What is the most common cause of infertility in males?
Varicocele - “bag of worms”
– Too much blood in the scrotum causing the newly created sperm to become nonfunctional.
What is the first step in evaluating infertility in males?
– Thorough History –
Then Seman Analysis
How should you read a semen analysis report?
- -Concentration should be 20mil/mL+
- -Motility needs to be 50%+
After intervening in fertility, how long until the changes take effect?
Approximately 90 days
- -70 days for development
- -20 days for traveling through the spermatocord
If there is a central pathology causing abnomrally low levels of LH, what might be the physiologic effect be?
– Low Testosterone
LH binds to Leytig Cells inducing steroidogenesis
If upon physical exam there seems to be a missing vas deferens, what might also be present?
- -Cystic Fibrosis Gene copy
- -5T-Allele
Do patients with CF still produce sperm normally?
– Spermatogenesis is not affected, but they do not produce as much fluid
If the patient is missing a vas deferens, but tested negative for any CF gene copies, what else might be going on?
- Renal Agenesis
Check for a missing kidney using Ultrasound!
-Can be completely asymptomatic before discovering they are infertile.
What are the two causes of premature puberty?
Gonadotropin-Dependent Prematurity
–unknown cause of early maturity of hypothalamic gonadal-axis
Gonadotropin-Independent Prematurity
–Excessive secretion of sex hormones from somewhere int he body
What are common associations with Gonadotropin-Dependent Prematurity?
- -Females
- Can be CNS tumor secreting gonadotropin or abnormality affecting the pituitary gland.
- Hydrocephalus, Trauma, CNS inflammation, etc
- -Hamartoma
What are the gene associations with GDPP?
Upregulation of:
- -Kisspeptin-1
- -KISS-IR
If you are seeing a 6 year old female in the office and suspect she is undergoing premature puberty and you initially test her LH levels resulting in a borderline elevated level, if you give GnRH and it elevates LH levels, what is her diagnosis?
GDPP – this is because the hypothalamic-pituitary steroidal axis has been activated and is elevating LH levels.
If you are seeing a 6 year old female in the office and suspect she is undergoing premature puberty and you initially test her LH levels resulting in a borderline elevated level, if you give GnRH and it has no effect on LH levels, what is her diagnosis?
GIPP – this is because the sex hormones are being secreted from somewhere else in the body independent of LH levels.
If you are seeing a 6 year old female of suspected early onset puberty and notice she has a several centimeter cafe au lait spot on her chest, what might be your concerns?
McCune Albright Syndrome Triad includes: - Premature Puberty - Cafe au Lait spots - Fibrous Dysplasia of Bone
How is GIPP different from incomplete premature puberty?
Incomplete Premature Puberty, is isolated to only male sexual characteristics.
GIPP - is full blown puberty
What are the most important exams to perform when evaluating for premature puberty?
- Fundoscopic – to look for CNS abnormals (hydrocephalus or tumor increasing pressure)
- Visual Field – optic nerve interruption
- Dermatologic – cafe au lait
- Tanner Staging/Bone Age
What is the overarching cause of GIPP?
- over expression of sex hormones from gonads, andrenal, or ectopic production of gonadotropin
- inducing pre-mature puberty
What can be a common cause of both male and female premature puberty?
Leydig/Theca Cell tumors
– secrete hormones without LH stimulation
hCG secreting germ cell tumors (anywhere located)
What are the common adrenal pathologies associated with GIPP?
- 11 Beta-hydroxylase deficiency
- 3 Beta-hydroxysteroid dehydrogenase
- Hexose 6 phosphate dehydrogenase
- PAPss2 Deficiency
- *Glomerulusa Reticularis Adenoma
How can you confirm a diagnosis of gonadotrophin dependent premature puberty?
- Look for elevated FSH / LH
- - If you give GnRH, then will elevate LH
How is the testing and plan of treatment for GIPP different from GDPP?
You are testing to see if the hypothalamus is the cause, if not then you are looking for the source in the body somewhere of the steroid hormone production.
If GDPP is confirmed with elevated LH levels, then what do you do next?
- You need to figure out if the other pituitary hormones are imbalanced as well. Test for TSH, Estrogen, T4
- Pituitary MRI to look for tumor causing it
How do you treat GDPP after diagnosis has been confirmed and there is no tumor?
Goal is to have patient is normal height in adulthood
- -Antagonize GnRH = Leuprilide (downregulates receptors)
- -Treat patient until they are appropriate to resume puberty, which occurs 17 months after stopping treatment
- Give dose of Leuprolide every 3 months, adjust dose if puberty is not being suppressed.
Once a diagnosis of GIPP has been confirmed what are the next steps to be taken?
- Locate the primary cause of the symptoms
- Aromatase Inhibitors
- Spironolactone
- Ketoconazole (inhibits androgen synthesis, hepatotoxicity though)
Upon diagnosing a patient with premature puberty their LH/FSH are suppressed, but their testosterone is elevated. What other tests might you perform to help narrow your diagnosis?
- Test for Cortisol levels
- hCG levels
- DHEA/DHEAS , 17hydroxyprogesterone
If you diagnose a patient with GIPP due to low LH levels, then discover they have elevated hCG, what might you be suspicious of?
- Can be Choriocarcinoma, check the mediastinum region, if that is location — Karotype the patient
- Could be Klinefelter’s (XXY)
What is the most common cause of delayed onset puberty?
– inadequate steroid secretion due to low LH/FSH or GnRH
If you are seeing a 15 year old male who has not undergone any puberty changes and you test his LH/FSH and its HIGH, what might be the next step?
Karotype
- if chromosomal abnormalities - XXY/ XX-male / XO
- if Normal 46 XY, then something more primary like adrenal insufficiency or testis dysfunction
- *The body is trying to make more steroids, but is unable to for some reason or another**
If you are seeing a 15 year old male who has not undergone any puberty changes and you test his LH/FSH and its Low along with low testosterone, what might be the next step?
If LH/FSH is low, Family History (watchful waiting?)
- -Could be Chronic Illness / Anorexia preventing the body from turning on puberty until its ready
- Elite Atheletes
- Enzyme deficiency?
If you are evaluating a 16 year old patient who has not undergone puberty. Testing indicates normal levels of FSH/LH, but low testosterone levels, what is the next step?
– MRI Head
With low testerosterone, FSH/LH should NOT be normal or Low at that. (inappropriately normal)
There is likely a central process occurring that is preventing increased secretion of FSH/LH
A patient is known to have a 5-alpha reductase deficiency, what might be the clinical presentation of the patient?
– ambiguous or small genitalia for a male
due to being unable to produce DHT, but at puberty there will be an increase in size of the genitalia since testosterone is increased more
If a male is diagnosed with a prolactinoma, what might be some sexual side effects experienced by the patient?
–Prolactin suppresses LH/FSH secretion, so the patient would be lowered testosterone and sexual dysfunction
