Polycystic ovarian syndrome (PCOS)

• Polycystic ovary disease
• Polycystic ovarian disease (PCOD)
• Polycystic ovarian syndrome
• Stein-Leventhal syndrome
• Functional ovarian hyperandrogenism
• Multicystic ovaries

Onset age/Commonly affected age group

• Late Adolescence
• Young Adult

About 5 to 10% of women between 15 and 44 years of age have PCOS. Most women find out about PCOS in their 20s and 30s. Also, PCOS may occur at a younger age in the girls who develop pubic hair and breasts earlier than the usual age group (10-12 years). It is very important to note that in adolescent girls, the periods may be irregular usually during the first 2 years of menarche (onset of first period). So, PCOS may be detected at least 2 years after the onset of menses.

 

The exact cause of polycystic ovary syndrome (PCOS) remains unclear. In fact, both genes and environment may contribute to the development of PCOS.  Various factors that may be responsible for your PCOS include the following: 

 

1. Hormonal imbalance (ovarian steroidogenesis)
2. Genetic factor
3. Resistance to Insulin (Abnormal insulin signaling)
4. Obesity
5. Excessive oxidative stress
6. Insulin-like growth factors (IGFs)

 

1. Hormonal imbalance (ovarian steroidogenesis)

 

You may develop PCOS due to several hormonal changes. Both male and female hormones are produced by the ovaries, but at times due to some reason, these two hormones are not in balance. This hormonal imbalance can adversely affect hormone production in the ovaries and impact normal egg production. The hormones may show the following changes in PCOS:

• Increased levels of male hormone (testosterone)
• Increased levels of luteinizing hormone (LH)
• Decreased levels of sex hormone-binding globulin (SHBG)
• Increased levels of prolactin.

2. Genetic factor:

 

If your mother, sister, or any closed relative, has PCOS, then you are at a higher risk of developing PCOS. This suggests that PCOS may have a genetic link. PCOS can run in families, though its association with any specific gene has not yet been identified.

 

3. Resistance to Insulin (Abnormal insulin signaling):

Insulin is mostly known for its role in blood glucose regulation. However, insulin also helps regulate the functions of the ovaries. Rise in insulin levels triggers the ovaries to produce more male hormones (male sex hormones such as testosterone) which can cause PCOS symptoms to appear. Extra insulin* is produced by the pancreas in many conditions, including insulin resistance. Resistance to insulin means that the cells are unable to use insulin properly, and the body’s insulin demand increases. This increased demand of insulin results in excess insulin secretion by the pancreas. (*For your reference, a condition in which relatively excess levels of insulin circulate in the blood is known as hyperinsulinemia).

4. Obesity

Obesity or weight gain has been identified both as a cause and an effect of PCOS. Obesity can impair insulin use by your body cells (insulin resistance) and eventually, increased insulin secretion, increased male sex hormones production by ovaries, and development of PCOS symptoms.   

5. Excessive oxidative stress

 

Your body cells process the oxygen that you breathe to produce energy and free radicals from it. Antioxidants neutralize the free radicals and act against their harmful effects. Any imbalance can cause oxidative stress which is damaging to your cells. PCOS has also been associated with increased oxidative stress which in turn induces insulin resistance and excess male hormones (hyperandrogenism)

 

6. Insulin-like growth factors (IGFs)

 

Some studies have also stated the role of insulin-like growth factors (IGFs) in causing PCOS. IGFs (IGF-I and IGF-II) are hormones that resemble insulin in structure. IGFs regulate the initiation of follicle growth in your ovaries. In PCOS, follicular growth in the early stages may be accelerated due to increased activity of IGFs. 

 

 

PCOS is considered a syndrome since it is a collection of symptoms and features, which cannot be diagnosed by any specific test. A complete medical history, physical examination, blood tests, and ultrasound of the pelvic region assist in diagnosing PCOS and also in excluding other potential causes of your symptoms.

• Medical history and physical examination: A detailed medical history and physical examination help provide information about family history for PCOS, unexplained weight gain, abnormalities in the menstrual cycle, male-pattern hair growth, skin changes, etc. 
• Laboratory blood tests: Blood tests can help assess blood glucose, hormone and lipid levels.

1. Serum FSH:
Both, follicle stimulating hormone (FSH) and luteinizing hormone (LH) are produced and released by the pituitary gland. This gland is pea-sized and is located at the base of your brain. FSH leads to stimulation of follicle (or egg) growth within the ovary, while spikes in LH levels set off release of the egg during ovulation. You may have normal or low FSH levels in PCOS.

