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Transcript
A case of PCOS:
A 30-year-old woman comes to clinic to discuss abnormal menstrual periods.
Menarche was at age 14. Her periods were never entirely predictable but over the past
year they have been occurring less often, about every two or three months. Her last
menstrual period was two months ago. She has not been sexually active for over a
year. She has no chronic medical problems. She takes ibuprofen occasionally for
headaches and menstrual cramps but otherwise is on no other medications.
Hypothalamic dysfunction is the most common cause of secondary amennorrhea
(excluding pregnancy).
 Hypothalamic dysfunction due to emotional and/or physical stress is one of
the most common causes of oligomenorrhea/secondary amenorrhea.
 Emotional stress, strict dieting, vigorous exercise, organic illness or anorexia
nervosa may lead to menstrual irregularities.
 These symptoms should not be assumed to cause menstrual irregularities
without a thorough physical and endocrine evaluation
She complains of feeling “fat” and states she can’t lose weight even though she walks
to work three times per week. She went for a facial last week and the beautician
recommended that she start waxing her chin. She has been frustrated lately because
she has been spending a lot of time plucking her chin hairs.
Signs/symptoms of hyperandrogenism include:
Non-virilizing
 Hirsutism: course hair growth in androgen-dependent body regions such as
sideburn area, chin, upper lip, periareolar area, chest, lower abdominal midline
and thigh.
 Acne
 Oily skin
 Abnormal menstrual cycles
 Infertility
Virilizing*
 Clitorimegaly
 Deepening of the voice
 Male pattern balding
 Masculinization of body habitus
 Increased libido
*Less commonly seen than non-virilizing symptoms

The syndrome has an initial onset in peri-pubertal years and is progressive.


Sudden onset of these symptoms suggests a different disorder such as Cushing’s
syndrome or a hormone producing adrenal or ovarian tumor.
Women with PCOS can display a wide range of clinical symptoms. Concerns
about menstrual irregularities, hirsuitism, acne, or infertility are the most
common reasons for seeking medical care.
Presenting symptoms of PCOS:
Symptom
Prevalence
Infertility
75%
Hyperandrogenism
70%
Amenorrhea
50%
Obesity
60-80%
Abnormal uterine bleeding 30%
Normal menstruation
20%
The etiology of PCOS is unknown but it is due to a steady state of high estrogen,
androgens, luteinizing hormone (LH) and insulin levels. High estrogen causes
cause suppression of pituitary follicle stimulating hormone (FSH) and a relative
increase in LH. The increased LH stimulates the ovary, which results in
anovulation, multiple cysts and theca cell hyperplasia with excess androgen
output. High insulin levels may also increase the production of testosterone by
the ovaries.
PCOS is a common endocrine disorder affecting 4-7% of women of reproductive age.
She read an article in her woman’s magazine about PCOS. She thinks she fits the bill.
She wants you to test her for PCOS.


There is not a confirmatory test for PCOS. It is a clinical diagnosis based on
certain criteria as shown below.
Ovarian cysts are not required for diagnosis. Cysts are present on ultrasound in
more than 90% of women with PCOS but also present in up to 25% of normal
women.
Criteria for diagnosis of PCOS
(4,5)
Hyperandrogenism
Sufficient to have elevated serum androgen levels or a
biological expression of hyperandrogenism (acne or
hirsutism)
Irregular menses
Anovulation or oligo-ovulation
Absence of other causes of anovulation
Thyroid disorders
Hyperprolactinemia
Cushing’s syndrome
Late onset congenital adrenal hyperplasia (CAH)
Ovarian and adrenal tumors
Her exam is significant for oily skin, mild acne, coarse hair on her chin, and obesity
(BMI 31). You tell her that you will check laboratory tests to screen for other
conditions that could be causing her menstrual irregularities and excess hair growth.
Initial work up in a patient with oligomenorrhea/secondary amenorrhea without signs
of hyperandrogenism
Test
Indication
Urine or serum B-HCG
To exclude pregnancy
TSH
To exclude hypo or hyperthyroidism
Serum prolactin level
Prolactin > 250ng/ml virtually diagnostic of prolactin
secreting pituitary adenoma
Fasting morning 17hydroxyprogesterone



Levels > 800 ng/dL (8ng/ml) highly suspicious
for late-onset congenital adrenal hyperplasia
(CAH)
Levels between 200-800 ng/dL (2-8ng/ml)
unclear
Levels < 200 ng/dL (2ng/ml) usually no CAH
Additional tests indicated in a patient with signs of hyperandrogenism
Test
Indication
Total testosterone level



