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NOTE: Information Updated 9/04
POLYCYSTIC OVARY SYNDROME - Rose Mary Russell, Womens Health NP
Functional Ovarian Hyperandrogenic Disorders
Hyperandrogenic Disorders
CHARACTERISTICS
- PCO characterized by excessive production of androgens & estrogen
- H-P-0 axis intact
- Ovary intrinsically without defects
- Ovary affected by excess androgens and conversion of androgens in periphery to estrogens.
- No known cause
PATHOPHYSIOLOGY
A. ANDROGENS
- Androgenic steroids
- testosterone - most potent
- dihydrotestosterone - potent tissue metabolite from skin and skeletal muscle.
- androstenedione, dehydroepiandrosterone (DHEA) &
free DHEA - S.
- Women secret testosterone equally from adrenal (25%) ovaries (25%) 50% is peripheral conversion. This is 5-20% of men.
- Testosterone and other circulate bound to SHBG and other binding proteins ie. albumin, so that ^ amts. of SHBG results in less free bioavailable hormone.
- SHBG produced in liver, ^ by estrogens and decreased by androgens and insulin, so less SHBG ^ amount of circulating testosterone.
- Thus, free testosterone level are a better marker of androgenic activity than total testosterone.
- Androgens aromatized to estrogen in peripheral fat, why women who are hyperandrogenic tend to have normal total estrogen levels.
- Decrease in (SBG) leads to increase active testosterone.
B. HYPERINSULINEMIA
- Hyperandrogenic women are significantly more insulin resistant, independent of obesity.
- Increased insulin stimulates ovarian androgen production.
- High insulin levels cause hyperandrogenemia in women with severe insulin essence.
- It is not clear if insulin leads to increased androgens or increased androgens contribute to hyperinsulinism.
- The degree of resistance correlates with the presence of acanthosis nigrican - darkening of rugal folds.
- Acanthosis nigricans associated with the highest fasting insulin.
- The greater the obesity the greater the fasting insulin.
INCREASED ESTROGEN, ANDROGEN, LH
- Increased estrone from:
- obesity ( conversion of ovarian and adrenal androgens to estrone in body fat)
- excessive levels of androgens seen in women of normal weight.
- High estrone causes suppression of pituitary FSH and increase of LH.
- Constant LH leads to anovulation, multiple cysts, theca cell hyperplasia with excess androgen output from ovary and adrenal gland.
- May see physical findings like Cushing's Syndrome ^ androgen levels.
- This leads to ^ androgen secretion by ovaries which contributes to
- premature follicular atresia and persistent anovulation, leading to
- PCO. There is an increased risk for breast and endometrial CA due to ^ estrogen.
DEFINITION
- Secondary amenorrhea; hyperandrogenic and menstrual irregularity in premenopausaul women.
- Amenorrhea/ Oligiomenorrhea
- LH>FSH 3:1
- LH.35 mIU/ml. 9% of infertility.
CHARACTERISTICS / DEMOGRAPHICS
- Hirsutism - 70%, androgen responsive skin zones. Coarse terminal
- hair. Virilization <1% of women with hirsutism. -distinguish from hypertrichosis, fine vellus hair, not androgen dependent.
- Obesity - 40%
- Virilization - 20%
- Secondary amenorrhea 50%
- Abnormal uterine bleeding - 30%
- Normal periods - 20%
- May be daughters who fathers balded early
- Onset teen years.
- Acne varies with race
- Asian and Am. Indians - no hair.
- Mediterranean - heavy facial and body
- African Am. and Hispanic- Acanthosis Nigricans
- Asians - increased acne.
- 38% of women with diffuse alopecia have evidence of hyperandrogene mia.
- 50% of women with acne have ^ androgen.
- Hyperandrogenemia women tend to have ^ chol, lower HDL, ^ waist to hip ratio.
DIFFERENTIAL DIAGNOSIS
- DC OCP
- Premature menopause - FSH & LH ^
- Rapid wt. loss, extreme exercise, or obesity
- Hyper/hypo thyroid
- Cushing syndrome
- Pituitary tumor - ^ prolactin
- Ovarian or adrenal tumors - suspect when onset is abrupt and not assoc. with puberty.
- Hyperprolactinemia - assoc. with ^ DHEA-S levels and hirsutism.
- ^ are mild
- no tumors on scan
- prolactin may ^ adrenal androgen.
LABORATORY EVALUATION
- UA Preg test/serum
- Menses calendar/ BBT
- LSH/FSH ratio
- Prolactin level
- TSH
- Serum testosterone (total and free)
- DHEA-S
- Pelvic US
-
GOALS OF MANAGEMENT
- effect of hirsutism/acne or self-concept
- regulate menses, decrease unopposed
estrogen effect
- Decrease insulin resistance
- determine risk factors
- fertility
S: Chief Complaint - Hirsutism (70%)
or Infertility
- Menses/OB/ Contraceptive Hx
- Menses hx including menarche, freg.. duration, past conception, use of OCP, symptoms of ovulation. Any abnormal bleeding, normal periods, c/o infertility.
- PMH - Medication hx - use of danazol for endometriosis
- use of androgenic OCP, Norgestrel
- Dilantin
- Minoxidil use
- FMH - Family h/o hair growth, diabetes, thyroid, adrenal diseases
- ROS - male pattern baldness
- ^ oil production
- deepening of voice
- ^ muscle mass or proximal muscle weakness darkening of rugal folds skin changes, acne, straie, bruising fat areas of neck supraclavicular
- ^ abd. girth, central obesity
- galactorrhea
- wt. gain
0:
- VS - A B/P
- Wt. Ht.
- Skin - distribution of androgen terminal hair,
quantity
- acne, ^ oil production
- presence of straie - cortisol production, bruising, fat dist.
- acanthosis nigricans
- Hair - temporal balding
- HEENT
- deepening of voice
- moon face
- eye exam
- Breast - decreased size, galactorrhea
- Pelvic -
- external - amt. of terminal hair; clitormegaly;
ambiguous genitalia
- internal - presence of cervical mucus, character, ferning
- ovaries - palpable, equal, tender, smooth
P:
- Obesity, lose wt.
- If no fertility desired-
- OCP
- pills to ^ SHBG
- keep on 6-12 months
- Ovcon/Modicon 0.4 - 0.5 norethidrone
- Ortho cept, Desogen & Orthotricyclen least andronergic effect on lipids.
- Women whose ovaries work may need BTB and increased estr/proges, Demulen 1/35
- Avoid androgenic - levonorgestrol, Nordette, Lo-ovral, and Lo-estrin
- Do not use if PRL levels increased
- Medroxyprogesterone 10 mg./day for 10 days of month.
- Spironolactone 50 - 100 mg BID
- Refer if fertility desired or ^ PRL
- Bromocriptine
- Clomiphene citrate
- GNRH
- Laser drilling
- Wedge resection
- Low dose dexamethasone suppression
- Mild hirsutism
- shaving
- bleach
- tweezing
- depilatories
- electrical epilators
- lasers
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