2. Serum LH:
Elevated levels of LH is a common finding in women with PCOS.

3. Testosterone:
Testosterone levels are typically elevated in most cases of PCOS. Levels of total, unbound and free testosterone (T) are measured. Testosterone is produced by the theca cells in the women. Theca cells are the specialized follicular cells that surround the eggs. In women with PCOS, theca cells are overactive and proliferate excessively, producing too much testosterone. As the follicles are often poorly developed in women with PCOS, they lack enough of another important component, the granulosa cells. The granulosa cells normally take testosterone and convert it into estrogen, in a process known as aromatization. In women with PCOS, the aromatization process is not effective due to the poor development of the granulosa cells, and as such, there is a build-up of testosterone which was produced by the ovary.

4. SHBG:
Sex hormone-binding globulin (SHBG) levels are decreased in PCOS. The concentration of SHBG may be reduced with an increase in the level of free androgens.

5. DHEAS:
Dehydroepiandrosterone sulfate is also an androgen. Levels of DHEAS are elevated in PCOS. 

6. OGTT:
Insulin resistance and PCOS are closely related to each other. So, diabetic screening is usually done. 

7. Lipid profile:
PCOS results in reduced good (HDL) cholesterol, increased bad (LDL) cholesterol, and increased triglycerides. 

• Radiological Investigation (Pelvic Ultrasound): Ovaries are scanned for cysts with a pelvic ultrasound. Many small cysts (fluid-filled sacs) may be visible in either or both ovaries. Also, ovaries may show 12 or more follicles measuring 2–9 mm in diameter and/or ovarian volume of more than 10 mL in either or both ovaries. Both transabdominal (TAS) or transvaginal (TVS) ultrasonography can be done. However, your doctor may prefer TVS over TAS if you are sexually active. It is important to mention here that being honest to your gynecologist will help in accurate diagnosis and effective treatment.  

 

Treatment options for PCOS could be:

 

• Lifestyle changes:

Polycystic ovary syndrome (PCOS) is majorly a lifestyle disorder. There is no definitive cure, however, lifestyle modifications serve as the first-line treatment to manage the symptoms. 

1. Weight loss: This forms the very first step in relieving symptoms. Even 10% of weight loss results in better uptake and use of insulin by body cells (insulin resistance), normalizes increased hormones levels, regularizes ovulation, and increases chances of conceiving.

2. Following a healthful diet:
This is significant in view of weight management, decreasing inflammation, and improving insulin use by cells. Eating healthy also aids in stabilizing and controlling blood glucose levels. (Principles of healthy eating have been explained under management in details.)

3. Increased physical activity:
Physical activity is related to improved insulin resistance and reduction in weight. Moreover, physical activity will help you boost your confidence. It is a matter of concern that women with PCOS show around threefold higher weight gain annually.

4. Stress reduction:
Stress can cause increased sympathetic activity, which may further lead to a rise in blood pressure, sweating, and heart rate. 

Serotonin levels are decreased in stressed individuals. A decline in serotonin levels in the brain results in depression, anxiety, and sleep trouble.

5. Emotional stability: Women are more sensitive on emotional front, as implicated by many studies. This does not mean that women are more emotional than men. This implies that women are better in picking up subtle cues or minor day-to-day events, that may go unnoticed by most men. The emotional outbursts may be frequent and at times, intense. 

 Emotional health is as important as physical health. Emotional instability can cause stress and depression which can further trigger various health problems. Learn to let go of minor issues and try to stay more stable in case of major issues. 

6. Getting enough sleep: Average 6-8 hours of sleep a day helps restore your body and mind. Mind is mentioned purposefully here, as your mind is more than just the brain. Lack of sleep can cause irritability, fatigue, or worsening of mood changes in PCOS.    

• Medications: The choice of treatment for PCOS depends on the symptoms (androgen-related, menstruation-related, and infertility):

Oral contraceptive pills

Antiandrogens (spironolactone, flutamide, finasteride)

Metformin

Clomiphene citrate

Aromatase inhibitors (letrozole)

 

 

1. Pharmacological treatment

 

Combined oral contraceptive pills

 

Medication for acne and hirsutism includes oral contraceptive pills (OCPs). The response to the medications may be generally seen after 6 months of treatment.

 

Combined hormonal (estrogen-progestin) contraceptives (CHCs) help treat PCOS-related hirsutism and acne by decreasing androgen levels. This may be achieved by:

• Decreasing its synthesis in ovaries by decreasing LH production
• Increasing sex hormone-binding globulin production
• Decreasing androgen secretion by adrenal gland
• Inhibiting conversion of testosterone to dihydrotestosterone
• Inhibiting binding of dihydrotestosterone to androgen receptors

 

If there has been no improvement, anti-androgens may be prescribed.

