Hypogonadism
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Questions and Answers

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

  • 60%
  • 38%
  • 95% (correct)
  • 2%

    • 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?

    <p>Adrenal cortex</p> Signup and view all the answers

    Which statement about free testosterone is correct?

    <p>It is approximately 2% of total testosterone.</p> Signup and view all the answers

    What is the primary causative factor for primary hypogonadism?

    <p>Infections such as mumps orchitis</p> Signup and view all the answers

    Which hormone levels are typically observed in primary hypogonadism?

    <p>↑ LH, ↑ FSH</p> Signup and view all the answers

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

    <p>1:500</p> Signup and view all the answers

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

    <p>Nontender, fibrotic testes</p> Signup and view all the answers

    Which of the following is a consequence of secondary hypogonadism?

    <p>Failure of GnRH secretion leading to low hormone levels</p> Signup and view all the answers

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

    <p>Kallman syndrome</p> Signup and view all the answers

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

    <p>Cryptorchidism</p> Signup and view all the answers

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

    <p>Clomiphene</p> Signup and view all the answers

    What is a contraindication for testosterone replacement therapy?

    <p>Untreated obstructive sleep apnea</p> Signup and view all the answers

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

    <p>Support of spermatogenesis</p> Signup and view all the answers

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

    <p>Adulthood</p> Signup and view all the answers

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

    <p>Lack of secondary sex characteristics</p> Signup and view all the answers

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

    <p>Elevated hematocrit levels</p> Signup and view all the answers

    What is a primary characteristic of secondary hypogonadism?

    <p>Failure of GnRH, LH, or FSH secretion</p> Signup and view all the answers

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

    <p>Klinefelter's syndrome</p> Signup and view all the answers

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

    <p>Low testosterone with high LH and FSH</p> Signup and view all the answers

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

    <p>Regular exercise</p> Signup and view all the answers

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

    <p>Firm, fibrotic, small, and nontender</p> Signup and view all the answers

    What role does the hypothalamus play in testosterone production?

    <p>It produces GnRH which stimulates the anterior pituitary.</p> Signup and view all the answers

    Which of the following statements about testosterone is true?

    <p>Testosterone is important for normal muscular development.</p> Signup and view all the answers

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

    <p>5%</p> Signup and view all the answers

    Which hormone acts on the Leydig cells of the testes?

    <p>LH</p> Signup and view all the answers

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

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

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

    <p>Kallman syndrome</p> Signup and view all the answers

    What is a likely outcome of untreated hypogonadism in adults?

    <p>Decreased energy and muscle mass</p> Signup and view all the answers

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

    <p>Clomiphene</p> Signup and view all the answers

    What is a contraindication for initiating testosterone replacement therapy?

    <p>Obstructive sleep apnea</p> Signup and view all the answers

    Which condition is considered a common cause of acquired hypogonadism?

    <p>Hyperprolactinemia</p> Signup and view all the answers

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

    <p>Lipid profile</p> Signup and view all the answers

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

    <p>Gynecomastia</p> Signup and view all the answers

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

    <p>Hypogonadism</p> Signup and view all the answers

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

    <p>Produce testosterone</p> Signup and view all the answers

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

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

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

    <p>DHEA</p> Signup and view all the answers

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

    <p>5%</p> Signup and view all the answers

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

    <p>Production of DHEA</p> Signup and view all the answers

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

    <p>Klinefelter’s syndrome</p> Signup and view all the answers

    What hormonal change is most characteristic of primary hypogonadism?

    <p>Reduced testosterone and elevated LH and FSH</p> Signup and view all the answers

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

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

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

    <p>Excessive physical exercise</p> Signup and view all the answers

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

    <p>Low testosterone with normal or low LH and FSH</p> Signup and view all the answers

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

    <p>Diabetes</p> Signup and view all the answers

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

    <p>Ambiguous genitalia</p> Signup and view all the answers

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

    <p>Increased LH and FSH levels</p> Signup and view all the answers

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

    <p>Untreated obstructive sleep apnea</p> Signup and view all the answers

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

    <p>It supports intra-testicular testosterone production</p> Signup and view all the answers

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

    <p>Gynecomastia</p> Signup and view all the answers

    Which of the following conditions is associated with secondary hypogonadism?

    <p>Pituitary disease</p> Signup and view all the answers

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

    <p>Altered libido</p> Signup and view all the answers

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

    <p>To produce testosterone in response to LH</p> Signup and view all the answers

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

    <p>Follicle-Stimulating Hormone</p> Signup and view all the answers

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

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

    What role does the adrenal cortex contribute to testosterone production?

    <p>It produces prohormones that can be converted to testosterone</p> Signup and view all the answers

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

    <p>Approximately 5%</p> Signup and view all the answers

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

    <p>Hypothalamic insufficiency</p> Signup and view all the answers

    What characterizes the hormone levels in primary hypogonadism?

    <p>Elevated LH and FSH with low testosterone</p> Signup and view all the answers

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

    <p>Excessive physical activity</p> Signup and view all the answers

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

    <p>Reduced penile size</p> Signup and view all the answers

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

    <p>Gynecomastia</p> Signup and view all the answers

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

    <p>Pituitary disease</p> Signup and view all the answers

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

    <p>Pre-adolescence</p> Signup and view all the answers

    What is a primary consequence of untreated hypogonadism in adults?

    <p>Decreased energy</p> Signup and view all the answers

    Which condition is specifically contraindicated for undergoing testosterone replacement therapy?

    <p>Severe lower urinary tract symptoms</p> Signup and view all the answers

    Which alternative therapy for hypogonadism is known to support spermatogenesis?

    <p>Clomiphene</p> Signup and view all the answers

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

    <p>Below 5 ml</p> Signup and view all the answers

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

    <p>Increased hematocrit levels</p> Signup and view all the answers

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

    <p>Gynecomastia</p> 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
    • 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.
    • 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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