How is testosterone produced?

Testosterone Production in Humans

Testosterone is primarily produced in the testes in males and in the ovaries and adrenal glands in females, with production regulated by complex hormonal pathways that differ between sexes.

Testosterone Production in Males

Primary Production Sites

• Testes: Leydig cells in the testes are the primary site of testosterone production in males 1
• Adrenal Glands: Contribute a smaller portion of circulating androgens

Developmental Timeline

• Fetal testosterone production begins as early as 7-8 weeks of gestation 2
• By 14-16 weeks, fetal testosterone reaches peak levels in the adult male range 2
• After birth, male infants experience a testosterone surge at 1-3 months of age 2
• Testosterone levels then decrease to prepubertal levels by 4-6 months of age 2
• Levels remain low until puberty when production increases significantly

Production Mechanism

• Testosterone biosynthesis occurs through a series of enzymatic reactions in steroidogenic organs 1
• The hypothalamic-pituitary-gonadal axis regulates production:
  • Hypothalamus releases GnRH
  • Pituitary responds with LH and FSH
  • LH stimulates Leydig cells to produce testosterone

Testosterone Production in Females

Production Sites and Amounts

• Ovaries: Contribute approximately 50% of testosterone in women 3
• Adrenal Glands: Contribute approximately 50% of testosterone in women 3
• Healthy young women produce approximately 300 micrograms of testosterone per day 3
• Female testosterone levels are approximately 15-fold lower than in males 1

Additional Production Pathways

• Peripheral conversion of androgen precursors (produced in adrenal cortex and ovaries) occurs in various tissues 1
• Androstenedione can be converted to testosterone in peripheral tissues 4

Physiological Roles of Testosterone

In Both Sexes

Testosterone influences:

• Bone density and skeletal health 5
• Muscle mass and strength 3, 5
• Cognitive function and mood 3
• Erythropoiesis (red blood cell production) 3
• Energy levels 3
• Metabolic health 5

Sex-Specific Effects

• In males: Primary male sex characteristics, muscle development, body hair, voice deepening
• In females: Sexual function, bone health, and energy levels 3

Testosterone Metabolism

Conversion Pathways

• Testosterone can be converted to dihydrotestosterone (DHT) via 5α-reductase enzyme 1
  • DHT is a more potent androgen than testosterone
  • This occurs in the "classic pathway" but alternate metabolic pathways also exist 1
• Testosterone can be converted to estradiol via aromatase enzyme 2, 5
  • This conversion is crucial for bone and vascular health in males 5
  • Aromatase is found in various tissues including brain regions 2

Clinical Implications

Testosterone Deficiency

• Can result from various conditions in women including:
  • Oophorectomy, adrenalectomy, adrenal disease
  • Pituitary disease, HIV infection
  • Premature ovarian failure, Turner's syndrome
  • Use of high-dose corticosteroids 3
  • Natural aging and menopause 3

Therapeutic Applications

• Testosterone replacement therapy may be used in:
  • Hypogonadism in males
  • Selected cases of female androgen deficiency 3
  • HIV-associated wasting (anabolic effects) 6

Important Considerations

• Testosterone and estradiol are produced in both sexes at sex-specific concentrations 5
• The correlation between adrenal and testicular androgen levels is weak, indicating different regulatory mechanisms 4
• In the brain, testosterone can be converted to estradiol, which influences brain development and function 2
• Testosterone's effects on cognition are significant; deficiency may impact cognitive function 2

Understanding testosterone production and metabolism is essential for managing conditions related to androgen deficiency and excess in both males and females.