Hypogonadism

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Questions and Answers

What percentage of total testosterone is produced by the testes in males?

60%

38%

95% (correct)

Which hormone is produced by the anterior pituitary and stimulates testosterone production?

DHEA

GnRH

LH (correct)

FSH

Which of the following is NOT a function of testosterone in men?

Promotion of lactation (correct)

Appropriate sexual development

Normal skeletal formation

Normal bone marrow function

What is the primary site of DHEA production in the body?

Adrenal cortex Signup and view all the answers

Which statement about free testosterone is correct?

It is approximately 2% of total testosterone. Signup and view all the answers

What is the primary causative factor for primary hypogonadism?

Infections such as mumps orchitis Signup and view all the answers

Which hormone levels are typically observed in primary hypogonadism?

↑ LH, ↑ FSH Signup and view all the answers

What is the incidence rate of Klinefelter's syndrome among males?

1:500 Signup and view all the answers

What characteristic is most associated with Klinefelter's syndrome in affected males?

Nontender, fibrotic testes Signup and view all the answers

Which of the following is a consequence of secondary hypogonadism?

Failure of GnRH secretion leading to low hormone levels Signup and view all the answers

Which of the following is NOT a condition that can lead to acquired hypogonadism?

Kallman syndrome Signup and view all the answers

What is a common physical manifestation of hypogonadism in the neonatal period?

Cryptorchidism Signup and view all the answers

Which therapy for hypogonadism is NOT FDA approved for this use?

Clomiphene Signup and view all the answers

What is a contraindication for testosterone replacement therapy?

Untreated obstructive sleep apnea Signup and view all the answers

What is the potential benefit of using Human Chorionic Gonadotropin in hypogonadal men?

Support of spermatogenesis Signup and view all the answers

At what age does infertility typically manifest due to hypogonadism in males?

Adulthood Signup and view all the answers

Which of the following is a sign of hypogonadism in pre-adolescents?

Lack of secondary sex characteristics Signup and view all the answers

Which of these is associated with greater cardiovascular risks when treating hypogonadism?

Elevated hematocrit levels Signup and view all the answers

What is a primary characteristic of secondary hypogonadism?

Failure of GnRH, LH, or FSH secretion Signup and view all the answers

Which of the following conditions is most commonly associated with primary hypogonadism?

Klinefelter's syndrome Signup and view all the answers

What hormonal pattern is typically observed in a male with primary hypogonadism?

Low testosterone with high LH and FSH Signup and view all the answers

Which factor is NOT associated with an increased prevalence of hypogonadism?

Regular exercise Signup and view all the answers

What is the typical testicular development in males with Klinefelter's syndrome?

Firm, fibrotic, small, and nontender Signup and view all the answers

What role does the hypothalamus play in testosterone production?

It produces GnRH which stimulates the anterior pituitary. Signup and view all the answers

Which of the following statements about testosterone is true?

Testosterone is important for normal muscular development. Signup and view all the answers

What percentage of total testosterone is produced by the adrenal glands in males?

5% Signup and view all the answers

Which hormone acts on the Leydig cells of the testes?

LH Signup and view all the answers

What is the primary form in which testosterone exists in the bloodstream?

The majority is bound to proteins, primarily albumin and SHBG Signup and view all the answers

Which syndrome is characterized by hypogonadism and may include anosmia or hyposmia?

Kallman syndrome Signup and view all the answers

What is a likely outcome of untreated hypogonadism in adults?

Decreased energy and muscle mass Signup and view all the answers

Which therapy is known to support spermatogenesis in men with hypogonadism?

Clomiphene Signup and view all the answers

What is a contraindication for initiating testosterone replacement therapy?

Obstructive sleep apnea Signup and view all the answers

Which condition is considered a common cause of acquired hypogonadism?

Hyperprolactinemia Signup and view all the answers

What laboratory test should be performed to monitor cardiovascular risk in patients undergoing hypogonadism treatment?

Lipid profile Signup and view all the answers

Which of the following adverse effects is less likely with the use of Human Chorionic Gonadotropin?

