Polycystic%20ovarian%20syndrome Treatment

• Goals of therapy include reducing risk factors for type 2 DM and CVD, managing underlying metabolic abnormalities, addressing overweight and obesity, treating hyperandrogenic features, preventing endometrial hyperplasia and carcinoma, inducing ovulation in women who wish to become pregnant and providing contraception for those who are not pursuing pregnancy
• A specialist referral, eg endocrinologist, gynecologist, dietitian, may be needed for the management of metabolic abnormalities, ovulatory dysfunction and weight concerns

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 oral contraceptives (OCs)
• Does not provide birth control

Management for Excess Androgen*

Antiandrogen Agents

• Eg Cyproterone, Flutamide
• Used empirically in women with PCOS; evidence of use in PCOS is relatively limited 
• 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, thus effective contraception must be utilized
  • Discontinue antiandrogen therapy if contemplating pregnancy
• Used in combination with COCs
  • For hirsutism, consider combination therapy with COCs if without symptom improvement after ≥6 months of COC use and cosmetic treatment 
  • Antiandrogen and COC combination therapy could also be considered for androgen-related alopecia
• Consider antiandrogen agents in patients who are intolerant of or have contraindications to COCs for the treatment of hirsutism and androgen-related alopecia 
• 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 
  • 35 mcg Ethinyl estradiol plus Cyproterone acetate should not be considered 1st line treatment due to adverse effects including venous thromboembolic (VTE) risks

Combination Oral Contraceptives (COCs)

• 1st-line agents for managing menstrual irregularity and hyperandrogenism, these are 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 a minimum of 6 months to notice a benefit in hirsutism and acne
• May be used in PCOS patients who do not desire pregnancy
  
  • Low-dose preparations with minimal androgenic potential (eg Norgestimate, Desogestrel, Gestodene, Drospirenone, Dienogest and Etynodiol diacetate; 20-30 mcg of Ethinyl estradiol or equivalent) are preferred for long-term management
  • Consider natural estrogen preparations balancing efficacy, side effects, metabolic risk profile, cost and availability
• Help reduce the risk of endometrial hyperplasia and carcinoma by antagonizing estrogen’s proliferative effect on the endometrium through withdrawal bleeding
• 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
• Assess patient for risk factors (eg high BMI, hypertension, hyperlipidemia) when prescribing COCs and also for risk factors for VTE (eg age, obesity, family history of VTE) 
• Follow WHO COC general population guidelines for relative and absolute contraindications and risks 
• Many COCs are available. Please see the latest MIMS for specific formulations and prescribing information

Eflornithine

• Inhibits growth of facial hair  
  • Onset of action may take 4-8 weeks for facial hirsutism  
• Postulated mechanism of action includes irreversible inhibition of ornithine decarboxylase activity in the skin resulting in reduced rate of hair growth

Finasteride

• An antiandrogen 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 antiandrogen 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 if hyperandrogenic symptoms are unresponsive to COC monotherapy and to prevent erratic vaginal bleeding

*Please see Acne Vulgaris disease management chart for further information

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
• May be considered as 2nd-line agent in those who cannot take or are intolerant of hormonal contraceptives for the treatment of anovulation 
• Metformin and lifestyle modification can be considered in adolescents and in adults for weight treatment (BMI ≥25 kg/m²) and for hormonal and metabolic outcomes
• Consider combination therapy with Metformin and COC in patients whose treatment with lifestyle modification and COC had been unsuccessful for management of metabolic features
  • Could be considered in adolescents with PCOS and BMI ≥25 kg/m² if both COC and lifestyle changes failed to achieve treatment goals 
  • Metformin and COC combination therapy is most beneficial in high metabolic risk groups, eg individuals with diabetes risk factors, impaired glucose tolerance or high-risk ethnic groups
• 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
• Appears safe with long-term use; ongoing monitoring is required and it has been associated with low levels of vitamin B12 
  • Side effects, including gastrointestinal effects, are dose related and self-limiting; consider starting at a low dose with 500-mg increments every 1-2 weeks 

Other Agent

Inositol

• Currently considered as an experimental therapeutic agent in PCOS 
• Emerging evidence shows efficacy, though further research is needed