Ovarian Polycystic Disease

INTRODUCTION ¡@

Background: Polycystic ovarian disease or syndrome (PCOS) is a heterogenous disorder characterized by a disruption of the regular processes leading to ovulation. It is associated with hyperandrogenemia, normal or elevated estrogen levels, and elevated luteinizing hormone (LH) secretion, with raised LH–to–follicle-stimulating hormone (FSH) ratio.

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Pathophysiology: The underlying cause of PCOS is an abnormality of ovarian androgen production that results from dysregulation of key enzymes involved in theca cell androgen biosynthesis. Hyperandrogenemia in PCOS could be due simply to increased follicle number or theca cell hyperplasia. Both insulin and insulinlike growth factors have been demonstrated to potentiate the actions of LH on theca cell androgen production.

Body mass index (BMI) is positively correlated to serum insulin and testosterone levels and is inversely related to sex hormone-binding globulin (SHBG) levels.

Frequency:
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Mortality/Morbidity: PCOS is a treatable disease with good improvement in signs and symptoms.

Sex: PCOS is a disease that affects females. It is a familial condition, possibly autosomal dominant, with premature balding being the male phenotype. The gene (possibly more than 1 gene) involved in PCOS has not yet been identified.

CLINICAL ¡@

History: Patients present with various symptoms, including the following:

Physical: PCOS is associated with obesity in women, as well as hirsutism.

Causes: PCOS is a familial condition, possibly autosomal dominant. However, the genetic components of PCOS have not yet been identified.

DIFFERENTIALS ¡@


Other Problems to be Considered:

Cushing syndrome (central obesity, moon face, plethoric complexion, buffalo hump, proximal myopathy, thin skin, abdominal striae)
Late-onset congenital adrenal hyperplasia
Adrenal tumors

WORKUP ¡@

Lab Studies:
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Imaging Studies:
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TREATMENT ¡@

Medical Care:

Surgical Care: Ovarian diathermy has replaced wedge resection, which can result in extensive ovarian, periovarian, and tubal adhesions. Only minimal damage to the ovary is required to stimulate ovulation. The method involves 4-point diathermy set at 40 W for 4 seconds at each point.

Consultations: Consultation with a nutritionist may be appropriate, especially in patients who are overweight.

Diet: Low-caloric diet is recommended for patients with BMI greater than 25 kg/m or for patients with truncal obesity.

Activity: No restriction of activity is needed; encourage regular exercise. Aerobic exercise in patients who are overweight is recommended for weight loss.

MEDICATION ¡@

Treatment of hirsutism involves cyproterone acetate and ethynylestradiol, cyproterone, spironolactone.
Treatment of infertility includes antioestrogens such as clomiphene citrate.
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Drug Category: Antiandrogens -- Decrease production of androgen, causing improvement in hirsutism.

Drug Name
¡@		 Cyproterone acetate (2 mg) and ethynylestradiol (0.035 mg) (DIANE-35) -- CPA exerts both antiandrogen and progestational effects. Ethynylestradiol inhibits ovulation and causes changes in cervical secretion. Provides contraceptive protection and stabilizes cycle. During first 10 d of cycle, 50-100 mg CPA also is administered. Not commercially available in US.
Adult Dose 1 tab PO qd for 21 d, starting d 1 of cycle
Pediatric Dose Not established
Contraindications Documented hypersensitivity; thrombophlebitis; thromboembolic phenomena; cerebrovascular disorders or past history of these conditions; known or suspected breast tumors or other estrogen-dependent neoplasm
Interactions Can increase oral antidiabetics or insulin requirements
Pregnancy X - Contraindicated in pregnancy
Precautions Caution in patients with liver disease, asthma, eczema, migraine, diabetes, hypertension, optic neuritis, retrobulbar neuritis, or convulsive disorders; associated with depression, weight gain, and breast tenderness
Drug Name
¡@		 Cyproterone (Androcur) -- Selectively inhibits pituitary function and suppresses ovulation. Depressed ovarian function results in decreased production of androgen, causing improvement in hirsutism. Administered during the first 10 d of cycle with a progestogen-estrogen preparation (ie, DIANE 35), which is administered PO qd for first 21 d of cycle to provide contraceptive protection. Not commercially available in US.
Adult Dose 50-100 mg PO qd for first 10 d of cycle
Pediatric Dose Not established
Contraindications Documented hypersensitivity; pregnancy; lactation; hepatic dysfunction; Dubin-Johnson syndrome; rotor syndrome; severe depression; previous or existing thromboembolic processes; severe diabetes with vascular changes; sickle cell anemia
Interactions Can increase oral antidiabetics or insulin requirements
Pregnancy X - Contraindicated in pregnancy
Precautions Monitor liver function, adrenocortical function, and check RBC regularly; associated with hepatic toxicity (ie, jaundice, hepatitis, hepatic failure)
Drug Name
¡@		 Spironolactone (Aldactone) -- Aldosterone antagonist inhibits ovarian and adrenal production of androgens. Competes with dihydrotestosterone binding at hormone receptor sites on hair follicle cells. Also reduces 17-alpha-hydroxylase activity, lowering plasma levels of testosterone and androstenedione.
Adult Dose 50-200 mg/d PO qd or divided bid
Pediatric Dose Not established
Contraindications Documented hypersensitivity; anuria; renal failure; hyperkalemia
Interactions May decrease effect of anticoagulants; potassium and potassium-sparing diuretics may increase toxicity of spironolactone
Pregnancy D - Unsafe in pregnancy
Precautions Caution in renal and hepatic impairment

Drug Category: Ovulation stimulators -- Stimulate release of pituitary gonadotropins.

Drug Name
¡@		 Clomiphene (Clomid, Milophene, Serophene) -- Blocks the inhibitory influence of estradiol on hypothalamus, preventing estrogen from reducing output of gonadotropins that ultimately stimulate ovulation.
Adult Dose 50-200 mg/d PO for 5 consecutive doses, starting day 2 and ending day 6 of cycle
Pediatric Dose Not established
Contraindications Documented hypersensitivity; liver disease; abnormal uterine bleeding; uncontrolled thyroid or adrenal dysfunction; suspected pregnancy
Interactions Danazol may reduce response to clomiphene
Pregnancy X - Contraindicated in pregnancy
Precautions Visual symptoms and abdominal pain may occur; enlarged ovaries (cysts >20 mm, free fluid in abdomen, and estradiol levels >5500 pmol/L); increased sensitivity, administer minimal doses; chances of multiple births are twins 10%, triplets 1%; with >100 mg qd, USG monitoring for follicle size and number is important
FOLLOW-UP ¡@

Prognosis:
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Patient Education:
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MISCELLANEOUS ¡@

Medical/Legal Pitfalls:
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BIBLIOGRAPHY ¡@