Male Infertility and Erectile Dysfunction Flashcards
(58 cards)
1
Q
Infertility Statistics
A
- 15% of couples will be affected by infertility
- 30% male factor alone
- 20% male and female factors
- 50% of all infertile couples will have an abnormal male factor
2
Q
Male LH
A
- Released from ant. pituitary by GnRH or LHRH
- Pulasatile release; q60min
- Stimulates leydig cells to produce testosterone
3
Q
Male FSH
A
- Released from ant. pituitary by GnRH or LHRH
- Stimulates sertoli cells to initiate spermatogenesis
- Inhibin- postulated as neg. feedback substance
4
Q
Male Prolactin
A
- Released from ant. pituitary
- Inhibits GnRH release
- Hyperprolactinemia produces hypogonadotropic hypogonadism
5
Q
Male Testosterone Physiology
A
- Circadian production; highest in am
- Pulsatile release
- Bound in peripheral circulation
- Small % is unbound and bioavailable
- Can be aromatized to estradiol and 5alpha reduced to DHT
- Acts as neg. feedback to hypothalamus
6
Q
Spermatogenesis
A
- Smpermatogonia (stem cell)
- Spermatocyte (undergo meiosis)
- Spermatids
*develops a cap (acrosome)
*develops a tail (9 paired microtubules
*forms a blood-testes barrier
- Process takes approx. 74 days
- Highly sensitive to environmental factors
7
Q
Ejacalatory Mechanism
A
- Epididymis- maturation and storage of spermatozoa in the cauda
- Vas deferens- transport
- Seminal vesicles- formation of coagulum
- Prostate- proteases for liquefaction
- Neurologic innervation- “point and shoot”
*point = erection and is parasympathetically controlled
*shoot = ejaculation and is sympathetically controlled
8
Q
Post-coital test
A
- Test that looks at cervical mucus, anti-sperm antibodies
9
Q
What disease causes congenital absence of vas deferens?
A
- Cystic fibrosis
10
Q
Anatomic causes of male infertility
A
- Congenital absense of the vas
- Cryptorchidism (absence of 1 or both testes in the scrotum
- Ejaculatory duct obstruction
- Varicocele
11
Q
Behavioral and environmental causes of male infertility
A
- Obesity
- Environmental exposure
- Substance abuse (opiods, exogenous T, vit. deficiencies)
- Chemoradiation
- Meds
- Surgery
- Infections/inflamation
12
Q
Male infertility syndromes
A
- Cystic fibrosis (autosomal recessive, congenital absence of the vas)
- Primary ciliary dyskinesia (autosomal recessive, kartagener’s syndrome)
- Kallmans syndrome (absence of GnRH)
- Klinefelters syndrome (47 XXY, 48 XXXY)
13
Q
What test is performed to examine for ejaculatory duct obstruction?
A
- Trans rectal ultrasound (TRUS)
14
Q
Male infertility physical exam
A
- Signs of hypogonadism/gynecomastia
- Testicular size
*seminiferous tubules 85% of testes volume
- Prostate, penis, epididymis, vas (CF)
- Spermatic cords- varicocele
- Ejaculatory duct obstruction (TRUS)
15
Q
Male infertility lab exam
A
- Urinalysis
- Semen analysis:
*2 seperate specimens, 48-72hrs of abstinence
*volume, sperm density, motility, forward progression and morphology
*leukocytes
- Hormonal eval
*freq. of primary endocrine defects <3%
*FSH, LH, prolactin, testosterone
16
Q
Oligospermia
A
- Sperm density <50 million total
17
Q
Asthenospermia
A
- Defects in sperm motility
18
Q
Azoospermia
A
- Defects in sperm visualized
19
Q
Necrospermia
A
- Dead or immotile sperm identified
20
Q
Tetraspermia
A
- Defects in morphology
21
Q
Cryptospermia
A
- Live sperm seen in a centrifuged pellet
22
Q
Abnormalities of seminal fluid tests
A
- Quantitation of leukocytes in semen
*difficult to distinguish leukocytes from immature, round germ cells, use monoclonal assay
- Antisperm antibody testing
*ASA (anti-sperm antibody) should be suspected in clumping or agglutination, diminished motility and a poor post-coital test
*blood-testis barrier is breached
*immunobead test
23
Q
Abnormalities of sperm function tests
A
- Sperm capacitation assays
*capacitation is the hyperactive motility w/ cellular changes before the spermatozoa can bind to the zona pellucida and undergo the acrosome reaction
