Male Reproductive Endocrinology Flashcards
Androgen Regulation
- negative feedback may occur by androgens directly or after conversion to estrogen
- testosterone (from Leydig cells) primarily involved in negative feedback on LH and GnRH, whereas inhibin (from Sertoli cells) suppresses FSH secretion
Tests of testicular function
- testicular size (lower limit = 4 cm x 2.5 cm)
- LH, FSH, total, bioavailable, and/or free testosterone
• human chorionic gonadotropin (hCG) stimulation test
■ assesses ability of Leydig cell to respond to gonadotropin
• semen analysis
■ semen volume, sperm concentration, morphology, and motility are the most commonly used parameters
• testicular biopsy
■ indicated with normal FSH and azoospermia/oligospermia
Hypothalamo-pituitary-gonadal axis
E45
Hypogonadism and infertility definition
• deficiency in gametogenesis or testosterone production
Hypogonadism and infertility etiology
- causes include primary (testicular failure), secondary (hypot alamic-pituitary failure), and idiopathic
- primary hypogonadism is more common than secondary
Diagnosis of Testosterone Deficiency Syndrome aka adult onset primary hypogonadism
- requires clinical manifestations of testosterone deficiency (see sidebar) AND documented testosterone levels below local lab ranges
- rule out secondary causes
Two distinct features of primary hypogonadism
- The decrease in sperm count is affected to a greater extent than the decrease in serum testosterone level
- Likely to be associated with gynecomastia
Hypergonadotropic hypogonadism (primary) hypogonadism definition
Primary testicular failure
Inc LH and FSH, Inc FSH:LH ratio
Dec testosterone and sperm count
Two features of secondary hypogonadism
- Associated with an equivalent decrease in sperm count and serum testosterone
- Less likely to be associated with gynecomastia
Hypergonadotropic hypogonadism (primary) hypogonadism etiology
Congenital Chromosomal defects (Klinefelter’s, Noonan) Cryptorchidism Dsorders of sexual development (DSD) Bilateral anorchia (vanishing testicle syndrome) Myotonic dystrophy Mutation of FSH or LH receptor gene Disorders of androgen synthesis
Germ cell defects
Sertoli cell only syndrome
Leydig cell aplasia/failure
Infection/Inflammation
Orchitis – TB, lymphoma, mumps, leprosy
Genital tract infection
Physical factors
Trauma, heat, irradiation, testicular torsion, varicocele
Drugs
Marijuana, alcohol, chemotherapy, ketoconazole, glucocorticoid, spironolactone
Hypergonadotropic hypogonadism (primary) hypogonadism diagnosis
Tes icular size and consistency (soft/firm)
Sperm count
LH, FSH, total, and/or bioavailable testosterone
hCG stimulation (mainly used in pediatrics)
Karyotype
Hypogonadotropic hypogonadism (secondary) hypogonadism definition
Hypothalamic-pituitary axis failure
dec LH + FSH (LH sometimes inappropriately normal) dec testosterone and sperm count
Hypogonadotropic hypogonadism (secondary) hypogonadism etiology
Congenital
Kallman’s syndrome
Prader-Willi syndome
Abnormal subunit of LH or FSH
Infection
Tuberculosis, meningitis
Endocrine Adrenal androgen excess Cushing’s syndrome Hypo or hyperthyroidism Hypothalamic-pituitary disease (tumour, hyperprolactinemia hypopituitarism)
Drugs
Alcohol, marijuana, spironolactone, ketoconazole, GnRH agonists, androgen/estrogen/progestin use, chronic narcotic use
Chronic illness
Cirrhosis, chronic renal failure, AIDS
Sarcoidosis, Langerhan’s cell histiocytosis hemochromatosis
Critical illness
Surgery, MI, head trauma
Obesity
Idiopathic
Hypogonadotropic hypogonadism (secondary) hypogonadism diagnosis
Testicular sze and consistency (soft/firm)
Sperm count
LH, FSH total, and/or bioavailable testosterone
Prolactin levels
MRI of hypothalamic-pituitary region
Hypogonadism and infertility treatment
• goal: testosterone replacement (improve libido, muscle mass strength, body hair growth, bone mass)
■ IM injection, transdermal testosterone patch/gel, oral
■ side effects: acne, fluid retention, erythrocytosis, sleep apnea, benign prostatic hypertrophy, uncertain effects on cardiac events/mortality in older men
■ contraindicated if history of metastatic prostate cancer, breast cancer, severe LUTS associated with BPH, uncontrolled or poorly controlled CHF PSA>4, hematocrit >50%
■ testosterone therapy only to treat symptoms of hypogonadism, often results in decreased spermatogenesis by further suppression of hypothalamic-pituitary-gonad axis
• goal: fertility
■ Treat underlying cause
■ GnRH agonist if hypothalamic dysfunction with intact pituitary, administered SC in pulsatile fashion using an external pump
■ hCG ± recombinant follicular stimulating hormone (rFSH) in cases of either hypothalamic or pituitary lesions
■ Dopamine agonist (eg. bromocriptine, cabergoline) if prolactinoma
■ testicular sperm extraction (TESE) or microscopic sperm extraction (MICROTESE) – only if testicular tissues are not functioning