and anti-oxidative properties.162

It has been suggested that vitamin D deficiency may play some undetermined role in the development of the metabolic syndrome, and that treatment might be beneficial.163164 However, a systematic review of 2015 found no evidence that vitamin D supplementation reduced or mitigated metabolic and hormonal dysregulations in PCOS.165 As of 2012, interventions using dietary supplements to correct metabolic deficiencies in people with PCOS had been tested in small, uncontrolled and nonrandomized clinical trials; the resulting data are insufficient to recommend their use.166

Medications

Medications for PCOS include oral contraceptives and metformin. The oral contraceptives increase sex hormone binding globulin production, which increases the binding of free testosterone. This reduces the symptoms of hirsutism caused by high testosterone and regulates return to normal menstrual periods.167 Anti-androgens such as finasteride, flutamide, spironolactone, and bicalutamide do not show advantages over oral contraceptives, but could be an option for people who do not tolerate them.168 Finasteride is the only oral medication for the treatment of androgenic alopecia, that is FDA approved.169

Metformin is a medication commonly used in type 2 diabetes mellitus to reduce insulin resistance and is used off label (in the UK, US, AU, and EU) to treat insulin resistance seen in PCOS. In many cases, metformin also supports ovarian function and a return to normal ovulation.170171 A newer insulin resistance medication class, the thiazolidinediones (glitazones), have shown equivalent efficacy to metformin, but metformin has a more favorable side effect profile.172173 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.174175 Metformin may not be effective in every type of PCOS, and therefore there is some disagreement about whether it should be used as a general first-line therapy.176 In addition to this, metformin is associated with several unpleasant side effects: including abdominal pain, metallic taste in the mouth, diarrhoea and vomiting.177 Metformin is thought to be safe to use during pregnancy (pregnancy category B in the US).178 A review in 2014 concluded that the use of metformin does not increase the risk of major birth defects in women treated with metformin during the first trimester.179 Liraglutide may reduce weight and waist circumference in people with PCOS more than other medications.180 The use of statins in the management of underlying metabolic syndrome remains unclear.181

Infertility

Main article: Infertility in polycystic ovary syndrome

It can be difficult to become pregnant with PCOS because it causes irregular ovulation. Medications to induce fertility when trying to conceive include the ovulation inducer clomiphene or pulsatile leuprorelin. Evidence from randomised controlled trials suggests that in terms of live birth, metformin may be better than placebo, and metformin plus clomiphene may be better than clomiphene alone, but that in both cases women may be more likely to experience gastrointestinal side effects with metformin.182

For women who do, anovulation or infrequent ovulation is a common cause and PCOS is the main cause of anovulatory infertility.183 Other factors include changed levels of gonadotropins, hyperandrogenemia, and hyperinsulinemia.184 Like women without PCOS, women with PCOS that are ovulating may be infertile due to other causes, such as tubal blockages due to a history of sexually transmitted diseases.185

For overweight anovulatory women with PCOS, weight loss and diet adjustments, especially to reduce the intake of simple carbohydrates, are associated with the resumption of natural ovulation.186 Digital health interventions are particularly effective in providing combined therapy to manage PCOS through both lifestyle changes and medication.187

For those women that, after weight loss, are still anovulatory, or for anovulatory lean women, ovulation induction using the medications letrozole (Femara) or clomiphene citrate are the principal treatments used to promote ovulation.188189190 Clomiphene can cause mood swings and abdominal cramping for some.191

Previously, the anti-diabetes medication metformin was a recommended treatment for anovulation, but it appears less effective than letrozole or clomiphene.192193

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).194

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),195 which often results in either resumption of spontaneous ovulations196 or ovulations after adjuvant treatment with clomiphene or FSH.197 (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.198

Mental health

Women with PCOS are far more likely to have depression than women without. Symptoms of depression might be heightened by certain physiological manifestations of this disease such as hirsutism or obesity that can lead to low self-esteem or poor body image.199  Researchers suggest that there be mental health screenings performed in tandem with PCOS assessment to identify these complications early and treat them accordingly.200

PCOS is associated with other mental health-related conditions besides depression such as anxiety, bipolar disorder, and obsessive–compulsive disorder.201 Additionally, it has been found to significantly increase the risk of eating disorders.202  Screening for these mental health conditions will also be helpful in the treatment of PCOS.

Lifestyle changes for people with PCOS have been proven to be difficult due to a lack of intrinsic motivation, altered risk perception, or other PCOS-related barriers. However, self-management techniques and behavior change can be taught in a multidisciplinary approach to support women with PCOS in managing their symptoms.203

Hirsutism and acne

Further information: Hirsutism

A standard contraceptive pill is frequently effective in reducing hirsutism.204 Progestogens such as norgestrel and levonorgestrel should be avoided due to their androgenic effects.205 Metformin combined with an oral contraceptive may be more effective than either metformin or the oral contraceptive on its own.206

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) 207

Other medications with anti-androgen effects include flutamide,208 and spironolactone,209 which can improve hirsutism. 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 are likely to respond to metformin. Eflornithine (Vaniqa) is a medication that 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.210 5-alpha reductase inhibitors (such as finasteride and dutasteride) may also be used;211 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 individuals212), 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.213

Menstrual irregularity

If fertility is not the primary aim, then menstruation can usually be regulated with a contraceptive pill.214 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.215

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.216 If menstruation occurs less often or not at all, some form of progestogen replacement is recommended.217

Screening for cardiometabolic risks

Given the higher risk of cardiometabolic conditions, monitoring is recommended.218 Two-hour oral glucose tolerance test (GTT) in women with risk factors (obesity, family history, history of gestational diabetes)219 may indicate impaired glucose tolerance (insulin resistance) in 15–33% of women with PCOS.220 Frank diabetes can be seen in 65–68% of women with this condition.221 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.222