Gynecomastia Signup and view all the answers

What condition is characterized by a lack of secondary sex characteristics in pre-adolescents?

Hypogonadism Signup and view all the answers

What is the primary role of Leydig cells in the testes?

Produce testosterone Signup and view all the answers

Which statement accurately reflects the relationship between testosterone and its binding proteins in the bloodstream?

Only free testosterone is capable of binding to target receptors Signup and view all the answers

Which hormone is produced in the adrenal cortex that can eventually lead to testosterone production?

DHEA Signup and view all the answers

What percentage of testosterone production in males is attributed to the adrenal glands?

5% Signup and view all the answers

Which physiological function does testosterone NOT play a significant role in?

Production of DHEA Signup and view all the answers

Which of the following conditions is a primary cause of primary hypogonadism?

Klinefelter’s syndrome Signup and view all the answers

What hormonal change is most characteristic of primary hypogonadism?

Reduced testosterone and elevated LH and FSH Signup and view all the answers

Which of the following statements best describes the incidence and effects of Klinefelter's syndrome?

It occurs in approximately 1 in 500 males, typically discovered at puberty. Signup and view all the answers

Which of the following factors is least associated with the increased prevalence of hypogonadism?

Excessive physical exercise Signup and view all the answers

In secondary hypogonadism, which of the following hormonal patterns would you expect?

Low testosterone with normal or low LH and FSH Signup and view all the answers

Which condition is known to potentially lead to hypogonadism in adulthood?

Diabetes Signup and view all the answers

What physical characteristic is likely observed in males with hypogonadism during the neonatal period?

Ambiguous genitalia Signup and view all the answers

What is an expected laboratory finding in a male with hypogonadotropic hypogonadism when treated with Clomiphene?

Increased LH and FSH levels Signup and view all the answers

Which of the following is a contraindication for testosterone replacement therapy?

Untreated obstructive sleep apnea Signup and view all the answers

What best describes the role of Human Chorionic Gonadotropin in treating hypogonadal men?

It supports intra-testicular testosterone production Signup and view all the answers

What is an observable change in male adolescents with untreated hypogonadism during pre-adolescence?

Gynecomastia Signup and view all the answers

Which of the following conditions is associated with secondary hypogonadism?

Pituitary disease Signup and view all the answers

What common effect is associated with chronic systemic illness regarding testosterone levels?

Altered libido Signup and view all the answers

What is the primary function of Leydig cells in the male reproductive system?

To produce testosterone in response to LH Signup and view all the answers

Which hormone is responsible for stimulating the Sertoli cells to produce sperm?

Follicle-Stimulating Hormone Signup and view all the answers

Which statement about testosterone's presence in the bloodstream is accurate?

98% of testosterone in the bloodstream is bound to proteins Signup and view all the answers

What role does the adrenal cortex contribute to testosterone production?

It produces prohormones that can be converted to testosterone Signup and view all the answers

How much testosterone production in males is attributed to the adrenal glands?

Approximately 5% Signup and view all the answers

Which condition is least likely to be caused by primary hypogonadism?

Hypothalamic insufficiency Signup and view all the answers

What characterizes the hormone levels in primary hypogonadism?

Elevated LH and FSH with low testosterone Signup and view all the answers

Which of the following factors is NOT commonly associated with increased prevalence of male hypogonadism?

Excessive physical activity Signup and view all the answers

What is the most common physical manifestation observed in males with Klinefelter's syndrome?

Reduced penile size Signup and view all the answers

Which of the following is a common treatment-related side effect in men receiving therapy for hypogonadism?

Gynecomastia Signup and view all the answers

Which of the following factors is a potential cause of acquired hypogonadism?

Pituitary disease Signup and view all the answers

In which age category is a lack of secondary sex characteristics most closely associated with hypogonadism?

Pre-adolescence Signup and view all the answers

What is a primary consequence of untreated hypogonadism in adults?

Decreased energy Signup and view all the answers

Which condition is specifically contraindicated for undergoing testosterone replacement therapy?

Severe lower urinary tract symptoms Signup and view all the answers

Which alternative therapy for hypogonadism is known to support spermatogenesis?

