Disease Profile for Polycystic Ovarian Syndrome (PCOS)

Name: polycystic ovarian syndrome

Synonyms: Stein-Leventhal syndrome, polycystic ovaries, sclerocystic ovaries, polycystic ovarian disease, PCOS, PCOD, PCO, anovulation with hyperandrogenism

General description: This disorder is characterized by changes to the ovaries such that multiple follicles accumulate in the ovaries without ovulation. The ovary secretes higher levels of testosterone and estrogens. This results in irregular or no menses, excess body hair growth, occasionally baldness, and often obesity, diabetes and hypertension.

The main concerns of this condition are body changes (hair excess, obesity) and infertility due to anovulation. Because of the anovulation, women with polycystic ovarian syndrome are at risk for irregular and heavy menstrual bleeding problems, endometrial hyperplasia and even endometrial cancer. They are also thought to be at increased risk for premature heart attacks and cardiac disease due to weight and diabetes effects although this has been recently questioned.

Is it common?

Estimates range around the 5% level if both anovulation and excess hair growth are used in the definition but they can range over 10% in some select populations.

Differentiating features

Testosterone levels may be normal (20-80 ng/dl, 0.7-2.8 nmol/l) or elevated but usually less than 200 ng/dl. Serum androstenedione and dehydroepiandrosterone sulphate (DHEA -S) are usually normal but may be elevated. FSH and LH levels are normal to high normal, often (25%) with a ratio of LH to FSH of 3.0 or more. Luteinzing hormone - LH - is usually greater than 9 mu/ml (9 U/L) when ovaries appear polycystic on ultrasound.

Adrenogenital syndrome and ovarian androgen secreting tumors can produce this syndrome but the serum testosterone is used to screen for these. If the total serum testosterone is over 150 ng/dl (5 nmol/l) then adrenal or tumor causes should be investigated. TSH and prolactin levels are usually normal but are drawn to rule out pituitary or thyroid causes of the clinical symptoms. Measurement of abnormal glucose tolerance often indicates abnormality in the fasting and 2 hour blood sugar, post 75 gm glucose challenge, or the fasting glucose/insulin ratio or hemoglobin A1c.

Ultrasound findings often include multicystic ovaries with the follicle cysts lining up on the periphery of the ovary but it does not always meet the criteria of ten or more follicle cysts in each ovary. Of women who have classic polycystic ovaries on ultrasound scanning, only 50% have the classic hirsutism and anovulation. Of women who are felt to have polycystic ovarian syndrome on a clinical and laboratory basis but not on ultrasound criteria, 66-82% have the classic ultrasound appearance expected of polycystic ovaries.

Usually the diagnosis includes both anovulation and androgen (testosterone) excess but many related conditions have become lumped together in the literature under the term polycystic ovarian syndrome. Woman with polycystic ovaries on ultrasound do not all have androgen excess, but insulin resistance is manifest in equal frequencies whether or not there are elevated androgens. Because of this mixed clinical picture, those conditions all collected under the term polycystic ovarian syndrome in the medical literature may include:

traditional PCOS -- anovulatory, increased androgens, no insulin resistance
endocrine syndrome X -- anovulatory, increased androgens, insulin resistance or type 2 diabetes
non-traditional PCOS --anovulatory, normal androgens, obese, insulin resistant or type 2 diabetes
non-traditional PCOS -- ovulatory, increased androgens, mild insulin resistance
idiopathic hirsutism -- ovulatory, increased androgens, no insulin resistance

Other features

Obesity with a body mass index (BMI) of over 27 is often present and it represents a central, android obesity (waist to hip ratio of greater than 0.85). Male pattern baldness (top of head) occurs if testosterone levels are quite high or if there is a genetic predisposition to the hair loss (autosomal dominant). Cause

High Insulin levels due to insulin resistance may be a primary cause. The insulin levels cause the increased androgen levels. In some cases, the insulin resistance is a genetic abnormality. Some instances of polycystic ovarian syndrome associated with male pattern baldness are thought to be due to an autosomal dominant genetic defect but it is important to note that this does not explain all cases. Since this is a syndrome that likely includes different categories of diseases, it is also likely that some instances are caused by genetic abnormalities while other instances are caused by environmental or as yet unknown conditions.

Valproate or divalproex (Depakote®), a drug used for epileptic seizures and some mood disorders, has been associated with a higher incidence of polycystic ovaries and hyperandrogenism.

Unnecessarystudies: ovarian biopsy, laparoscopy for diagnosis, CAT scans or MRI (ultrasound is sufficient).

Natural history

The anovulation persists until menopause. After age 40, women with polycystic ovarian syndrome have similar lipid profiles to matched control women without polycystic ovaries. However there does seem to be some worsening of heart disease because women with more severe arteriosclerotic changes on cardiac catheterization will have a higher incidence of polycystic ovarian disease. Goals of

therapy (Rx) Restoring ovulation and decreasing the testosterone level are main goals of therapy. Weight loss to decrease the risk for long term early mortality is also a goal. Finally, prevention of endometrial cancer should be a goal of treatment. 1st choice therapy Clomiphene (Clomid®) to induce ovulation if pregnancy is desired can result in as high as a 70% pregnancy rate.

Weight loss following a low carbohydrate/diabetic diet.

Flutamide (Eulexin®) , slightly more efficacious than finasteride (Propecia®), is used for the hirsutism.

Either treatment with oral contraceptives containing estrogen or a withdrawal menses induced every 2-3 months with progestins (e.g., Provera®) if there is not a spontaneous menses, in order to prevent endometrial cancer.

Other therapies used Other ovulation induction agents may be necessary if the ovaries are refractory to clomiphene (Clomid®).

Metformin has been used in women with PCOS and insulin resistance (fasting insulin levels over 20 ug/ml) to induce ovulation.

Finasteride (Propecia®) may be used to reduce hirsutism.

Saw palmetto in a dose of about 320 mg per day may be effective in reducing the effect of the androgens since it blocks the effect of 5-alpha-reductase on their receptors when used to treat benign prostatic hypertrophy.

Estrogens in the form of birth control pills or with added progestins can regulate any abnormal bleeding as well as decrease some of the androgen excess.

Ovarian diathermy (heat) or electrocautery at laparoscopy may be useful to induce ovulation if medications have been unsuccessful.

Treatments to avoid

androgens (testosterone) worsen the excess hair growth and balding problem

diets high in simple carbohydrates worsen insulin resistance

ovarian drilling with a laser/cautery or ovarian wedge resection are last resort treatments if at all because they often cause adhesions which worsen infertility.

Reason for Rx choices

Weight loss - polycystic ovarian syndrome with insulin resistance is uncommon in women with a body mass index (BMI) of less than 27.

Flutamide (Eulexin®) is slightly more efficacious than finasteride (Propecia®), in improving hirsutism.

Regular periodic sloughing of the uterine lining (endometrium) is thought to reduce the risk for endometrial hyperplasia and cancer that occurs at an earlier age in women with polycystic ovarian disease.

References See hyperlinks Other resources Taking Clomid to Induce Ovulation
Evaluation of Excessive Hair Growth (Hirsutism)
Diagnosis of Polycystic Ovarian Syndrome
Diabetic Tendency in Polycystic Ovary Syndrome
PCOS Information at Womens-Health.co.uk