What Are Androgens?
Androgens are steroid hormones that serve as the primary male sex hormones, with testosterone and dihydrotestosterone (DHT) being the most important, though they are also produced in smaller amounts in females and play critical roles in female physiology. 1, 2
Core Definition and Types
Androgens are steroid hormones that exert their effects primarily through binding to the androgen receptor (AR), a ligand-activated transcription factor that modulates gene expression. 1, 2
The two most important androgens are testosterone and 5α-dihydrotestosterone (DHT), each with distinct physiological roles during development and throughout life. 1
Testosterone is produced primarily by the testes in males (specifically by Leydig cells) and in much smaller amounts by the ovaries and adrenal glands in females. 3, 4
Role in Male Development and Function
Testosterone is responsible for development of Wolffian duct-derived structures (epididymis, vas deferens, seminal vesicles), while DHT, a metabolite of testosterone, drives development of the urogenital sinus and external genitalia during fetal development. 1
High intratesticular testosterone levels are essential for spermatogenesis, with testosterone binding to androgen receptors in Sertoli cells to initiate and maintain sperm production while inhibiting germ cell death. 3
Androgens are critical for puberty, development and maintenance of secondary male characteristics (facial hair, deep voice, muscle mass), male sexual function, and fertility. 2, 3
Role in Female Reproductive Health
In females, androgens are produced in smaller amounts but have direct and significant physiological effects, including serving as precursors to estrogens through aromatization. 4
Female androgen levels are much lower than in males and decrease further with aging, making accurate measurement technically challenging but clinically important for diagnosing gonadal and adrenal disorders. 4
Androgenic side effects from medications (such as progestin-only contraceptives) can include acne, hirsutism, and weight gain, though these occur rarely. 5
Critical Developmental Windows
Testosterone levels diverge between sexes as early as 7-8 weeks of gestation, with male fetal testosterone peaking at 14-16 weeks (reaching adult male range) while female fetuses maintain consistently low levels. 6
A postnatal testosterone surge occurs in male infants at 1-3 months of life (called "mini-puberty"), followed by a decline to prepubertal levels by 4-6 months, while female infants maintain constantly low levels throughout the first year. 6
These critical periods (weeks 8-24 of gestation and months 1-6 of life) represent windows when androgens permanently masculinize the developing nervous system through irreversible organizational effects on neural circuits. 7
Mechanism of Action
Androgens exert most effects through genomic mechanisms: the hormone binds to the androgen receptor (AR), which then translocates to the nucleus and acts as a transcription factor to modulate gene expression. 1, 2
The AR gene is located on the X-chromosome at Xq11-12 and codes for a protein of approximately 110 kDa molecular mass. 1
In the brain, testosterone is converted to estradiol by the enzyme aromatase, and this estradiol then binds estrogen receptors to promote masculine neural differentiation—this is known as the "estrogen hypothesis" of brain masculinization. 7
Clinical Significance in Intersex Conditions
Complete androgen insensitivity syndrome (CAIS) demonstrates the essential role of functional androgen receptors: individuals with 46,XY karyotype and severe AR defects develop female external genitalia, female gender identity, and feminine behavior despite having testes and male-range testosterone levels. 8, 9, 1
Females with congenital adrenal hyperplasia (CAH) exposed to excess androgens during gestation show masculinized behavior patterns (tomboyish personality, male-typical toy preferences, increased rough play) but typically maintain female gender identity when diagnosed and treated early. 8, 7
Androgen exposure during critical developmental periods causes permanent, irreversible changes to neural organization, and interventions after 4-6 months of age cannot reverse established brain masculinization. 7