PCOS Flashcards
1
Q
Describe the ovarian wedge resection procedures.
A
- surgical removal of ½ to ¾ of each ovary (bilateral ovarian wedge resection)
- many patients resumed regular menses and became pregnant s/p surgery
2
Q
What type of cysts are characteristic of PCOS?
A
Follicular cysts
*growth arrested at antral stage
3
Q
Describe the pathophysiology of PCOS
A
- the cysts of PCOS are actually follicles
- the follicles are arrested in development accumulate in the ovary
“PCOS women do not throw away their old follicles”
4
Q
Follicle dynamics at birth
A
- 2,000,000 primordial follicles
- random development to 1o follicles
- in absence of FSH, apoptosis, and resorption
5
Q
Follicle dynamics at puberty
A
- 200,000 primordial follicles
- increased GnRH pulses
- increased FSH
- follicle development → ovulation
- remaining follicles undergo apoptosis
6
Q
Outline follicle growth
A
- initial phase: gonadotropin-independent
- recruitment and maturation:FSH dependent
- FSH induces estradiol production and LH receptors
7
Q
Appearance of ovaries in PCOS
A
“String of pearl” appearance
8
Q
What factors contribute to anovulation in PCOS?
A
- elevated testosterone suppresses FSH
- FSH levels do not reach the level required to induce follicle maturity
- follicle arrest, anovulation
- absence of progesterone leads to elevated LH
9
Q
What is the NIH major criteria for PCOS?
A
- Chronic anovulation (oligo- or amenorrhea)
- Clinical and/or biochemical evidence of hyperandrogenism
- Exclusion of other causes of anovulation and hyperandrogenism
10
Q
What is the 2003 Rotterdam ESHRE/ASRM Consensus on PCOS?
A
** 2 of 3 required:
1. Chronic anovulation (Oligo- or anovulation)
2. Clinical and/or biochemical signs of hyperandrogenism (Unchanged)
3. Exclusion of other disorders (Unchanged)
4. Polycystic ovaries (minor criterion) –> Major
> or = 12 follicles measuring 2-9 mm, and/or
> 10 ml ovarian volume (0.5 x length x width x thickness)
11
Q
Why is there controversy in PCOS diagnosis?
A
high prevalence (up to 68%) of PCOM in normal young women
12
Q
What is the Androgen Excess and PCOS Society consensus on PCOS?
A
- all 3 required:
1. Hyperandrogenism (clinical and/or biochemical)
2. Ovarian dysfunction (oligo-anovulation and/or polycystic ovaries)
3. Exclusion of related disorders
13
Q
So, what is PCOS??
A
- A heterogeneous disorder of unclear etiology
- An important cause of menstrual irregularity and androgen excess in women
14
Q
Describe “classic” PCOS when fully expressed.
A
manifestations include:
- Ovulatory dysfunction
- Androgen excess
- Polycystic Ovaries
- Obesity
15
Q
Diagnostic tests for PCOS
A
1. Anovulation: Menstrual history (< 9 menses/year or > 3 consecutive months without menses) 2. Hyperandrogenism: -Physical exam: Hirsutism (note hair removal methods), acne -Serum androgen levels: Testosterone (T), Free T, DHEA-S 3, Pelvic Ultrasound 4. DIAGNOSIS OF EXCLUSION***
16
Q
What is the most common cause of secondary amenorrhea?
A
Pregnancy**
17
Q
What are the exclusion diagnostic tests?
A
- Pregnancy: Serum HCG!!!!
