male repro disorders Flashcards
estrogen production in men
Estradiol in men is derived from direct production from the testes and from conversion from testosterone in peripheral tissues such as fat by aromatase.
Functions/locations of inhibin, activin, and follistatin
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
- Describe the anatomy and physiology of the reproductive axis in the male.
Sex steroids negatively feed back on the pituitary and hypothalamus.
Levels of LH, FSH, testosterone and Sx of hypogonadotropic hypogonadism
Low LH, FSH and test. Impotence.
Congenital causes of hypogonadotropic hypogonadism
Kallman’s syndrome- failure of migration of GnRH neurons to migrate to the hypothalamus. Have anosmia as well
Acquired causes of hypogonadotropic hypogonadism
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.
hypergonadotropic hypogonadism levels of LH, FSH and testosterone
High LH and FSH, low test
Congenital causes of hypergonadotropic hypogonadism
Congenital anorchia, vanishing testes syndrome (insult to fetus before 10-12 weeks gestation interrupts testicular development. Defects in androgen receptor
Klinefelters LH, FSH and test
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.
Klinefelters syndrome pathogenesis and Sx
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.
Klinefelters other risks
breast cancer
Presentation of defect in androgen receptor
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
LH, FSH, testosterone and estradiol levels in androgen receptor defects
HIGH LH, FSH, Testosterone and Estradiol, but no clinical effects of the androgen because of the steroid receptor mutation.
Causes of acquired hypergonadotropic hypogonadism
includes mechanical and cytotoxic trauma to the testes such as torsion, mumps orchitis, alcohol, chemotherapy or radiation, infiltrative diseases, diabetes
labs in acquired hypergonadotropic hypogonadism
early rise in FSH,(due to loss of inhibin) followed later by increase in LH and decline in testosterone.
Which tumors cause hypergonadotropic hypogonadism and signs
glycoprotein tumor of the pituitary that overproduces inactive pituitary gonadotropins (a, LHb, and/or FSHb). Headache, blurred vision, elevated prolactin (stalk compression)
Treatment of male hypogonadism
- 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.
Androgens are contraindicated in who?
men with hormone dependent malignancy, i.e. prostate cancer
Androgen risks
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.
What is pulsatile GnRH therapy used for
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
Drug induced causes of gynecomastia
- antiandrogens: spironolactone, flutamide. 2. psychoactive drugs: phenothiazines, antidepressants. 3. abuse: alcohol, heroin, marijuana
Endocrine causes of gynecomastia
- primary hypogonadism due to leydig cell damage (klinefelters, testicular trauma, chemotherapy). 2. hyperprolactinemia. 3. hyperthyroidism. 4. androgen receptor mutations (testicular feminization)
Tumors causing gynecomastia
- 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)
differential diagnosis for erectile dysfunction
- 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
drugs that cause erectile dysfunction
- 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
Erectile dysfunction treatment
drugs: type 5 phosphodiesterase inhibitors (sildenafil, vardenafil, tadenafil), penile injections of prostaglandin E, vacuum pump devices
how do type V phosphodiesterase inhibitors work in ED
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.
