Endocrine Infertility Flashcards
Draw the hypothalamo-pituitary-gonadal axis for males and females
See diagram and notes
LH stimulates testosterone production in the leydig cells - testosterone has a negative feedback effect.
FSH stimulates sertoli cells in the seminiferous tubules - sperm and inhibin A. Inhibin also has a negative feedback
Oestradiol initially has a negative feed back on FSH and LH. At high enough concentration it switches to a positive feedback.
What are the main actions of testosterone?
Secondary sexual characteristics and spermatogenesis Anabolic effect (muscle and bone) Maintains fertility in adult hood Development of the male genital tract
What are the phases of the menstrual cycle?
28 day menstrual cycle
Follicular phase (same as men; draw HPG axis)
Ovulation (surge in LH -egg maturation and ovulation)
Luteal phase
See notes
Define infertility
Inability to conceive after 1 year of regular unprotected sex. Affects 1:6 couples
Caused by abnormalities
1) in males 30%
2) in females 45%
3) unknown 25%
Describe primary gonadal failure
The testes/ovaries are defective resulting in low testosterone/oestradiol but a high GnRH and high LH and FSH
Describe hypo/pituitary disease
Inability for pituitary gland to produce FSH and LH so low levels of FSH and LH as well as low oestradiol/testosterone.
What are the clinical features of male hypogonadism?
Loss of libido Impotence Small testes Decrease muscle bulk Osteoporosis
What are the causes of male hypogonadism?
Hypothalamic-pituitary disease
1) Hypopituitarism
2) Kallmans syndrome (anosmia(lack of smell) & low GnRH)
3) Illness/underweight - mainly due to low levels of leptin which tells your body you are too underweight, not a suitable time to reproduce
Primary gonadal disease
1) Congenital: Klinefelters syndrome (XXY)
2) Acquired: Testicular torsion, chemotherapy
Hyperprolactinaemia
Androgen receptor deficiency - RARE
How do you investigate male hypogonadism?
Measure LH, FSH, Testosterone - if all are low they then carry out an MRI for the pituitary to check for pituitary problem
Measure prolactin
Spermcount: Azoospermia and Oligospermia. You look under the microscope to check numbers and motility
Chromosomal analysis (XXY)
See notes - intracytoplasmic sperm injection
Define azoospemia and oligospermia
azoospermia = absence of sperm in ejaculate oligospermia = reduced numbers of sperm in ejaculate
How do you treat male hypogonadism?
Replace testosterone - increase their muscle bulk and protect against osteoporosis
For fertility: if hypothalamic/pitutary disease - subcutaneous gonadotrophin injections which induce spermatogenesis
Hyperprolactinaemia - dopamine agonist (cabergoline)
What are the endogenous sites of production of androgens?
1) Interstitial leydig cells of the testes
2) Adrenal cortex
3) Ovaries
4) Placenta
5) Tumours
How does testosterone move around in the circulation?
Heavily protein bound - 98% protein bound
What can testosterone be converted to and how?
Testosterone is converted to dihydrotestosterone (DHT) by 5a-reductase which acts via the androgen receptor
It can also be converted to 17b-oestradiol by aromatase which acts via the oestrogen receptor.
Tissue dependent on what testosterone is converted to.
Both receptors act via nuclear receptors - intracellular. They have to go through the nucleus to have an effect
What are the clinical uses of testosterone?
Increase: Lean body mass Muscle size and strength Bone formation and bone mass Libido and potency
It will not restore fertility
What are the gonadal disorders in females?
Amenorrhoea
Polycystic Ovarian Syndrome
Hyperprolactinanaemia
Describe ammenorrhoea
Abscence of periods
Primary - failure to begin spontaneous menstruation by age 16 years. Suggests congenital problem
Secondary - absence of menstruation for 3 months in a woman who has previously had cycles
Oligomenorrhoea = irregular long cycles
What are the causes of ammenorrhoea I (at the ovaries)?
Pregnancy
Lactation - high prolactin suppresses periods
Ovarian failure
1) Premature ovarian failure (early menopause)
2) Ovariectomy/chemotherapy
3) Ovarian dysgenesis (turners 45XO) - lacking X chromosome
What are the features of Turner’s syndrome?
Short stature
Cubitus Valgus (where the forearm is angles away from the body to a greater degree than normal when fully extended)
Gonadal dysgenesis (defective development)
1:5000 live female births
What are the causes of ammenorrhea II (hypothalamo-pituitary level)?
Gonadotropin failure
1) Hypo/pituitary disease
2) Kallmann’s syndrome (anosmia, Low GnRH)
3) Low BMI
4) Post pill ammenorrhoea - Periods won’t come back for 12 months after stopping it after a long use. Stop using pill every 4 years
Hyperprolactinaemia
Androgen excess: gonadal tumour - easy to diagnose since T in excess. RARE
How do you investigate ammenorrhoea?
Pregnancy test LH, FSH, oestradiol Day 21 progesterone Prolactin, Thyroid function tests Androgens (testosterone, androstenedione, DHEAS) Chromosomal analysis (Turner's) Ultrasound scan ovaries/uterus
See notes
How do you treat ammenorrhoea?
Treat the cause (e.g low weight) Primary ovarian failure - infertile, HRT Hypothalamic/pituitary disease 1) HRT for oestrogen replacement 2) Fertility: gondadotrophins (LH and FSH) - part of IVF treatment
Describe PCOS
Polycystic ovarian syndrome. 1:12 women affected of reproductive age
Associated with increased cardiovascular risk and insulin resistance
What are the criteria to diagnose PCOS?
Polycystic ovaries on USS
Oligo-/anovulation
Clinical/biochemical androgen excess
