Best Dx/Best Rx: Polycystic Ovary Syndrome

From: Subject: Best Dx/Best Rx: Polycystic Ovary Syndrome Date: Wed, 3 Jun 2009 21:26:40 -0700 MIME-Version: 1.0 Content-Type: multipart/related; type="text/html"; boundary="----=_NextPart_000_01C2_01C9E491.FC1698E0" X-MimeOLE: Produced By Microsoft MimeOLE V6.00.2900.5579 This is a multi-part message in MIME format. ------=_NextPart_000_01C2_01C9E491.FC1698E0 Content-Type: text/html; charset="utf-8" Content-Transfer-Encoding: quoted-printable Content-Location: http://www.acpmedicine.com/acp/newrxdx/rxdx/dxrx1605.htm =EF=BB=BF Best Dx/Best Rx: Polycystic Ovary Syndrome

Polycystic = Ovary=20 Syndrome

Robert L. Barbieri, M.D.
Harvard = Medical=20 School

Defin= ition/Key=20 Clinical Features
Diffe= rential=20 Diagnosis
Best = Tests
Best = Therapy
Best = References

Definition/Key Clinical=20 Features

Hyperandrogenism and oligo-ovulation = (menstrual cycle=20 > 35 days long)
Hirsutism, acne, male-pattern hair loss =
Irregular and infrequent menstrual = cycles=20
Anovulatory infertility=20
Insulin resistance, obesity, increased risk of = type 2=20 diabetes=20
Endometrial hyperplasia/cancer=20
Associated with metabolic syndrome, = cardiovascular=20 disease, nonalcoholic steatohepatitis, sleep apnea

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Differential = Diagnosis

Idiopathic hirsutism=20
Nonclassic 21-hydroxylase deficiency=20
Androgen-secreting tumor, ovarian or = adrenal=20
Virilization syndromes=20
Ovarian hyperthecosis
Cushing syndrome=20
Valproic acid side effect=20
Exposure to exogenous androgens =

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Best=20 Tests

History=20
- Onset of oligomenorrhea, hirsutism, acne in=20 perimenarchal years=20
- Irregular menstrual cycles starting at = menarche=20
- Slowly progressing hirsutism=20
- Family history of PCOS and/or type 2 = diabetes=20
- Long-term use of valproate
- Smoking
Physical exam=20
- Assess hirsutism=20
- Assess insulin resistance=20
  - BMI > 25=20
  - Waist-to-hip ratio > 0.85
  - Waist circumference > 89 cm=20
  - Acanthosis nigricans or achrochordons = (skin=20 tags)
- Assess for metabolic syndrome=20
  - Waist circumference > 35 in=20
  - BP > 130/85 mm Hg=20
  - Fasting blood sugar > 100 mg/dl=20
  - Triglycerides > 150 mg/dl=20
  - HDL-C < 50 mg/dl
- Signs of virilization indicate = androgen-secreting=20 tumor
Laboratory tests=20
- Total serum testosterone (normal range, = 0.60=E2=80=930.80=20 ng/ml); > 2 ng/ml indicates ovarian stromal hyperthecosis or = tumor=20
- 17-Hydroxyprogesterone > 2 ng/ml at 8 = A.M.=20 indicates probable nonclassic adrenal hyperplasia; confirm by ACTH=20 stimulation test=20
- Dehydroepiandrosterone sulfate (DHEAS) > = 10.7 =C2=B5g/dl=20 suggests adrenal tumor (normal range 0.12=E2=80=935.35 = =C2=B5g/dl)=20
- Serum prolactin to rule out pituitary = tumor=20
- Serum TSH=20
- LH:FSH ratio more informative than single = serum LH=20 measurement=20
- Antim=C3=BCllerian hormone level elevated in = PCOS=20
- Screen for diabetes mellitus, fasting = glucose=20
Pelvic ultrasound if ovaries palpable and = enlarged or if=20 total testosterone > 2.0 ng/ml

