Male reproductive physiology and hypogonadism Flashcards
What 2 structures do the testes contain
seminiferous tubules composed of Sertolli cells and germ cells
Interstitial containing Leydig cells that produce testosterone
What stimulates the secretion of GnRH
hypothalamic neurones
What stimulates the release of LH and FSH
Pulsatile GnRH
How does GnRH stimulate the release of LH and FSH
it binds to receptors on the plasma membrane of pituitary gonadotrophs and stimulates their release by a calcium-dependent mechanism that may involved diacyclglycerol
What are LH and DSH composed of
two glucoprotein chains
What do LH and FSH do
They interact with cell membrane receptors and stimulate adenylate cyclase
What does LH stimulate in males
The production of testosterone by Leydig cells
The synthesis of testoereon by actin gone the steroidogenic acute regulatory protein which delivers cholesterol to the inner mitochondrial membrane where it is converted to pregnenolone
Sperm are produced under the stimulation of what
testosterone and FSH
What inhibits FSH secretion
inhibin B as well as testosterone and estradiol
What modulate GnRH secretion
several hormones, neurotransmitters and cytokines
When might testosterone levels be reduced
acute and chronic illnesses and fasting
How much plasma testosterone is free (unbound)
2%
Some testosterone is bound to a hepatic glycoprotein. What is this called
sex hormone-binding globulin
What is the other protein that testoesterone can be bound to
albumin
What can cause an increase in SHGB
Ageing antiepileptic agents liver disease oestrogens thyrotoxicosis growth hormone deficiency
What can cause a decrease in SHGB
Diabetes mellitus Obesity corticosteroids, anabolic steroids hypothyroidism acromegaly
Why is it that changes in the SHBG levels do not affect free androgen levels
Hypothalamic-pituitary system responds to acute changes in the concentrations of bioavailable testosterone by altering testosterone synthesis
What are the physiological actions of tester one
The result of the combined effects of testosterone and its active metabolites
What are the major functions of androgens in males
regulation of gonadotrophin secretion from the hypothalamic-pituitary system
initiation and maintenance of spermatogenesis
formation of the male genital tract during embryogenesis
development of male secondary sexual characteristics and sexual potency at puberty and their maintenance there after
What is male hypogonadism
a syndrome of decreased testosterone production, sperm production or both
What might hypogonadism result from
disease of the testes (primary hypogonadism)
disease of the pituitary or hypothalamus (secondary hypogonadism)
Why is primary hypogonadism also sometimes known as hypergonadotrophic hypogonadism
reduced testosterone levels result in elevated gonadotrophin levels (negative feedback effect)
What are some of the congenital causes of primary hypogonadism
Klinefelter’s syndrome
Cryptorchidism
Other chromosomal abnormalities
What is the most common cause of primary hypogonadism
Klinefelter’s syndrome
What causes Klinefelter’s syndrome
1 or more extra chromosome
This results in damaged seminiferous tubules and Leydig cells
What is the most common Klinefelter’s genotype and what does it result from
47XXY
Non-disjunction of the sex chromosomes of either parent during meiotic division
What are some other symptoms of Klinefelter’s syndrome
Intellectual dysfunction and behaviour abnormalities that cause difficulty in social interactions
Predisposition to developing chronic bronchitis, bronchiectasis and emphysema, breast cancer, non-Hodgkin’s lymphoma, varicose veins, leg ulcer,s diabetes mellitus
What does Cryptorchidism refer to
unilateral or bilateral undescended tests (in the abdominal cavity or in the inguinal canal) that cannot be manipulated manually in the scrotum by the age of 1 year
What are some acquired causes of primary hypogonadism
Infections Testicular trauma or torsion chemotherapy radiotherapy autoimmune damage chronic illness e.g. COPD congestive cardiac failure Crohn's disease coeliac disease chronic liver disease RA chronic kidney disease AIDS
What is secondary hypogonadism due to
Impaired secretion of hypothalamic GnRH or pituitary gonadotrophins
What might congenital secondary hypogonadism be associated with
anosmia in Kallmann’s syndrome
What is Kallmann’s syndrome sometimes associated with
red-green colour blindness
midline facial abnormalities (e.g. cleft palate)
urogenital tract abnormalities
synkinesis (mirror movements of the hands)
hearing loss
What might secondary hypogonadism be caused by
Any pituitary or hypothalamic disease such as pituitary adenoma, craniopharyngioma, pituitary surgery, infarction, infection, infiltrative disorders such as haemochromatosis, sarcoidosis, histiocytosis, TB and fungal infections
What can suppress gonadotrophin secretion
chronic systemic illness diabetes mellitus hyperprolactinaemia androgen excess cortisol excess oestrogen excess chronic opiate administration GnRH analogues
What does the clinical presentation depend on
whether the onset of hypogonadism is before or after puberty
What are the clinical presentation of hypogonadism before the onset of puberty
Delayed puberty
Testes
What are the clinical presentation of hypogonadism after the onset of puberty
Fatigue, reduced energy and lowered physical strength
low mood, irritability and poor concentration
reduced libido and/or sexual function. loss of spontaneous morning erections and infertility
osteoporosis and fragility fractures
Soft tests
What is the major action of testosterone on male sexuality
libido
What is primary hypogonadism more likely to be associated with
gynaecomastia - due to the stimulation of testicular aromatase activity by the increased serum FSH and LH resulting in increased conversion of testosterone to estradiol and also increased testicular secretion of estradiol relative to testosterone
How can a diagnosis of hypogonadism be confirmed
by finding low serum testosterone and or decreased sperm in the semen
Describe the variation in levels of serum testosterone
Diurnal variation - maximum at about 9 am and lower levels in the evening
What levels of LH and FSH indicate testicular damage (primary hypogonadism)
High concentrations
What levels of LH and FSH indicate pituitary or hypothalammic disease
Low or inappropriately normal
What should men with primary hypogonadism have done
A peripheral leukocyte karyotype to determine whether Klinefelter’s syndrome is present
What is the treatment for hypogonadism
Directed at any underlying disorders
Relieve symptoms and preserve bone density
Pre-puberty boys should be started on low doses of testosterone that are gradually increased
Where is testosterone gel applied
Should and upper arm
What are some advantages of and disadvantages of the gel
Advantages - self-administration, avoidance of painful injections, dries quickly
Disadvantages - could be transferred to partner through skin contact , patients should not shower for 6 hours
What are some disadvantages of IM testosterone
Pain at injection site
More mood swings
Only every 2-3 weeks
What are some advantages and disadvantages of subcutaneous testosterone implants
Only every 6 months
Minor surgery
Complications include infection, bleeding, extrusion and scarring
What are some side effects of testosterone replacement
Acne on the upper trunk Prostate enlargement Polycythaemia Gynaecomastia Fluid retention Sleep apnoea mood fluctuations
What are some contraindications of testosterone replacement
Prostate cancer Polycythaemia breast carcinoma sleep apnoea conditions in which fluid retention may be harmful
How are men with secondary hypogonadism who desire fertility treated?
With gonadotrophin replacement or pulsatile GnRH therapy
What should be asked about in a follow up appointment
Improvements in symptoms Weight gain peripheral oedema gynaecomastia In men over 40, PR exam
What lab tests should be measured in follow up
Haemoglobin
Prostate -specific antigen (PSA)
LFT and fasting lipid profile
Testosterone levels