Clomiphene Signup and view all the answers

What would be a typical expectation for testicular size in a male experiencing hypogonadism during pre-adolescence?

Below 5 ml Signup and view all the answers

What is a likely physiological consequence of testosterone therapy in relation to hemoglobin levels?

Increased hematocrit levels Signup and view all the answers

Which of the following is a common side effect associated with testosterone therapy that may concern patients?

Gynecomastia Signup and view all the answers

Study Notes

Androgens

Testosterone: produced primarily in the testes, most potent androgen, converted to dihydrotestosterone or estrogen
DHEA: produced in the adrenals, less potent, can be converted to testosterone in the periphery

Testosterone in Men

Required for appropriate sexual development
Necessary for normal skeletal formation and maintenance
Crucial for normal bone marrow function
Promotes normal muscular development and maintenance
Contributes to a sense of well-being, libido, and potency

Testosterone Production

Hypothalamus produces GnRH, which acts on the anterior pituitary.
Anterior pituitary produces LH and FSH which act on the testes.
LH stimulates Leydig cells to produce testosterone
FSH stimulates Sertoli cells to produce sperm
Only 2% of testosterone is free, 98% is bound
- Albumin-bound T: 38%
- SHBG-bound T: 60%
Testes produce ~95% of testosterone in men

Testosterone Production (cont.)

Adrenal cortex secretes multiple prohormones that are converted to testosterone in peripheral tissues
Adrenal glands produce ~5% of testosterone in men

Male Hypogonadism

Deficient testosterone secretion by the testes
Affects 4-5 million men in the US
Prevalence increases with age, obesity, diabetes, HIV, COPD, CHD, renal disease, opioid or glucocorticoid therapy.

Hypogonadism Classifications

Primary hypogonadism (hypergonadotropic): Testicular dysfunction (decreased spermatogenesis and/or decreased testosterone)
- Increased LH, increased FSH
Secondary hypogonadism (hypogonadotropic): Hypothalamus and/or pituitary gland dysfunction (failure of GnRH, LH, or FSH secretion)
- Decreased/normal LH & FSH

Primary Hypogonadism Causes

Klinefelter’s syndrome
Unilateral or bilateral cryptorchidism
Varicocele
Infections, such as mumps orchitis
Drugs: Opioids, marijuana, spironolactone, corticosteroids, ketoconazole, anticonvulsants, immunosuppressants
Toxins, such as heavy metals or alcohol
Testicular trauma, such as radiation or chemotherapy
Chronic renal failure

Klinefelter’s Syndrome

Most common chromosomal abnormality among males
Caused by an abnormal karyotype, typically 47,XXY
Incidence of about 1:500 males
Found only in males and detected at puberty
Testes usually become firm, fibrotic, small, and nontender
Increased risk of cryptorchidism, decreased penile size, delayed speech, learning disabilities, psychiatric disturbances, and mediastinal malignancies
Up to 75% of affected boys experience gynecomastia at puberty

Secondary Hypogonadism Causes

Congenital:
- GnRH deficiency (e.g., Kallman syndrome, Prader-Willi syndrome) +/- anosmia/hyposmia
Acquired (more common):
- Pituitary disease
- Head or pituitary trauma
- Sellar mass lesions
- Hyperprolactinemia
- Diabetes
- Obesity
- Neoplasms
- Chronic systemic illness, such as chronic obstructive pulmonary disease
- Drugs: Opioids, glucocorticoids, GnRH analogues, exogenous estrogen or androgen

The Effect of Hypogonadism Based On Age of Onset

Neonatal period:
- Cryptorchidism
- Microphallus
- Ambiguous genitalia
Pre-adolescence:
- Lack of secondary sex characteristics
- Eunuchoid body habitus
- Gynecomastia
- Pre-pubertal testes
Adult:
- Infertility
- Decreased libido/potency
- Decreased energy/muscle mass
- Decreased bone density
- Possibly decreased testicular size (normal testes = 15-20 ml) or consistency

Testosterone Replacement Therapy (TRT)

