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Polycystic Ovary (Stein-Leventhal) Syndrome: Etiology, Complications, and Treatment

Clinical Laboratory Science, Summer 2004 by Hoyt, Karri Lynn, Schmidt, Margaret C

Polycystic ovary syndrome (PCOS) occurs in approximately 3% to 5% of the female population and may be the leading cause of infertility in those of reproductive age. PCOS presents clinically with a variety of signs and symptoms; the most common being menstrual irregularities, hyperandrogenism, infertility, and obesity. The true pathophysiology has not been clearly elucidated; however, there is growing agreement that gonadotropin dynamic dysfunction, hyperandrogenism, and insulin resistance are key features. The diagnosing of PCOS involves radiologic and laboratory studies. Radiologic studies typically include pelvic ultrasound; laboratory data should be obtained regarding pertinent gonadotropins and other hormone levels. PCOS is not a benign condition. It may lead to complications involving glucose metabolism, dyslipidemias, cardiovascular disease, and cancer. The goals of treatment should focus on restoring menstrual regularity, decreasing androgen excesses, and decreasing insulin resistance.

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ABBREVIATIONS: AN = acanthosis nigricans; FSH = follicle stimulating hormone; GnRH = gonadotropin releasing hormone; HAIRAN = hyperandrogenic-insulin resistance-acanthosis nigricans; hCG = human chorionic gonadotropin; HDL = high-density lipoproteins; LDL = low-density lipoprotein; LH = luteinizing hormone; OCP = oral contraceptive pill; PCOS = polycystic ovary syndrome; SHBG = sex hormone binding globulin; TSH = thyroid stimulating hormone.

INDEX TERMS: amenorrhea; follicle stimulating hormone; hyperandrogenism; infertility; luteinizing hormone; polycystic.

Clin Lab Sci 2004;17(3):155

CASE STUDY

A 27-year-old female presents to her primary care provider with complaints of amenorrhea times 11 months. Patient's past medical history is significant for starting menses at age 14. Menses have never been regular and when they do occur they are light. The longest time without a menstrual cycle is 18 months. A prior provider initiated progesterone withdrawal as a treatment; however, patient only used treatment once. Patient indicates that she is not pregnant at this time. Family history is significant for a sister and several paternal cousins with menstrual irregularities.

On physical exam the patient is of normal weight for height; it is noted that patient has slightly darker hair above the upper lip, small breasts with sparse hair around the areola, hair in the midline below the umbilicus, and hair on the inner thigh. It is also noted that patient has acne scarring and active pustules on back, upper chest, and shoulders.

Laboratory data are collected including follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone, human chorionic gonadotropin (hCG), prolactin, glucose, and insulin levels. Results indicate an LH:FSH ratio of >6, testosterone >50 mg/dL; negative hCG, and prolactin, glucose, and insulin levels within normal reference range.

Radiologic studies (abdominal ultrasound) reveal bilateral cystic ovaries; however the ovaries do not appear to be significantly enlarged.

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders seen in women of reproductive age.1,2 It may also be the most common cause of infertility for the same age group.1,3 The classic picture of PCOS was first described by Stein and Leventhal in 1935.4 They reported on seven women who had the associated characteristics of amenorrhea, hyperandrogenism, and obesity in association with bilaterally enlarged polycystic ovaries. Six of the seven women had menstrual irregularity that began in early menarche progressing to amenorrhea; five of the seven were infertile. Laparotomy revealed ovaries with thickened tunica and multiple cysts. Resection of half to three-fourths of the ovaries resulted in normal menstrual function for all of the women. Stein and Leventhal concluded that the crowding of the cortex led to the observed symptoms. Increases in our understanding of this syndrome have disproved this theory. Instead, it is now accepted that there are multiple hormonal factors that contribute to the symptoms of PCOS and the clinical presentation is much more variable including amenorrheic women who appear otherwise healthy. However, the description given by Stein and Leventhal remains the basis for defining the syndrome.

Data on prevalence is inconsistent, owing to the lack of well-accepted criteria for diagnosis. The incidence of PCOS is reported to be 3% to 6% of the female population on average with a range as high as 21% to 22% in a study of Pima Indians.2,5 Studies using the criteria of oligomenorrhea and hyperandrogenism report a slightly lower frequency of occurrence in black females (3.4%) as opposed to white females (4.6%).2 The disease has no predilection for race, although the presenting signs and symptoms may differ with ethnicity. The best estimate of prevalence may come from a population-based study by Knochenhauer.6 These researchers assessed 277 women undergoing routine pre-employment physical exams using the criteria of menstrual cycle characteristics and clinical androgen excess. The serum androgen levels were measured in 198 of the women who were not using hormonal therapy and PCOS prevalence was estimated to fall within the range of 3.5% to 11.2%.

Polycystic Ovary (Stein-Leventhal) Syndrome: Etiology, Complications, and Treatment

Clinical Laboratory Science, Summer 2004 by Hoyt, Karri Lynn, Schmidt, Margaret C

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