- Congenital Adrenal Hyperplasia: 17-OH progesterone(in high-risk populations)
- Hyperprolactinemia: Prolactin
- Thyroid abnormalities: TSH
- Androgen secreting tumor: DHEAS, Testosterone (suspected if T > 200 ng/dL or DHEAS > 700 mcg/dL)
- Cushing’s syndrome: 24 hour urinary cortisol
18
Q
PCOS prevalence
A
- Affects 6-8% of reproductive age women
- MCC of female infertility in the United States
- Onset is likely pre-pubertal but difficult to detect until late adolescence
19
Q
Which populations get PCOS
A
- Multifactorial origin
- Genetic predisposition (behaves like autosomal dominant trait)
- Phenotypic expression determined by environmental factors that begin in utero (high AMH in mom might predispose female fetus to have PCOS in adulthood)
- Factors that influence insulin secretion affect the phenotype
20
Q
List the risk factors for PCOS in adolescents
A
- Low birth weight: < or = 2500 g
- Premature pubarche: Onset before 8yo
- Family history (1st degree relative)
- Obesity
21
Q
What is the underlying problem in PCOS?
A
- HYPERANDROGENISM**
- Hypothalamic-pituitary-ovarian (HPO) axis disturbance
- Insulin resistance and hyperinsulinemia
**primary
22
Q
In PCOS, which organ primarily produces the excess androgen?
A
Ovaries
23
Q
Explain the hyperandrogenism pathophysiology in PCOS
A
- Excess androgen production comes from the ovary
- Increased thecal cell volume
- Increased expression of LH receptors on theca cells
- Exaggerated androgen production occurs when LH binds to receptors on the theca cells of the ovary
24
Q
Explain the HPO axis pathophysiology in PCOS
A
- LH and FSH secretion abnormalities
- Decreased FSH release
- Increased LH release
- Increased LH pulse frequency and amplitude
- Increased LH:FSH ratio
25
Elevated LH level and pulse frequency may be due to...
Lack of progesterone (anovulation): ↑LH
Feedback effect of androgens: ↓FSH
26
What is the relationship between HPO and hyperandrogenism?
- Disruption of hypothalamic-pituitary-ovarian axis (HPO) is believed to be a secondary defect
- Hyperandrogenism (and anovulation) comes first
27
Explain the insulin sensitivity (specifically hyperinsulinemia) pathophysiology in PCOS
* Insulin resistance is a feature of PCOS in obese and non-obese women
- Activation of insulin receptor (IGF) in the ovary: augmented thecal androgen response to LH
- Suppression of hepatic SHBG production: increased free androgen proportion
- Direct stimulation of LH secretion by insulin
- Sensitization of LH secreting cells to GnRH
28
Relationship between insulin resistance and PCOS
- IR itself is not enough to cause PCOS (Only about 25% of reproductive-aged women with type 2 diabetes have PCOS)
- Screening for IR is indicated in patients with PCOS
29
What is the relationship between insulin resistance and hyperandrogenism?
- Insulin resistance is believed to be a secondary defect
- Hyperandrogenism comes first
*controversial
30
PCOS and metabolic syndrome (MBS)
| -relationship
Associated with significant risk for early cardiovascular disease
31
PCOS and metabolic syndrome
| -criteria for diagnosis
* must have 3 of 5:
- Abdominal obesity > 88 cm
- Triglycerides > 150 mg/dl
- HDL-C < 50 mg/dl
- BP > 130/>85 mmHg
- OGTT: 110-126 mg/dl and/or 140-199 mg/dl
32
In PCOS patient, what are the screenings for long term health consequences?
- 2 hour oral glucose tolerance test or Hemoglobin A1C (75gm glucose load – serum drawn before drinking it // blood drawn at 1 hr and 2 hr)
- Lipid profile
- Blood pressure
- Endometrial biopsy (d/t increased risk for endometrial cancer)
- Waist circumference
33
What symptoms are you treating in PCOS?