Initiate TRT for men with confirmed hypogonadism and symptomatic testosterone deficiency
Monitor TRT patients for:
- Hemoglobin/Hematocrit: Initially, Hct may initially rise to 54 while on TRT, hold TRT until hematocrit normalizes.
- Lipid Profile: Treat any lipid abnormality to minimize cardiovascular risk
- Hemoglobin A1C: Screen for diabetes
- Sleep Study: Untreated sleep apnea is a contraindication to testosterone therapy
- Tobacco dependency (Smoking): Contraindication to TRT

Testosterone Therapy Not Recommended For Those Who:

Desire fertility in the near future
Have breast or prostate cancer
Have a palpable prostate nodule or induration
PSA > 4
PSA > 3 with a high prostate cancer risk
Elevated hematocrit
Untreated obstructive sleep apnea
Severe lower urinary tract symptoms
Uncontrolled heart failure
Myocardial infarction or stroke within the last 6 months
Thrombophilia

Alternative Hypogonadism Therapies

Clomiphene:
- Not FDA approved for use in the treatment of hypogonadism
- Treatment for hypogonadotropic hypogonadism
- Selective estrogen receptor modulator → blocks the estrogen receptor in the hypothalamus and pituitary gland, increasing FSH & LH
- Not associated with adverse effects on PSA, hematocrit, and gynecomastia
Human Chorionic Gonadotropin (hCG):
- Traditionally used in hypogonadal men desiring fertility
- Supports spermatogenesis and intratesticular testosterone production
- Less likely to cause adverse effects on prostate health, hematocrit, sleep apnea, and gynecomastia

Androgens

Testosterone is the most potent androgen and is primarily produced in the testes.
Testosterone can be converted into Dihydrotestosterone or estrogen.
DHEA is made in the adrenal glands and can be converted into testosterone in the periphery.

Testosterone in Men

Testosterone is essential for male sexual development.
Testosterone is required for normal skeletal formation and maintenance.
Testosterone is needed for normal bone marrow function.
Testosterone provides normal muscular development and maintenance.
Testosterone is responsible for a sense of well-being, libido, and potency.

Testosterone Production

The hypothalamus produces GnRH.
GnRH acts on the anterior pituitary.
The anterior pituitary produces LH and FSH.
LH acts on Leydig cells to produce testosterone.
FSH acts on Sertoli cells to produce sperm.
98% of testosterone is bound to proteins, primarily albumin and sex hormone-binding globulin (SHBG).
Only 2% of testosterone is free.

Testosterone Production Continued

The adrenal glands produce a small percentage (about 5%) of testosterone in men.
The adrenal glands secrete prohormones that are converted into testosterone in peripheral tissues.

Male Hypogonadism

Male hypogonadism is characterized by deficient testosterone secretion from the testes.
4 to 5 million men in the US are affected by hypogonadism.
Hypogonadism is more prevalent in older men and those with obesity, Diabetes Mellitus, HIV, COPD, CHD, renal disease, and individuals on opioids or glucocorticoid therapy.

Classification of Male Hypogonadism

Primary Hypogonadism: (hypergonadotropic) Testicular dysfunction leads to a decrease in spermatogenesis and/or testosterone.
Secondary Hypogonadism: (hypogonadotropic) Dysfunction in the hypothalamus or pituitary gland leads to a failure of GnRH, LH, or FSH secretion.

Causes of Primary Hypogonadism

Genetic: Klinefelter's syndrome
Testicular Issues: Unilateral or bilateral cryptorchidism, Varicocele, Testicular trauma, Testicular infections (mumps orchitis)
Other: Chronic Renal Failure, Alcohol, Drugs (Opioids, marijuana, spironolactone, corticosteroids, ketoconazole, anticonvulsants, immunosuppressants, and toxins (heavy metals)

Klinefelter's Syndrome

Klinefelter's syndrome is the most common chromosomal abnormality in males.
It is caused by an abnormal karyotype, most commonly 47, XXY.
The incidence is approximately 1:500 males.
Affected males typically have small, firm, fibrotic, nontender testes.
Individuals with Klinefelter's syndrome have increased risk of cryptorchidism, decreased penile size, delayed speech, learning disabilities, psychiatric issues, and mediastinal malignancies.
Up to 75% of affected boys experience gynecomastia at puberty.