- Sperm penetration assay (Humster test)
*sperm are mixed w/ zona free hamster ovum
*timed penetration of the ovum
*SPA has a high predictive value for IVF outcome
24
Q
Male infertility genetic factors
A
- 13% of men w/ obstructed azoospermia and 6% of men w/ severe oligospermia have microdeletions of the “Y” chromosomes
- Klinefelter’s syndrome (XXY) can be found in 4-10% of men w/ non-obstructive azoospermia
- Congenital b/l absence of the vas deferens is caused by a mutation of the gene for cystic fibrosis transmembrane conductance regulator (CFTR)
- Careful consideration must be given to the potential for transmission of undesirable genes
25
Germinal Aplasia FSH, LH and Testosterone Levels compared to normal
- FSH = Elevated
- LH = Normal
- Testosterone = Normal or decreased
26
Testicular Failure FSH, LH and Testosterone Levels compared to normal
- FSH = Elevated
- LH = Normal or elevated
- Testosterone = Normal or decreased
27
Hypogonadotropic Hypogonadism FSH, LH and Testosterone Levels compared to normal
- FSH = Decreased
- LH = Decreased
- Testosterone = Decreased
28
Hypergonadotropic Hypogonadism FSH, LH and Testosterone Levels compared to normal
- FSH = elevated
- LH = Elevated
- Testosterone = Low-normal or decreased
29
Varicocele
- Most common surgically correctable cause of male infertility
- 33% of infertile males
- 15% in general pop.
- 90% left sided
- 50-90% show improved semen analysis
- 30-50% pregnancy rates
30
Hyperprolactinemia treatment
- Disease which can contribute to male infertility
- Bromocriptine
31
Kallmann's syndrome treatment
- Disease which can contribute to male infertility
- Gonadotropin (hCG) followed by hMG (pergonal)
32
Antisperm antibodies treatment
- Disease state which can contribute to male infertility
- Steroids
33
Retrograde ejaculation treatment
- Can be caused by damage to the bladder neck
- Antihistamine and alpha stimulation
\*used to attempt to tighten the bladder neck
34
Congenital adrenal hyperplasia treatment
- Glucocorticoids
35
Male Infertility Emperic Therapy
30-40% of infertile couples have no discernable etiology
- Anti-estrogens- clompiphene, tamoxifen
- hCG, hMG
- GnRH, LHRH
- Kallikrein
- Testosterone rebound
36
Intracytoplasmic Sperm Injection
- Partial zona dissection, subzonal insertion
- Significant improvement in IVF results w/ severe male factor
- 1 sperm is injected into the cytoplasm of 1 egg
- Sperm may be obtained directly from epididymis
- 66-70% fertilization rate
- "There no longer seems to be any category of male factor infertility that cannot be treated w/ ICSI"
- Extremely expensive
37
Erectile Dysfunction Diagnosis Statistics
- In the US, 83% of ED is not diagnosed
- Only 10-11% of total ED pop. is treated
38
Erectile Dysfunction Definition
- The inability to attain and/or maintain penile erection sufficient for satisfactory sexual performance
39
Erectile Dysfunction Prevalence
- Occurs in ~5% of men at age 40, w/ prevalence increasing to b/w 15-25% by age 65
- Community samples indicate a prevalence of 4-10%
- Prevalence of ED increases w/ age, but ED is not an invevitable and untreatable consequence of aging
40
3 Neuroeffector systems control smooth muscle relaxation and penile blood flow
- Adrenergic fibers
- Cholinergic fibers
- Nonadrenergic-noncholinergic (NANC) fibers
- Vasodilation mediated by nitric oxide and cGMP following activation of cholinergic and NANC fibers
- Prostaglandin E1: relaxes corpus cavernosum
- Flaccid state: penis under venous O2 tension and pressure
41
Causes of ED
- Vascular disease
- Neuropathy
- Iatrogenic factors
- Congenital abnormalities
- Peyronie's disease
- Psychological processes
- Drugsd
42
Treatment for ED
First-line therapeutic options
- Oral therapy: PDE5 inhibitors
- Psychosexual therapy
- Vacuum constriction devices
Second-line therapeutic options
- Intraurethral therapy
- Injection therapy
- Combination therapy
Third-line therapeutic options
- Surgery
43
Vascular Surgery for ED
