Flashcards in Ovulation disorders and male hypogonadism Deck (91):
Briefly describe the hypothalamic-pituitary-gonadal axis
Hypothalamus secretes gonadotrophin releasing hormone >
GnRH acts upon the anterior pituitary >
Anterior pituitary secretes LH and FSH >
LH and FSH stimulate gamete formation (FSH only in males) directly and via the production of steroid and peptide hormones within the gonads
What type of hormones are oestrogens?
Where and by which cells does glandular oesteogen synthesis occur?
Ovaries - theca and granulosa cells
Which type of cells does LH stimulate? Which hormone production does it induce?
Describe the process of oestradiol production
Pregnenolone diffuses form the granulosa cells to theca cells >
Theca cells convert pregnenolone to androstenedione using 17,20-lyase and 3beta-HSD >
Androstenedione returns to the granulosa cells where it is converted to oestrone by aromatase >
Oestrone is further converted to oestradiol by 17beta-HSD
What does FSH do? How does it do this?
Stimulates the conversion of androstenedione to oestrone via aromatase
Stimulates the conversion of oestrone to oestradiol via 17beta-HSD
Where and how does extra-glandular oestrogen synthesis occur?
Aromatase expression in fat and bone allows conversion of androstenedione to oestrone
Explain progesterone synthesis
3beta-HSD converts pregnenolone to progesterone in the corpus luteum, placenta (during pregnancy) and adrenals (pathway to androgen and mineralocorticoid synthesis)
What receptors numbers increase in the presence of oestrogen?
Intracellular progesterone receptor
How do the products of hormone synthesis vary with the menstrual cycle?
Follicular phase - oestradiol
Luteal phase - progesterone
When are LH and FSH highest?
Just before and during ovulation
What does oligomenorrhea mean?
Less than 9 periods a year
What does primary amenorrhea mean?
Failure of menarche before age 16
What does secondary amenorrhea mean?
Cessation of periods for over 6 months in an individual who has previously menstruated
What categories do the causes of amenorrhea fall under?
Secondary (ovarian, uterine, hypothalamic, pituitary)
How should amenorrhea be investigated?
What is female hypogonadism?
Low levels of oestrogen
Where does the problem lie with primary and secondary hypogonadism respectively?
Primary - ovaries
Secondary - hypothalamic or pituitary
What is hypergonadotrophic hypogonadism?
What is hypogonadotrophic hypogonadism
What is premature ovarian failure?
Amenorrhea, oestrogen deficiency and elevated gonadotrophs occurring before the age of forty
What is the diagnostic criteria for premature ovarian failure?
FSH > 30 on two separate occasions at least 1 month apart
What are the causes of premature ovarian failure?
Genetic mutation (FSH/LH receptor)
What are the chromosomal causes of premature ovarian failure?
What are the iatrogenic causes of premature ovarian failure?
What are the autoimmune causes of premature ovarian failure?
What is kallman's syndrome a problem with?
Wilson's syndrome can cause hypogonadism. T/F
False - haemochromatosis
What is idiopathic hypogonadotrophic hypogonadism?
Absent/delayed sexual maturation with low gonadotrophs in the absence of anatomical or functional problem with the hypothalamic-pituitary-gonadal axis
Where is the problem with idiopathic hypogonadotrophic hypogonadism?
Hypothalamus - inability to activate GnRH secretion
There are a number of genetic defects associated with idiopathic hypogonadotrophic hypogonadism. T/F
True - GnRH secretion is pretty complex
What is the role of kisspeptin in the regulation of GnRH production?
Kisspeptin binds to the KISS1P gene to induce GnRH secretion
What are the effects of kisspeptin?
Gatekeeper of puberty
Regulator of male and female fertility
Involved in feedback control of oestrogen and therefore menstruation and ovulation
What is Kallman's syndrome?
A genetic disorder causing the loss of GnRH secretion and anosmia/hyposmia due to failure of hypothalamic migration
How is the pituitary affected in Kallman's syndrome?
Normal apart from reduced LH/FSH due to lack of stimulation from GnRH
What does a brain MRI show in Kallman's syndrome?
No olfactory bulbs
Which sex is affected by Kallman's most often?
Is Kallman's associated with a family history or nah?
How can you differentiate between Kallman's syndrome and idiopathic hypogonadotrophic hypogonadism?
Presence or absence of anosmia
How are the hormone levels affected in pituitary dysfunction?
What causes of pituitary dysfunction can cause hypogonadism?