- Infertility
- Skin manifestations, hirsutism
- Dysfunctional uterine bleeding, endometrial cancer prevention
- Obesity, diabetes prevention (lifestyle changes)
34
Infertility treatment
| -ovulation induction
- Weight loss (don’t have to be “normal” BMI to start ovulating again)
- Clomiphene citrate (approx. 50-80% ovulate with clomid alone)
- Aromatase inhibitors (first line, but off label)
- Injectable gonadotropins
- Laparoscopic ovarian drilling
- Insulin-lowering medications - Metformin
35
Insulin sensitizers
| -metform action
*Oral biguanide anti-hyperglycemic approved for NIDDM (Glucophage)
- Decreases hepatic gluconeogenesis
- Increases peripheral glucose uptake (muscle, adipose tissue)
- Increases insulin sensitivity at the post-receptor level
36
Insulin sensitizers in women with PCOS
- Improves menstrual cyclicity, restores spontaneous ovulation (up to 30% ovulate with metformin alone)
- Improves symptoms of hyperandrogenism
- May improve body composition (BMI, WHR) and lipid profile
37
Skin manifestations, hirsutism treatment
- Oral contraceptives
| - Anti-androgens
38
List the anti-androgens for hirsutism/skin manifestations
- Spironolactone
- Flutamide
- Finasteride
- GnRH agonists
39
Oral contraceptives in PCOS
- Currently considered first line therapy for those not currently desiring fertility
- Use low dose estrogen (20-30 mcg ethinyl estradiol) and non-androgenic progestin (e.g. desogestrel or drospirenone)
- Decreases risk of endometrial cancer
40
Oral contraceptives action
- Increases SHBG
- Decreases bio-available androgen
- Restores regular menstrual cycles
- Decreases hirsutism, acne
- Provides effective contraception
41
PCOS and anti-androgens
- Effectively reduces biochemical and clinical hyperandrogenism
- May be more effective in treating hirsutism than metformin
- Improves menstrual cyclicity
- No improvement in metabolic abnormalities
42
PCOS and anti-androgens
| -Flutamide
non-steroidal antagonist acting at nuclear receptor
43
PCOS and anti-androgens
| -Spironolactone
- K+-sparing diuretic with anti-androgen effect
- MC choice in U.S.
- 50-100 mg/day have been reported to be effective
44
PCOS and anti-androgens
| -Cyproterone acetate
anti-androgenic progestogen, combined with ethinyl estradiol
| *not available in U.S.
45
PCOS Symptom-dependent tx
| -dysfunctional uterine bleeding
- Endometrial biopsy
| - Oral contraceptives or cyclic progestins
46
PCOS Symptom-dependent tx
| -obesity
- Lifestyle management
- Diet and exercise
- Metformin
47
Which of the following has been shown to be the MOST effective in prevention of diabetes in PCOS?
Diet and exercise
48
Lifestyle intervention and weight loss in PCOS
- Shown to effectively prevent diabetes in high risk groups*
- Importance is emphasized, but difficult to achieve
- Current recommendation is combination of lifestyle modification with pharmacologic therapy
49
Effects of lifestyle intervention and weight loss
- decrease testosterone
- decrease insulin levels
- increase SHBG
50
Initial evaluation in PCOS
- H&P
- Total T, TSH, prolactin (could also consider: DHEA-S, 17-hydroxyprogesterone, LH, FSH)
- Pelvic ultrasound
51
PCOS periodic screening once diagnosis is established
-2 hour oral glucose tolerance test
-Lipid profile
-Blood pressure
+/- Endometrial biopsy
52
Treatment in PCOS
| -symptom dependent
- Encourage healthy diet and exercise
- Possibly do better with Low Carb diet
- Ovulation induction with clomid if pregnancy is desired
- Low-dose (20 mcg) OCPs if pregnancy is not desired
- Obese and IR patients: Metformin
- Marked hirsutism refractory to OCPs: Consider spironolactone
*lifelong therapy may be needed
53
Which of the following is considered the primary pathophysiologic defect in PCOS?
Hyperandrogenemia
54
PCOS: CONCLUSIONS
| -pathophysiology
Primary defect: Ovarian hyperandrogenism
Secondary defects:
- HPO axis disturbance
- Insulin resistance
