How does polycystic ovary syndrome (PCOS) cause anovulation?

How Polycystic Ovary Syndrome Causes Anovulation

PCOS causes anovulation through a cascade of hormonal disruptions: accelerated GnRH pulsatility drives excessive LH secretion, which stimulates ovarian theca cells to overproduce androgens, while simultaneously the FSH-granulosa cell axis becomes dysfunctional, resulting in follicular arrest before ovulation can occur. 1

The Core Pathophysiologic Mechanism

The fundamental problem in PCOS is inappropriate gonadotropin secretion combined with insulin resistance and hyperinsulinemia, which together create a self-perpetuating cycle of ovarian dysfunction 1, 2, 3. This is not simply a matter of "hormonal imbalance"—it represents specific, identifiable disruptions at multiple levels of the reproductive axis.

The Hypothalamic-Pituitary Dysfunction

• Accelerated pulsatile GnRH secretion is the upstream driver, causing the pituitary to release LH in excessive amounts and at abnormal frequencies 1
• The LH/FSH ratio becomes elevated (typically >2), which is diagnostically significant and mechanistically critical 1
• LH hypersecretion directly stimulates ovarian theca stromal cells to produce excessive androgens, particularly testosterone 1, 4
• Meanwhile, FSH levels remain relatively low or normal, creating hypofunction of the FSH-granulosa cell axis 1

The Ovarian-Level Consequences

• Theca stromal cell hyperactivity produces excessive androgens (testosterone, androstenedione) in response to elevated LH 1
• Granulosa cells fail to mature properly due to inadequate FSH stimulation and the toxic effects of excess androgens 1
• Follicles arrest at 2-8mm diameter rather than progressing to dominant follicle selection—this creates the characteristic "polycystic" appearance on ultrasound with >10 peripheral cysts 1
• No dominant follicle emerges, so ovulation cannot occur, resulting in chronic anovulation 1, 5

The Metabolic Component: Insulin's Critical Role

Insulin resistance and hyperinsulinemia are not just associated findings—they are active drivers of anovulation in PCOS 1, 2, 3. This is why metabolic interventions can restore ovulation even without directly targeting the ovaries.

How Insulin Drives Anovulation

• Hyperinsulinemia directly stimulates ovarian androgen production by theca cells, independent of LH 2, 3, 6
• Insulin suppresses hepatic production of sex hormone-binding globulin (SHBG), increasing free (biologically active) testosterone levels 1, 6
• Insulin resistance creates downstream metabolic dysregulation that perpetuates the entire hormonal cascade 1, 2
• This explains why weight loss and insulin-sensitizing agents (metformin) can restore ovulation by breaking this cycle 1, 7, 6

Confirming Anovulation in PCOS

Low mid-luteal phase progesterone (<6 nmol/L) is the laboratory confirmation of anovulation 1. This is measured 7 days before expected menses (typically cycle day 21 in a 28-day cycle, but adjusted based on cycle length).

Additional Diagnostic Markers

• Elevated LH (>11 IU/L) and LH/FSH ratio >2 measured on cycle days 3-6 1
• Elevated testosterone (>2.5 nmol/L) on cycle days 3-6 1
• Ultrasound showing >10 peripheral follicles 2-8mm in diameter in one plane, with thickened ovarian stroma 1

Critical Diagnostic Pitfall: PCOS vs. Functional Hypothalamic Amenorrhea

Up to 48% of women with functional hypothalamic amenorrhea (FHA) also have polycystic ovarian morphology on ultrasound, creating significant diagnostic confusion 1. This matters because the treatments are completely different.

How to Distinguish FHA-PCOM from True PCOS

• History is paramount: FHA is triggered by excessive exercise, significant weight loss, or psychological stress 1, 8
• Hormonal patterns differ: FHA shows low LH (<7 IU/mL), low estradiol, low androgens, and elevated SHBG, whereas PCOS shows the opposite pattern 1
• Metabolic profiles diverge: FHA patients typically have normal insulin sensitivity and low insulin levels, while PCOS patients have insulin resistance even when lean 1, 8
• Progestin challenge test: Negative in FHA (no withdrawal bleed), though up to 60% of FHA patients may still bleed, limiting reliability 1

The Bottom Line on Mechanism

PCOS-induced anovulation results from follicular arrest, not follicular absence. The ovaries contain multiple small follicles that begin development but cannot complete maturation due to the toxic combination of excessive LH, inadequate FSH, hyperandrogenism, and hyperinsulinemia 1, 5. This is why treatments that normalize these hormonal abnormalities—whether through weight loss, insulin sensitizers, ovarian drilling, or exogenous FSH—can successfully restore ovulation 1, 7, 6.

The genetic predisposition interacts with environmental triggers (particularly weight gain) to manifest the full syndrome 2, 5. Certain medications, notably valproate, can also trigger or exacerbate PCOS 2. Understanding this multifactorial pathogenesis explains why treatment must address both the hormonal and metabolic components to achieve optimal outcomes 3, 6.