What are the causes of hyperprolactinemia?
What are the ovarian causes of amenorrhea?
What is the rotterdam criteria for PCOS?
What are the signs of hyperandrogenism?
Elevated free testosterone
What types of congenital problems can cause amenorrhea?
Congenital adrenal hyperplasia
Describe the pathophysiology of polycystic ovarian syndrome?
Genetic predisposition to excess androgen secretion >
Increased testosterone >
Hirsutism ; increased LH ; insulin resistance + hyperinsulinaemia >
Increased LH & hyperinsulinaemia further increase testosterone and cause anovulation ; hyperinsulinaemia causes the liver to secrete less sex hormone binding globulin propagating hirsutism
What is hirsutism?
Excess hair in the male pattern distribution in females
What causes hirsutism?
Excess androgen at hair follicles caused by increased circulating androgen and increased peripheral conversion at the hair follicle
Where is androgen synthesised?
Ovaries and adrenals
What are the causes of hirsutism?
Non-classical adrenal hyperplasia
How can adrenal/ovarian tumours causing hirustism be differentiated from other causes?
Tumours - short history, virilisation
Other causes - long history, testosterone not crazy high, no virilisation
What is virilisation?
What is congenital adrenal hyperplasia?
Group of genetic disorders causing a deficiency in an enzyme essential for cortisol synthesis
What is the most common enzyme responsible for congenital adrenal hyperplasia?
21 alpha hydroxylase
Is congenital adrenal hyperplasia dominant or recessive?
When is classical CAH diagnosed?
When is non-classical CAH diagnosed?
Adolescence or adulthood
How does classical and non-classical CAH present respectively?
Classical - virilisation, salt-wasting
Non-classical - hirsutism, menstrual disturbance, infertility
What should be particularly elevated in CAH after synacthen?
Progesterone (ACTH drives androgen production)
How do androgen secreting tumours present?
What can be done to investigate a suspected androgen secreting tumour?
MRI adrenals and ovaries
How is PCOS treated?
Oral contraceptive pill
Anti androgens (cyproterone acetate)
Local anti-androgens (efflornithine cream)
Cosmesis (laser, electrolysis)
How is non-classical CAH treated?
Low dose glucocorticoid
What is the chromosomal abnormality in Turner's syndrome?
Only one X chromosome
Which sex is affected by turner's syndrome?
How does turner's syndrome present?
Shield chest w/ wide spaced nipples
What is XX gonadal dysgenesis?
Absent ovaries with no chromosomal abnormality
What is testicular feminisation/androgen insensitivity syndrome?
Genetically XY but phenotypically female (pseudohaemaphrodite)
What is primary male hypogonadism?
What is secondary male hypogonadism?
What are some causes of primary hypogonadism?
Acquired (cirrhosis, testicular trauma, radiation, mumps, etc)
What aspects of a history are important to cover in male hypogonadism?
Sexual function (libido, erections & ejaculation)
Age of puberty
Symptoms of pituitary disease
Duration of symptoms
What signs may be found in male hypogonadism?
Lower than expected stage of puberty
Small testicular volume
Features of pituitary disease (e.g visual field defects)
How should male hypogonadism be investigated?
Testosterone (free and total)
LH & FSH
What is klinefelter's syndrome?
Congenital form of primary hypogonadism caused by chromosomal abnormality XXY
Which sex is affected by klinefelter's syndrome?
What are the features of klinefelter's?
Reduced testicular volume
How should klinefelter's syndrome present biochemically?
High sex hormone binding globulin
What are the causes of secondary male hypogonadism?
When should testosterone level be measured?
What are the congenital causes of secondary male hypogonadism?
Idiopathic hypogonadotrophic hypogonadism
Congenital adrenal hyperplasia
When is testosterone therapy indicated?
Hypogonadism in young men (>50 seek specialist advice)
Does testosterone therapy restore fertility?
No. May even act as a contraceptive
What are the benefits of testosterone therapy?
Improved sexual function (young > old)
Improved bone health (IM > transdermal)
Improved muscle strength and decreased fat
Minimal affect on diabetes
How does gynecomastia result?
Increase oestrogen effect on breast tissue
What are the causes of gynecomastia?
Endocrine pathology (thyrotoxicosis, cushing's)
Which aspects of a history are important in gynecomastia?
Which aspects of an examination are important in gynecomastia?
Breast tissue vs fat
Unilateral vs symmetrical
General examination (liver disease)
How should gynecomastia be investigated?