Evidence based information
Written by Medical editorial team head SIAHMSR
Medically reviewed by Dr. Sanjana V.B

Polycystic ovarian syndrome 

Overview

    Polycystic ovary syndrome (PCOS) is a complex condition characterized by elevated androgen levels, menstrual irregularities, and/or small cysts on one or both ovaries.

   According to the National Institutes of Health Office of Disease Prevention, PCOS affects approximately 5 million women of childbearing age in the U.S.A. This clinical condition affects at least 7% of adult women. Research data suggests that 5% to 10% of females 18 to 44 years of age are affected by PCOS.

 Hyperinsulinaemia and insulin resistance associated with PCOS may eventually lead to hyperandrogenism or high androgen secretion by ovaries .  In PCOS, the ovaries produce unusually high levels of hormones called androgens. High androgen levels prevent ovulation and therefore irregular menstrual cycles. Irregular ovulation can also cause small, fluid-filled sacs to develop on the surface ovaries. High androgen levels may lead to acne and hirsutism in women having PCOS.

Hyperandrogenism, the clinical hallmark of PCOS, can cause inhibition of follicular development, micro cysts in the ovaries, anovulation, and menstrual irregularities.

   Polycystic ovarian syndrome is associated with various other health risks to female population as  data shows that women with PCOS have higher rates of endometrial cancer, cardiovascular disease, dyslipidemia, and type-2 diabetes mellitus. PCOS women tend to have chronic low-grade inflammation. 

Causation & pathology

 It has been found that PCOS runs in families. Some evidence shows PCOS has a genetic or hereditary component. However, familial links to PCOS still remain unclear. An autosomal dominant pattern of inheritance is proposed by current research reviews. To date, no gene has been identified that causes or contributes substantially to the development of a PCOS phenotype.

Environmental factors implicated in PCOS include physical inactivity, erratic diet &junk food patterns [3].

  The pathophysiology of PCOS is linked with primary defects in the hypothalamic–pituitary axis, insulin secretion and action, and ovarian function.

 Follicular maturation arrest is a hallmark sign of PCOS. Clinical signs of PCOS include elevated luteinizing hormone (LH) and gonadotropin–releasing hormone (GnRH) levels, whereas follicular-stimulating hormone (FSH) levels are muted or unchanged. Due to the elevated levels of GnRH, stimulation of the ovarian thecal cells can produce more androgens. Thecal cells in patients with PCOS produce higher amounts of testosterone, progesterone, and 17-hydroprogesterone.

 Follicular arrest in PCOS can be addressed by elevating endogenous FSH levels or by providing exogenous FSH as a treatment option.

Clinical presentation

 PCOS may occur in females at any age after puberty. Most people are diagnosed in their 20s or 30s.    

·        Menstrual irregularities: Abnormal menstruation involves missing periods or not having a period at all. It may also involve heavy bleeding during periods. Women with PCOS often have irregular menstrual cycles. Problems with ovulation and elevated androgen levels occur in the majority of women with PCOS.

·        Hirsutism: excess facial hair or hair growth on arms, chest and abdomen.

 Acne: PCOS can cause acne, especially on your back, chest and face.

Hirsutism, acne, and alopecia are directly linked with hyperandrogenism in PCOS.

·         The prevalence of polycystic ovaries on pelvic ultrasound [USG]exceeds 70% in women with PCOS.

Small follicle cysts (fluid-filled sacs with immature eggs) may be visible on the ovaries on ultrasound due to anovulation in women with PCOS. Polycystic ovaries contain a large number of harmless follicles that are up to 8mm (approximately 0.3in) in size.

·        Infertility :PCOS is one of the most common causes of infertility.

·        Obesity : Between 40% and 80% of women with PCOS have obesity.

·         Acanthosis nigricans: patches of dark velvety skin, especially in the folds of your neck, armpits, groin etc.

The hormones that play key roles in PCOS are:

·        Androgens (testosterone and androstenedione).

·        Luteinizing hormone (LH).

·        Follicle-stimulating hormone (FSH).

·        Estrogen.

·        Progesterone.

·        Insulin

Impact of PCOS on health of women 

 The major health impacts of PCOS on the body are insulin resistance, hormonal imbalances, metabolic syndrome with obesity, hyper tension, dyslipidemia. These factors may enhance the risk of cardiovascular diseases and cancers.

PCOS can progress to type 2diabetes also.

