male reproductive issues richard e. freeman md mph 2013 lock haven university
TRANSCRIPT
Male Reproductive Issues
RICHARD E. FREEMAN MD MPH
2013
LOCK HAVEN UNIVERSITY
SPERMATOGENESIS
SPERMATOGENESIS
INFERTILITY
DEFINITION: Inability to conceive a child WHO
– A couple may be considered infertile if, after two years of regular sexual intercourse, without contraception, the woman has not become pregnant (and there is no other reason, such as breastfeeding or postpartum amenorrhea)
USA– a woman under 35 has not conceived after 12 months of contraceptive-free
intercourse
– a woman over 35 has not conceived after 6 months of contraceptive-free intercourse.
Primary infertility is infertility in a couple who have never had a child. Secondary infertility is failure to conceive following a previous pregnancy.
GENERAL ~ 10% couples are affected by
infertility ~40% are from male factors! ~30% of the 40% male factors…cause
is unknown
History
DETAILED SEXUAL HISTORY DETAILED PREGNANCY HISTORY
Medical History
Childhood illnesses– post pubertal mumps orchitis and testicular trauma or
torsion Cancer chemotherapy/radiation – destroys germinal epithelium-dose dependent Diabetic neuropathy
– may result in either retrograde ejaculation or impotence DES exposure
– epididymal cysts or cryptochordism Precocious puberty
– adrenal-genital syndrome• Congenital adrenal hyperplasia
Delayed puberty– Klinefelter's syndrome or idiopathic hypogonadism
History
Hernia repair Cystic fibrosis (CBAVD) Mumps Thyroid disease Prolactinoma
History - Drugs Influence Reproductive cycle and male
hormone– anabolic steroids, cimetidine, and
spironolactone Sperm Motility
– sulfasalazine and nitrofurantoin Decrease count and hormone interference
– Illicit drugs and alcohol (Liver failure)– Seizure meds… FSH
SOCIAL HISTORY
Occupational and environmental toxins,
Excessive heat-iron foundry worker Radiation- x-ray tech Illicit drug use
Physical Exam
Look for HYPOGONADISM!– poorly developed secondary sexual
characteristics– eunuchoidal skeletal proportions
• Arm span longer than height• Crown to pubis:Pubis to floor ratio <1
– sparse male hair distribution– infantile genitalia– muscle mass & development
Physical Exam
Hypogonadism may be associated with:– anosmia- inability to smell – color blindness,– cerebellar ataxia, hair lip, and cleft palate.
(Kallmann syndrome-isolated gonadotropin – FSH/LH – deficiency with anosmia)
Thyroid Liver Neuro GU prostate exam
LABS
FSH, LH DHT TSH ACTH GH Post coital
DFI Anti sperm
antibodies SPA (semen
penetration assay)
Special Tests
Vasography Testicular biopsy Ultrasound – color flow
Sperm Count
Fresh sample (to lab within 30 mins.) –most sperm in initial ejaculateMale should be abstinent for 48 to 72 hours
sperm concentration > 20 million per mltotal count > 60 million/SAMPLEejaculate volume > 1.5 mltotal motile count > 30 millionviable sperm > 50%normal shapes (morphology) > 60%
Sperm TermsNormozoospermiaNormal ejaculate
AsthenozoospermiaIatrogenic/abstinence
Varioceles, cilia anomalies, Anti-spm Ab
Teratozoospermia
Azoospermia
Aspermia
Normal ejaculate Sperm concentration >20 million/ml<50% spermatozoa with forward progression<30% spermatozoa with normal morphology
No spermatozoa in the ejaculateNo ejaculate
MALE INFERTILITY:CLASSIFICATION PRE-TESTICULAR TESTICULAR POST-TESTICULAR
Hypothalamic disease HYPOGONADROTROPIC HYPOGONADISM
– Isolated gonadotropin deficiency (Kallmann's syndrome)
– Isolated LH deficiency• ("Fertile eunuch")
– Isolated FSH deficiency – Congenital hypogonadrotropic
syndromes
PRE-TESTICULAR CAUSES OF INFERTILITY:secondary testicular failure
Pituitary disease – Pituitary insufficiency
• (tumors, infiltrative processes, operation, radiation)
– Hemochromatosis – EXOGENOUS HORMONES – Estrogen excess– Androgen excess– Glucocorticoid excess– Hyperprolactinemia – Hyper and hypothyroidism
PRE-TESTICULAR CAUSES OF INFERTILITY: secondary testicular failure
ENDOCRINE CAUSES– EXOGENOUS HORMONES – Estrogen excess:
– Inhibits GnRH » also direct effects on spermatogenesis
– Low FSH/LH/Testosterone • ETIOLOGY
– Hepatic disease – estrogen secreting tumor
OBESITY– Androgen excess:
– Direct feedback inhibition on the hypothalmus– Low intratesticular testosterone (necessary for
spermatogenesis– Endogenous-congenital adrenal hyperplasia, tumors– Exogenous – anabolic steroids
– Glucocorticoid excess
– – Hyper and hypothyroidism
Hyperprolactinemia ETIOLOGY:
medications, stress, pituitary adenoma S/S:
erectile dysfunction low testosterone decreased libido
Dx: Screening-- low yield Prolactin level MRI –sella tursica
TX: Surgical excession of pituitary tumor
(adenoma) Cabergoline(Dostinex)
dopamine 2 receptor agonist
TESTICULAR CAUSES: GENETICSPrimary Testicular failure
Y Chromosomal abnormalities (Klinefelter's syndrome, XX disorder (sex reversal syndrome), XYY syndrome)
Noonan's syndrome (male Turner's syndrome)
