Polycystic Ovarian Disease

 

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 a raised LH–to–follicle-stimulating hormone (FSH) ratio.

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
  •  PCOS affects about 6-10% of women. Incidence in women who are infertile is 30%.

Mortality/Morbidity:

PCOS is a treatable disease with good improvement in signs and symptoms.

  • Patients are prone to cardiovascular diseases because of hypertension and dyslipidemia.
  • Patients are at risk of type II diabetes because of insulin resistance.
  • The chances of endometrial carcinoma are increased.

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 PRESENTATION

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

  • Menstrual disorders (80%)
  • Oligomenorrhea (71.4%)
  • Amenorrhea (28.6%)
  • Infertility (74%) - Accounts for 30% of overall infertility
  • Recurrent pregnancy losses (common)
  • Hirsutism (69%)
  • Obesity (49%)
  • Acne vulgaris
  • Asymptomatic
Physical Examination:

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.

DIFFERENTIAL DIAGNOSIS

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

 LABORATORY STUDIES

 

  • Increased androgen levels in blood (testosterone and androstenedione)
  • Increased LH levels, exaggerated surge
  • Serum LH-to-FSH ratio - Exceeds 2
  • Increased fasting insulin
  • Increased prolactin levels
  • Increased oestradiol and oestrone levels
  • Decreased SHBG levels
Imaging Studies:
  • Ultrasonography is the most sensitive diagnostic study. Ultrasonographic criteria for establishing the diagnosis of PCOS are 10 or more cysts that are 2-8 mm in diameter and are peripherally arranged around an echodense stroma.
    • Transabdominal ultrasonography
    • Transvaginal ultrasonography

 

TREATMENT

Medical Care:

  • Weight reduction is associated with normalization of hormonal disturbances and the resumption of regular ovulation. It also has a beneficial impact on the consequences of PCOS (eg, cardiovascular diseases, impaired glucose tolerance, hypertension, dyslipidemia).
  • Cigarette smoking should be stopped because it stimulates adrenal androgens.
  • Medical treatment of hirsutism includes antiandrogen, progestogen with nonandrogenic progesterone (combined pill), adrenal suppression by dexamethasone, 5-alpha reductase inhibitors, and cosmetic methods (eg, waxing, shaving [shaving does not increase hair growth, but it may make hair coarse], bleaching, electrolysis).
  • Medical treatment of infertility includes antiestrogens (clomiphene citrate), adrenal suppression by dexamethasone along with clomiphene, gonadotropin therapy, gonadotropin-releasing hormone (GnRH) analogue, and metformin therapy.

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: A low-calorie 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, and spironolactone.
Treatment of infertility includes antiestrogens such as clomiphene citrate.

Drug Category: Antiandrogens -- Decrease production of androgen, causing improvement in hirsutism.

CYPROTERONE ACETATE (2mg) & ETHINYL ESTRADIOL (0.035mg):

1 tab PO qd for 21 d, starting on day 1 of the cycle

CYPROTERONE:

50-100 mg PO qd for first 10 d of cycle

SPIRONOLACTONE:

50-200 mg/d PO qd or divided bid

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

CLOMIPHENE:

50-200 mg/d PO for 5 consecutive doses, starting day 2 and ending day 6 of cycle

 FOLLOW-UP

Prognosis:

  • With proper diagnosis and treatment, most PCOS symptoms can be adequately controlled or eliminated.
  • Infertility can be corrected and pregnancy achieved in most patients. In some patients, hormonal disturbances and anovulation may recur.
  • Monitor patients for endometrial cancer.
  • Because of the high rate of hyperinsulinemia observed in PCOS, women with the disorder should have their glucose levels checked regularly to monitor for the development of diabetes.
  • Blood pressure and cholesterol screening are also needed because women with PCOS tend to have high levels of low-density lipoprotein (LDL) cholesterol and triglycerides, which puts them at risk for developing heart disease.

Patient Education:

  • No known way to prevent PCOS exists, but, if diagnosed and treated early, risks for complications, such as heart disease and diabetes, may be minimized.
  • Weight control through diet and exercise stabilizes hormones and lowers insulin levels.

Medical Pitfalls:

  • The exact cause of PCOS is unknown. Certainly, a miscommunication occurs among the hypothalamus (within the brain), pituitary gland (at the base of the brain), ovaries, and fatty tissue. Where the miscommunication originates from is a matter of great controversy and remains unknown.
  • A higher incidence of PCOS exists within certain families, but the genetic basis for the disease has not yet been fully elucidated.