The pathogenesis of polycystic ovary syndrome (PCOS) is not precisely known. There are several mechanisms that have been suggested to play a role in the pathogenesis of PCOS, including hormonal imbalance, insulin resistance, and genetic inheritance.
Polycystic ovaries are enlarged on both sides and have a smooth, thick, avascular capsule. Notably, hyperplasia of the cells surrounding the follicles can prevent the release of the egg and ovulation.
PCOS is associated with abnormal production and metabolism of hormones, such as androgens and estrogen, in the body. There are typically high levels of androgenic hormones such as testosterone, androstenedione, and dehydroepiandrosterone sulfate (DHEA-S), although there is often considerable variation among patients.
Some research has suggested that the secretion of luteinizing hormone (LH) from the anterior pituitary gland increases the stimulatory effect on the ovarian theca cells and may lead to the raised levels of androgenic hormones and irregular or absent ovulation. The level of follicle stimulating hormone (FSH) is reduced with respect to LH, which reduces the reaction to aromatize the androgen hormones to estrogen. As a result, there is less estrogen available and ovulation may not be able to occur.
Some research has also linked the CYP450 C17 enzyme to PCOS as the rate-limiting step for the synthesis of androgenic hormones such as testosterone in the body. Although further research is needed to support this, abnormalities in this enzyme or the presence of other substances that inhibit or induce this enzyme may be involved in the pathogenesis of PCOS.
There is a strong correlation between PCOS and resistance to insulin the body. This may be secondary to an abnormality in the binding to the insulin receptors, resulting in changes in the signaling pathways. It has been suggested that the raised levels of insulin alter the effect of gonadotropins and the function of the ovaries, leading to PCOS.
Specifically, the excess insulin may cause the ovaries to produce more testosterone and alter the development of follicles needed for ovulation to take place. Ovulation may be inhibited or delayed as a result, leading to PCOS.
The effect of insulin resistance in the pathogenesis of PCOS is amplified when a woman is overweight or obese. The excess fat can worsen the resistance to insulin and, therefore, lead to more severe symptoms associated with the condition.
Another hormone called adiponectin that is involved in the control of lipid and glucose levels in the blood might also play a role in the pathogenesis of the condition. Higher concentrations of this hormone are usually evident in women affected by PCOS.
Research investigating a genetic link to the pathogenesis of PCOS has suggested an autosomal dominant pattern of inheritance in families with a history of the condition. Fathers may be carriers of the genetic abnormality and may display some characteristics of PCOS, such as excessive hair growth.
Some studies have investigated the role of regulatory genes of the CYP17, CYP19, FST, and INSR enzymes in association with PCOS. Of these, there may be susceptibility in the INSR gene, although the research is not sufficient to claim that in may cause the condition. Other studies have investigated other genes, such as PON1 and IGF2. However, it remains unclear which specific gene mutation may cause PCOS in women.