Androgens

1. Overview

Androgens are a group of steroid hormones primarily responsible for the development and maintenance of male characteristics, although they are also present and functionally important in females. The most well-known androgen is testosterone, but others include dihydrotestosterone (DHT), dehydroepiandrosterone (DHEA), and androstenedione. These hormones influence reproductive development, libido, muscle mass, bone density, and hair growth, and are integral to both sexual differentiation and overall metabolic function.

2. Location

Androgens are produced in multiple sites:

• Testes (Leydig cells): The primary site of androgen production in males, especially testosterone.

• Adrenal Cortex (Zona Reticularis): Produces weaker androgens such as DHEA and androstenedione, important in both sexes but especially significant in females.

• Ovaries (Theca cells): Produce small amounts of androgens, which serve as precursors for estrogen synthesis.

• Peripheral Tissues: Some tissues (e.g., skin, liver, adipose tissue) convert precursor androgens into more active forms like testosterone and DHT.

3. Structure

Androgens are steroid hormones derived from cholesterol. They share a common four-ring cyclopentanoperhydrophenanthrene nucleus. Examples include:

• Testosterone: C19H28O2, with a hydroxyl group at position 17.

• Dihydrotestosterone (DHT): A more potent derivative of testosterone, formed via 5α-reductase enzyme.

• DHEA and androstenedione: Weaker androgens serving as precursors for testosterone and estrogens.

Their lipophilic nature allows them to diffuse through cell membranes and bind to intracellular androgen receptors to exert genomic effects.

4. Function

Androgens serve multiple functions across different organ systems:

• Sexual differentiation: Drive male genital development in the fetus and initiate puberty in males.

• Secondary sex characteristics: Promote facial and body hair, deepening of the voice, and increased muscle mass in males.

• Libido and reproductive health: Maintain sexual drive, spermatogenesis, and erectile function.

• Metabolic effects: Influence red blood cell production, bone growth, fat distribution, and protein synthesis.

• Female physiology: Androgens contribute to pubic/axillary hair growth, libido, and serve as precursors for estrogens.

5. Physiological role(s)

Androgens have widespread physiological importance in both males and females:

• Fetal development: Androgens stimulate the development of male internal and external genitalia; absence of androgen leads to female differentiation.

• Puberty: Surge in testosterone triggers growth of testes, penis, and body hair, along with a growth spurt and voice changes in boys.

• Musculoskeletal system: Promote anabolic effects such as increased muscle mass and bone mineralization.

• Skin and sebaceous glands: Androgens stimulate sebum production, which may contribute to acne during puberty.

• Central nervous system: Influence mood, cognition, and libido in both sexes.

• Aging: Declining androgen levels in men (andropause) can lead to reduced libido, fatigue, and decreased muscle strength.

6. Clinical Significance

Abnormalities in androgen production or action can lead to various clinical disorders:

• Androgen Excess in Females:

  • Polycystic Ovary Syndrome (PCOS): Characterized by elevated androgens, leading to hirsutism, acne, menstrual irregularities, and infertility.

  • Congenital Adrenal Hyperplasia (CAH): Enzyme deficiencies (e.g., 21-hydroxylase) cause excess adrenal androgens and virilization in females.

  • Adrenal tumors: May secrete excess DHEA or androstenedione, resulting in masculinization.

• Androgen Deficiency in Males:

  • Hypogonadism: Results in low testosterone, causing fatigue, infertility, reduced libido, gynecomastia, and loss of muscle mass.

  • Klinefelter Syndrome: A genetic disorder (47,XXY) that leads to testicular failure and androgen deficiency.

  • Age-related androgen decline: May present as decreased energy, mood changes, or sexual dysfunction (late-onset hypogonadism).

• Androgen Insensitivity Syndrome (AIS):

  • Genetic males (46,XY) are unresponsive to androgens due to receptor defects, leading to female external genitalia despite high testosterone levels.

• Therapeutic Uses of Androgens:

  • Testosterone replacement therapy (TRT) is used in male hypogonadism.

  • Androgens are sometimes abused in the form of anabolic steroids for muscle enhancement, which can cause cardiovascular, hepatic, and reproductive side effects.