male repro disorders

Question 1

estrogen production in men

Answer 1

Estradiol in men is derived from direct production from the testes and from conversion from testosterone in peripheral tissues such as fat by aromatase.

Question 2

Functions/locations of inhibin, activin, and follistatin

Answer 2

All are made in gonad. Inhibin inhibits FSH (inhibin B only. Inhibin A is not important in males) Activin activates FSH. Follistatin is an activin binding protein that controls local activity of activin

Question 3

1. Describe the anatomy and physiology of the reproductive axis in the male.

Answer 3

Sex steroids negatively feed back on the pituitary and hypothalamus.

Question 4

Levels of LH, FSH, testosterone and Sx of hypogonadotropic hypogonadism

Answer 4

Low LH, FSH and test. Impotence.

Question 5

Congenital causes of hypogonadotropic hypogonadism

Answer 5

Kallman’s syndrome- failure of migration of GnRH neurons to migrate to the hypothalamus. Have anosmia as well

Question 6

Acquired causes of hypogonadotropic hypogonadism

Answer 6

Acquired defects are the most common cause of low Testosterone: observed after severe illness, surgery, or stress, or with obstructive sleep apnea, narcotics or repeated glucocorticoid injections. Low FSH and LH can be caused by infiltrative disease such as hemochromatosis (iron deposition in gonadotropes). Tumors producing prolactin, GH or ACTH will inhibit GnRH.

Question 7

hypergonadotropic hypogonadism levels of LH, FSH and testosterone

Answer 7

High LH and FSH, low test

Question 8

Congenital causes of hypergonadotropic hypogonadism

Answer 8

Congenital anorchia, vanishing testes syndrome (insult to fetus before 10-12 weeks gestation interrupts testicular development. Defects in androgen receptor

Question 9

Klinefelters LH, FSH and test

Answer 9

Hypergonadotropic hypogonadism: elevated FSH (lack of inhibin B), normal LH and low normal testosterone. With time, progressive tubular fibrosis and destruction of leydig cells causes test to drop and LH to rise.

Question 10

Klinefelters syndrome pathogenesis and Sx

Answer 10

failing testes, with no spermatogenic elements, no Sertoli cells, but intact Leydig cells. present with small testes and delayed or incomplete puberty, gynecomastia, eunuchoid body habitus and infertility.

Question 11

Klinefelters other risks

Answer 11

breast cancer

Question 12

Presentation of defect in androgen receptor

Answer 12

If mild they present with hypospadias, or ambiguous genitalia. If complete they present as females with inguinal gonads and a blind vaginal pouch and the disorder is called testicular feminization

Question 13

LH, FSH, testosterone and estradiol levels in androgen receptor defects

Answer 13

HIGH LH, FSH, Testosterone and Estradiol, but no clinical effects of the androgen because of the steroid receptor mutation.

Question 14

Causes of acquired hypergonadotropic hypogonadism

Answer 14

includes mechanical and cytotoxic trauma to the testes such as torsion, mumps orchitis, alcohol, chemotherapy or radiation, infiltrative diseases, diabetes

Question 15

labs in acquired hypergonadotropic hypogonadism

Answer 15

early rise in FSH,(due to loss of inhibin) followed later by increase in LH and decline in testosterone.

Question 16

Which tumors cause hypergonadotropic hypogonadism and signs

Answer 16

glycoprotein tumor of the pituitary that overproduces inactive pituitary gonadotropins (a, LHb, and/or FSHb). Headache, blurred vision, elevated prolactin (stalk compression)

Question 17

Treatment of male hypogonadism

Answer 17

1. Androgens for all types of hypogonadism- patches reduce the highs and lows of therapy. Side effect is contact dermatitis. No oral androgens due to hepatotoxicity. 2. Gonadotropin therapy used for pituitary or hypothalamic defects- minimum 12-18 months treatment to stimulate maturation of testis and spermatogenesis.

Question 18

Androgens are contraindicated in who?

Answer 18

men with hormone dependent malignancy, i.e. prostate cancer

Question 19

Androgen risks

Answer 19

Polycythemia and benign prostatic hypertrophy and elevation of LDL (bad) cholesterol are significant risks with use of androgen replacement, especially if the dose is supra-physiologic.

Question 20

What is pulsatile GnRH therapy used for

Answer 20

Men with hypothalamic defects. A pump with a catheter infuses GnRH every 2 hours. Takes 18-24 months to recapitulate puberty and achieve sperm production

Question 21

Drug induced causes of gynecomastia

Answer 21

1. antiandrogens: spironolactone, flutamide. 2. psychoactive drugs: phenothiazines, antidepressants. 3. abuse: alcohol, heroin, marijuana

Question 22

Endocrine causes of gynecomastia

Answer 22

1. primary hypogonadism due to leydig cell damage (klinefelters, testicular trauma, chemotherapy). 2. hyperprolactinemia. 3. hyperthyroidism. 4. androgen receptor mutations (testicular feminization)

Question 23

Tumors causing gynecomastia

Answer 23

1. Germ cell tumors (make choronic gonadotropin (hCG) that stimulates estrogens and androgens). 2. Leydig cell tumors (make estrogens +/- testosterone). 3. feminizing adrenal tumors (make estrogens)

Question 24

differential diagnosis for erectile dysfunction

Answer 24

1. Vascular: predicted by hypertension, high cholesterol. 2. Neurogenic: diabetes, spinal cord injury, toxins (alcohol, lead). 3. Hormonal. 4. Psychogenic: performance anxiety. 5. Iatrogenic: something patient takes or we give- a. antiandrogens, b. psychotropic medications, c. narcotics, marijuana, cocaine

Question 25

drugs that cause erectile dysfunction

Answer 25

1. antihypertensives: beta blockers, diuretics, alpha blockers (NOT ACE inhibitors). 2. Androgen receptor blockers: cimetidine, spironolactone. 3. Psych meds: all antipsychotics and antidepressants. 4. other: reglan, cocaine, marijuana, herbals

Question 26

Erectile dysfunction treatment

Answer 26

drugs: type 5 phosphodiesterase inhibitors (sildenafil, vardenafil, tadenafil), penile injections of prostaglandin E, vacuum pump devices

Question 27

how do type V phosphodiesterase inhibitors work in ED

Answer 27

erection is stimulated when NO activates guanylate cyclase which converts GTP/GMP to cGMP, causing smooth muscle relaxation and erection. Phosphodiesterase breaks down cGMP back into GMP, reducing erection, so phosphodiesterase inhibitors prevent this.