Reproductive Flashcards
What is polycystic ovarian syndrome (PCOS)?
Disease characterised by excess ovarian androgen production
What is the pathophysiology of polycystic ovarian syndrome (PCOS)?
Poorly understood but related to insulin resistance
Insulin increases LH secretion
Insulin lowers sex-hormone binding-globulin increasing free testosterone
How is polycystic ovarian syndrome (PCOS) diagnosed?
2 or more of
- oligo/amenorrhoea
- polycystic ovaries on US
- hyperandrogenism (acne, oily skin, hirsutism)
What would you expect to see with the following blood tests in polycystic ovarian syndrome (PCOS)?
- LH
- FSH
- oestrogen
- testosterone
- progesterone
LH: high FSH: low (high LH:FSH ratio) Oestrogen: normal Testosterone: high Progesterone: high
What are the treatments for polycystic ovarian syndrome (PCOS)?
- Lifestyle modification
- Clomifene citrate + metformin
- Gonadotrphin injection or ovarian drilling
What risk does ovulation induction pose?
Multiple pregnancy (twin-twin-transfusion-syndrome, perinatal mortality, prematurity)
What is idiopathic hypogonadotrophic hypogonadism (IHH)?
Inability to activate GnRH secretion causing hypogonadism
What is Kallman’s syndrome?
Inability to activate GnRH secretion causing hypogonadism, delayed puberty and anosmia
What is Turner’s syndrome and what is its phenotype?
Genetic XO karyotype
Short, webbed neck, shield chest, low ears
How does Turner’s syndrome cause amenorrhoea?
Chromosomal abnormality (XO) causes gonadal dysgenesis resulting in non-functioning ovaries.
If this occurs in childhood = primary amenorrhoea
If this occurs in adulthood = secondary amenorrhoea
How does Turner syndrome affect pubertal development?
No breast development (if ovaries fail in childhood)
Pubic hair development spared as androgen production functioning
What is primary amenorrhoea and what does it raise suspicion of?
No periods by 16
Underlying genetic disorder
What gene is associated with idiopathic hypogonadoptrophic hypogonadism (IHH)?
Kisspepsin gene
What is secondary amenorrhoea and what causes it?
Cessation of periods
Problem with HPO axis (hypothalamus, pituitary, ovaries) or the uterus
What can cause functional hypothalamic amenorrhoea?
Stress
Excessive exercise
Low bMI
What pituitary problems can cause amenorrhoea?
Prolactinoma
Panhypopituitarism
Infarction (apoplexy, Sheehan)
What is premature ovarian failure and what can cause it?
Menopause before 40 years
Chromosomal abnormalities (e.g. Turners)
Pelvic radio/chemotherapy
What blood test is used to confirm pregnancy?
Human chorionic gonadotrophin
What blood test is used to confirm ovulation?
Mid-luteal (d21) progesterone
What test confirms normal oestrogen levels?
Progesterone challenge test
menstrual bleed 5 days after progesterone course confirms normal oestrogen levels
What are the three classifications of anovulation and what pattern would they show on blood tests?
Hypothalamic-pituitary failure (Group I)
- low gonadotrophin
- normal prolactin
- low oestrogen
Hypothalamic-pituitary dysfunction (Group II)
- abnormal gonadotrophin (e.g. high LH:FSH ratio in PCOS)
- possible high prolactin (e.g. prolactinoma)
Ovarian failure (Group III)
- high gonadotrphin
- low oestrogen
What blood tests would you do in a patient with irrefular menstrual cycles?
Pregnancy test (hCG)
Confirm if ovulation (mid-luteal progesterone)
If anovulatory, classify it with
- gonadotorphin
- prolactin
- oestrogen
Measure thyroid status (thyroid dysfunction can cause ovulatory disorders)
What can cause hypothalamic-pituitary failure anovulation (group I)
Physioloigcal stress
Pituitary tumour
Idiopathic hypogonadotrophic hypogonadism
How can ovulation be induced in patients with hypothalamic-pituitary failure anovulation (group I)?
Pulsatile GnRH (subcutaneous pump)
Gonadotrophin injection
What does gonadotrophin injection replacement therapy carry a risk of?
Multiple pregnancy
What are symptoms of oestrogen deficiency?
Flushing
Painful sex
Fatigue
Amenorrhoea
What is Klinefelter’s syndrome?
Karyotype 47 XXY resulting in primary hypogonadism
How does Klinefelter’s present
- clinically?
- biochemically?
Tall
Gynaecomastia
Reduced testivular volume
Infertility to due azoospermia
High LH/FSH
Low testosterone
How does Klinefelter’s syndrome affect pubertal development?
Normal puberty but low testicular volume
What are indications for testosterone replacement?
Young men with hypogonadism
Testosterone replacement will restore fertility if used early enough. True or false?
False
Does not restore fertility, may even have contraceptive action
What risks does testosterone replacement therapy carry?
Exacrerbate prostate cancer (doesn’t cause, just worsens)
Polycythaemia risking blood clots
What are the functions of
- germ cells?
- sertoli cells?
- leydig cells?
Germ cells
- Undergo meiosis/differentation to form spermatozoa
Sertoli cells
- Stimuletd by FSH to produce androgen binding globulin and inhibin
- Support germ cells
Leydig cells
- stimulated by LH, produce testosterone
What cells produce testosterone and what stimulates them to do it?
Leydig cells
LH
Describe the steps involved in the formation of oestrogen.
LH acts on ovarian theca cells to uptake cholesterol and convert it to androgen
(activin - , inhibin +)
FSH acts on granulosa cells to activate aromatase which converts the androgen to oestrogen
(activin + , inhibin -)
What are the functions of
- inhibin
- activin?
Inhibin
- inhibits oestrogen production in granulosa cells
- inhibits LH/FSH release
(- stimulates androgen production in theca cells)
Activin
- stimulates oestrogen production in granulosa cells
- stimulates LH/FSH release
(- inhibits androgen formation in theca cells)
What stimulates ovulation?
LH surge
What hormone rises after ovulation?
Progesterone
produced by coprus luteum
What hormone rises first?
FSH
What causes the LH surge?
Positive feedback of oestrogen on LH release