Causes of Secondary Hypogonadism

Congenital:
- GnRH Deficiency can lead to Kallman syndrome or Prader-Willi syndrome, often with anosmia or hyposmia (loss of smell).
Acquired:
- Pituitary disease
- Head or pituitary trauma
- Sellar mass lesions
- Hyperprolactinemia
- Diabetes
- Obesity
- Neoplasms
- Chronic systemic illness (like COPD)
- Drugs (opioids, glucocorticoids, GnRH analogues, exogenous estrogen, or androgen)

Effect of Hypogonadism based on age of onset:

Neonatal Period: cryptorchidism, micropenis, ambiguous genitalia
Pre-adolescence: lack of secondary sex characteristics, eunuchoid body habitus (tall stature with long limbs), gynecomastia, pre-pubertal testes.
Adult: infertility, decreased libido and potency, decreased energy and muscle mass, decreased bone density, potential for decreased testicular size.

Treatment Options for Hypogonadism

Testosterone Replacement Therapy (TRT):
- Dosage: 1-2 mg/day of testosterone cypionate or enanthate
- Monitoring: Hematocrit (should not exceed 54% while on TRT), PSA (prostate-specific antigen), lipid profile, sleep study (untreated sleep apnea is a contraindication for TRT), and smoking cessation (contraindicated with TRT)

Contraindications for Testosterone Therapy

Desire for fertility in the near future
Breast or prostate cancer
Palpable prostate nodule or induration
PSA > 4
PSA > 3 with high prostate cancer risk
Elevated hematocrit
Untreated obstructive sleep apnea
Severe lower urinary tract symptoms
Uncontrolled heart failure
Myocardial infarction or stroke within the last 6 months
Thrombophilia

Alternative Hypogonadism Therapies

Clomiphene:
- Not FDA approved for hypogonadism
- Treats hypogonadotropic hypogonadism
- Selective estrogen receptor modulator (blocks estrogen receptors in the hypothalamus and pituitary gland, raising FSH and LH)
- Fewer side effects and is not associated with changes in PSA, hematocrit, or gynecomastia.
Human Chorionic Gonadotropin (hCG):
- Traditionally used for fertility in hypogonadal men
- Supports spermatogenesis and intra-testicular testosterone production
- Less likely to cause adverse effects on prostate health, hematocrit, sleep apnea, or gynecomastia.

Androgens

Testosterone is the most potent androgen produced primarily in the testes.
Testosterone is converted to Dihydrotestosterone or estrogen.
DHEA is a less potent androgen made in the adrenals and can be converted to testosterone in the periphery.

Testosterone in Men

Necessary for appropriate sexual development.
Essential for normal skeletal formation and maintenance.
Contributes to normal bone marrow function.
Promotes normal muscular development and maintenance.
Influences the sense of well-being, libido, and potency.

Testosterone Production

The hypothalamus produces GnRH which acts on the anterior pituitary.
The anterior pituitary produces LH & FSH which act on the testes.
LH stimulates Leydig cells to produce testosterone.
FSH stimulates Sertoli cells to produce sperm.
Only 2% of testosterone is free, while 98% is bound to albumin (38%) and SHBG (60%).

Adrenal Androgen Production

The adrenal cortex secretes multiple prohormones that are converted into testosterone in the peripheral tissues.
The adrenal glands contribute to approximately 5% of testosterone production in males.

Male Hypogonadism

Characterized by deficient testosterone secretion by the testes.
Affects an estimated 4 to 5 million men in the US.
Prevalence increases with age, obesity, diabetes, HIV, COPD, CHD, renal disease, opioid or glucocorticoid therapy.

Hypogonadism Classifications

Primary hypogonadism (hypergonadotropic): Testicular dysfunction, leading to decreased spermatogenesis and/or testosterone. Elevated LH and FSH levels.
Secondary hypogonadism (hypogonadotropic): Dysfunction of the hypothalamus and/or pituitary gland, resulting in a failure of GnRH, LH, or FSH secretion. Decreased or normal LH & FSH levels.