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.223224 A 2012 and 2017 review have found myo-inositol supplementation appears to be effective in improving several of the hormonal disturbances of PCOS.225226 Myo-inositol reduces the amount of gonadotropins and the length of controlled ovarian hyperstimulation in women undergoing in vitro fertilization.227 A 2011 review found not enough evidence to conclude any beneficial effect from D-chiro-inositol.228 There is insufficient evidence to support the use of acupuncture, current studies are inconclusive and there's a need for additional randomized controlled trials.229230

Epidemiology

PCOS is the most common endocrine disorder among women between the ages of 18 and 44.231 According to the World Health Organization (WHO), PCOS affects over 6 to 13% of reproductive-aged women.232 A 2022 review noted a prevalence between 5% to 18%.233 When someone is infertile due to lack of ovulation, PCOS is the most common cause and could guide to patients' diagnosis.234

The prevalence of PCOS depends on the choice of diagnostic criteria.235 Using the Rotterdam criteria, around 10–13% of women have PCOS.236 Based on the NIH criteria, the global prevalence was 5.5%, increasing to approximately 7.1% when using the Androgen Excess Society criteria. Irrespective of criteria, the prevalance of PCOS is increasing, likely due to an aging population, more awareness and increasing obesity rates.237

Prevalance seems fairly even among people with different ethnicities, but is perhaps higher in people from South East Asia and the Eastern Mediterranean.238 PCOS may express differently however. For instance, in African and Hispanic American people with PCOS, there is more insulance resistance compared to other ethnic groups.239 The same is true for South Asian people with PCOS, who also have more metabolic symptoms and higher BMIs. East Asian women typically have less hirsutism and lower BMI compared to other groups.240

Ultrasonographic findings of polycystic ovaries are found in 8–25% of women non-affected by the syndrome.241242243244 14% women on oral contraceptives are found to have polycystic ovaries.245 Ovarian cysts are also a common side effect of levonorgestrel-releasing intrauterine devices (IUDs).246

History

Historical descriptions of possible PCOS symptoms date back to ancient Greece, where Hippocrates described women with "thick, oily skin and absence of menstruation."247 The earliest known description of what is now recognized as PCOS dates from 1721 in Italy.248 Cyst-related changes to the ovaries were described in 1844.249

In modern times, 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.250251 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.252

Etymology

Other names for this syndrome include polycystic ovarian syndrome, polycystic ovary disease, functional ovarian hyperandrogenism, ovarian hyperthecosis, sclerocystic ovary syndrome, and Stein–Leventhal syndrome. The eponymous last option is the original name; it is now used, if at all, only for the subset of women with all the symptoms of amenorrhea with infertility, hirsutism, and enlarged polycystic ovaries.253

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.254

Research

Stem cell models

Human embryonic stem cells (hESCs) derived from the inner cell mass of blastocyst-stage embryos of women with PCOS have shown abnormal lipid metabolism, consistent with the pathophysiology of the disease.255 When the hESCs are differentiated into adipocytes, gene expression data from these fat cells reveal a downregulation or a decrease in genes linked to glucose, lipid, and steroid metabolism.256

As of 2024 studies have successfully developed in vitro PCOS disease models through Induced pluripotent stem cell technology (iPSC).257 Similar to hESCs, iPSC cells can be derived from patients and can differentiate into various cell types. Using adult somatic cells, iPSCs can reprogram the cells into a pluripotent state, which can then be specified to replicate PCOS-like traits. Furthermore, 3D “organoid” models of female reproductive tissue, such as the uterus and ovaries, produced from iPSCs, present a powerful way to stimulate the development of reproductive disorders such as PCOS in vitro.258

Although not widely used, some researchers have explored the use of this biotechnology to model PCOS. One study that characterized the link between obesity and PCOS reprogrammed PCOS-derived urine epithelial cells into adipocytes and found that iPSC lines had greater glucose consumption along with lower insulin response compared to controls.259 These are results consistent with symptoms of the disease. Studies on iPSCs have also contributed significantly to understanding the behavior of ovarian granulosa cells, which maintain follicular development and secrete steroid hormones.260 The transcriptome data from the PCOS-derived iPSCs indicate dysfunctions in folliculogenesis and disruptions in the oocyte microenvironment.

Current growing data shows a strong association between mitochondrial malfunction and PCOS. iPSCs from PCOS patients have provided some evidence of impairments in glycolytic and mitochondrial functions.261 These cells exhibited a higher number of copies of mitochondrial DNA compared to the control. This may support the idea that mitochondrial biosynthesis is elevated in these patients as a compensatory response to the aberrations seen in the metabolic processes.262

Society and culture

In 2005, 4 million cases of PCOS were reported in the US, costing $4.36 billion in healthcare costs.263 In 2016 out of the National Institute of Health's research budget of $32.3 billion for that year, 0.1% was spent on PCOS research.264 Among women aged between 14 and 44, PCOS is conservatively estimated to cost $4.37 billion per year.265

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.266 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.267268

Public figures

Several celebrities and public figures have spoken about their experiences with PCOS, including:

See also

  • Medicine portal

Cited sources

  • Teede HJ, Tay CT, Laven JJ, Dokras A, Moran LJ, Piltonen TT, et al. (2023). International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome 2023. Melbourne, Australia: Monash University. ISBN 978-0-6458209-0-4.
  • Goodarzi MO (2024). BMJ Best Practice: Polycystic ovary syndrome (PDF). BMJ Publishing Group. Retrieved 29 June 2025.

Further reading

  • Media related to Polycystic ovary syndrome at Wikimedia Commons

References

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