ovulation disorders and male hypogonadism Flashcards
oestrogen synthesis
oestrogen are a class of steroid hormones which control the development and maintenance of female sex characteristics
glandular oestrogen synthesis occurs in
the granulose and theca cells as well as in the corpus lute
granulose cells are stimulated by
LH to produce pregnelone, pregneolne then diffuses into adjacent theca cells where it is converted to androstenedione via DHEA.
the androstenedione
then returns to the granulose cells where it is converted to oestone via Aromatase and then to estradiol via 17-beta-HSD
expression of aromatase and 17-beta- HSD is controlled by
FSH stimulation
extra-glandular synthesis of oestrogen
aromatase is also expressed in non-gonadal tissue (one and fat) so in the peripheries aromatisation can occur allowing the conversion of androgens to oestrogen
progesterone is synthesised from
pregnelone by the action of 3-beta-HSD in the corpus lute, placenta during pregnancy and the adrenal cortex as a step in androgen and mineralocorticoid synthesis
actions of progesterone are mediated by
an intra-cellular progesterone receptor which numbers are increased in the presence of oestrogen
products of the follicular and luteal phase
oestradiol is the main production of the follicular phase and progesterone is the main product of the luteal phase
oligomenorrhea
reduction in the frequency of an individuals period to less than 9 a year
primary amenorrhoea
failure of menarche by the age of 16
secondary amenorrhoea
cessation of menarche for more than 6 months in an individual who has previously had periods
physiological causes of amenorrhoea
- physiological: pregnancy and post-menopausal
causes of primary amenorrhoea
consider congenital causes such as turners syndrome and kallmans syndrome
causes of secondary amenorrhoea
- ovarian problems; Polycystic ovarian syndrome, premature ovarian failure
- uterine problems; uterine adhesions
- hypothalamic dysfunction: caused by excessive weight loss, over-exercise, stress, infiltrative causes
- pituitary causes: hyperprolactinaemia, hypopituitarism
investigating ammenorrhoea
- in all woman of a child breaking age your first test should always be a pregnancy test measure HcG levels
- LH, FSH and estradiol levels
- Thyoird function test, prolactin levels
- ovarian ultrasound and testosterone levels if PCOS suspected
- pituitary hormone levels and MRI if pituitary problem suspected
- Karyotype for those with primary amenorrhoea
next step is too establish
if hypogonadism is present, in females hypogonadism is identified by low levels of oestrogen
types of female hypogonadism
primar hypogonadism and seondary hypogonaism
primary hypogonadism
- problem is within the ovaries
- low oestrogen levels but high FSH and LH levels
- also known as hypergonadotrophic hypogonadism
- example of primary hypogonadism: premature varian failure
secondary hypogonadism
- problem is within the hypothalamus or the pituitary
- low oestrogen levels and low FSH and LH levels
- also known as hypogonadotrophic hypogonadism
- examples: prolactinoma and hypopituitarism
premature ovarian failure is also known as
primary ovarian insufficiency
defintion
amenorrhoea, oestrogen fedicient and elevated gonadotrophin in a female before the age of 40 caused by loss of ovarian function
causes
- most commonly is idiopathic
- chromosomal abnormalities: turners syndrome (missing or structurally altered X chromosome)
- gene mutation: BRCA 1 gene, fragile X syndrome (expansion of trinucleotide repeat within a gene on the X chromosome)
- iatrogenic causes: chemotherapy and radiotherapy
- autoimmune disease: addisons, thyroid disease
50% of females with premature ovarian failure
have intermittent ovarian function so may rarely get pregnant this would be impossible in actual menopause
symptoms of premature ovarian failure
- hot flushness
- night sweats
- vaginal dryness causing painful sex (dyspareunia)
- osteoporosis
diagnosis
FSH level greater than 30 on 2 occasions more than one month apart
management
hormone replacement therapy
turner syndrome is a cause of
primary ovarian failure
turners syndrome
normally females have two X chromosomes: 46 XX, in turners syndrome one X chromosome is missing: 45 XO (there are other genotypes where the second X chromosome is present but is structurally altered)
clinical features of turners syndrome
- short stature
- webbed neck
- underdeveloped ovaries which will eventually fail which causes primary or secondary amenorrhoea depending on when the ovaries fail
- infertility
- shield shed chest with nipples that are far apart
- lymphoedeema
- coarctation of the aorta
- elbow deformity