Primary Hypogonadism Causes

Genetic: Klinefelter’s syndrome
Testicular Issues: Unilateral or bilateral cryptorchidism, varicocele, testicular trauma (radiation or chemotherapy).
Infections: HIV/AIDS, mumps orchitis.
Drug-Related: Opioids, marijuana, spironolactone, corticosteroids, ketoconazole, anticonvulsants, immunosuppressants.
Other: Toxins (heavy metals or alcohol), chronic renal failure.

Klinefelter’s Syndrome

Most common chromosomal abnormality among males.
Caused by an abnormal karyotype, typically 47,XXY.
Affects approximately 1 in 500 males.
Diagnosed at puberty.
Testes become firm, fibrotic, small, and nontender.
Increased risk of cryptorchidism, decreased penile size, delayed speech, learning disabilities, psychiatric disturbances, and mediastinal malignancies.
Up to 75% of affected boys experience gynecomastia at puberty.

Secondary Hypogonadism Causes

Congenital:
- GnRH deficiency: (Kallman syndrome, Prader-Willi syndrome) +/- anosmia/hyposmia
Acquired (more common)
- Pituitary disease
- Head or pituitary trauma
- Sellar mass lesions
- Hyperprolactinemia
- Diabetes
- Obesity
- Neoplasm
- Chronic systemic illness (e.g., chronic obstructive pulmonary disease)
- Drugs: Opioids, glucocorticoids, GnRH analogues, exogenous estrogen or androgen

Hypogonadism Effect Based on Age of Onset

Neonatal Period: Cryptorchidism, microphallus, ambiguous genitalia.
Pre-adolescence: Lack of secondary sex characteristics, eunuchoid body habitus, gynecomastia, pre-pubertal testes
Adult: Infertility, decreased libido/potency, decreased energy/muscle mass, decreased bone density, potentially decreased testicular size or consistency (normal testes: 15-20 ml).

Testosterone Replacement Therapy (TRT) Monitoring

Hemoglobin/Hematocrit: Monitor and treat any elevated hematocrit, especially above 54. Hold TRT until it normalizes.
Lipid Profile: Treat any lipid abnormalities to minimize cardiovascular risk.
Hemoglobin A1C: Screen for diabetes.
Sleep Study : Untreated sleep apnea is a contraindication to testosterone therapy.
Tobacco Dependency (Smoking): Contraindication to TRT.

Testosterone Therapy Not Recommended For

Desire for fertility in the near future
Breast or prostate cancer
Palpable prostate nodule or induration
PSA > 4
PSA > 3 with high prostate cancer risk
Elevated hematocrit
Untreated obstructive sleep apnea
Severe lower urinary tract symptoms
Uncontrolled heart failure
Myocardial infarction or stroke within the last 6 months
Thrombophilia

Alternative Hypogonadism Therapies

Clomiphene (not FDA approved for hypogonadism):
- Treatment for hypogonadotropic hypogonadism.
- Selective estrogen receptor modulator, blocks estrogen receptors, increasing FSH & LH.
- Not associated with negative effects on PSA, hematocrit, gynecomastia.
Human Chorionic Gonadotropin (hCG):
- Traditionally used in hypogonadal men desiring fertility.
- Supports spermatogenesis and intratesticular testosterone production.
- Less likely to cause adverse effects on prostate health, hematocrit, sleep apnea, and gynecomastia.

Testosterone

Production:
- Primarily in testes
- Most potent androgen
- Converted to Dihydrotestosterone or estrogen
Actions:
- Needed for appropriate sexual development
- Normal skeletal formation and maintenance
- Normal bone marrow function
- Normal muscular development and maintenance
- Sense of well being, libido, potency

Testosterone Production Pathway

Hypothalamus: Produces GnRH
Anterior Pituitary: Responds to GnRH, producing LH & FSH
Testes:
- LH acts on Leydig cells: Produces testosterone
- FSH acts on Sertoli cells: Produces sperm

Testosterone in the Body

Only 2% is free testosterone
- 98% is bound:
  - Albumin-bound T - 38%
  - SHBG-bound T - 60%
Testes account for ~95% of production in males
Adrenal cortex secretes ~5% of production in men
Adrenal prohormones converted to testosterone in peripheral tissues

