PCOS Flashcards
Describe the ovarian wedge resection procedures.
- surgical removal of ½ to ¾ of each ovary (bilateral ovarian wedge resection)
- many patients resumed regular menses and became pregnant s/p surgery
What type of cysts are characteristic of PCOS?
Follicular cysts
*growth arrested at antral stage
Describe the pathophysiology of PCOS
- 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”
Follicle dynamics at birth
- 2,000,000 primordial follicles
- random development to 1o follicles
- in absence of FSH, apoptosis, and resorption
Follicle dynamics at puberty
- 200,000 primordial follicles
- increased GnRH pulses
- increased FSH
- follicle development → ovulation
- remaining follicles undergo apoptosis
Outline follicle growth
- initial phase: gonadotropin-independent
- recruitment and maturation:FSH dependent
- FSH induces estradiol production and LH receptors
Appearance of ovaries in PCOS
“String of pearl” appearance
What factors contribute to anovulation in PCOS?
- 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
What is the NIH major criteria for PCOS?
- Chronic anovulation (oligo- or amenorrhea)
- Clinical and/or biochemical evidence of hyperandrogenism
- Exclusion of other causes of anovulation and hyperandrogenism
What is the 2003 Rotterdam ESHRE/ASRM Consensus on PCOS?
** 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)
Why is there controversy in PCOS diagnosis?
high prevalence (up to 68%) of PCOM in normal young women
What is the Androgen Excess and PCOS Society consensus on PCOS?
- all 3 required:
1. Hyperandrogenism (clinical and/or biochemical)
2. Ovarian dysfunction (oligo-anovulation and/or polycystic ovaries)
3. Exclusion of related disorders
So, what is PCOS??
- A heterogeneous disorder of unclear etiology
- An important cause of menstrual irregularity and androgen excess in women
Describe “classic” PCOS when fully expressed.
manifestations include:
- Ovulatory dysfunction
- Androgen excess
- Polycystic Ovaries
- Obesity
Diagnostic tests for PCOS
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***
What is the most common cause of secondary amenorrhea?
Pregnancy**
What are the exclusion diagnostic tests?
- 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
PCOS prevalence
- 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
Which populations get PCOS
- 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
List the risk factors for PCOS in adolescents
- Low birth weight: < or = 2500 g
- Premature pubarche: Onset before 8yo
- Family history (1st degree relative)
- Obesity
What is the underlying problem in PCOS?
- HYPERANDROGENISM**
- Hypothalamic-pituitary-ovarian (HPO) axis disturbance
- Insulin resistance and hyperinsulinemia
**primary
In PCOS, which organ primarily produces the excess androgen?
Ovaries
Explain the hyperandrogenism pathophysiology in PCOS
- 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
Explain the HPO axis pathophysiology in PCOS
- LH and FSH secretion abnormalities
- Decreased FSH release
- Increased LH release
- Increased LH pulse frequency and amplitude
- Increased LH:FSH ratio
Elevated LH level and pulse frequency may be due to…
Lack of progesterone (anovulation): ↑LH
Feedback effect of androgens: ↓FSH
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
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
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
What is the relationship between insulin resistance and hyperandrogenism?
- Insulin resistance is believed to be a secondary defect
- Hyperandrogenism comes first
*controversial
PCOS and metabolic syndrome (MBS)
-relationship
Associated with significant risk for early cardiovascular disease
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
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
What symptoms are you treating in PCOS?
- Infertility
- Skin manifestations, hirsutism
- Dysfunctional uterine bleeding, endometrial cancer prevention
- Obesity, diabetes prevention (lifestyle changes)
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
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
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
Skin manifestations, hirsutism treatment
- Oral contraceptives
- Anti-androgens
List the anti-androgens for hirsutism/skin manifestations
- Spironolactone
- Flutamide
- Finasteride
- GnRH agonists
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
Oral contraceptives action
- Increases SHBG
- Decreases bio-available androgen
- Restores regular menstrual cycles
- Decreases hirsutism, acne
- Provides effective contraception
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
PCOS and anti-androgens
-Flutamide
non-steroidal antagonist acting at nuclear receptor
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
PCOS and anti-androgens
-Cyproterone acetate
anti-androgenic progestogen, combined with ethinyl estradiol
*not available in U.S.
PCOS Symptom-dependent tx
-dysfunctional uterine bleeding
- Endometrial biopsy
- Oral contraceptives or cyclic progestins
PCOS Symptom-dependent tx
-obesity
- Lifestyle management
- Diet and exercise
- Metformin
Which of the following has been shown to be the MOST effective in prevention of diabetes in PCOS?
Diet and exercise
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
Effects of lifestyle intervention and weight loss
- decrease testosterone
- decrease insulin levels
- increase SHBG
Initial evaluation in PCOS
- H&P
- Total T, TSH, prolactin (could also consider: DHEA-S, 17-hydroxyprogesterone, LH, FSH)
- Pelvic ultrasound
PCOS periodic screening once diagnosis is established
-2 hour oral glucose tolerance test
-Lipid profile
-Blood pressure
+/- Endometrial biopsy
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
Which of the following is considered the primary pathophysiologic defect in PCOS?
Hyperandrogenemia
PCOS: CONCLUSIONS
-pathophysiology
Primary defect: Ovarian hyperandrogenism
Secondary defects:
- HPO axis disturbance
- Insulin resistance
