Polycystic ovary syndrome (PCOS)

Last updated date: 03-Mar-2023

Originally Written in English

Polycystic ovary syndrome (PCOS)

Polycystic ovary syndrome


Polycystic ovarian syndrome (PCOS) is a common disorder, accounting for the single most frequent endocrine-metabolic disorder in reproductive-aged women. PCOS is one of the most frequent reasons of female infertility, affecting 6% to 12% of reproductive-age women in the United States. The precise causes are unknown at this time, however androgen levels that are greater than usual play a role. Menstrual abnormalities, anovulation, and hyperandrogenism are all prominent symptoms of PCOS.


What is Polycystic ovary syndrome (PCOS)? 

Polycystic ovary syndrome

Polycystic ovarian syndrome (PCOS) is the most frequent endocrine disorder in reproductive females across the world. It was first described by Stein and Leventhal in 1935. Depending on the diagnostic criteria used, the prevalence ranges between 5% and 15%.

According to specialist society recommendations, the presence of at least two of the following three criteria is required for the diagnosis of PCOS:

  • Chronic anovulation, 
  • Hyperandrogenism (clinical or biological), and
  • Polycystic ovaries. 

It is an exclusion diagnosis, and illnesses that mirror clinical characteristics of PCOS must be ruled out. Thyroid disease, hyperprolactinemia, and non-classical congenital adrenal hyperplasia are examples. If clinical characteristics point to another cause, some individuals may require a more complete workup.

Despite its high incidence, PCOS is underdiagnosed and typically requires more than one visit or many physicians to be recognized, and this generally takes more than a year. For the patient, it is an extremely frustrating procedure. Delays in diagnosis can cause comorbidities to worsen, making it more difficult to undertake lifestyle interventions, which are crucial for improving PCOS symptoms and quality of life.


Multiple morbidities are associated with PCOS, including:

There are different screening guidelines for each of these diseases, however the doctor must have a low workup threshold in PCOS patients if any symptom is seen.


How Prevalent is PCOS?

PCOS, as previously stated, is the most prevalent endocrine disorder in reproductive-aged females globally, affecting between 5% and 15% of females depending on the diagnostic criteria. The Rotterdam criteria have a higher incidence than the 1990 National Institute of Health Criteria. PCOS is thought to afflict around 5 million reproductive-aged females in the United States. The yearly cost of identifying and treating PCOS to the healthcare system is roughly $4 billion, not counting the expense of major comorbidities associated with PCOS.


Polycystic Ovarian Syndrome Causes

PCOS is a disorder with several causes. Several susceptibility genes have been identified as contributing to the disease's pathogenesis. These genes are engaged in steroidogenesis and androgenic pathways at varying degrees. According to twin studies, heritability is around 70%. Furthermore, the environment has an important role in the expression of these genes as well as the genesis and course of the illness.

Two prevalent views contend that individuals with a genetic predisposition exposed to particular environmental circumstances manifest PCOS symptoms. Obesity and insulin resistance are two of the most frequent environmental variables. Fetal androgen exposure is also mentioned in certain ideas. 


How does PCOS Develop?

PCOS Develop

PCOS is a hyperandrogenic condition characterized by oligo-anovulation that cannot be explained by another ailment. It is an exclusionary diagnosis. Nonetheless, it accounts for the vast majority of hyperandrogenic symptoms.

Almost of PCOS causes are caused by functional ovarian hyperandrogenism (FOH). Two-thirds of PCOS cases show classic functional ovarian hyperandrogenism, which is defined by androgen secretory dysregulation and an excess of 17-hydroxyprogesterone (17-OHP) in response to gonadotropin stimulation. The remaining PCOS patients with atypical FOH do not have 17-OHP overresponse, but testosterone elevation can detect it after inhibiting adrenal androgen production.

About 3% of PCOS patients have isolated functional adrenal hyperandrogenism. The majority of PCOS instances are mild. There is no indication of steroid secretory problems in these individuals, and the most of them are obese, which practitioners believe explains for their atypical PCOS. In the present day, specific testing for the FOH subgroup has little clinical use.

The basic symptoms of PCOS are hyperandrogenism, oligoanovulation, and polycystic ovary morphology. The causes of functional ovarian hyperandrogenism are multifaceted, involving both hereditary and environmental factors. Excess insulin, which is known to sensitize the ovary to luteinizing hormone (LH) by interfering with the process of homologous desensitization to LH in the normal ovulation cycle, as well as an inherent imbalance among intraovarian regulatory systems, are the causes of this dysregulation.

