Reproductive Disorders: Male

Question 1

General outline of reproductive axis in male

Answer 1

• hypothalamus, pituitary, testes
• Hypothalamus secretes GnRH in a pulsatile fashion (homeostatic pattern
• Pituitary secretes FSH and LH in response to GnRH, also in a pulsatile fashion
  
  • LH stimulates Leydig cells to produce testosterone
  • FSH stimulates Sertoli cells which nurture maturing sperm
• Testes/Gonads produce Testosterone, DHT, and Estradiol

Question 2

Pituitary role in reproductive axis

Question 3

Testes/Gonads role in reproductive axis

Answer 3

• Testes/Gonads produce Testosterone, DHT, and Estradiol
• Testosterone.
  
  • Testosterone connects to Androgen receptors
  • Testosterone works throughout the body
• DHT is made from Testosterone (5 α reductase) and
  
  • 5 α reductase is not located in all tissues
  • DHT acts locally on the external genitalia, hair follicles, sebaceous glands and prostate.

Question 4

Approach to disorders of hypothalamic-pituitary-gonadal (testicular) axis

Answer 4

• multiple feedback loops exist between the hypothalamus (GnRH), the anterior pituitary (FSH, LH) and the testes.
  
  • Hypogonadism can result from a defect at any level of the HPG axis.
• Disorders can be congenital or acquired and may include:
  
  • Mechanical causes (e.g. missing/damaged parts)
  • Hormonal causes such as a defect in GnRH, LH and/or FSH or testosterone production

Question 5

Etiologies of hypogonadism

Answer 5

• Hypogonadotropic Hypogonadism
  
  • Congenital vs. Acquired causes
• Hypergonadotropic Hypogonadism
  
  • Congenital hypergonadotropic hypogonadism
  • Klinefelter’s Syndrome
  • Mutations in the androgen receptor
  • Acquired hypergonadotropic hypogonadism
  • Glycoprotein tumor of the pituitary

Question 6

Congenital causes of hypogonadotropic hypogonadism

Answer 6

• Hypogonadotropic Hypogonadism: ↓ LH + ↓ FSH + ↓ testosterone = impotence
• Congenital cause → ↓ GnRH
• Called Kallman syndrome if associated with anosmia
• GnRH neurons never made it to hypothalamus when migrating from the olfactory placode
• Think Kallman syndrome → Kan’t smell

Question 7

Acquired causes of hypogonadotropic hypogonadism

Answer 7

• Two most common: High dose pain meds, Obstructive Sleep Apnea
• High dose glucocorticoids
• Severe Illness
• Non Functioning pituitary tumor
  
  • Prolactinoma
  • Hemochromatosis
  • Hypothyroidism leads to ↑ prolactin
• Surgery
• Stress

Question 8

Lab results in acquired hypogonadotropic hypogonadism

Answer 8

• Acquired causes of GnRH or LH and FSH deficits (much more common)
• Low or low normal LH and FSH, and low testosterone

Question 9

Characteristics of congenital hypergonadotropic hypogonadism

Answer 9

• Anorchism (absence of 1 or 2 testes) → some insult causes gonads to fail prior to 10-12 weeks gestation
• ↑ FSH and ↑ LH result in attempt to grow the failed testes
• ↓ Testosterone
• Cryptorchidism → failure of testis to descend

Question 10

Characteristics of Klinefelter’s syndrome

Answer 10

–XXY: 1/400-1/1000 live births
–delayed puberty, eunuchoid body habitus, gynecomastia
–Low inhibin B levels
–Progressive tubular fibrosis, no sperm
–Eventual need for T replacement, mammograms

Question 11

Characteristics of Cryptocrchidism

Answer 11

n3% of newborn males (30% premies, 1% by 1 year)
nEtiologies: prematurity, low birth weight, SGA, twinning, maternal exposure to E in first trimester and rare genetic defects
nRisks: abnormal spermatogenesis, impaired fertility, increase in testicular cancer (15-fold unilateral, 33-fold bilateral)

Question 12

Characteristics of acquired hypergonadotropic hypogonadism

Answer 12

• Trauma or torsion
• Mumps orchitis
• Alcohol: direct testicular toxin
• Diabetes
• Radiation/chemotherapy
• Autoimmune testicular failure: check for other autoimmune diseases (TSH, glucose, B12, vit D)
• Gonadotrope (nonfunctioning) pituitary tumors: hi FSH>LH

Question 13

Characteristics of gonadotrope pituitary tumor

Answer 13

History: headaches, visual disturbance, erectile dysfunction

Exam: Visual fields, signs of hypogonadism, softening of testes

Labs: High FSH +/- LH and low T +/- mildly increased prolactin

Treatment: Surgery

Question 14

Types of treatment in male hypogonadism

Answer 14

• androgens
• gonadotropin therapy
• pulsatile GnRH therapy

Question 15

Characteristics of gonadotropin therapy

Answer 15

• Gonadotropin therapy for hypothalamic or pituitary defects (central defects)
  
  • 12-18 mos nec. for maturation of testes and spermatogenesis
  • If no FSH production → human menopausal gonadotropin or recombinant FSH for duration of therapy
    *

Question 16

Characteristics of pulsatile GnRH

Answer 16

• Pulsatile GnRH therapy is available for GnRH defects in men.
• Pump + catheter infuses supraphysiologic GnRH levels.
• 18-24 months to recapitulate puberty and achieve sperm production

Question 17

Definition/pathophys of gynecomastia

Answer 17

Definition: palpable breast tissue in a male.

Pathophysiology: Disruption of balance of estrogen/androgen effects on breast tissue. Unopposed estrogen effects cause gynecomastia.

Question 18

Characteristics of testosterone tx in men

Answer 18

nTreat for signs sx and low T levels after confirming etiology
nT gels: 2.5, 5, 10 g daily (different concentrations, different application sites)
nT patch: 2, 4 mg daily
nDepoT: 200mg IM q 2-3wks (trough at 150-200 ng/dl), nonphysiologic highs and lows
nCBC, PSA watch for rise >1.5 ng/dl
nReassess risk benefit

Question 19

Etiologies of erectile dysfuncion

Answer 19

nVascular
nNeurogenic
nPsychogenic
nIatrogenic
nHormonal

Question 20

Sources of iatrogenic impotence

Answer 20

nAntihypertensives: beta blockers, diuretics, alpha blockers but not ACE inhibitors
nAndrogen receptor blockers: cimetidine, spironolactone
nPsych meds: all antipsychotic and antidepressants (SSRIs independent effects on libido)
nOther: metaclopramide (Reglan), cocaine, maryjuana, herbals

Question 21

Tx of erectile dysfxn

Answer 21

Psychotherapy: no randomized studies

Change meds, stop alcohol, improve systemic diseases

Drug therapy: type 5 phosphodiesterase inhibitors (sildenafil, vardenafil, tadenafil)

Penile injections: prostaglandin E

Vacuum pump device