Male Hormones (Androgens) Lecture Review

Dr. D'Souza Material

What are androgens?

A group of steroids found in males and females.

What does androgens produce?

Anabolic and/or musicalizing effects in both males and females.

What are the 2 main hormones?

Testosterone and 5α-Dihydrotestosterone (DHT)

What organs synthesize androgens?

Testis, adrenal gland, & ovaries

What are the three stages where there is a spike in androgen levels in a male child?

Fetal, Neonatal, and Pubertal

What two hormones spike during the fetal stage?

Testosterone and Dihydrotestosterone (DHT)

What happens when testosterone spikes during the fetal stage?

Development of the male internal genitalia: the testis, epididymis, vas deferens, and seminal vesicles

What happens when dihydrotestosterone spikes during the fetal stage?

Development of the male external genitalia: the penis, scrotum, and prostate

What happens when there is a testosterone spike during the neonatal stage?

Not fully known → May play a role in gender identity.

What happens when there is a testosterone spike during the pubertal stage?

development of external and internal genitalia, sexual hair, acne, voice changes, increase in muscle mass and strength, bone changes, and increase in hemoglobin (erythropoiesis)

What are the androgenic functions of androgens?

Normal maturation of the male and sperm production

What are the anabolic functions of androgens?

- Increased synthesis of muscle proteins and hemoglobin

- Decreased bone absorption (from decreased testosterone)

Synthesis of androgens are regulated by hormones synthesized in what two parts of the brain?

Hypothalamus and pituitary

What hormone gets secreted by the hypothalamus?

GnRH (Gonadotropin releasing hormone)

What two hormones does the pituitary secrete?

LH (Luteinizing hormone) and FSH (Follicle stimulating hormone)

What does GnRH regulate?

Secretion of LH and FSH from the pituitary (Positively stimulates release)

What does LH do?

Acts on Leydig cells to produce testosterone.

What are Leydig cells?

Specialized cells in the testis that secrete testosterone.

What does FSH do?

Stimulates testicular growth and enhances the production of an testosterone-binding protein by the Sertoli cells.

What are Sertoli cells?

Special cells located in the seminiferous tubules help in sperm maturation produce testosterone-binding protein and produce inhibin that provides feedback to the pituitary.

Describe the feedback loop that regulates production of androgens in males?

Inhibin, testosterone, DHT provide feedback inhibitory feedback to the pituitary and decrease secretion of LH and FSH.

How can you decrease the effects of DHT?

Block 5α-reductase

In what clinical condition will you want to decrease effects of DHT?

Benign prostatic hyperplasia

How else can you decrease the effects testosterone and DHT?

Block androgen receptors

What if testosterone doesn’t get converted into DHT in a fetus?

Poor development of external genitalia

What happens during androgen insensitivity syndrome?

- Dysfunction in androgen receptor

- Increase or normal testosterone levels

- Increase or normal DHT levels

- Sex Male (XY)

- External genitalia like female

- Physical appearance like female

- Undescended testis

- No uterus/fallopian tubes

- Internal male genitalia not formed

What happens during 5α-reductase deficiency (congenital)?

- Androgen receptor fully functional

- Increased or normal testosterone levels

- Decreased DHT levels

- Sex Male (XY)

- Ambiguous external genitalia

- Small or absent penis; bifid scrotum

- Undescended testes

- No uterus/fallopian tubes

- Internal male genitalia is formed

What happens during primary hypogonadism?

- Testis is damaged or dysfunctional

- Decrease in testosterone and DHT levels

- Increase in LH and FSH levels

What causes primary hypogonadism?

- Testicular trauma

- Mumps

- Testicular cancer

- Undescended testis

- Kinefelters’s syndrome (47, XXY)

What happens during secondary hypogonadism?

- Dysfunction of pituitary and/or hypothalamus

- Decrease in testosterone and DHT

- Decrease in LH and FSH

What causes secondary hypogonadism?

- Infection (meningitis, TB)

- Autoimmune (sarcoidosis)

- Tumors (Brain, pituitary)

- Head trauma

What is mumps?

A contagious disease mainly seen in children.

What is primarily affected by mumps?

The salivary glands which results in swelling of the face.