Most steroidogenic enzymes and proteins involved in androgen production are overexpressed in PCOS theca cells, indicating a significant anomaly in the amount and activity of steroidogenic enzymes, including P450c17, which has been extensively studied. Granulosa cells luteinize prematurely due to androgen and insulin overload.

Excess androgen promotes the first recruitment of primordial follicles into the growth pool.

Simultaneously, it initiates premature luteinization, which compromises the selection of the dominant follicle. This causes the characteristic PCOS histopathologic and gross anatomic alterations that define PCOM. Increased LH promotes PCOS but does not cause it. LH excess is prevalent and required for the development of gonadal steroidogenic enzymes and sex hormone release, although it is less likely to be the major source of ovarian androgen excess due to LH-induced desensitization of theca cells.

Approximately one-half of women with functional ovarian hyperandrogenism have an aberrant level of insulin-resistant hyperinsulinism, which acts on theca cell, boosting steroidogenesis and prematurely luteinizing granulosa cells, as well as stimulating fat formation. Hyperandrogenemia causes an increase in LH, which subsequently acts on both theca and luteinized granulosa to maintain the cycle.

Ovarian hormonal dysregulation changes the pulsatile release of gonadotropin-releasing hormone (GnRH), perhaps leading to a relative increase in LH vs FSH production and secretion. LH boosts ovarian androgen synthesis, but FSH deficiency precludes appropriate stimulation of aromatase activity inside granulosa cells, resulting in decreased androgen conversion to the powerful estrogen estradiol. This develops into a self-sustaining noncyclic hormonal rhythm.

Elevated serum androgens are converted to estrogens, mostly estrone, in the peripheral. Because conversion happens largely in adipose tissue stromal cells, estrogen production will be increased in obese PCOS individuals. In contrast to the typical oscillations in feedback found in the presence of a developing follicle and quickly fluctuating estradiol levels, this conversion leads in persistent feedback at the hypothalamus and pituitary gland. Endometrial hyperplasia may result from unopposed estrogen stimulation of the endometrium.


Polycystic Ovarian Syndrome Symptoms

Polycystic ovarian syndrome symptoms

A thorough medical history and physical examination are required to diagnose PCOS. Two out of three diagnostic criteria are based on history and physical exam, including menstrual history and hyperandrogenism characteristics. Furthermore, PCOS is an exclusion diagnosis, and detecting clinical manifestations of other illnesses should be done.


Polycystic Ovarian Syndrome Diagnosis

Polycystic ovarian syndrome Diagnosis

Most societal guidelines have recognized PCOS diagnosis; most fulfill two of three criteria: chronic anovulation, clinical or biological hyperandrogenism, and polycystic ovary morphology in the absence of any other disorder.

Adolescent PCOS diagnosis is extremely difficult due to developmental difficulties in this age group. Many PCOS symptoms, such as acne, menstrual abnormalities, and hyperinsulinemia, are typical during adolescence. Menstrual abnormalities with anovulatory cycles are caused by the hypothalamic-pituitary-ovarian axis' immaturity during the first 2 to 3 years following menarche. Beyond this interval, persistent oligomenorrhea indicates chronic menstrual abnormalities and a higher risk of underlying ovarian or adrenal disease. Ultrasound is especially ineffective in teens due to the prevalence of big, multicystic ovaries.

  • Chronic Anovulation

A cycle duration of more than 35 days indicates chronic anovulation, although a cycle length of 32 to 35-36 days should be evaluated for ovulatory dysfunction. The oligomenorrhea threshold in adults is 35 days and 40 days in teenagers. Progesterone levels in the mid-luteal phase can be measured in patients with cycles shorter than 35 days (days 20 to 21). Infertility, endometrial hyperplasia, and endometrial cancer are all consequences of ovulatory failure.

  • Hyperandrogenism

Adult women with hirsutism, alopecia, and acne are diagnosed with clinical hyperandrogenism, which is a good alternative for biochemical hyperandrogenism. However, adolescent-only hirsutism should not be mistaken with biological hyperandrogenism. Hair loss patterns vary, often occurring in a vertex, crown, or diffuse pattern. Women with severe hyperandrogenemia may experience bitemporal hair loss as well as loss of the frontal hairline. Adolescents who have severe or resistant acne to oral and topical antibiotics have a 40% chance of developing PCOS. Females in their mid-20s to 30s with chronic or worsened acne are at significant risk of hyperandrogenism.