Hyperandrogenism or elevated levels of male hormones in PCOS may cause hirsutism or excessive growth of body hairs as well as female pattern alopecia in women. PCOS is associated with thinning of hair on scalp.

PCOS make women predisposed to gestational diabetes (which puts the pregnancy and the baby at risk and can lead to type 2 diabetes later in life for both the mother and child.

Obesity and infertility are observed in 70-80% of women with PCOS 

Women with PCOS have insulin resistance and eventually, increasing their risk for type 2 diabetes 

Polycystic ovary syndrome is also linked to depression and anxiety although the exact mechanism is poorly understood.

PCOS may also lead to hypertension, cardiovascular diseases and uterine cancer. 

Endometrial hyperplasia and Endometrial cancer risk is high in women with PCOS.

Pregnant women with PCOS may have an increased rate of miscarriage, gestational diabetes, pre-eclampsia, and premature delivery. 

Diagnosis 

If PCOS is suspected in a woman a complete medical history, physical examination, blood tests, and a pelvic ultrasound should be performed.

It can provide the physician with information about unexplained weight gain, menstrual irregularities, hirsuitism, skin changes, and hypertension.

 Assess hormone, glucose, and lipid levels, and a pelvic ultrasound is performed to scan for ovarian cysts.

Other potential causes associated with reproductive, endocrine, and metabolic dysfunction should be excluded by the physician such as adrenal hyperplasia, Cushing’s syndrome, and hyperprolactinemia etc. before the diagnosis of PCOS is confirmed. 

Investigations : 

Ultra sound abdomen

C-reactive protein (CRP)

Hormonal assays LH, FSH, prolactin , Androgen 

Diagnosis of PCOS is based on:

§  Irregular or missed periods. Some people with PCOS have very heavy bleeding when they do have a period.

§  Signs of excess androgens such as acne or excessive hair growth. Or a blood test confirming high androgen levels.

§  Enlarged ovaries or polycystic appearance of ovaries on ultrasound. Many people don’t develop cysts.

§   Polycystic  ovarian morphology

  It is an imaging descripton of a particular type of change in ovarian morphology. Polycystic ovary morphology (PCOM) is an ultrasonographic finding that can be present in women with ovulatory disorder and oligomenorrhea due to hypothalamic, pituitary, and ovarian dysfunction.

Features include:

·        increased follicle number per ovary (FNPO): usually ≥20

·        individual follicles are generally similar in size and measure 2-9 mm in diameter

·        peripheral distribution of follicles; this can give a "string of pearls" appearance 

·        background ovarian enlargement (volume greater than 10 mL)

·        central stromal brightness +/- prominence (increased ovarian stromal area to total ovarian area (S/A) ratio

Adult Diagnostic Criteria for Polycystic Ovary Syndrome

·        Clinical and/or biochemical evidence of hyperandrogenism

·        Evidence of oligo-anovulation

·        Ultrasonographic evidence of a polycystic ovary 

          Insulin-resistance and obesity are common in PCOS, they are not recognized as diagnostic criteria. 

Rotterdam criteria for diagnosing PCOS 

Based on various combinations of hyperandrogenism, anovulation, and a polycystic ovarian morphology [PCOM]  there are 4 phenotypes, which fall on a spectrum of decreasing specificity .

Phenotype 1 (Classic PCOS)

Clinical and/or biochemical evidence of hyperandrogenism

Evidence of oligo-anovulation

Ultrasonographic evidence of a polycystic ovary [PCOM]

Phenotype 2 (Essential National Institutes of Health Criteria)

Clinical and/or biochemical evidence of hyperandrogenism

Evidence of oligo-anovulation

Phenotype 3 (Ovulatory PCOS)

Clinical and/or biochemical evidence of hyperandrogenism

Ultra-sonographic evidence of a polycystic ovary [PCOM] 

Phenotype 4 (Non-hyperandrogenic PCOS)

Evidence of oligo-anovulation

Ultrasonographic evidence of a polycystic ovary[PCOM]

The phenotype of each individual woman with PCOS can vary widely. 

Is it appropriate to diagnose PCOS based only on ovarian morphology ? What are the fall outs?

  The sonographic assessment, Polycystic ovarian morphology (PCOM) has, over time, become the dominant indicator of PCOS and is often either over interpreted or misinterpreted.

 Polycystic ovarian morphology (PCOM) is present in 25% of normal women in the absence of polycystic ovary syndrome (PCOS). Post‐menarcheal girls almost always have at least one ovary with > 12 visible follicles and diagnosing them as ‘polycystic’ can lead to unnecessary investigations, inappropriate management.It is quite normal for adolescent girls.

