30. Androgens & Hypogandism 2025

What type of hormone is testosterone?

An androgenic steroid hormone

What are three major physiological roles of testosterone?

Male development, reproduction, and anabolism (e.g., muscle growth)

Where is testosterone produced in males?

Leydig cells of the testes

What controls testosterone production?

The hypothalamic-pituitary-gonadal (HPG) axis

What is the average daily testosterone production in healthy males?

About 6 mg/day

What is the normal daily range of testosterone production?

3–10 mg/day

When are serum testosterone levels highest?

In the morning (around 8 AM)

When are serum testosterone levels lowest?

At night (around 10 PM)

What morning serum testosterone level suggests deficiency?

Below 300 ng/dL

What does testosterone deficiency refer to?

Reduced or absent testosterone production

What enzyme converts testosterone into estradiol (E2)?

Aromatase

What enzyme converts testosterone into dihydrotestosterone (DHT)?

5-alpha-reductase

How do androgens exert biological effects in cells?

By binding to androgen receptors (ARs) in the nucleus

What does the AR-ligand complex do?

Binds DNA and modulates gene transcription

What hormone stimulates LH release from the pituitary?

GnRH (gonadotropin-releasing hormone)

What does LH stimulate in males?

Testosterone production by Leydig cells

What kind of feedback do testosterone, DHT, and E2 provide?

Negative feedback on GnRH and LH secretion

What is the pattern of GnRH release?

Pulsatile

What causes testosterone deficiency at the HPG axis level?

Defects in hypothalamus, pituitary, or testis

What effect does testosterone have on the CNS?

Increases libido, energy, spatial perception, and well-being

What effect does testosterone have on the hypothalamus and pituitary?

Decreases GnRH, LH, and FSH; increases GH

What effect does testosterone have on the larynx?

Increases vocal fold thickness and lowers pitch of voice

What effect does testosterone (via E2) have on the breast?

Increases breast size

What effect does testosterone have on the liver?

Decreases SHBG and HDL

What hormone does testosterone increase production of in the kidney?

Erythropoietin

What effect does testosterone have on male genitals?

Enhances development, spermatogenesis, and erections

What effect does testosterone have on the prostate?

Increases size and secretions

What effect does DHT have on the skin?

Increases facial/body hair and sebum; decreases scalp hair

What effect do T and E2 have on bone?

Increase bone mineral density (BMD)

What effect does testosterone have on muscle?

Increases lean mass and strength

What effect does testosterone have on adipose tissue?

Decreases abdominal fat

What effect does testosterone have on the immune system?

Decreases autoimmunity

What effect does testosterone have on blood?

Increases hematocrit

What are the three levels where dysfunction can cause testosterone deficiency?

Testicular, pituitary, and hypothalamic

What is primary hypogonadism?

Testicular failure

What is the hormone profile in primary hypogonadism?

Low T, high LH, high GnRH

What is an example of primary hypogonadism?

Klinefelter syndrome (47,XXY)

What is another example of primary hypogonadism?

Orchiectomy

What is secondary hypogonadism?

Pituitary dysfunction

What is the hormone profile in secondary hypogonadism?

Low T, low or normal LH, high GnRH

What are examples of secondary hypogonadism?

Prolactinoma, acromegaly, craniopharyngioma, beta-thalassemia

What is tertiary hypogonadism?

Hypothalamic dysfunction

What is the hormone profile in tertiary hypogonadism?

Low T, low or normal LH, low GnRH

What are examples of tertiary hypogonadism?

Kallmann syndrome, head trauma, opioid use, obesity, aging

What is the broader term for pituitary and hypothalamic hypogonadism?

Central hypogonadism

Can GnRH levels be measured clinically?

No

What types of chronic conditions are associated with testosterone deficiency?

Diabetes, HIV/AIDS, COPD, chronic renal failure, rheumatoid arthritis, cancer

What medications are associated with testosterone deficiency?

Glucocorticoids and opioids

What other conditions are associated with testosterone deficiency?

Malnutrition, burn injuries, and aging

Are mechanisms linking chronic illness to low testosterone well understood?

No, they remain unclear in many cases

What are common symptoms of testosterone deficiency in post-pubertal males?

Decreased libido, erectile dysfunction, low energy, depressed mood, hot flashes/night sweats

What is a classic symptom related to erectile dysfunction in testosterone deficiency?

