Hormonal & Metabolic Lab Values in PCOS

1. FSH (Follicle-Stimulating Hormone)

• Value: Normal or low-normal (typically 3-10 mIU/mL)
• FSH is not elevated in PCOS; elevated FSH (>30 mIU/mL) instead suggests ovarian failure
• Incipient ovarian failure is considered when basal FSH is ≥15 mIU/mL
• In PCOS, FSH may be at the lower end of normal, suppressed by the chronically elevated estrogen environment

2. LH (Luteinizing Hormone)

• Value: Elevated - the hallmark finding
• LH:FSH ratio >2:1 (classically >3:1, even up to 4:1) is the classic pattern
• LH levels are often elevated so the LH:FSH ratio is increased; however, some PCOS women may show LH levels within the normal follicular-phase range
• This elevated LH:FSH ratio is considered a minor (supportive) diagnostic criterion under Rotterdam 2003 criteria, not a major one

3. Prolactin

• Value: Normal in typical PCOS
• Prolactin is checked to exclude hyperprolactinemia as a cause of anovulation/oligomenorrhea
• Prolactin may be elevated in up to one-third of women with amenorrhea in general, but a truly elevated prolactin shifts the diagnosis away from PCOS
• If prolactin is minimally elevated, it should be repeated before further workup (it rises nonspecifically with stress, sleep, food)

4. Testosterone

• Value: Normal to mildly elevated (free testosterone is the more sensitive marker)
• Mildly elevated free testosterone is the key androgen finding in PCOS
• Total serum testosterone is typically 50-150 ng/dL in PCOS (mild-moderate elevation)
• Total testosterone >200 ng/dL should raise concern for an androgen-secreting ovarian or adrenal neoplasm - not typical PCOS
• DHEAS is also measured if an adrenal tumor is suspected (high DHEAS >700 mcg/dL suggests adrenal source)
• 17-hydroxyprogesterone (17-OHP) should be checked to rule out congenital adrenal hyperplasia (CAH)
• SHBG is decreased (hyperinsulinemia inhibits hepatic SHBG synthesis), which increases the bioavailable free testosterone fraction

5. Fasting Insulin

• Value: Elevated (hyperinsulinemia) - a key pathophysiologic feature
• Normal fasting insulin: <20-24 μIU/mL
• In HAIR-AN syndrome variant: fasting insulin often >25 μIU/mL
• Fasting glucose-to-insulin ratio <4.5 indicates insulin resistance (IR)
• 10% of non-obese and 40-50% of obese PCOS women have impaired glucose tolerance (2-hr glucose ≥140 mg/dL) on oral GTT
• 30-45% of obese PCOS women have glucose intolerance or frank type 2 DM
• Hyperinsulinemia is uniquely associated with PCOS (not with hyperandrogenism in general) and acts synergistically with LH to stimulate ovarian theca cell androgen production

• 2-hour post-75g OGTT for BMI >30 or lean PCOS women ≥40 years, with gestational DM history, or family history of T2DM
• HbA1c alone misses impaired glucose tolerance

6. Lipid Profile

• Dyslipidemia present in up to 70% of US PCOS patients
• The typical dyslipidemia pattern:

• LDL particle quality is altered (smaller, denser LDL particles - more atherogenic)
• Dyslipidemia is driven by IR and hyperandrogenism in combination with diet/exercise/genetics

Summary Table

Why is LH Raised in PCOS?

Step 1 - Normal GnRH Pulse Physiology (Baseline)

• Fast GnRH pulse frequency → favors LH synthesis and secretion
• Slow GnRH pulse frequency → favors FSH synthesis and secretion
• Progesterone normally slows GnRH pulse frequency, keeping LH in check
• Inhibin B from the ovary specifically suppresses FSH at the pituitary

Step 2 - The Core Defect in PCOS: Loss of Progesterone Feedback

• Without progesterone → GnRH pulses accelerate (frequency increases)
• Faster GnRH pulses → pituitary preferentially secretes LH over FSH
• Result: LH rises, FSH stays low or normal → elevated LH:FSH ratio

Step 3 - Chronically Elevated Estrone Contributes

• Normal cyclical estradiol swings provide negative feedback on LH - this feedback is disrupted in PCOS
• The tonic low-level estrogen instead provides a small positive signal to the pituitary, keeping LH secretion active
• Estrogen at the pituitary enhances GnRH receptor sensitivity, making gonadotropes more responsive to each GnRH pulse

Step 4 - Insulin and Hyperinsulinemia Amplify LH Action

• Insulin directly amplifies theca cell androgen production in response to LH
• This produces more androgens → more peripheral estrone → maintains the tonic estrogen signal → sustains the dysregulated LH secretion
• The cycle becomes self-perpetuating

Step 5 - Why FSH Stays Low (While LH Goes Up)

The Vicious Cycle - Summary Diagram

No ovulation → No corpus luteum → No progesterone
        ↓
GnRH pulse frequency increases
        ↓
LH preferentially elevated over FSH
        ↓
LH drives ovarian theca cells → Excess androgens
        ↓
Insulin amplifies theca cell response → More androgens
        ↓
Androgens → peripheral conversion to estrone (tonic estrogen)
        ↓
Tonic estrogen + absent progesterone → no negative feedback
        ↓
GnRH pulses remain fast → LH stays elevated ← (cycle continues)

Key Points to Remember