 In women with regular, ovulatory cycles also presence of PCOM [as an incidental ultrasonogram finding] may be wrongfully labelled ‘polycystic’.

   A meta‐analysis performed by the Androgen Excess and Polycystic Ovary Syndrome Society in 2014 found that the median follicle number per ovary  in women of reproductive age is between 13 and 16 and strongly recommended to raise the threshold for polycystic ovarian morphology to ≥ 25 follicles. This recommendation is also supported by the International Society of Ultrasound in Obstetrics and Gynaecology Consensus Group.

  Before interpreting the sonographic results, the menstrual cycle day, length and pattern should be ascertained along with hormone (particularly oral contraceptive) use, where the follicle count is clinically unreliable.

Record the follicle number per ovary [FNPO] as well as the total antral follicle count (AFC), especially in case of fertility treatment where the follicle numbers have implications for ovarian stimulation protocols and outcomes and describe the presence and dimensions of the dominant follicle or corpus luteum.

Women with an increased follicle count (≥ 25 FNPO) may be at higher risk for hyperandrogenic anovulation, and correlation with clinical and biochemical factors are necessary.

Treatment

Therapeutic interventions are designed to reduce insulin levels and ovarian androgen secretion.

1.  Hormonal birth control: Options include birth control pills, patches, shots, a vaginal ring or an intrauterine device (IUD). Hormonal birth control helps to regulate your menstrual cycle

2.  Insulin-sensitizing medicine to control insulin resistance.

3.  Medications to block androgens

4.  Drugs to induce ovulation in females having infertility

5.  Surgery: laparoscopic ovarian drilling (LOD)

 A surgical procedure can help restore ovulation by removing tissue in your ovaries that produces androgen hormones. Nowadays it is rarely chosen as medications can manage PCOS.

6.  In vitro fertilization (IVF): This is an option for people with PCOS when medication doesn’t help with ovulation.

7.  Excess hair growth or acne is hurting your confidence, cosmetic treatments.

The impact of PCOS may change over time so that you become less aware of the condition. However, there is no permanent cure.

Life style modification and dietary changes are recommended for managing PCOS.

Prevention of PCOS:

Eating nutritious foods, exercising regularly and managing a healthy weight for your body can help you avoid the effects of PCOS.

Alternative and complementary medicinal intervention 

Homeopathy

Homeopathy offers some medicinal treatment to regulate ovulation and menstrual cycle. Medicines are used to manage menstrual irregularities according to the symptoms and signs manifested in the patients.

Homeopathic medicines are prescribed in an individualized way. Acne, comedones, obesity , depression are treated with medications as well as life style and dietary changes.

Physical exercise is recommended as a life time routine to be followed. Nourishing and weight loss promoting diets are suggested for women with PCOS  as the disease can cause many obesity related and hormonal complications which  may enhance the risk for heart problems ,infertility ,stroke and cancers. Moderate physical activity and dietary modifications such as inclusion of Mediterranean and DASH diets are very effective in prevention as well as management of PCOS.

References  

1.     Umland EM, Weinstein LC, Buchanan EM. Menstruation-related disorders. In: DiPiro JT, Talbert RL, Yee GC, et al., editors. Pharmacotherapy: A Pathophysiologic Approach. 8th ed. New York: McGraw-Hill; 2011. p. 1393. [Google Scholar]

2.     https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3737989/

3.     Diamanti-Kandarakis E, Kandarakis H, Legro RS. The role of genes and environment in the etiology of PCOS. Endocrine. 2006;30:19–26.

 https://pubmed.ncbi.nlm.nih.gov/17185788/

4.      Urbanek M. The genetics of polycystic ovary syndrome. Natl Clin Pract Endocrinol Metab. 2007;3:103–111. https://pubmed.ncbi.nlm.nih.gov/17237837/

5.     https://pubmed.ncbi.nlm.nih.gov/19888063/ 

6.     https://pubmed.ncbi.nlm.nih.gov/7671850/

7.     https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4387116/

8.     https://academic.oup.com/jcem/article/91/10/3878/2656479

9.     https://www.sciencedirect.com/science/article/abs/pii/S1083318821000280

10.            https://radiopaedia.org/articles/polycystic-ovaries

11.            https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8409808/#:~:text=According%20to%20the%20Rotterdam%20consensus,in%20at%20least%20one%20ovary).