Endocrine Infertility Flashcards
Describe the normal reproductive physiology in males and females
Males – GnRH stimulates LH and FSH release to act on Sertoli and Leydig cells in the testis to produce testosterone and inhibin (which then negatively acts in the pituitary and hypothalamus).
Females – have a 28-day menstrual cycle consisting of; follicular phase, ovulation and the luteal phase. .
- follicular phase - increased GnRH, LH and FSH -> follicles -> oestradiol
- One major difference is that high levels of oestradiol trigger a switch to positive feedback on the hypothalamus triggering a large GnRH and LH release
- In the luteal phase, if implantation does not occur, the endometrium is shed (menstruation) but if implantation does occur, pregnancy
What is infertility?
the inability to conceive after 1 year of regular unprotected sex.
*Affects 1: 6 couples.
Caused by abnormalities in:
- Males – 30%.
- Females – 45%.
- Unknown reason – 25%.
Due to:
- Primary gonadal failure – gonads fail so HIGH GnRH and LH/FSH but no inhibin/ testosterone etc.
- Hypo/pituitary disease – hypothalamus/pituitary fail so low FSH/LH and low/no inhibin/ testosterone etc
What are the clinical features of male hypogonadism?
- Loss of libido
- Impotence
- Small testes
- Decreased muscle bulk
- Osteoporosis
What are the causes of male hypogonadism?
Hypothalamic-pituitary disease:
- Hypopituitarism.
- Kallmans syndrome (anosmia & low GnRH).
- Illness/underweight (low BMI).
Primary gonadal disease:
- Congenital: Klienfelter’s syndrome (XXY).
- Acquired: Testicular torsion, chemotherapy.
Hyperprolactinaemia.
Androgen receptor deficiency
How can you investigate male hypogonadism?
LH, FSH, testosterone levels – if all LOW, MRI pituitary.
Prolactin.
Sperm count.
- Azoospermia – absence of sperm in ejaculate.
- Oligospermia – reduced sperm in ejaculate.
Chromosomal analysis – i.e. Klienfelter’s syndrome
What is the treatment for male hypogonadism?
HRT – replace testosterone for ALL patients
For fertility – testosterone isn’t enough, need SC gonadotrophins (LH&FSH)
Hyperprolactinaemia – dopamine agonist to inhibit prolactin
Where is testosterone/androgens produced? What are the actions of testosterone?
Testosterone/ androgens are produced in:
- Leydig cells of the testis
- Adrenal cortex
- Ovaries
- Placenta
- Tumours
Main actions of testosterone:
- Development of male genital tract
- Secondary sexual characteristics
- Maintenance of adult fertility
- Anabolic effects (muscle and bone growth)
- 98% of circulating testosterone is protein bound.
- 5a-reductase action turns testosterone -> DHT - Acts on AR – androgen receptor.
- Aromatase action turns testosterone -> 17b-oestradiol - Acts on ER – oestrogen receptor
What are the clinical uses of testosterone?
In adulthood, testosterone will increase:
- Lean body mass.
- Muscle size and strength.
- Bone formation and mass (in young adults).
- Libido and potency.
*does not restore fertility without gonadotrophins
What is amenorrhoea?
Primary amenorrhoea – failure to begin spontaneous menstruation by age 16 (congeinital)
Secondary amenorrhoea – absence of menstruation for 3 months in a woman that has previously had cycles (usually not congenital)
Oligomenorrhoea – irregular long cycles
What are some causes of amenorrhoea?
Pregnancy or lactation.
Ovarian failure:
- Premature ovarian failure.
- Ovariectomy/ chemotherapy.
- Ovarian dysgenesis – Turner’s syndrome (45X).
Gonadotrophin failure:
- Hypo/pit disease.
- Kallmann’s syndrome (anosmia with low GnRH).
- Low BMI – low leptin will shut off the reproductive system.
- Post-pill amenorrhoea.
Hyperprolactinaemia.
- Androgen excess – gonadal tumour.
How can you investigate amenorrhoea?
- Pregnancy test.
- LH, FSH, oestradiol and androgen blood test.
- Day 21 progesterone – can tell you if the woman ovulated in the previous cycle.
- Prolactin, thyroid function tests.
- Chromosomal analysis – i.e. Turner’s syndrome.
- Ultrasound scan ovaries/uterus.
What are the treatment options for amennorhoea?
Treat the cause – i.e. low BMI.
Primary ovarian failure – infertile so HRT.
Hypo/pit disease – HRT for oestrogen replacement and gonadotrophins for fertility treatment
What is polycystic ovarian syndrome?
Incidence is 1: 12 women of reproductive age.
Associated with increased CVS risk and insulin resistance (diabetes) – no evidence as to why.
Diagnosis required 2 of the following:
- Polycystic ovaries on ultrasound scan.
- Oligo-/anovulation – irregular or no ovulation.
- Androgen excess – can be assessed by clinical evaluation (i.e. hirsutism).
Clinical Features:
- Hirsutism.
- Menstrual cycle disturbance.
- Increased BMI.
What is the treatment for PCOS?
- Metformin
- Clomiphene -This is an anti-oestrogenic drug in the HPA.
- Oestrogen-antagonist.
- Clomiphene binds to the oestrogen receptors in the hypothalamus and blocks normal negative feedback resulting in an increase in GnRH and gonadotrophin secretion. - Gonadotrophin therapy (as part of IVF treatment).
What are the causes of hyperprolactinaemia?
- Dopamine antagonist drugs:
Anti-emetics (e.g. metoclopramide).
Anti-psychotics (e.g. phenothiazines) - Prolactinoma
- Stalk compression due to pituitary adenoma - Stalk compression may stop DA and TRH passing down and as there is a majority negative feedback, a compressed stalk allows an autonomous output to begin
- PCOS
- Hypothyroidism – primary
- Oestrogens, pregnancy and lactation
- Idiopathic