Serum DHEAS level



24 hour urine cortisol
orovernight dexamethasone
Slightly elevated in PCOS
Total testosterone > 200 ng/dL suspicious for
adrenal or ovarian tumor
Additional evaluation with pelvic US, CT or
MRI indicated
Slightly elevated in PCOS
DHEAS level > 8 ng/ml suspicious for
adrenal tumor
Additional evaluation should include adrenal
gland imaging with CT or MRI
Urine free cortisol >20 ug/d is suggestive of
Cushing’s Syndrome
The rapid development (< 6 months) of symptoms of androgen excess such as
menstrual irregularities, hirsutism, and weight gain are concerning for adrenal tumors,
ovarian tumors or Cushing’s syndrome.* Although these are rare diseases, they must
be screened for in women presenting with these symptoms.
Prevalence per million population
Adrenal tumors
2
Cushing’s Syndrome
2
Androgen secreting ovarian tumors less than 1
*Cushing’s Syndrome
This term refers to the manifestations of excessive corticosteroids due to any number
of underlying causes. Signs of corticosteroid excess include:
 Central obesity
 Violaceous abdominal striae
 Buffalo hump
 Moon facies
 Hypertension
PCOS and late onset CAH are distinguished from each other only by laboratory
testing.
Congenital Adrenal Hyperplasia (CAH)
 Late-onset CAH (or non-classical), an autosomal recessive disease, presents in
early adulthood with symptoms of oligomenorrhea and/or hirsutism.
 90% of CAH is due to 21-hydroxylase deficiency.
 Patients with 21-hydroxylase deficiency do not form cortisol in normal
amounts. The body recognizes the low levels of cortisol resulting in an
upregulation of ACTH in an attempt to stimulate the adrenal cortex. This
leads to adrenal stimulation and increased production of androgens.
 The diagnostic test for CAH is an elevated fasting level of 17hydroxyprogesterone. These levels are always greater than 200 ng/dL (6
nmol/L) in CAH. All abnormal tests should be confirmed with an ACTH
stimulation test.
Adrenal Gland Steroid Production Pathway
You check lab tests and she has normal levels of TSH, 17-hydroxyprogesterone,
prolactin, and DHEAS. She has a mildly elevated total testosterone level. You decide
she most likely has PCOS. You counsel her on the complications of PCOS.
Ovarian cancer
Women with PCOS are not at increased risk for developing ovarian cancer. They are
at increased risk for the following:
Endometrial hyperplasia
 Chronic anovulation, obesity and hyperinsulinemia are associated with
endometrial hyperplasia and endometrial cancer.
 This is likely due to prolonged exposure to unopposed estrogen.
 The risk of endometrial cancer in this population is hard to determine because
there are so few cases of endometrial cancer in women under 40 (<4% of all
cases) and few studies of endometrial cancer in women with PCOS. One
retrospective study of 1270 anovulatory women found the RR of endometrial
cancer to be 3.1 compared to the general population.
Dyslipidemias
 70% of women with PCOS will have abnormal lipid panels.
 Elevated triglycerides and LDL and low HDL are the most common
abnormalities.
Obesity
 60-80% of women with PCOS are obese.
 It is predominantly of the android type with increased hip to waist ratio (>0.8).
Impaired glucose tolerance and Type 2 diabetes
 Up to 40% of women with PCOS have impaired glucose tolerance (IGT) due to
decreased insulin mediated glucose uptake by skeletal muscle.
 Risk of IGT and type 2 Diabetes Mellitus (DM) is increased in both obese and
non-obese women with PCOS. Retrospective studies have shown two to five
fold increase of type 2 diabetes in women with PCOS.
 A Prospective study of 254 women with PCOS without known diabetes was
compared to a control group without PCOS or diabetes. In the PCOS group
(obese and non-obese), the overall prevalence of IGT and type 2 diabetes was
31.1% and 7.5%, respectively. In the control group, the prevalence of IGT and
type 2 diabetes was 14% and 0%, respectively.
She is very concerned about her hirsutism and wants to know what her treatment
options are.
All combination oral contraceptive pills (OCPs) are effective in treating hirsutism,
even those containing the more androgenic progestins (14). They decrease androgen
levels by suppressing LH and stimulating serum hormone binding globulin (SHBG).
OCPs with low androgenic progestins (norgestimate, desogestrel) may be the most
effective.
Treatment of Hirsutism
Mechanical
 Shaving or depilation
 Electrolysis
 Laser epilation
Combination Oral Contraceptive Pills
 OCPS with low androgenic progestins may be
the most effective
Androgen Receptor Blockers
 A full clinical effect may take 6 months or
more
 Spironolactone 25-100mg bid.
 Flutamide 250 mg once a day
 Finasteride 1 mg a day
Ornithine Decarboxylase Inhibitor (Vaniqa)
 A full clinical effect may take 6 months or
more
 13.9% cream BID
Weight loss, OCPs, metformin and cyclic progesterone are all treatment options for
oligomenorrhea/secondary amenorrhea and for preventing the development of
endometrial hyperplasia.
Treatment of Oligomenorrhea/Secondary Amenorrhea and Prevention of Endometrial
Hyperplasia
Weight Loss
 Decreases serum androgen, insulin, and LH levels
 Cyclic menstruation has been reported with weight loss as little as 5% of initial
weight
Oral Contraceptive Pill
 Regulates menstrual cycles
 Associated with a > 50% reduction in endometrial cancer risk in general
population , but magnitude of risk reduction in women with PCOS not yet
known
 Use 30-35 mcg of ethinyl estradiol and progestin with little androgenic activity
(avoid norgestrel and levonorgestrel)
Cyclic Progesterone
 Type of progestin, dose, and frequency to prevent endometrial cancer in
women with PCOS is not known.
 Oral medroxyprogesterone 10mg daily for ten days either monthly or every
three months
Metformin
 500mg bid-tid
 Restores menstrual cyclicity in 68-95% of patients treated for as short of a
time as four to six months
NOTE. For oligo/amenorrheic women who do not want to use medications on a regular
basis, a transvaginal ultrasound every 6-12 months should be obtained. Women who
are found to have an endometrial thickness of > 10mm should undergo an artificially
induced bleed. If the endometrium is still thickened on follow-up ultrasound, an
endometrial biopsy is recommended.