Hypogonadism: Deficient Testosterone

4 to 5 million men in the US affected
Higher prevalence with: older age, obesity, DM, HIV, COPD, CHD, renal disease, opioid or glucocorticoid therapy
Two main types:
- Primary, Testicular dysfunction:
  - Decreased Spermatogenesis
  - Decreased Testosterone production
  - Increased LH & FSH
- Secondary, Hypothalamus &/or pituitary gland dysfunction:
  - Failure of GnRH, LH or FSH secretion
  - Decreased/Normal LH & FSH
Causes of Primary Hypogonadism:
- Klinefelter’s syndrome
- Unilateral or bilateral cryptorchidism
- Varicocele
- HIV/AIDS
- Infections such as mumps orchitis
- Drugs: Opioids, marijuana, spironolactone, corticosteroids, ketoconazole, anticonvulsants, & immunosuppressants
- Toxins: Heavy metals or alcohol
- Testicular trauma: Radiation or chemotherapy
- Chronic renal failure

Klinefelter's Syndrome

Most common chromosomal abnormality among males
Karyotype: 47,XXY
Incidence: 1:500 males
Only found in males, detected at puberty
Testes: usually become firm, fibrotic, small, and nontender to palpation
Increased risk of cryptorchidism, decreased penile size
Potential complications: Delayed speech, learning disabilities, psychiatric disturbances, & mediastinal malignancies
75% experience some gynecomastia at puberty

Secondary Hypogonadism Causes

Congenital (less common):
- GnRH deficiency: Kallman syndrome, Prader-Willi syndrome
  - May have anosmia/hyposmia (loss of smell)
Acquired (more common):
- Pituitary disease
- Head or pituitary trauma
- Sellar mass lesions
- Hyperprolactinemia
- Diabetes
- Obesity
- Neoplasm
- Chronic systemic illness
- Drugs: Opioids, glucocorticoids, GnRH analogues, exogenous estrogen or androgen

Hypogonadism based on Age of Onset

Neonatal Period:
- Cryptorchidism
- Microphallus
- Ambiguous genitalia
Pre-Adolescence:
- Lack of secondary sex characteristics
- Eunuchoid body habitus
- Gynecomastia
- Pre-pubertal testes
Adult:
- Infertility
- Decreased libido/potency
- Decreased energy/muscle mass
- Decreased bone density
- Possibly decreased testicular size (normal size 15-20 ml)

Testosterone Therapy

Considerations for starting TRT:
- History & Physical: including prostate exam
- PSA: Screen for prostate cancer
- Hct: Monitor hematocrit levels (↑ can cause thrombosis)
  - If Hct >54 while on TRT → hold TRT until normalized
- Lipid Profile: Treat any lipid abnormality to minimize cardiovascular risk
- Hemoglobin A1C: Screen for diabetes
- Sleep Study: Untreated sleep apnea can be a contraindication
- Tobacco Dependency: Smoking is a contraindication to TRT

Testosterone Therapy: Contraindications

Desire fertility in near future
Breast or prostate cancer
Palpable prostate nodule or induration
PSA > 4
PSA >3 with high prostate cancer risk
Untreated obstructive sleep apnea
Severe lower urinary tract symptoms
Uncontrolled heart failure
Myocardial infarction or stroke within last 6 months
Thrombophilia
Elevated Hct

Alternative Hypogonadism Therapies

Clomiphene:
- Not FDA approved for use in treatment of hypogonadism
- Treatment for hypogonadotropic hypogonadism
- Selective estrogen receptor modulator
  - Blocks estrogen receptor in hypothalamus & pituitary, increasing FSH & LH
- Less likely to cause adverse effects on prostate health, hematocrit, sleep apnea, and gynecomastia
Human Chorionic Gonadotropin (hCG):
- Traditionally used in hypogonadal men desiring fertility
- Supports spermatogenesis & intratesticular testosterone production
- Less likely to cause adverse effects on prostate health, hematocrit, sleep apnea, & gynecomastia

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