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Androstenedione
(Δ4-Androstenedione - Adrenal & Gonadal Steroid Precursor)
Synonyms
- Androstenedione
- Δ4-Androstenedione
- ASD
- Androst-4-ene-3,17-dione
- Steroid precursor of testosterone & estrone
Units of Measurement
nmol/L, ng/mL, ng/dL, ng/100mL, ng%, ng/L, µg/L
(Most common: ng/dL or nmol/L via LC-MS/MS.)
Description
Androstenedione is an adrenal and gonadal steroid hormone that serves as a precursor to:
- Testosterone
- Estrone
- Estradiol
It is produced by:
- Adrenal zona reticularis
- Ovaries (theca cells)
- Testes (Leydig cells)
Androstenedione measurement is essential in evaluating:
- Polycystic ovary syndrome (PCOS)
- Congenital adrenal hyperplasia (CAH)
- Adrenal tumors
- Androgen-secreting ovarian tumors
- Hyperandrogenism in females
- Early puberty or virilization
Physiological Role
- Precursor of testosterone and estrogens
- Produced mainly under control of ACTH
- Reflects adrenal androgen production
- In ovaries: produced by LH-stimulated theca cells
- Mild diurnal variation (morning higher)
Clinical Significance
Elevated Androstenedione
Seen in:
1. Polycystic Ovary Syndrome (PCOS)
- Mild to moderate elevation
- Reflects increased ovarian theca activity
2. Congenital Adrenal Hyperplasia (CAH)
Especially:
- 21-hydroxylase deficiency (most common)
- 11β-hydroxylase deficiency
- 3β-HSD deficiency
Levels may be markedly elevated.
3. Adrenal Tumors
- Adrenocortical carcinoma
- Adrenal adenomas
- Very high levels (>1000–2000 ng/dL)
4. Ovarian Tumors
- Sertoli-Leydig tumors
- Granulosa-theca cell tumors
5. Premature Adrenarche
- Early rise in adrenal androgens in children
6. Severe Insulin Resistance
- Hyperinsulinemia stimulates ovarian theca production
Low Androstenedione
Seen in:
- Primary adrenal insufficiency (Addison disease)
- Hypopituitarism (low ACTH)
- Certain enzyme defects (17α-OH deficiency)
- Androgen-suppressing medications
Low levels have limited clinical significance compared to elevated levels.
Reference Intervals
(Based on Tietz 8E + ESAP 2024 + Mayo Clinic LC-MS/MS)
Values vary by age, sex, and Tanner stage.
Adult Females
- 0.7 – 3.1 ng/mL
- 70 – 310 ng/dL
- 2.4 – 11 nmol/L
Adult Males
- 0.6 – 3.1 ng/mL
- 60 – 310 ng/dL
- 2.1 – 11 nmol/L
Postmenopausal Women
- 0.3 – 1.4 ng/mL
Children
- Very age-dependent
- Rises during adrenarche (age 6–8 years)
In PCOS
- Often 1.5–2× upper limit
- Higher values suggest CAH or tumor
Unit Meanings
| Unit | Meaning |
| nmol/L | nanomole per liter |
| ng/mL | nanogram per milliliter |
| ng/dL | nanogram per deciliter |
| ng/100mL | same as ng% |
| ng% | nanogram per 100 mL |
| ng/L | nanogram per liter |
| µg/L | microgram per liter (= ng/mL × 1000) |
Diagnostic Uses
1. PCOS Evaluation
- Supports diagnosis in hyperandrogenic women
- Combined with testosterone & DHEAS
2. CAH Diagnosis & Monitoring
- Androstenedione increases when 21-OH/11β-OH pathways are blocked
3. Adrenal or Ovarian Tumors
- Markedly high androstenedione → tumor work-up needed
4. Hirsutism & Virilization Work-Up
Useful with:
- Testosterone
- DHEA-S
- 17-OHP
- LH/FSH
5. Early Puberty (Adrenarche)
Differentiates:
- Central puberty
- Peripheral androgen excess
Analytical Notes
- Best measured by LC–MS/MS for accuracy
- Immunoassays may overestimate at low levels
- Morning sampling preferred
- Avoid biotin supplements for 12–24 hours before testing
- Hemolysis has minimal effect
Clinical Pearls
- In PCOS: androstenedione may be more sensitive than testosterone.
- Very high levels (>300–500 ng/dL) → think CAH or tumor, not PCOS.
- DHEAS disproportionately high → adrenal source;
Androstenedione + testosterone high → ovarian source. - In CAH monitoring: androstenedione & 17-OHP used together.
- Postmenopausal women normally have very low values—mild rise can be significant.
Interesting Fact
Before testosterone assays were perfected, androstenedione was often used as an early biomarker of androgen excess due to its more stable serum concentration.
References
- Tietz Clinical Chemistry and Molecular Diagnostics, 8th Edition - Steroid Hormone Section.
- ESAP 2024 - Endocrine Reference Ranges.
- Mayo Clinic Laboratories - Androstenedione (LC-MS/MS).
- ARUP Consult - Hyperandrogenism & CAH Testing.
- Endocrine Society PCOS Guidelines.
- NIH / MedlinePlus - Androstenedione Overview.
- IFCC Steroid Measurement Standards.