Polycystic Ovary Syndrome: Causes

Pathogenesis (disease development)

The cause of polycystic ovary syndrome is not yet fully understood. It is likely that a genetic disposition underlies it. This causes a chromosomal miscoding that leads to a defect in the insulin receptor and thus to insulin resistance (reduced effectiveness of the body’s own insulin at the target organs skeletal muscle, adipose tissue, and liver). This enzyme defect impairs the action of FSH (follicle-stimulating hormone) at the ovary. The simultaneous presence of overstimulation by LH (luteinizing hormone) results in increased production of androgens (male sex hormones).

In a cluster analysis, researchers were able to assign the symptoms of PCO patients to different course forms and link these variants to specific gene variants in a genome-wide association study (GWAS). After cluster analysis, the following subtypes could be delineated:

  • Reproductive subtype (ie. reproductive): characterized by elevated serum levels of luteinizing hormone (LH and sex hormone-binding globulin (SHBG; transport protein for estrogens and androgens); normal body mass index (BMI) and low serum insulin levels are often present; patients had more frequent associations with variants in the PRDM2/KAZN, BMPR1B/UNC5C, and CDH10 genes and also with rare variants in the DENND1A gene (ca. 23% of cases)
  • Metabolic subtype (i.e., affecting metabolism): characterized by higher BMI, glucose, and insulin levels with lower SHBG and LH levels; patients had a link to the KCNH7/FIGN gene (approximately 17% of cases)
  • Neither reproductive nor metabolic subtype; these patients also had gene variants associated with PCO syndrome (approximately 60% of cases)

Etiology (causes)

Biographical causes

  • Genetic burden from parents, grandparents (strong familial clustering).

Behavioral causes