Objectives: The purpose of this article is to educate nurse practitioners about polycystic ovarian syndrome. After reading this article, the nurse practitioner should be able to:

• explain the pathogenesis of PCOS
• identify diagnostic criteria for PCOS
• describe clinical manifestations associated with PCOS
• identify appropriate PCOS management principles.

Polycystic ovarian syndrome (PCOS) is one of the most common endocrine disorders in women, affecting 1 in 15 women of childbearing age. It has significant reproductive, metabolic and dermatologic consequences.¹

The term PCOS first described the coexistence of amenorrhea, hirsutism, obesity and polycystic ovaries. A great deal of research has been conducted to determine the association among these symptoms.²

PCOS is known as a syndrome, not a disease.³A syndrome is a symptom complex with no known cause. It is associated with specific characteristics, and it is defined by its consequences.

Women with PCOS are at increased risk for chronic conditions including diabetes, coronary artery disease, hypertension, dyslipidemia, endometrial cancer, infertility and obesity.⁴PCOS symptoms affect quality of life, leading to a higher frequency of depression and psychosexual morbidity in affected patients.⁵

Pathophysiology

Multiple pathophysiologic mechanisms contribute to PCOS, but a comprehensive explanation is still lacking. Key features of the syndrome are abnormal pituitary function, abnormal steroidogenesis and insulin resistance.⁶Androstenedione is a steroid hormone produced in the adrenal glands and gonads that is converted to testosterone or estrogen. The enzyme 17-beta hydroxysteroid dehydrogenase is required for conversion to testosterone, and the enzyme aromatase is required for conversion to estrogen.

Studies suggest that ovarian theca cells in women with PCOS are more efficient than normal theca cells at converting the androgenic precursors to testosterone. In women, androstenedione is released into the blood by theca cells that provide androstenedione substrate for estrogen production in the granulosa cells. Theca cells lack aromatase, which is required to make estrogen. Theca cells and granulosa cells work together to form estrogen. Androgens are synthesized by the ovarian theca cells in response to stimulation by luteinizing hormone (LH). LH regulates the androgenic synthesis of theca cells, and follicle-stimulating hormone (FSH) regulates the aromatase activity of granulosa cells, determining the amount of estrogen synthesized from androgenic precursors. When the LH concentration is greater than that of FSH, the ovaries preferentially produce more androgens. Excessive LH secretion relative to FSH was the first laboratory abnormality identified in association with PCOS, but not all patients with PCOS have elevated LH levels.⁷ pproximately 40% of patients with PCOS have normal LH:FSH ratios.⁸The ratio of LH to FSH is partly determined by the frequency of hypothalamic gonadotropin-releasing hormone (GnRH) stimulation. Increased pulse frequency of GnRH increases the LH:FSH ratio, and decreased pulse frequency reduces the ratio. Women with PCOS appear to have increased LH pulse frequency, indicating an increased pulse frequency of GnRH. It is unclear whether this is due to an intrinsic abnormality in the GnRH pulse generator or is caused by low levels of progesterone from infrequent ovulatory events. The low circulating progestin levels in women with PCOS may cause a rise in the pulse frequency of GnRH, increasing levels of LH and of ovarian androgens.⁷Polycystic ovaries have two to six times more follicles than healthy ovaries.⁵In anovulatory women with PCOS, the antral follicle stops growing at the stage just before the emergence of a dominant follicle. Excessive stimulation of follicular cells by insulin, LH or both is related to follicular arrest. Arrested follicles show signs of premature luteinization. Androgen excess results in excessive growth of small ovarian follicles and inhibition of the follicular maturation and development of the dominant follicle, resulting in the polycystic appearance of the ovary. Polycystic ovaries also have a thickened thecal layer that secretes excessive androgens.⁵Insulin influences the pathogenesis of hyperandrogenemia in PCOS. Insulin enhances the androgen production of theca cells by working synergistically with LH. It also inhibits hepatic synthesis of sex hormone-binding globulin (SHBG), the main protein that binds to testosterone. This increases the bioavailability of testosterone. Women with PCOS often have hyperinsulinemia, which elevates free testosterone concentration.⁷Insulin may act directly on the hypothalamus or pituitary gland - or both - to regulate gonadotropin release.⁹Hyperinsulinemia causes the pituitary gland to hypersecrete LH, which results in anovulation and thickening of the ovarian theca. This leads to higher androgen levels, specifically testosterone. Elevated testosterone may cause many of the symptoms associated with PCOS.⁸ The ovarian enzymatic activity involved in the synthesis of testosterone precursors is most likely the main cause for increased testosterone levels. Elevated LH levels, together with hyperinsulinemia, lead to an increase in androgen production by ovarian theca cells.⁹The pathogenesis of PCOS suggests that it is a complex multigenic disorder. Both genetic and environmental factors are implicated in causation.⁵The popular understanding is that PCOS is the result of intrinsic ovarian genetic traits that interact with other congenital or environmental factors to cause dysregulation of steroidogenesis.⁶Diagnostic criteria are outlined in Table 1.