- Generally considerd low success
- May be used to correct demonstrated venous leakage
- May have a limited role in correcting congenital vascular abnormalities or traumatic injury
- Long-term outcome may be poor
44
ED Hormonal Therapy
- Androgenic steroids
- May be effective in a small fraction of ED pts. w/ documented hypogonadism
- Oral, parenteral, transdermal preparations available
45
ED Hormonal Therapy ADRs
- Androgenic steroids can suppress remaining endogenous androgen production
- May be metabolized to estradiol w/ potentially detrimental effects on sexual function
- May increase risk of prostate hypertrophy
- Oral therapy may lead to liver dysfunction
46
Vacuum Constriction Devices for ED
- Most common device used for ED
- No tests required beyond initial evaluation
- High success rate, pt. satisfaction
\*90% achieve erections sufficient for intercourse
\*\>80% of pts. cont. use
47
Vacuum Constriction Devices for ED Adverse Effects
- Hematoma, ecchymosis, and petechiae
- Pain, numbness of penis; blocked and/or painful ejaculation; pulling of scrotal tissue into the vacuum cylinder
48
Penile Implants for ED
- 2 types: semirigid and multicomponent inflatable
- Pt. satisfaction rates range from 81-97%
- Avg. functional life of prostheses is 7-10yrs
- Useful in pts who fail or refuse other treatments
- Requires pt./partner screening and education
49
Penile Implant Complications
- Perioperative infection (~2%)
- Device malfunction (~4%)
- Repeat surgery (~9%)
50
Vasoactive Intracavernosal Pharmacotherapy for ED
- Intracavernosal injection of vasoactive agent (eg, alprostadil, phentolamine, papavarine)
- Relaxes cavernous and arterial smooth muscle
- Allows filling of the penile sinusoids w/ blood and restriction of venous outflow
- Agents may be used alone or in combination to increase efficacy and reduce adverse events
- Alprostadil most common; up to 94% efficacy
- Effective in pts. w/ neurogenic, vascular, hormonal and psychogenic dysfunction
51
Vasoactive Intracavernosal Pharmacotherapy Disadvantages
- Poor long-term tolerability: many pts. stop therapy during the 1st yr
- Bruising
- Prolonged erection
- Pain
- Induration, plaque or nodule
- Curvature of the penis
- Superfical infection
- Dizziness
52
Oral Pharmacologic Treatments for ED
- Yohimbine
- Trazodone
- L-arginine
- FDA-approved agents; PDE-5
\*sildenafil (viagra)
\*vardenafil (levitra)
\*tadalifil (cialis)
\*avanafil (stendra)
53
First-Line Treatment for ED
- PDE5 inhibitors
54
PDE5 Inhibitors MOA Graph
- PDE 5 inhibition causes cGMP accumulation ⇒ Increased cGMP accumulation relaxes the smooth muscle in the corpus cavernosum ⇒ Blood flow and erection are facilitated
55
Adverse Events with PDE5 Inhibitors
- Headache
- Facial flushing
- Dyspepsia
- Rhinitis/congestion
- Back pain
- Myalgia
- Vision disturbance
56
PDE5 Inhibitors Pharmacodynamic Interactions
- PDE5 inhibitors, nitrates and alpha-blockers all can cause vasodilation and decrease BP
- Nitrates stimulate cGMP production by delivering nitric oxide
- PDE5 inhibitors reduce breakdown of cGMP
\*systemic vasodilatory properties may result in transient decreases in BP in healthy
- Alpha-blockers inhibit pressor effects of epinephrine, leading to a fall in peripheral vascular resistance and venous return
\*assoc. w/ first-dose postural hypotension and syncope
- Additive effects of combining these classes of agents may cause increased risk for postural hypotension and syncope
57
PDE5 Inhibitors Metabolism
- PDE5 inhibitors are metabolized by cytochrome P450 enzymes in the liver, primarily CYP3A4
- Drugs that inhibit CYP3A4 will cuase decrease clearance of PDE5 inhibitors
\*erythromycin
\*ketoconazole
\*itraconazole
\*ritonavir
\*indinavir
58
Stepa after a patient failes PDE-5 inhibitor therapy
- Reeducate and re-challenge w/ same agent
- Switch to another PDE-5 inhibitor
- Try diff. therapeutic approach
\*vacuum constriction devices
\*PGE1 injections
\*implants