Hirsutism is characterized by coarse, black, terminal hairs that grow in a masculine pattern. Virilization symptoms such as increased muscular mass, decreased breast size, voice deepening, and clitoromegaly are not common in PCOS. Virilization indicates greater testosterone levels, and additional evaluation is warranted; the doctor should be on the lookout for an androgen-producing tumor of the ovary or adrenal gland.

  • Polycystic Ovaries Morphology

Transvaginal ultrasonography is more accurate for assessing ovarian morphology. PCOM (polycystic ovarian morphology) may now be diagnosed using new ultrasound equipment in people who have at least 25 tiny follicles (2 mm to 9 mm) across the ovary. The usual ovarian size threshold remains 10 ml.

The existence of at least 12 follicles measuring 2 mm to 9 mm in the whole ovary or an increased ovarian size of more than 10 ml, according to the Rotterdam criteria of 2004, indicates PCOM. Ultrasound technology has progressed and can help in PCOS diagnosis.

The ovary size has not been altered. Recent research suggests that detecting anti-Mullerian hormone can help with PCOS diagnosis when a precise ovarian ultrasound is unavailable.

  • Additional Assessment

PCOS is associated with an increased risk of cardiovascular, metabolic, and other comorbidities. Appropriate evaluation and actions are required.

  •  Infertility

All patients should be screened for ovulatory status, according to Endocrine Society guidelines. Anovulation can be detected in patients with eumenorrheic menstrual cycles using mid-luteal serum progesterone. Other reasons of infertility should also be ruled out.

Several studies have found an increased risk of endometrial cancer in PCOS individuals. Both illnesses share a number of risk factors. In asymptomatic individuals, the Endocrine Society advises against regular ultrasonography (US) endometrial thickness monitoring. Women, on the other hand, should be encouraged to report any unusual or unexpected uterine bleeding.

  • Obesity, metabolic disorder, impaired glucose tolerance (IGT), and cardiovascular disease

PCOS women and adolescents must be screened for obesity using body mass index (BMI) and waist circumference. Obesity raises the likelihood of hyperandrogenemia and metabolic problems, both of which are detrimental to PCOS. Blood pressure and cholesterol screening should be performed.

Insulin resistance has been strongly linked to PCOS. Insulin resistance is abnormal in one-third to two-thirds of PCOS patients. Obesity prevalence is comparable among populations, with significant variation. Obesity promotes insulin resistance, which leads to hyperinsulinism, which aggravates hyperandrogenism. Metabolic problems associated to insulin resistance and obesity are sometimes more relevant in the mechanism of anovulation in PCOS than androgen excess in certain obese women.

To screen for IGT and type 2 diabetes mellitus, the Endocrine Society recommends an oral glucose tolerance test, comprising fasting and 2-hour glucose following a 75 g oral glucose tolerance test (OGTT). Due to decreased sensitivity in PCOS patients, OGTT is preferable over HbA1c. Because risk factors are more common in this population, rescreening should be done every 3 to 4 years.

Furthermore, obese and overweight individuals should be checked for OSA symptoms and referred for sleep studies if the test results are positive.

  • Depression

PCOS women were shown to have a higher risk of depressive symptoms when compared to non-BMI-matched controls. Major depression, recurring depression, and suicidal ideation were also more common in PCOS women. It is necessary to screen for and detect depression and anxiety disorders. Appropriate care should be provided.


Polycystic ovarian syndrome Management

Polycystic ovarian syndrome Management

  • Lifestyle Modification

Exercise and calorie-restrictive diets are the most effective first-line therapies for weight reduction in overweight and obese PCOS women and adolescents. Several studies have indicated that hirsutism can enhance menstrual cycle and ovulation management. Low-carbohydrate diets have been employed in the hope that they will have a greater effect on hyperinsulinism, however studies have revealed no difference in results.

