Endocrine infertility Flashcards
Which cells within the testes does LH stimulate, and what do these cells produce?
Leydig Cells
They are stimulated to produce testosterone
Which cells within the testes does FSH stimulate, and what do these cells do?
Sertoli cells (in the seminiferous tubules) They help in the process of spermastogenesis (by nourishing germs cells), and produce inhibin A and B
What does inhibin do?
Inhibits FSH secretion from the anterior pituitary (negative feedback)
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 at the level of the hypothalamus and pituitary
What happens right before ovulation when oestradiol reaches a certain level? State the impact of this
It switches to having a positive feedback effect at the level of the hypothalamus - increasing GnRH secretion and LH sensitivity to GnRH.
Causes an LH surge necessary for ovulation
Define infertility.
Inability to conceive after 1 year of regular unprotected sex
What is primary gonadal failure?
It is a problem with the gonads
The testes/ovaries don’t produce enough testosterone/oestradiol => no negative feedback on the HPG axis => high GnRH, high LH and high FSH.
Describe the levels of GnRH, LH and FSH in the case of hypothalamic/pituitary disease causing infertility.
Low GnRH
Low FSH
Low LH
State some of the clinical features of male hypogonadism.
Loss of libido Impotence Small testes Decreased muscle bulk Osteoporosis
State and catagorise 5 causes of male hypogonadism.
Hypothalamic-pituitary failure:
- Hypopituitarism
- Kallman’s syndrome (anosmia & low GnRH)
- Illness
- Underweight (due low levels of leptin hormone produced by adipose tissue)
Primary gonadal disease:
- Congenital = Klinefelters syndrome (XXY)
- Acquired = testicular torsion, Chemotherapy
Hyperprolactinaemia
Androgen receptor deficiency
What are the main investigations that may be carried out for male hypogonadism?
- If LH, FSH and testosterone levels are all low, do an MRI scan to check for a pituitary problem
- Check prolactin levels
- Do a sperm count; Azoospermia = absence of sperm in ejaculate
Oligospermia = reduced numbers of sperm in ejaculate - Chromosomal analysis (check for Klinefelters)
What is given to all patients with hypogonadism?
Testosterone replacement
How would you treat a patient with secondary hypogonadism who is looking to restore fertility?
Subcutaneous gonadotrophin (LH, FSH) injections
What is the treatment for hyperprolactinaemia?
- Dopamine agonists e.g. bromocriptine and cabergoline
- Pituitary surgery (rarely used) if vision is affected by the prolactinoma
State some endogenous sites of production of androgens
- Interstitial leydig cells in the testes
- Adrenal cortex (males and females)
- Ovaries
- Placenta
- Tumours
What are the main actions of testosterone?
- Development of the male genital tract
- Maintain fertility in adulthood
- Control of secondary sexual characteristics (puberty)
- Anabolic effects in muscle and bone
Testosterone is heavily plasma protein bound 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)
- Converted by aromatase (in brain and adipose tissue) to 17-beta-oestradiol (E2)
Name and state the type of receptors that DHT and E2 act on
DHT - androgen receptors
E2 - oestrogen receptors
They are Nuclear receptors
State the clinical uses of testosterone replacement. What will it NOT do?
To increase:
- lean body mass
- muscle size and strength
- bone formation and bone mass (in young men)
- libido and potency
It will not restore fertility
What is the difference between primary and secondary amenorrhoea? What is oligomenorrhoea?
Primary Amenorrhoea = failure to begin spontaneous menstruation by the age of 16 years
Secondary Amenorrhoea = absence of menstruation for 3 months in a woman who has previously had cycles
Oligomenorrhoea = irregular long cycles
List some causes of amenorrhoea.
- Pregnancy
- Lactation
- Ovarian failure due to premature ovarian insufficiency, ovariectomy/chemotherapy, or ovarian dysgenesis (in Turner’s syndrome)
- Gonadotrophin failure due to hypo/pit disease, Kallman’s syndrome, low BMI, or post pill amenorrhoea
- Hyperprolactinaemia
- Androgen excess due to a gonadal tumour
State some investigations that may be carried out for amenorrhoea
- Pregnancy test
- Measure LH, FSH, oestradiol
- Measure day 21 progesterone (which should be high to prepare the endometrium for the potential of pregnancy after ovulation)
- Measure prolactin
- Thyroid function tests (since hypo/hyperthyroidism affects menstrual cycle)
- Measure androgens (testosterone, androstenedione, DHEAS)
- Chromosomal analysis (Turners 45 XO)
- Ultrasound scan of ovaries/uterus
Describe the treatment of amenorrhoea
For premature ovarian insufficiency - hormone replacement therapy but they’re infertile
For hypothalamic/pituitary disease - oestrogen replacement therapy and, to restore fertility, give LH and FSH
What are the criteria for diagnosing PCOS?
They must have at least 2 of the following:
- Polycystic ovaries on ultrasound scan
- Clinical/biochemical signs of androgen excess
- Oligoovulation/anovulation
*1 in 12 women of reproductive age
What other problems are associated with PCOS?
Increased risk of cardiovascular disease Insulin resistance (leading to diabetes)
What are the clinical features of PCOS?
Hirsuitism
Menstrual cycle irregularities
Increased BMI
Describe the treatment for PCOS - what are the functions of the drugs used?
METFORMIN – insulin sensitiser
CLOMIFENE – fertility drug that binds to oestrogen receptors in the hypothalamus thereby blocking negative feedback => increased GnRH and gonadotrophin secretion
GONADOTROPHIN THERAPY as part of IVF treatment
Which hypothalamic hormone has a stimulatory effect and which has an inhibitory effect on prolactin release?
(+) TSH
(-) Dopamine
What two effects does hyperprolactinaemia have on the HPG axis?
- It inhibits GnRH pulsatility (so that it is released at a basal level all the time)
- It inhibits LH actions on the ovaries and testes
State some causes of hyperprolactinaemia.
- Dopamine antagonist drugs: Anti-emetics against vomiting/nausea (metoclopramide)
and Anti-psychotics (phenothiazines) - Stalk compression due to pituitary adenoma (so dopamine can’t get to adenohypophysis)
- PCOS
- Hypothyroidism
- Oestrogens (OCP)
- Pregnancy
- Lactation
- Idiopathic
What are the clinical features of hyperprolactinaemia?
- Galactorrhoea
- Reduced GnRH and gonadotrophin secretion => HYPOGONADISM
- Prolactinoma causing visual field defect and/or headache
