Male gonad disorders

Question 1

Know the clinical presentations of male hypogonadism (neonatal, teen, adult)

Answer 1

Neonatal: ambiguous genitalia. Child/puberty: delayed puberty. Adult: delayed puberty, delayed growth spurt, sparse chest/pubic/axillary hair growth, erectile dysfunction and/or poor libido, gynecomastia, osteoporosis and fractures, infertility, poor muscle development, hip fat

Question 2

Know questions to ask on Past History in a patient with hypogonadism

Answer 2

known ambiguous genitalia, undescended testes; mumps orchitis or testicular trauma; prior radiation, chemotherapy; chronic childhood disease (can lead to delay); fam Hx of delayed development or male gonadal abnormalities; did you go through puberty

Question 3

Know the reversible and irreversible effects of testosterone

Answer 3

Reversible: Libido, spontaneous erections, Male pattern hair growth, Bone mass, Changes in blood proteins (T stimulates erythropoiesis), Sebaceous glands, Sperm production, Muscle strength and size, Prostate and seminal vesicle size, Testes size. Irreversible: Deep voice (laryngeal hypertrophy), Male sexual orientation, Penis size, Body proportions, Baldness, Linear height

Question 4

5a reductase abnormality

Answer 4

Enzyme that converts T to DHT. Needed to develop external genitalia, prostate, facial and body hair

Question 5

Know how to investigate male hypogonadism

Answer 5

Lab tests needed. Test T and LH and maybe Prl

Question 6

Know the causes of primary male hypogonadism and the expected hormonal abnormalities

Answer 6

aka testicular failure. Lab: low T, high LH/FSH. Testicular damage: mumps, trauma, radiation, chemotherapy, drugs; Genetic diseases eg Klinefelter’s syndrome; Sequelae of developmental abnormalities eg undescended testes

Question 7

Know the causes of secondary male hypogonadism and the expected hormonal abnormalities

Answer 7

aka Hypothalamic/Pituitary Failure. Lab: low T, normal/low LH. Kallmann’s syndrome (LHRH deficiency); Aging (declining LHRH signals with age), “andropause” or ADAM (Androgen Decline in the Aging Male); Pituitary destruction eg tumors, surgery; Increased prolactin (drugs, pituitary tumors); Systemic disease – protective mechanism (ie this isn’t a priority right now!)

Question 8

Example diagnoses

Answer 8

22yo w/ low T, high LH/FSH, normal prolactin - Most likely Dx: Klinefelter’s syndrome. How to confirm? karyotype Most likely diagnosis if LH/FSH were normal: Kallmann’s syndrome (low LHRH). Most likely diagnosis if he were 16-18 years old: delayed puberty

Question 9

Know the treatment options for testosterone replacement

Answer 9

Oral: 17alpha alkylated testosterones, T undecanoate (Andriol). I.M.: T enanthate and cypionate. Topical: Patches - Androderm; Gels - AndroGel, Testim, Axiron

Question 10

Know the adverse effects of testosterone therapy and how to monitor a patient on therapy

Answer 10

ALL androgens in supraphysiological doses may cause: Polycythemia (stimulate erythropoiesis: decreased hepcidin, increased EPO [?]) - stroke; Decrease HDL cholesterol. 17alpha alkylated oral androgens: do NOT use for hypogonadism therapy; may cause cholestatic jaundice, peliosis of liver (blood filled cysts), liver carcinoma (?).

Question 11

What conditions can T therapy not change?

Answer 11

can’t change testes/penis size or infertility if it wasn’t around for the developmental/puberty years

Question 12

Know the mechanism of gynecomastia

Answer 12

Imbalance of estrogen/testosterone ratio.

Question 13

Know the causes of gynecomastia (lots!)

Answer 13

Drugs - testosterone excess (abuse - excess gets converted to E.), digitalis (some plant), prolactin-stimulating drugs, estrogens, substance abuse (marijuana, amphetamines, heroin), herbs/health products; Environmental estrogens/phytoestrogens; Hypogonadism (low testosterone – testicular or hypothalamic/pituitary); Pubertal (common but mild and usually regresses); Hyperthyroid (increased aromatase); Liver cirrhosis (liver supposed to destroy excess E); Genetic defects; Refeeding gynecomastia (malnourished who then eat - axis was thrown off); Testicular cancer (hCG from tumor stimulates T and E production, E>T); Aromatase increase (increased T to E2 conversion)

Question 14

Know the lab tests done to investigate gynecomastia

Answer 14

Testosterone, Estradiol, Prl, TSH, LH, ß hCG.

Question 15

Testicular cancer

Answer 15

Common in younger men. Detected with high hCG, often higher estradiol and gynecomastia. hCG binds to testicular LH receptors, stimulating T and E2 synthesis

Question 16

Know the mechanism of erectile function

Answer 16

Can be: declining hypothalamic GnRH with age; increasing SHBG; increasing sensitivity of hypothalamus to T feedback (ie tolerates low T). No ejaculatory disorder, Very infrequent nocturnal erections, Desire (libido) poor, No performance anxiety

Question 17

Know the causes of erectile dysfunction

Answer 17

Drugs – antihypertensives, antidepressants (SSRIs – not bupriopion), dopaminergic, alcohol; Neurovascular – diabetes, vascular disease, chronic systemic disease, multiple sclerosis, other nerve injuries; Psychiatric; Testosterone deficiency (not as common)

Question 18

Know the effects of narcotics for pain on hypothalamic –pituitary-gonadal function

Answer 18

All men receiving narcotics at any dosage should have testosterone measured, as 2/3 have low T; Mechanism: narcotics interact with hypothalamic neurotransmitters to decrease GnRH release, and also interfere with libido; Hypogonadal symptoms do not predict who has low T (chronic pain itself causes poor libido)

Question 19

Physical findings that are associated with ED

Answer 19

Fine wrinkling around eyes, mouth; Decreased body hair; Pale skin; Testes normal (he thinks they might be slightly smaller); Neuro: mild sensory peripheral neuropathy (diabetes); Cardiovascular: decreased foot pulses; elevated BMI

Question 20

Nonhormonal contributors to ED

Answer 20

alcoholism, diabetes (neurovascular), vascular

Question 21

Effects of obesity on T measurements

Answer 21

Obesity lowers SHBGm so “total serum testosterone” measurements will be artificially low. COMMONEST diagnostic problem/error in practice. Need to measure “free testosterone” or “bioavailable testosterone”, Bioavailable T probably best to separate SHBG effects

Question 22

What other conditions have low levels of T?

Answer 22

Obesity, diabetes, hypertension, hyperlipidemia. But this might not be actually true - did they test total T or bioavailable??

Question 23

Know the effects of testosterone therapy on a hypogonadal patient and the dose response effects of testosterone

Answer 23

Aim for mid-normal range. There is a dose response to T in muscle, lower fat, but not others. If someone is truly hypogonadal, benefits include muscle, strength, lower fat, mood, sexual function, bone density. Risks? Maybe prostate cancer or benign prostate hypertrophy. No short term problems.

Question 24

Followup with T therapy in men over 45

Answer 24

Yearly prostate exam, test hematocrit (may increase), lipid levels may change.

Question 25

Know the mechanism of action of PDE5 inhibitors

Answer 25

Ex. Viagra (sildenafil). PDE-5 breaks down cGMP, which is needed to cause smooth muscle relaxation and create erection. Viagra inhibits PDE-5 so it makes it possible to achieve erection.