17-OH-Progesterone
17-hydroxyprogesterone — differential CAH vs PCOS
What it is
17-OH-progesterone (17-hydroxyprogesterone) is a steroid precursor produced by the adrenal glands and, to a lesser extent, the ovaries. It is a key intermediate in cortisol synthesis: the enzyme 21-hydroxylase converts 17-OH-progesterone into 11-deoxycortisol, an essential step on the way to cortisol production.
When 21-hydroxylase is deficient — the most common cause of congenital adrenal hyperplasia (CAH) — this conversion is impaired and 17-OH-progesterone accumulates. This is why its measurement is the reference test for screening CAH.
Why it matters in PCOS
Non-classic CAH (late-onset form, presenting after puberty) can almost perfectly mimic PCOS: menstrual irregularities, acne, hirsutism, anovulation, and even polycystic-appearing ovaries on ultrasound. The prevalence of non-classic CAH in the general population is approximately 1–2%, but rises to 2–5% among women with a clinical picture suggestive of PCOS and hyperandrogenism. Missing it leads to inappropriate treatment.
A normal 17-OH-progesterone (< 2 ng/mL) fasting in the early follicular phase effectively excludes CAH. A level between 2 and 10 ng/mL is intermediate and warrants an ACTH stimulation test (Synacthen test) to confirm or rule out CAH. A level > 10 ng/mL is strongly suggestive of classic CAH.
The classic form of CAH presents at birth (virilisation, sexual ambiguity, salt-wasting crisis). The non-classic form is the main clinical concern in the PCOS differential: it appears at puberty or in adulthood with signs of hyperandrogenism.
Normal values
- Normal fasting on days 2–4: < 2 ng/mL (< 6 nmol/L)
- Intermediate zone: 2–10 ng/mL → ACTH stimulation test indicated
- Non-classic CAH (post-ACTH): > 10 ng/mL
- Classic CAH: often > 10–100 ng/mL at baseline
17-OH-progesterone varies with cycle phase (higher in the luteal phase) and with time of day (circadian variation). Testing must therefore be performed fasting, in the morning, in the early follicular phase (days 2–4).
When is it measured?
17-OH-progesterone is included in the initial PCOS differential workup, particularly in people with marked hyperandrogenism. It must be drawn fasting in the morning on days 2–4 of the cycle. In amenorrhoea, any-time testing is acceptable but less reliable; waiting for a follicular window is preferable when possible.
Key takeaways
- Key marker to exclude non-classic CAH mimicking PCOS
- Normal < 2 ng/mL fasting on days 2–4 → CAH unlikely
- 2–10 ng/mL → ACTH stimulation test indicated
- Non-classic CAH: 2–5% of women with PCOS-like hyperandrogenism
- Must be drawn fasting, morning, early follicular phase