Myotonic dystrophy
Bilateral anorchia (vanishing testes syndrome)
Sertoli-cell-only syndrome (germinal cell aplasia)
TESTICULAR CAUSES:Primary Testicular failure
VARICOCELE Gonadotoxins (drugs, radiation) Orchitis Trauma Systemic disease
– (renal failure, hepatic disease, sickle cell disease)
Defective androgen synthesis or action Cryptorchidism IDIOPATHIC-Majority
VARICOCELE Most common Attributable cause of Primary and secondary infertility in
males- 40% Left sided
– -right angled insertion of L testicular vein into the L renal vein- less valves– Theories– Temperature elevation
– Reflux of toxic renal and adrenal metabolites– Gonadotoxin metabolite clearance impairment
Treatment: LIGATION – improves sperm count and semen quality INDICATIONS
– Palpable varicocele on exam
– known infertility
– Female partner has normal fertility
– Male- abnormal semen parameters
– +- discomfort
– ADOLESCENT MALE: Testicular hypotrophy (20% discrepancy in size)
Disorders of sperm transport – Congenital disorders-
• Congenital Bilateral absence of the Vas deferens (CBAVD)
• - Cystic Fibrosis- CF transmembrane conductance regulator test
– Acquired disorders – Functional disorders
POST-TESTICULAR CAUSES OF INFERTILITYSPERM TRANSPORT
POST-TESTICULAR CAUSES OF INFERTILITY:SPERM MOTILITY Disorders of sperm motility or
function – Congenital defects of the sperm tail
• Primary Ciliary Dyskinesia (PCD) effects other organs with cilia
– Maturation defects• Globozoospermia –
– “round-headed sperm syndrome” – No acrosin-no penetration of zona pellucida
• Fibrous Sheath Dysplasia- – “stump tail syndrome” – short coiled immotile tails (genetic counseling suggested)
– Immunologic disorders- – Infection
SPERM DNA FRAGMENTATION
If greater than 30% have a DNA fragmentation index (DFI):
– Reduced fertility potential– Reduction in term pregnancies– Doubling in miscarriages– “Normal” (morphology and motility) sperm
may have DNA fragmentation!
Causes of DFI
Age…>46 Pollution Smoking Febrile illness Drugs Radiation Chemicals
Testicular cancer Varicocele Prolonged heat:
– Hot tubs– Truck drivers– Cyclists
AZOOSPERMIA
TRUS=Transrectal ultrasound
Obstructive – 40%
INFERTILITY Treatment Find the cause!!!! PESA/MESA
– microsurgical epididymal sperm aspiration TESE
– testicular sperm extraction IVF-
– invitro fertilization AIDS
– –artificial insemination by donor TUREJD
– -Transurethral resection of the ejaculatory ducts.shtml
INFERTILITY MEDICATIONS
Gonadotropin-Releasing hormone agonists
Gonadotropins- LH FSH Anti-estrogens:
• - Clomiphene, Tamoxifen
Aromatase inhibitors: • – Testolactone /Anastrozole
– aromatase converts testosterone to estradiol
Antioxidants– -L-carnitine, Kallikrein, Thyroid
Male Menopause
Male Menopause - Andropause
Occurs between 45-60 and is a gradual decline over the years
1/10 will experience hot flashes Also called…
– Hypogonadism– Male climacteric– Viropause – ADAM (androgen decline in aging
males)
Andropause
By age 80, testosterone levels are around pre-pubertal levels!
Physical Symptoms Taking longer to recover from injuries and illness. Less endurance for physical activity. Feeling fat and gaining weight. Difficulty reading small print. Loss or thinning of hair. Sleep disturbances and fatigue. "Sore body syndrome" - stiffness. Excessive sweating. Cold hands and feet. Itching.
Psychological Symptoms
Irritability. Indecisiveness. Anxiety and fear. Depression. Loss of self-confidence and joy. Loss of purpose and direction in life. Feeling lonely, unattractive and unloved. Forgetfulness and difficulty concentrating.
Sexual Symptoms Reduced interest in sex. Increased anxiety and fear about losing
sexual potency. Increased fantasies about having sex
with a new and younger partner. More relationship problems and fights
over sex, love and intimacy. Loss of erection during sexual activity
(impotence).
Sexual Symptoms cont’d
There is less of an urge to ejaculate. The force of ejaculation is not as strong
as it once was. The amount of the ejaculate is less and one may have fewer sperm.
The testicles shrink and the scrotal sack droops. The sack does not bunch up as much during arousal.
Low T2 in men may cause…
Angina Atherosclerosis High blood cholesterol High blood triglycerides High blood pressure. High body mass index (obesity). Osteoporosis
Labs
DHEA SulfateDihydrotesterone(DHT)EstradiolLHIGF-1Testosterone, Total & Free Total Testosterone Free Testosterone %Free
Thyroid Panel Free T3 Free T4 TSH
PSA
Treatment
Viagra, Levitra, Cialis Testosterone replacement therapy - TRT
– Side Effects:• Increase cholesterol • Increase blood pressure• Growth of body hair• Male-pattern baldness• Acne • Fluid retention• aggression
TRT – Cont’d
Monthly injections Patch - scrotum Implants q 4 mos
QUESTIONS ?????
SOURCE: Wein: Campbell-Walsh Urology 10th ed Chapter 21 Male infertility 2011 Saunders
Can be accessed on MD Consult