Endocrine Infertility Flashcards
Which cells within the testes does LH stimulate and what does it make these cells produce?
Leydig Cells –> they are stimulated to produce testosterone
Which cells within the testes does FSH stimulate and what does it makes these cells produce?
Sertoli cells (in the seminiferous tuules) –> they are stimulated to produce sperm and inhibin A and B
What does inhibin inhibit?
Pituitary FSH secretion
What are the three phases of the menstrual cycle?
Follicular Phase
Ovulation
Luteal Phase
What does LH stimulate in the ovaries?
Oestradiol and progesterone production
What does FSH stimulate in the ovaries?
Follicular development and inhibin production
What effect does oestrogen have on the HPG axis in the follicular phase of the menstrual cycle?
It has a negative feedback effect – inhibits FSH and LH (until a point)
What does the leading follicle develop into by around day 10?
Graffian Follicle
Once oestrogen reaches a certain level it switches to positive feedback. How does it do this?
It increases the GnRH secretion
It increases LH sensitivity to GnRH
Define infertility.
Inability to conceive after 1 year of regular unprotected sex
What is primary gonadal failure and what effects does it have on the HPG axis?
- gonads fail
- testes/ovaries don’t produce enough testosterone/oestrogen so there is no negative feedback on the HPG axis meaning that you get high GnRH, high LH and high FSH but NO inhibin
Describe the levels of the different hormones in the HPG axis in the case of hypothalamic/pituitary disease causing infertility.
-hypothalamus/pituitary fail so Low GnRH Low FSH Low LH - and low/no inhibin/testosterone
State some of the clinical features of male hypogonadism.
Loss of libido Impotence Small testes Decreased muscle bulk Osteoporosis (testosterone has anabolic action in the bone) - due to no testosterone
State 5 causes of male hypogonadism.
- Hypothalamic-pituitary disease
- Hypopituitarism
- Kallmans syndrome (anosmia-loss of smell & low GnRH)
- Illness/underweight (low BMI) - Primary gonadal disease
- Congenital: Klinefelters syndrome (XXY)
- Acquired: Testicular torsion- spermatic cord twists, cutting off the blood supply to the testicle, Chemotherapy - Hyperprolactinaemia
- Androgen receptor deficiency
State some congenital and acquired causes of primary gonadal disease.
Congenital: Klinefelter’s Syndrome (XXY)
Acquired: Testicular torsion, chemotherapy
What are the main investigations for male hypogonadism?
- LH, FSH and testosterone (if all are low –> MRI to check pituitary problem)
- Prolactin
- Sperm count (azoospermia – absence of sperm in ejaculate; oligospermia – reduced number of sperm in ejaculate)
- Chromosomal analysis (check for Klinefelter’s)
What is given to all patients with hypogonadism?
HRT
Testosterone to increase muscle bulk and protect against osteoporosis
How do you restore fertility in someone with hypothalamic/pituitary disease?
Subcutaneous gonadotrophin (LH & FSH) injections – stimulates testosterone release
What is the treatment for hyperprolactinaemia?
Dopamine agonists to inhibit prolactin – bromocriptine and cabergoline
State some endogenous sites of production of androgens.
- Interstitial leydig cells in the testes
- Adrenal cortex
- Ovaries
- Placenta
- Tumours
What are the main actions of testosterone?
- Development of the male genital tract
- Maintains fertility in adulthood
- Control of secondary sexual characteristics
- Anabolic effects (muscle, bone)
Testosterone is heavily plasma protein bound (98% circulating) and it can be converted to other hormones in various tissues. State two products that testosterone can be converted to and the enzymes responsible for these conversions.
- Converted by 5-alpha-reductase to dihydrotestosterone (DHT), which acts on androgen receptors (AR)
- Converted by aromatase to 17-beta-oestradiol (E2), which acts on oestrogen receptors (OR)
What type of receptors does DHT and E2 act on?
Nuclear receptors (as they are steroid hormones)
What are the clinical uses of testosterone?
INCREASES: 1. Lean body mass 2. Muscle size and strength 3. Bone formation and bone mass 4. Libido and potency NOTE: it does NOT restore fertility without gonadotrophins
