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Polycystic Ovary Syndrome (PCOS)

Causes and Risk Factors for PCOS

PCOS was once regarded solely as a reproductive disorder affecting women of childbearing age. Anovulation (a menstrual cycle in which ovulation does not occur) and androgen excess have been considered the hallmark diagnostic criteria of the syndrome.14 However, insulin resistance is now identified as a significant contributor to the pathogenesis of PCOS, the metabolic and cardiovascular consequences of which are widely acknowledged within the scientific community.11 To date, several factors involved in the development of PCOS have been identified.

LH Secretion and Androgen Excess

Past research has emphasized the role of neuroendocrine abnormalities in the persistent and excessive secretion of luteinizing hormones (LH), one of two glycoprotein hormones that stimulate the final ripening of the follicles and the secretion of progesterone. Excessive LH triggers premature ovulation, disrupting the follicle’s maturation process and leading to an increase in androgen production by ovarian theca cells. Some research points to increased LH as the driving force for PCOS in slender and normal body-weight women.27

Hyperinsulinemia and Androgen Excess

Hyperinsulinemia produces hyperandrogenism in women with PCOS via two distinct and independent mechanisms. The first is the stimulation of ovarian androgen production. Studies have shown that insulin acts synergistically with LH to enhance androgen production in ovarian theca cells.28,29 The second is by directly and independently reducing serum sex hormone-binding globulin (SHBG) levels.

Genetics and Androgen Excess

An increase in LH, as well as hyperinsulinemia, leads to an increase in androgen production by ovarian theca cells.29 Research indicates that morphological changes in the ovaries, including ovarian cyst development and theca-cell (steroid-producing cells in the ovaries) dysfunction, may be an indication of a genetic basis for PCOS. Researchers suspect there is a genetically determined ovarian defect present in women with PCOS, causing the ovary to overproduce androgen.29-32 Indeed, abnormal theca cell activity seems to be a primary source for excess androgens.33

The following risk factors are also thought to have a strong influence over the progression of PCOS.

Obesity

Studies have found that obesity not only contributes to the development of PCOS, but arises also as a result.16 The adipose tissue of women with PCOS is characterized by enlarged fat cells (hypertrophic adipocytes) and impairments in the body’s ability to break down fat (lipolysis) and regulate insulin. Whether these abnormalities are primary or secondary to hyperandrogenism or other PCOS-related abnormalities is not yet known.34

Age at Onset

Some research suggests that girls who develop pubic hair early (often before the age of eight, a condition known as premature pubarche) have many of the signs and symptoms of PCOS. In one study that followed prepubescent girls throughout puberty, premature pubarche resulted in excess testosterone production and irregular periods consistent with PCOS, leading researchers to conclude that premature pubarche may be an early form of PCOS.35

Other Risk Factors

Other risk factors that may play a role in the pathogenesis of PCOS include chronic inflammation36; exposure to endocrine-disrupting chemicals37; autoimmune disorders, especially those involving the ovaries, pancreas, thyroid and adrenal glands38; and the use of medications that increase prolactin production.39

Laying aside etiology, women with PCOS are prone to defects in insulin signaling, which aggravates the synthesis of androgens in the ovaries and adrenal gland.29 Excess androgens encourage insulin resistance, leading to elevated insulin levels, which in turn stimulate further androgen synthesis. This vicious cycle results in a “snowball effect” worsening PCOS symptoms and making sufferers especially susceptible to obesity and diabetes, conditions that significantly compound the syndrome’s progression.11,40

What You Need to Know

  • Polycystic ovary syndrome is a common female endocrine disorder.
  • Though symptoms vary from person to person, it is characterized by multiple ovarian cysts, irregular, heavy or nonexistent periods, excessive facial/body hair, male pattern baldness, decreased sex drive, skin tags, infertility, depression and weight gain.
  • Insulin resistance is one of the most common features of PCOS, and a condition in which the cells of the body become resistant to the effects of insulin.
  • The root cause of PCOS is unknown but genetic predisposition, insulin resistance, excess androgen production, and obesity all play a role.
  • Since the symptoms of PCOS vary in severity and form, many treatments are used. Conventional options include drug treatments for hirsutism and acne; drugs such as clomiphene, tamoxifen and gonadotropins to induce ovulation for infertility; surgery to induce ovulation by reducing androgen levels, and promising insulin-sensitizing drugs such as metformin.
  • The most important aspect of long term care of PCOS is managing cardiovascular risks such as obesity, insulin resistance, diabetes, hypertension and elevated blood cholesterol. Early recognition and intervention are considered to be the cornerstones of PCOS treatment.
  • Emerging evidence suggests that lifestyle choices such as weight reduction and exercise, along with specific nutraceuticals targeted to safely and effectively deal with symptoms, underlying causes and associated risk factors, might help reduce the incidence and severity of PCOS.
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