Androstenedione, DHEA, and DHEA-S

Sample

1. This may be done on 24 hours urine sample.
2. Venous blood is needed to prepare the serum.
   1. Keep the serum on ice or in a cool place and perform the test within one hour.
   2. The serum sample can be stored at 4 °C for 2 days or months at -20 °C.
3. Collect the sample from females at least one week before or after the menstrual cycle.
   • Take 3 to 5 ml of blood in the disposable syringe. Keep the syringe for 15 to 30 minutes and then centrifuge for 2 to 4 minutes. This will give a clear serum.

Purpose (Indications) of the test for androgens

1. This test is done to evaluate virilizing syndrome:
   1. Excessive hair growth.
   2. Irregular period.
   3. Infertility.
2. This test can evaluate the adrenal glands’ function.
3. This test is done to assess delayed puberty.
4. D/D of Cushing syndrome (DHEA-S).

Pathophysiology of Adrenal Androgens

1. The most important androgens are:
   1. Dehydroepiandrosteronene (DHEA).
   2. Dehydroepiandrosterone-sulphate (DHEA-SO4). It is a metabolite of DHEA.
      1. Its daily production in young men is 30 mg/day and 20 mg/day in young women.
      2. Its half-life is 8 to 11 hours.
      3. It is 30 to 60 minutes for unconjugated androgens.
      4. DHEA and DHEA-S levels fall during illness, depression, and other stresses.
   3. Testosterone.
2. Adrenal androgens reach their peak between 20 to 30 years of age and then gradually fall.
3. Androstenedione and DHEA are androgenic steroids produced by the adrenal cortex, ovaries, and testes.
4. These are metabolically converted into testosterone and other androgens. 
5. Adrenal androgens are produced from the Zona fasciculta and Zona reticularis from pregnenolone and 17-OH pregnenolone.

6. These hormones are converted into a relatively high level of testosterone by the peripheral tissue.
7. In the female, androstenedione from peripheral tissues and ovaries is converted into testosterone and estrogen.

6. DHEA and DHEA-S are a precursor of testosterone and estrogen produced by the gonads and adrenal glands.
7. DHEA-S is produced at 8 to 16 mg/day, which is more than 90% of the plasma circulation.
8. Androstenedione is elevated and gives rise to hirsutism and virilization.

9. ACTH stimulates adrenal glands’ secretion from adrenal glands.

Adrenal androgens:

1. It changes with age. It starts around 9 years of age, just before puberty onset.
2. Paek level is around the third decade.
3. ACTH controls the adrenal gland secretions. ACTH partially regulates the adrenal cortex secretion in adults.
   1. DHEA and androstenedione are secreted along with cortisol.
   2. Glucocorticoid therapy suppresses the secretion of adrenal androgens.
   3. The adrenal cortex average secretion is:
      1. DHEA = 4 mg/day.
      2. DHEA-S = 10 mg/day.
         1. Half-life is 8 to 11 hours.
      3. Testosterone = 0.05 mg/day.
      4. Androstenedione = 1.5 mg/day.

Androgens in female:

1. The mean androgen production rate in women is:
   1. Testosterone = 0.25 mg/day.
   2. Androstenedione = 3.4 mg/day (during menstrual period).
   3. 1.6 mg/day during the menopausal period.
   4. DHT (Dihydrotestosterone) = 0.056 mg/day
2. In Female testosterone:
   1. 50 to 60% is made from peripheral tissues.
   2. 30% is produced by adrenal glands.
   3. 20% is produced from the ovary.

Androgens in males:

1. Testosterone is the main androgen in males and leads to:
   1. Masculinization of the male genital tract.
   2. Maturation of male secondary sex characteristics.
   3. Increase muscle bulk, and bone mass.
   4. Increase Libido.
   5. Increase sexual performance in the male.
   6. The main androgen production rate in male is:
      1. Testosterone = 7 mg/day.
      2. Androstenedione = 1.4 mg/day.
      3. DHT (Dihydrotestosterone) = 0.3 mg/day.

14. Raised level of androstenedione leads to:
    1. Hirsutism.
    2. Change in voice
    3. Sterility.
    4. This test is done to differentiate sex character problems.
    5. This test may help assess delayed puberty.
15. DHEA is an androgenic steroid that both men and women secrete.
    1. DHEA levels are gradually increased during childhood and adolescence, rise rapidly after puberty, peak at age 20, and then decline.
    2. It decreases in the elderly more rapidly than other steroids.
    3. There is a moderate decrease in pregnancy.
    4. DHEA and Androstenedione have diurnal variations, highest in the morning. Their secretion is episodic similar to cortisol.
       1. DHEA-S does not show diurnal variation and is present in the serum at a level much higher than DHEA and Androstenedione.
       2. Polycystic ovary (Stein-Leventhal syndrome) = High level of Androstenedione.
       3. Adrenal carcinoma = High level of DHEA-S.
       4. Cushing’s disease = Moderately raised the level of DHEA-S.
          1. Cushing’s syndrome (a benign adrenal tumor) = Normal Androstenedione.
       5. Congenital Adrenal hyperplasia = Moderately raised the level of DHEA-S.

Measuring methods for DHEA:

• DHEA is measured by gas-liquid chromatography, RIA, and gas chromatography.

Normal values of adrenal Androgen

Androstenedione

• Newborn = 20 to 290 ng/dL
• Puberty = 8 to 50 ng/dL
• Male = 75 to 205 ng/dL
• Female = 85 to 275 ng/dL
• Postmenopausal = <10 ng/dL

Another source

• Premature = 80 to 446 ng/dL
• Newborn = 20 to 290 ng/dL
• 1 to 12 months = 6 to 68 ng/dL
• 10 to 17 years = 8 to 240 ng/dL
• Adult
  • Male = 75 to 205 ng/dL
  • Female = 85 to 275 ng/dL
• Source 2
  • Male = 0.6 to 2.7 ng/mL
  • 0.5 to 2.7 ng/mL

NORMAL Urine DHEA

• Adult male : 0.1 to 2.0 mg / day
• Adult Female: 0.1 to 1.5 mg / day
• Child Less than 0.1 mg / day

Normal Serum DHEA

Source 2

• Adult Male = 1.0 to 9.5 ng /mL
• Adult Female = 0.4  to 3.7 ng /mL
• Pregnant Female = 0.5 to 12.5 mg /mL

Another source

• Male = 180 to 1250 ng/dL
• Female = 130 to 980 ng/dL
  • Urine =
  • Male = <3.1 mg/24 hours
  • Female = <1.5 mg/24 hours

Normal serum DHEA-S

Source 2

• Male = 280 to 640 µg /dL
• Female = 65 to 380 µg /dL

Another source

• Male = 125 to 619 µg /dL
• Female 29 to 781µg /dL

(Difference literature gives different values)

The increased level is seen in:

1. Hirsutism.
2. Polycystic Ovaries Syndrome.
3. Virilizing adrenal tumors.
4. Precocious puberty.
5. Cushing disease.
6. Ectopic ACTH-producing tumor.
7. Congenital adrenal hyperplasia.

The decreased level is seen in:

1. Hyperlipidemia.
2. Psychosis.
3. Psoriasis.
4. With the increasing age of men and women.
5. Hypopituitarism.
6. Patient on glucocorticoid treatment.

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