  • Hormonal Contraceptive

A hormonal contraception, such as an oral contraceptive, a patch, or vaginal rings, is the first-line therapy for monthly irregularities, hirsutism, and acne. The Endocrine Society does not advocate for one option over another. The progestin component reduces LH levels while raising sex hormone-binding globulin and indirectly lowering ovarian androgen synthesis. Furthermore, several progestins have been demonstrated to have direct antiandrogenic characteristics as a direct inhibitor of 5 alpha-reductase activity, preventing free testosterone from being converted to its more powerful form, 5 alpha-dihydrotestosterone. As a result, they are extremely successful in treating hyperandrogenism symptoms and controlling the menstrual cycle.

All individuals should be screened for contraindications to hormonal contraception. Women over the age of 35 who smoke more than 15 cigarettes per day, have uncontrolled hypertension more than 160/100, and have uncontrolled diabetes with severe peripheral vascular disease are absolute contraindications.

In terms of the metabolic effect of hormonal contraceptives, increased estrogen activity raises HDL cholesterol while decreasing LDL cholesterol. There was no difference in body weight and fat distribution between PCOS and healthy women.

  • Metformin

Metformin should be started in PCOS patients with DM2 or IGT who have failed to respond to lifestyle changes, according to the Endocrine Society. It slows the transition from IGT to DM2. Metformin also improves menstrual periods, an irregular waist-to-hip ratio, and vascular indicators in non-obese PCOS women.

Metformin is also used as a second-line treatment for menstrual abnormalities in people who cannot use hormonal contraception. It is often used as monotherapy in adolescents, and it aids in the restoration of regular menstruation, weight loss, and the reduction of insulin resistance. Although it should not be used to treat clinical hyperandrogenism, it can help with androgen excess symptoms.

  • Infertility Treatment

Clomiphene citrate is the first-line treatment for infertility in PCOS patients. This substance is a selective estrogen receptor modulator (SERM), a competitive inhibitor of estrogen receptors (ERs), and it has both agonist and antagonist action.

Clomiphene improves fertility and ovulation by acting on the hypothalamus, where it binds to estrogen receptors and depletes them, reducing the negative feedback inhibitory effect of circulating endogenous estrogen. This causes the pulsatile release of a hypothalamic gonadotropin-releasing hormone (GnRH), which promotes FSH and LH production and indirectly stimulates ovulation.

Metformin is recommended as an adjuvant therapy for infertility, assisting in the prevention of ovarian hyperstimulation syndrome in patients undergoing IVF. It has proven to be more beneficial in obese people. After a pregnancy is confirmed, persons with diabetes or glucose intolerance can continue to take the prescription for sugar management, although caution should be exercised to avoid maternal gastrointestinal issues.

  • Treatment for Hyperandrogenism

Clinical hyperandrogenism necessitates long-term therapy and takes several months to manifest. Cosmetic procedures should begin as soon as the drugs begin to act. Bleaching and temporary hair removal treatments, employing galvanic or mixed electrolysis for targeted regions with an expert operator, and laser photo-epilation for global hirsutism, are examples.

Pharmacological therapies for face hirsutism include topical eflornithine, which can be a costly therapy with potentially dangerous adverse effects if absorbed by the body.

Low-dose neutral or antiandrogenic oral contraceptives, which successfully suppress testosterone levels and effect, are the first-line therapy for hirsutism. Furthermore, contraceptive characteristics are advantageous when taken with antiandrogenic medicines, as the latter need consistent contraception due to their high teratogenicity. Mild hirsutism can be treated with just OCP.

Spironolactone, a nonselective mineralocorticoid receptor antagonist that decreases testosterone levels, is the most often administered adjuvant anti-androgen drug following OCP. When compared to OCP, spirolactone shows greater advantages in terms of CVD risk. Combinations of spironolactone and metformin outperformed either medicine alone in terms of better menstrual periods, hyperglycemia during OGTT, as measured by the area under the curve, and testosterone levels.



Polycystic ovary syndrome (PCOS)

Polycystic ovary syndrome (PCOS) is a commonly occurring endocrine disorder characterized by hirsutism, anovulation, and polycystic ovaries. Often comorbid with insulin resistance, dyslipidemia, and obesity, it also carries significant risk for the development of cardiovascular and metabolic sequelae, including diabetes and metabolic syndrome.

The evaluation of patients suspected of having PCOS includes a thorough history and physical examination, assessment for the presence of hirsutism, ovarian ultrasonography, and hormonal testing to confirm hyperandrogenism and oligo-anovulation as needed and to exclude similar or mimicking disorders. Therapeutic decisions in PCOS depend on the patients' phenotype, concerns, and goals