Polycystic Ovary Syndrome (PCOS)

Polycystic ovary syndrome or PCOS is a hormonal disorder in women characterized by excessive testosterone levels. It is also known as hyperandrogenism, infrequent menses, and anovulation, with numerous small collections of fluid in the ovaries, known as cysts.

No one knows the exact cause, but it seems to be a complex multigenic disorder with strong environmental influences, including diet and other lifestyle issues.

There appears to be an inappropriate secretion of gonadotropins by the pituitary gland that leads to ovarian dysfunction that in turn worsens the hypothalamic-pituitary function. A raised blood testosterone level is always almost seen in the disease.

Incidence and prevalence

PCOS is an extremely common endocrine disease in women of reproductive age, with a prevalence of 4-10 percent. There is a great deal of racial variability in different ethnicities, with very little hirsutism seen in Asian women, even with elevated testosterone levels.

While PCOS affects women of reproductive age, it probably begins before the onset of menarche; however, it is not commonly diagnosed until symptoms of hirsutism and irregular menses bring the woman to the consultation of a gynecologist or family practitioner.

Predisposing factors

Family history is the biggest risk factor for PCOS. Women who have a first-degree relative with PCOS have an increased risk of also having the disorder. Women with diabetes and obesity are also at a higher risk, although these are also features and complications of the disease.

Signs and symptoms

The major signs and symptoms of PCOS relate to the menstrual cycle. These women have irregular periods due to anovulation.

Non-menstrual symptoms include hirsutism, acne, hyperinsulinemia, obesity, metabolic syndrome or insulin resistance, infertility, excess fat around the abdomen, hair growth in unwanted places, loss of hair on the head, acne, brownish patches around groin, neck, armpits—acanthosis nigricans.

A study out of Poland and a few others showed an increased prevalence of various psychiatric disorders that can be observed in women with PCOS such as depression, generalized anxiety disorder, personality disorders, social phobia, obsessive-compulsive disorder, and attention deficit hyperactivity disorder (ADHD), and eating disorders.

The higher prevalence of psychiatric disorders in patients with PCOS, especially depression and anxiety disorders, may be due to both hyperandrogenism (excess testosterone) and the widely fluctuating estrogen and progesterone levels from lack of ovulation.

Clinical presentation

There are several different proposed criteria for diagnosing PCOS. According to the US National Institutes of Health (NIH), the criteria include 1) oligo-ovulation or anovulation manifested by amenorrhea or oligomenorrhea, 2) hyperandrogenism or hyperandrogenemia, and 3) the exclusion of other related disorders.

According to the ESHRE (European Society for Human Reproduction and Embryology) and the ASRM (American Society for Reproductive Medicine), at least two of the following three criteria must be present to make the diagnosis:

1) anovulation or oligo-ovulation as seen by decreased frequency of menstruation, 2) clinical evidence of androgens excess or laboratory evidence of elevated androgens, and 3) polycystic ovaries on a pelvic ultrasound. These are known as Rotterdam criteria. Other etiologies must be excluded such as congenital adrenal hyperplasia, androgen-secreting tumors, Cushing syndrome, thyroid dysfunction, and hyperprolactinemia.

There are high levels of testosterone in the bloodstream, and sometimes androstenedione and dehydroepiandrosterone sulfate (DHEA-S) are high too, but also normal androgen levels are possible.

PCOS is also associated with insulin resistance and hyperinsulinemia. Most cases are obese, which contributes to the risk of developing type 2 diabetes.

This elevated level of insulin may enhance the effects of gonadotropins on the female ovaries. It may also cause suppression of the liver’s ability to make sex-hormone binding globulin, thereby increasing the free androgen levels.

The elevated insulin levels appear to relate to the levels of adiponectin in the body. Adiponectin is a hormone secreted by fat cells that regulate the metabolism of lipids and the levels of glucose in the body. Women with PCOS have decreased adiponectin levels when compared to women without PCOS.

High insulin levels are also responsible for the elevation of lipids in the body and high levels of plasminogen activator inhibitor-1 (PAI-1) in PCOS patients. High levels of PAI-1 increase the patient’s risk for thrombosis.

Treatment and management

The first-line treatment for PCOS is lifestyle changes. Patients with obvious hirsutism, anovulation, and menstrual difficulties can receive medical therapy, which will improve the symptomatology.

The major lifestyle changes that help women with PCOS include weight loss and exercise, which can improve anovulation and can restore ovulatory cycles, besides, reducing the chances of developing diabetes mellitus. It is good first-line therapy for adolescents with the disorder who have just been diagnosed with PCOS.

The first-line treatment for hirsutism and menstrual irregularities is hormonal contraceptives because they control menses and decrease androgen levels. For couples with infertility due to anovulation, the first-line treatment is clomiphene citrate, which stimulates ovulation.

For those who have hyperinsulinemia an adjunct treatment, additionally to lifestyle changes, would be metformin. Metformin can be used in combination with contraceptives or clomiphene to improve the symptoms so decrease androgen levels and aid in weight loss.

In patients with hirsutism, besides contraceptives, drugs like eflornithine have been used along with laser therapy to remove the hair excess on the body. Spironolactone, finasteride, and leuprolide are all anti-androgens that can also be given to reduce androgens levels in PCOS.

Any type of acne treatment can be effective in PCOS, such as topical acne preparations (benzoyl peroxide or tretinoin cream), antibiotic therapy, or Isotretinoin, which is given orally for severe acne.

Complications

There is evidence suggesting that women with PCOS have a higher risk of developing cerebrovascular disease (strokes) and cardiovascular disease (heart attacks). They have elevated LDL-cholesterol levels and a cardiac risk profile that is similar to men.

About 40 percent of PCOS patients will develop insulin resistance as part of their disease. There is a higher incidence in obese women but it can be seen in women who are not obese. For this reason, all women with PCOS should be screened for type 2 diabetes with a glucose tolerance test or a fasting blood sugar as they have a high risk of developing the disorder.

There is an increased risk for endometrial hyperplasia which is the presence of precancerous cells that may lead to cancerous cells in the uterus.

There is ongoing estrogen stimulation of the endometrial lining without the protective effect of progesterone, increasing the thickness and atypia of the endometrial tissue and secondarily increasing the risk of cancer of the endometrium.

For this reason, experts recommend giving progesterone to promote uterus withdrawal bleeding at a minimum of every three months. There is no evidence of increased risk in PCOS for either breast cancer or ovarian cancer.