Polycystic Ovary Syndrome

Joyce King, CNM, RN, FNP, PhD

Disclosures

J Midwifery Womens Health. 2006;51(6):415-422. 

In This Article

Pathogenesis

A complete understanding of the underlying pathophysiology of PCOS is still lacking. Because of the heterogeneity of this disorder, there are most likely multiple underlying pathophysiologic mechanisms. Several theories have been proposed to explain the pathogenesis of PCOS.[8] 1) An alteration in gonadotropin-releasing hormone secretion results in increased luteinizing hormone (LH) secretion. 2) An alteration in insulin secretion and insulin action results in hyperinsulinemia and insulin resistance. 3) A defect in androgen synthesis that results in increased ovarian androgen production. We will discuss each of these theories in more detail.

LH Secretion

LH hypersecretion is a characteristic hallmark of PCOS. LH is secreted in a pulsatile manner. Women with PCOS have an increase in both the LH pulse frequency and amplitude, resulting in increased 24-hour secretion. This increase in LH secretion is thought to occur as a result of increased frequency of hypothalamic gonadotropin-releasing hormone (GnRH) pulses. Increased LH, in turn, leads to an increase in androgen production by the theca cells within the ovary.[3,8]

Hyperinsulinemia and Insulin Resistance

Insulin resistance, defined as reduced glucose response to a given amount of insulin, is a characteristic metabolic disturbance associated with PCOS. Both obese and nonobese women with PCOS have a higher incidence of insulin resistance and hyperinsulinemia than age-matched controls; however, obese women with PCOS have significantly decreased insulin sensitivity compared with nonobese women who have PCOS.

Insulin resistance is known to precede the development of type 2 diabetes mellitus. Studies have shown that 30% to 40% of women with PCOS have impaired glucose tolerance, and as many as 10% develop type 2 diabetes mellitus by the age of 40.[3,8]

Several studies have also shown a strong correlation between insulin resistance and hyperandrogenism. This association dates back to 1921, when Achard and Thiers reported on a bearded woman who was also a diabetic.[5] Insulin acts synergistically with LH to enhance androgen production in the ovarian theca cells. Insulin also decreases hepatic synthesis and secretion of sex hormone-binding globulin, the hormone that binds testosterone in the circulation, thus increasing the amount of free testosterone that is biologically available.[8,9] Women with PCOS and hyperinsulinemia typically have elevated free testosterone, but the total testosterone concentration may be at the upper range of normal or only modestly elevated.[8]

Androgen Excess

The increase in LH, together with hyperinsulinemia, leads to an increase in androgen production by ovarian theca cells.[8] The most likely primary factor driving the increase in testosterone secretion in PCOS is an increase in ovarian enzymatic activity involved in the synthesis of testosterone precursors.[10]

Genetics

A familial pattern in some cases suggests a genetic component, but the candidate genes have yet to be identified.[8]

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