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Best=20 Therapy

Irregular and = Infrequent=20 Menses=20

Cyclic estrogen-progestin contraceptive =
- Any agent except androgenic progestin (e.g., = norgestrel)
- Long-cycle regimens may work better than = standard=20 cycle regimens=20
- Twofold greater risk for coronary vascular = disease in=20 PCOS
Metformin=20
Cyclic progestin (e.g., medroxyprogesterone = acetate, 10=20 mg daily for 14 days each mo)

Hirsutism=20

Cyclic estrogen-progestin oral contraceptive, = alone or=20 with an antiandrogen (e.g., spironolactone, 100 mg/day)
Shaving, electrolysis, laser treatment=20
Topical eflornithine
Avoid glucocorticoids

Infertility Resulting from = Oligo-ovulation or=20 Anovulation=20

Weight loss of =E2=89=A5 10% if BMI > = 27=20
Drug therapy=20
- Clomiphene citrate=20
  - Dose: 50 or 100 mg/day for maximum 5 days = per=20 cycle=20
    - Cost/mo: $28
  - After spontaneous menses or induction of = menses with=20 progestin withdrawal maneuver (medroxyprogesterone acetate, 10 mg = p.o.=20 daily for 5 days), start clomiphene, 50 mg/day, for 5 days on = cycle day 3,=20 4, or 5; 50% of patients will ovulate=20
    - By increasing dose to 100 mg/day, = another 25% of=20 patients will ovulate=20
    - Some patients require 150 mg/day for 5 = days=20
  - Determine ovulation by basal body = temperature,=20 ultrasound, luteal-phase progesterone measurements, or endometrial = biopsy=20 (when conception is not attempted)=20
  - Risk of multiple pregnancy
  - Spontaneous abortion rate ~ 15%=20
  - Vasomotor symptoms, adnexal tenderness, = nausea,=20 headache, blurring of vision or scotomata
- Metformin: alternate choice=20
  - Dose: 1,500 mg in divided doses with = meals; start=20 with 500 mg/day for first week, then 500 mg b.i.d. for second = week, then=20 500 mg t.i.d.; extended release: 1/day with dinner=20
    - Cost/mo: $51
  - Side effects: GI disturbances=20
  - Before starting, confirm that serum = creatinine <=20 1.4 mg/dl
- Metformin + clomiphene=20
  - Effective if clomiphene alone does not = produce=20 ovulation after 5=E2=80=9310 wk
- Clomiphene + glucocorticoid=20
  - If clomiphene alone does not produce = ovulation,=20 short course of dexamethasone followed by clomiphene may be = tried=20
Gonadotropin induction=20
- FSH, 75 U/day s.c. for 14 days; increase by = 37.5 units=20 q. 7 days until follicular ripening complete
- Can be used with clomiphene or = metformin=20
- Can cause ovarian hyperstimulation = syndrome=20
  - Abdominal pain, distention=20
  - Nausea, vomiting, diarrhea, dyspnea =
  - Weight gain, ovarian enlargement, ascites, = pleural=20 effusion, hemoconcentration, electrolyte imbalances, renal = dysfunction,=20 thrombosis
- Multiple pregnancy rate ~ 15% =
In vitro fertilization with embryo = transfer=20
Ovarian surgery
- Laparoscopic drilling of ovary: pregnancy = rate ~ 50%=20 at 12 mo and 70% at 24 mo=20
- Surgery to reduce androgen-secreting tissue: = only if=20 standard approaches fail to induce ovulation =

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Best References

Elnashar A: Human Reprod 21:1805, 2006 [PMID = 16543255]=20

Farquhar C: Cochrane Database Syst Rev = (4):CD000194, 2003=20 [PMID 14583916]

Grundy SM: Circulation 112:2735, 2005 [PMID = 16157765]=20

Hughes E: Cochrane Database Syst Rev (2):CD00056, = 2000=20 [PMID 10908458]

Lord JM: Cochrane Database Syst Rev (3):CD003053, = 2003=20 [PMID 12917943]

The author has no commercial = relationships with=20 manufacturers of products or providers of services discussed in this = module.=20

February=20 2007