Loss of spontaneous morning erections

What are physical exam findings suggesting testosterone deficiency?

Decreased facial/body hair, muscle atrophy, obesity, gynecomastia

What testicular volume suggests Klinefelter’s syndrome?

< 10 mL

What body proportion is characteristic of long-standing hypogonadism?

Eunuchoid proportions (arm span > height)

What visual symptom may suggest a pituitary tumor?

Decreased peripheral vision

What bone complication can result from chronic testosterone deficiency?

Osteoporosis

What is the first lab test for testosterone deficiency?

Morning total testosterone (TT)

What TT level is considered subnormal?

< 260 ng/dL

What TT range is considered low-normal?

261–300 ng/dL

What additional labs should be ordered after a low TT?

Free T or bioavailable T, SHBG, LH, FSH, and prolactin

What FT level confirms testosterone deficiency?

< 5 ng/dL

What BT level confirms testosterone deficiency?

< 100 ng/dL

When is a semen analysis indicated?

If fertility is a concern

When should pituitary MRI be considered?

In males < 40 with low T and low LH

What screening should occur before starting testosterone therapy?

Prostate cancer screening based on age and risk

What labs should be obtained before testosterone therapy?

CBC and lipid panel

What is the controversy around treating androgen deficiency in older men?

Benefits vs risks are unclear and under investigation

What percentage of men over 65 have subnormal testosterone levels?

More than 25%

At what age do total testosterone levels begin to decline?

After the third decade

How much do TT levels decrease annually after age 30?

About 1.6% per year

Why do FT and BT decline faster than TT with age?

Because SHBG levels increase with age

What tool may help identify older males for testosterone screening?

ADAM questionnaire (Androgen Deficiency in Aging Men)

What are two physiologic causes of low T in aging?

Reduced Leydig cell mass and altered HPG axis signaling

What is the typical hormone profile in older men with hypogonadism?

Low T and low LH

How may obesity contribute to age-related hypogonadism?

It disrupts hormonal balance

Why is testosterone treatment in older men controversial?

Risk of accelerating prostate tumor growth

Are there studies investigating testosterone therapy in aging males?

Yes, NIH-funded studies are ongoing

What are common causes of erectile dysfunction (ED)?

Vascular disease, neurologic disorders, endocrine conditions, medications, psychogenic factors, uremia

What sexual symptoms are typically associated with testosterone deficiency?

Decreased libido and erectile dysfunction

What is the mechanism of phosphodiesterase inhibitors (PDEs) like sildenafil?

Potentiate nitric oxide release in response to neurogenic stimuli

Do PDEs improve testosterone levels?

No

Do PDEs improve libido?

No

Can PDEs and testosterone have synergistic effects in ED?

Possibly, in men with both low T and vascular/neurogenic ED

Have large studies consistently shown synergy between PDEs and testosterone?

No

What aspects of sexual function are included in male sexual dysfunction?

Libido, orgasm, and ejaculatory disorders

Will additional SLGs discuss broader sexual dysfunction management?

Yes

What testosterone product names are used for intramuscular injections?

Testosterone enanthate (Delatestryl®), cypionate (Depo-Testosterone®), undecanoate (Aveed®)

What are advantages of intramuscular injections?

Long history of use, effective in raising serum testosterone

What are disadvantages of intramuscular injections?

Injection pain, peak-trough fluctuations, gynecomastia risk

What are examples of topical gels/solutions?

AndroGel®, Testim®, Fortesta®, Axiron®

What are advantages of topical gels?

Easy to apply, discreet, steady testosterone levels

What are disadvantages of topical gels?

Risk of transference to others, daily use, elevated DHT, high cost

What are examples of subcutaneous implant options?

Testopel® (pellets), Xyosted® (solution)

What are advantages of implants?

Long-acting, discreet, less frequent administration

What are disadvantages of implants?

Requires minor procedure, pellet extrusion, infection/fibrosis risk

What are oral testosterone derivatives?

Jatenzo®, Tlando®, Kyzatrex®

What are advantages of oral testosterone?

Convenient, discreet, no titration for Tlando®

What are disadvantages of oral testosterone?

BP warning (Jatenzo/Kyzatrex), potential liver toxicity

What are examples of transdermal patches?

Androderm® (Testoderm® discontinued)