How Aromatase Fuels Endometrial Risk in PCOS
Polycystic ovary syndrome (PCOS) affects up to 15% of women worldwide, causing hormonal chaos that impacts fertility, metabolism, and even the endometrium—the lining of the uterus. While irregular periods and ovarian cysts dominate discussions, a silent danger often develops unseen: endometrial hyperplasia (EH), a precancerous thickening of the uterine lining. New research reveals a surprising culprit—an enzyme called aromatase—that transforms PCOS into a perfect storm for endometrial risk. This article explores how a biochemical aberration turns the uterus into an estrogen factory, and what it means for millions living with PCOS 1 5 7 .
Affects 8-15% of reproductive-age women worldwide, making it the most common endocrine disorder in this group.
PCOS women have 3-4 times higher risk of endometrial cancer compared to the general population.
In PCOS, chronic anovulation (lack of ovulation) leads to prolonged estrogen exposure without progesterone's balancing effect. This imbalance triggers excessive endometrial growth. Studies show PCOS women face a 30% prevalence of endometrial hyperplasia (EH) or cancer (EC)—far higher than the general population. Alarmingly, 6% of PCOS women in one study had undiagnosed endometrial cancer, often before age 40 5 8 .
Aromatase (P450 arom) is the only enzyme that converts androgens (like testosterone) into estrogens. While normally absent in healthy endometrium, it becomes abnormally active in PCOS and endometriosis. This creates a dangerous intracrine system—a self-sustaining estrogen production line within the uterine tissue itself 2 4 7 .
Aberrant aromatase kickstarts a pathological loop:
This feedback loop turns endometrium into an estrogen-synthesizing powerhouse, independent of ovarian hormones 4 7 .
| Diagnosis | Prevalence (%) | Key Risk Factors |
|---|---|---|
| Normal Endometrium | 70% | Younger age, higher testosterone |
| Non-Atypical EH | 9% | Obesity, anovulation |
| Atypical EH (EIN) | 15% | Age >30, diabetes |
| Endometrial Cancer | 6% | Age >32, low testosterone |
Data from a prospective study of 208 PCOS women 5
A landmark 2014 study investigated aromatase's role in PCOS-related endometrial hyperplasia using:
| Treatment | Estradiol (E₂) Level | Aromatase mRNA | Interpretation |
|---|---|---|---|
| Control (no add) | Baseline (100%) | Baseline (100%) | Normal basal activity |
| + Testosterone | 300–400% of baseline | 220% of baseline | Androgens fuel estrogen synthesis |
| + Letrozole | 20–40% of baseline | 40% of baseline | Aromatase inhibition effective |
Data from cell stimulation experiments 1
This experiment revealed that PCOS endometrium isn't just responding to hormones—it's manufacturing them. Aromatase transforms excess androgens (a PCOS hallmark) into estrogen, creating local "hot spots" of endometrial stimulation. This explains why hyperplasia persists even when systemic hormones are controlled 1 7 .
Quantifies aromatase (CYP19A1) gene expression. Revealed 3–5× ↑ mRNA in PCOS endometrium 1 .
Letrozole—a breast cancer drug—now shows promise for PCOS:
Aromatase isn't just an enzyme—it's the linchpin of a pathological process turning PCOS endometrium into a self-sustaining estrogen engine. Understanding this mechanism transforms how we approach endometrial risk: not as a passive consequence of ovarian dysfunction, but as an active, targetable disease process. Future therapies may combine aromatase inhibitors with inflammatory blockers and insulin sensitizers, moving beyond symptom management to disrupt the core biology of PCOS complications.
"The aberrant expression of aromatase in PCOS endometrium creates a 'perfect storm'—excess androgens become fuel for localized estrogen overproduction, driving hyperplasia. This makes aromatase a bullseye for intervention."