 

 

Antiandrogens decrease androgen levels and reduce the signs of hirsutism and acne. They may also improve lipid levels. But in the long run, they increase the risk of abnormalities of physiological development (teratogenicity) by opposing genital formation in the male fetus (boy baby in the womb). Hence, contraception is recommended during treatment with antiandrogens.

 

 

Over-the-counter products for acne can have limited effectiveness. For some women, isotretinoin may be beneficial in severe acne. 

 

2. Non-pharmacological treatment options (Cosmetic Treatment)

 

Women with symptoms that show the presence of high levels of male hormones can opt for cosmetic treatment of hirsutism, acne, and hair loss (alopecia). Depilatories, waxing, shaving, laser hair removal, and electrolysis may be used to manage hirsutism. 

 

 

To regulate your menstrual cycle, your doctor might recommend:

 

Combined oral contraceptive pills (OCPs):

 

Low-dose combined hormonal contraceptives (CHCs) help treat PCOS-related menstrual disorders and improve menstrual regularity. Chronic anovulation associated with PCOS can increase the risk of endometrial hyperplasia and carcinoma. A low-dose CHC, containing estrogen and progestin can help inhibit endometrial proliferation.

 

Progestin Therapy:

 

If combined OCPs are contraindicated, then your doctor may recommend progestin-only pills or cyclic progestins. Progestin taken in the later half of your menstrual cycle can help regulate your periods.

 

Progestin therapy has no role in improving the androgen levels. Taking progestin as suggested by your doctor (usually 10 to 14 days every 1 to 2 months) can help to regulate your periods and provide protection against endometrial cancer. Progestin therapy does not prevent pregnancy. If you wish to avoid pregnancy, the progestin-only minipill or progestin-containing intrauterine device is a better choice.

 

 

 

1. Medicines:

Clomiphene citrate:

Clomiphene citrate (CC) helps induce ovulation in women with PCOS. It increases the release of follicle stimulating hormone (FSH) which helps the ovarian follicles to grow. If ovulation cannot be induced even at maximum dose, the woman with PCOS is considered to be clomiphene resistant. Clomiphene failure occurs when pregnancy is not achieved even after six ovulatory cycles.

Letrozol:

Aromatase inhibitors decrease estrogen activity and increase the release of FSH. Letrozole is the most commonly used aromatase inhibitor for ovulation induction. Compared to clomiphene citrate, it is associated with a similar ovulation rate but significantly higher pregnancy rate.

 

Metformin:

Metformin improves insulin resistance and lowers insulin levels. If you don't conceive using clomiphene, your doctor might recommend adding metformin.

 

2. Surgeries /Procedures: Laparoscopic ovarian drilling (explained under surgical options in details)

 

3. In-vitro fertilization (IVF): This is used as a last resort for the management of infertility when all other treatments fail. (Explained under surgical options in detail.)

 

 

Insulin-sensitizing drugs make the body’s tissues more sensitive to insulin. They are used as a novel treatment of PCOS. These agents include:

 

1. Metformin 

Treatment with metformin has proved to be beneficial in obese adolescents with PCOS. Metformin increases insulin sensitivity, lowers the level of insulin circulating in the blood and reduces elevated androgen levels. When administered 3 months prior to and simultaneously with standard infertility treatments (IVF/ICSI), it may play a significant role in improving live birth rates.

 

2. Inositol

Myo-inositol (MYO) and D-chiro-inositol (DCI) reduce insulin resistance, improve ovarian function, and reduce androgen levels in women with PCOS.

• Surgeries /Procedures: 

No surgery is as such required to remove the cysts from ovaries. Lifestyle modifications help resolving cysts and improve symptoms. Surgical options may have to be instituted if lifestyle changes and medicines fail to help in getting pregnant. A list of such treatments is mentioned hereinbelow:

 

1. Laparoscopic ovarian drilling: Laparoscopic ovarian drilling may be used for the treatment of infertility in clomiphene-resistant PCOS. In this procedure, laser or electrocautery is used to drill multiple holes on the surface of the ovary. The destruction of ovarian follicles results in a decrease in androgen levels and an increase in follicle-stimulating hormone (FSH) levels. The injury also produces inflammatory growth factors which further increase the effect of FSH on maturation of the follicle.

 

2. In vitro fertilization (IVF): In Vitro Fertilization (IVF) is an assisted reproductive technology (ART). This process of fertilization includes egg extraction from the female parent, retrieving sperm sample from the male parent, and then manually combining the egg and the sperm in a laboratory. Then, the embryo(s) is transferred to the uterus.

 

3. Bariatric surgery: If obese women cannot achieve weight loss through diet and exercise, then weight loss procedures can be considered. Bariatric surgery for weight loss may help improve cycle regularity, increase ovulation and increase spontaneous conception.