17-hydroxyprogesterone (17-OHP)

17-Hydroxyprogesterone (17-OH progesterone) is a crucial steroid hormone involved in the biosynthesis of glucocorticoids, androgens, and estrogens. It plays a particularly important role in adrenal function and reproductive health. Abnormal levels of 17-OH progesterone can indicate a variety of health issues, most notably Congenital Adrenal Hyperplasia (CAH).

What is 17-OH Progesterone?

Biochemical Overview

17-OH progesterone is an endogenous progestogen and an intermediate in the biosynthesis of cortisol and androgens. It is produced primarily in:

• The adrenal glands

• The gonads (ovaries and testes)

It serves as a precursor molecule that undergoes enzymatic conversion by 21-hydroxylase and 11β-hydroxylase enzymes in the adrenal cortex to produce cortisol and aldosterone.

Molecular Pathway

The synthesis pathway:
Cholesterol → Pregnenolone → Progesterone → 17-OH Progesterone → 11-Deoxycortisol → Cortisol
When there's a deficiency in enzymes (e.g., 21-hydroxylase), this pathway is disrupted, leading to the accumulation of 17-OH progesterone and diverted production toward androgens.

Clinical Importance of 17-OH Progesterone

Key Functions

• Precursor for cortisol, a vital stress hormone

• Involved in androgen production

• Affects sexual development and function

Role in Congenital Adrenal Hyperplasia (CAH)

The most critical clinical role of 17-OH progesterone is its elevation in CAH, a group of genetic disorders affecting adrenal steroid biosynthesis.

“Elevated 17-hydroxyprogesterone levels are a hallmark of 21-hydroxylase deficiency. Early detection through newborn screening can be life-saving.” — Dr. Mary Therese South, MD, Pediatric Endocrinologist, Mayo Clinic

17-OH Progesterone Blood Test

Why the Test is Ordered

A 17-OH progesterone blood test is primarily used to:

• Diagnose CAH in newborns and children

• Investigate hirsutism, infertility, or menstrual irregularities

• Evaluate adrenal tumours or hyperplasia

• Support hormonal investigations in reproductive or endocrine disorders

You can order a progesterone blood test here.

Normal Reference Ranges 

Sample Collection

• Timing: Best collected in the morning when hormone levels are highest.

• Fasting: Usually not required.

• Special Instructions: For women, testing should ideally occur during the follicular phase (day 3–5) of the menstrual cycle unless otherwise instructed.

Causes of Elevated 17-OH Progesterone

1. Congenital Adrenal Hyperplasia (CAH)

• Most common cause

• Autosomal recessive condition

• Enzyme: 21-hydroxylase deficiency in 95% of cases

• Leads to cortisol deficiency and androgen excess

2. Adrenal Tumours

• Rare adrenal adenomas or carcinomas may secrete excessive 17-OH progesterone

3. Polycystic Ovary Syndrome (PCOS)

• Mild elevations can be observed, but typically not as high as in CAH

“Differentiating PCOS from non-classic CAH is critical in women presenting with hyperandrogenic symptoms. A morning 17-OHP level >200 ng/dL warrants further evaluation with ACTH stimulation testing.” — Dr. Ricardo Azziz, Endocrinologist and PCOS expert

Causes of Low 17-OH Progesterone

Low levels are typically not concerning unless in the context of:

• Adrenal insufficiency (Addison’s disease)

• Hypopituitarism

• Over-suppression from steroid therapy

17-OH Progesterone and Female Health

Menstrual Irregularities

Excess androgens due to elevated 17-OHP can disrupt ovulation, causing irregular periods, amenorrhea, or infertility.

Hirsutism and Acne

Elevated 17-OHP leads to increased production of testosterone and DHEA, contributing to male-pattern hair growth and skin issues.

“In reproductive-aged women, symptoms like hirsutism and acne, especially when paired with irregular cycles, should prompt a hormonal workup including 17-OH progesterone.” — Dr. Andrea Dunaif, MD, Reproductive Endocrinologist

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17-OH Progesterone in Male Health

In men, elevated levels can indicate:

• CAH

• Testicular adrenal rest tumours (TARTs) in CAH patients

• Adrenal disorders
  It may also impact fertility due to hormonal imbalances.

ACTH Stimulation Test

When 17-OHP levels are borderline or mildly elevated, an ACTH stimulation test is used to confirm or rule out non-classic CAH.

Procedure:

• Baseline blood draw

• Administer synthetic ACTH (cosyntropin)

• Measure 17-OHP after 60 minutes

Interpretation:

• A stimulated level >1500 ng/dL strongly supports non-classic CAH

Treatment Options

For CAH

• Glucocorticoid replacement (e.g., hydrocortisone, prednisone)

• Mineralocorticoid replacement in salt-wasting forms

• Surgical treatment for severe virilisation

• Regular monitoring of 17-OHP to guide therapy

For PCOS or Mild Elevation

• Oral contraceptives

• Anti-androgens (e.g., spironolactone)

• Lifestyle and dietary interventions

Future of 17-OH Progesterone Testing

Advancements in genetic screening and LC-MS/MS (liquid chromatography-mass spectrometry) testing have improved accuracy.

“With better mass spectrometry-based assays, we can now distinguish between classic and non-classic CAH more reliably, even in borderline cases.” — Dr. William E. Rainey, Professor of Molecular & Integrative Physiology, University of Michigan

Summary

References

1. Speiser PW, White PC. "Congenital Adrenal Hyperplasia." N Engl J Med. 2003;349(8):776-788.

2. Azziz R. "The Evaluation and Management of Hirsutism." Obstet Gynecol. 2003;101(5 Pt 1):995-1007.

3. New MI. "An update on congenital adrenal hyperplasia." Curr Opin Endocrinol Diabetes Obes. 2012;19(3):166–170.

4. Trapp CM, Oberfield SE. "Diagnosis and management of congenital adrenal hyperplasia." Curr Opin Pediatr. 2012;24(4):527–533.