What prevents mumps?

MMR vaccine

What is sarcoidosis?

A rare autoimmune disorder that can affect multiple organs.

What does sarcoidosis cause?

Small patches of red and swollen tissue.

What can sarcoidosis affect?

The lungs, skin, brain, heart, lymph glands, liver, kidneys etc.

What happens during age-related testosterone deficiency?

- Natural decrease in testosterone production

- Associated with erectile dysfunction and decreased sexual desire

- Weight gain and lack of motivation

- May be associated with loss of bone density

Why can’t natural testosterone be administered orally?

Undergoes extensive first pass metabolism

What synthetic testosterone preparations can be given orally?

Danazol, Methyltestosterone, Oxandrolone, Fluoxymesterone

How do oral synthetic testosterone preparations differ from natural testosterone?

Synthetic testosterone preparations vary in their anabolic and androgenic properties.

What drug is abused by athletes and why?

Oxandrolone

• Has more anabolic effects than androgenic effects → increase muscle and bone strength

How often can testosterone depot injections be applied?

once every 2-3 weeks

What are the advantages of testosterone depot injections?

- Better compliance

- Prolonged action over several days

- Relatively inexpensive

What are the disadvantages of testosterone depot injections?

- Pain, fever, and swelling at site of injection/implantation

- Large fluctuation in testosterone levels

How often can testosterone gel be applied?

Can be applied once in the morning

What is the advantage of testosterone gel?

Low fluctuation in testosterone levels

What is the disadvantage of testosterone gel?

- Allergic reactions

- Potential transfer to sexual partners with come in contact with the patient (opposite sex partners may have adverse effects

- Expensive

How often can testosterone patches be applied?

Can be applied twice a day

What is the advantage of testosterone patches?

Low fluctuation in testosterone levels

What is the disadvantage of testosterone patches?

Allergic reactions

What are the adverse effects of excessive androgens in males?

- Decreased sperm count

- Growth of prostate

- Facial hair growth

- Loss of hair; male pattern baldness

- Acne

Why does excessive levels of androgens in the peripheral circulation decrease sexual functions?

Because of suppression of HPA axis and blood testis barrier

• Blood testis barrier does not allow exogenous testosterone to enter the testis

What are the adverse effects of excessive androgens in females?

- Menstrual irregularities

- Acne

- Facial hair growth

- Deepening of voice

- Loss of hair; male pattern baldness

- Excessive muscle development

What are the organ functions that are impacted because of excessive androgens in males and females?

- Increase IDL: HDL ratio

- Increase risk of coronary artery disease

- Elevation of liver enzymes; hepatic dysfunction

- Fluid retention → edema → weight gain

- Erythrocytosis (increase in hemoglobin) in COPD patients and untreated sleep apnea patients

Why are androgens abused by athletes?

Increase lean body mass, muscle strength, and endurance

What side effects can happen to athletes when they abuse androgens?

- Stunted growth

- Reduction in testicular size in male athletes

- Elevation of liver enzymes; hepatic dysfunction

- Mood changes; aggression; rode range

- Cosmetic changes in males and females

What are the androgen receptor antagonist agents?

- Flutamide

- Bicalutamide

What is the MOA of androgen receptor antagonist?

Block androgen receptors

What are the 5α-reductase inhibitors agents?

- Finasteride

- Dutasteride

What is the MOA of 5α-reductase inhibitors?

Decreases DHT, no alteration in testosterone and LH.

What are GnRH agonists agents?

- Nafarelin

- Leuprolide

- Buserelin

- Goserelin

What is the MOA of GnRH agonists?

Inhibits pituitary LH secretion, decreases testosterone and DHT

Why does natural GnRH not decrease androgen levels, but GnRH agonists do?

Because natural GnRH is released in spurts while GnRH agonists provide constant stimulation which downregulates the receptor leading to decrease LH and FSH release from the pituitary.

What are some major indications of antiandrogen use in males?

- Prostatic cancer

- Benign prostatic hyperplasia (BPH)

- Gender reassignment (male to female)

- Hypersexuality

What are some major indications of antiandrogen use in females?

- Severe forms of acne

- Hirsutism

- Androgenic alopecia