polycystic%20ovarian%20syndrome
POLYCYSTIC OVARIAN SYNDROME
Polycystic ovarian syndrome (PCOS) is the accumulation of underdeveloped follicles in the ovaries due to anovulation. It is is characterized by menstrual abnormalities and clinical or biochemical features of hyperandrogenism.
It results mainly from abnormal steroidogenesis that may be caused by insulin resistance leading to hyperinsulinemia.
There is increased sensitivity to androgens and the majority of women have elevated androgen levels.

Pharmacotherapy

Management for Amenorrhea

Medroxyprogesterone acetate

  • A synthetic progestogen that inhibits ovulation resulting in endometrial thinning
    • Has some androgenic and anabolic activities but no estrogenic effects
  • Used to induce withdrawal bleeding in PCOS women who have irregular menstrual cycle
  • May be given for patients who cannot take estrogen-containing pills or those who do not wish to take OCs
  • Does not provide birth control

Management for Excess Androgen

  • Antiandrogen Agents
  • Eg Flutamide, Eflornithine
  • Used empirically in women with PCOS
  • Antagonize binding of testosterone and other androgens to the androgen receptor
  • May result in improvements in body composition and circulating lipid levels
  • All appear to offer some benefit, although the best choice for hirsutism in PCOS is unknown
  • Teratogenic and pose a risk of feminization of the external genitalia in a male fetus
  • Used in combination with oral contraceptives (OCs)

Combination Oral Contraceptives (COCs)

  • May be used in PCOS patients who do not desire pregnancy
    • Low-dose preparations with minimal androgenic potential (eg Norgestimate, Desogestrel, Gestodene, Drospirenone and Etynodiol diacetate) are preferred for long-term management
  • Used to establish regular menstrual cycles and have been shown to control hirsutism and acne in PCOS
    • Patient should be made aware that it may take up to 3-8 months to notice a benefit in hirsutism
  • Inhibit gonadotropin stimulation of the ovary resulting in reduced androgen production
    • Cause lowering of LH levels without surges and the estrogen component stimulates SHBG production by the liver, which lowers bioavailable androgen. This androgen suppression causes significant increases in circulating triglyceride and HDL cholesterol levels
  • Many combination oral contraceptives are available. Please see the latest MIMS for specific formulations

Cyproterone Combined with Estrogen

  • Cyproterone is an antiandrogen which is progestogenic and when combined with an estrogen provides control of menses and contraception
  • It has been used successfully to treat hirsutism and severe acne caused by androgen excess

Finasteride

  • Finasteride is as effective as Spironolactone in treating hirsutism but should only be considered in women who do not desire pregnancy
  • A 5-α reductase inhibitor which acts by inhibiting the conversion of testosterone to dihydrotestosterone and by blocking androgen receptor
  • Better tolerated than other antiandrogens, with minimal hepatic and renal toxicity
  • Adequate contraception is necessary because of the risk to the male fetus

GnRH Analogues

  • Have been used especially in severe ovarian hyperandrogenism
  • Suppress androgen production by the ovaries
  • Use is limited by cost and complications due to long term estrogen deficiency, requires concurrent estrogen/progestin add-back therapy

Spironolactone

  • An anti-androgen that is useful in the treatment of hirsutism and acne in women who do not desire pregnancy
  • A mineralocorticoid antagonist with a structure similar to testosterone; it competes with androgen by binding to receptors
  • May reduce the caliber and growth rate of hair in 40-80% of cases but may require 8-14 months before clinical effects can be observed
    • Menses occasionally resumes
  • Usually combined with COCs to prevent erratic vaginal bleeding

Management for Metabolic Risks (Insulin Resistance and Glucose Intolerance)

Metformin

  • Has been shown to significantly improve insulin concentration, insulin sensitivity and serum androgen concentration along with a reduction in LH and an increase in SHBG concentration
  • Has been associated with a decrease in features of metabolic syndrome in premenopausal PCOS patients 
  • In hyperinsulinemic PCOS, Metformin has been used to restore menstrual cyclicity and induce ovulation with and without the addition of Clomifene
  • Inhibits hepatic glucose output, increases sensitivity of peripheral tissues to insulin action, and enhances muscle glucose uptake leading to decrease in insulin levels
    • Reduces ovarian gluconeogenesis, decreasing ovarian androgen production
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