- shorted metacarpal IV
- naevi
- renal malformations: horseshoe shaped kidney
- cubitus valgus
secondary hypogonadism
hypogonadism caused by a problem in the hypothalamus or pituitary (hypogonadotrophic hypogonadism)
- low levels of estradiol and low levels (or inappropriately normal levels) of FSH and LH
causes of secondary hypogonadism
- hypothalamic problem
- pituitary problem
- trader will syndrome
- haemochromatosis
hypothalamic problems causing secondary hypogonadism
functional hypothalamic disorders
kallmans syndrome
idiopathic hypogonadotrophic hypogonadism
pituitary problem
- hyperprolactinaemia
- hypopituitarism
functional hypothalamic amenorrhoea is a
diagnosis of exclusion
what is functional hypothalamic amenorrhoea
non-organic reversible disorder where the is loss of pulsatile gonadotrophin releasing hormone secretion from the hypothalamus as a physiological response in order to avoid pregnancy in times of physiological stress
3 main types of functional hypothalamic amenorrhoea
- weight loss related (i.e. anorexia)
- stress related
- exercise related (extreme exercise)
other causes of functional hypothalamic amenorrhoea
anabolic steroid abuse, systemic illness, recreational drugs, sarcoidosis
idiopathic hypogonadotrophic hypogonadism
absent or delayed sexual development associated with inappropriately low levels of gonadotrophin and sex hormone levels in the absence of anatomical or functional defects in the hypothalamic pituitary gonadal axis
cause of idiopathic hypogonadotrophic hypogonadism
many genes implicated either caused by a mutation in the genres that encode proteins for GnRH neuronal migration or for GnRH secretion
mutation of what is linked to idiopathic hypogonadotrophic hypogonadism
kisspeptin
kallmans syndrome
genetic disorder characterised by loss of GnRH secreting and ansomia (loss os sense of smell) or hyposmia (reduced sense of smell)
kallamns syndrome is a type of
hypogonadotrophic hypogonadism
kallmans syndrome is caused by a
genetic mutation leading to a defect in the migration of neutrons coming out of the olfactory placed: olfactory neutrons and GnRH neutrons
kallmans syndrome is
4x more common in males
lows levels of
sex hormones (testosterone in males ad oestrogen and progesterone in females) leads to failure to start or complete puberty
male presentation of kallmans
- small penis and testes
- improper testicualr descent
- lack of facial hair
- low sperm count
- no deepening of voice
female presentation of kallmans
- amenorrhoea or oligomenorrhoea
- lack of breasts and pubic hair
in both males and females kallmas can cuase
osteoporosis due to the loss of the protective affect of oestrogen and testosterone on bone and infertility
pituitary causes of secondary hypogonadism
- any case of hypopituitarism
- hyperproalctinaemia
causes of hypopituitarism causing secondary hypogonadism
- non-functioning macro adenoma
- trauma: road traffic accidents, iatrogenic
- infection: meningitis
- infarction: sheehans syndrome, pituitary apoplexy
- granulomatous causes: sarcoidosis, tuberculosis, histiocytosis X
- empty sella syndrome
causes of hyperprolactinaemia causing secondary hypogonadism
- micro or macro prolactinoma
- drugs: dopamine antagonists SSRIS
- hypothyroidism
congenital adrenal hyperplasia most common type
deficiency of 21-alpha-hydroxylase enzyme
steroid biosynthesis pathway
draw out diagram
congenital adrenal hyperplasia is inherited
autosomal recessively
in baby girls congenital adrenal hyperplasia presents as
ambiguous genitalia caused by virilization
in baby boys congenital adrenal hyperplasia presents
wishin around one week with salt wasting with dehydration, hyponatrameia, hyperkalaemia and a metabolic acidosis
in congenital adrenal hyperplasia the inability to produce cortisol
means there is no negative feedback on the hypothalamus or the pituitary gland meaning that ACTH is excessively secreted which causes the excessive production of androgens and hyperplasia of the adrenal glands
diagnosis of congenital adrenal hyperplasia
serum cortisol levels are always low
the levels of 17-alpha- hydoxyprogesterone are elevated especially after synachtne test
non-classical congenital adrenal hyperplasia
partial deficiency in 21-alpha- hydorxylase which will present in adolescent or adulthood with normal aldosterone and cortisol levels but causes hirsutism, menstrual disturbance and infertility caused by anovulation
androgen secreting tumours
tumours secreting male sex steroids that arise in females and cause virilization
levels of testosterone in androgen secreting tumours
very high usually greater than 5nmol/l
androgen secreting tumours can be of the
ovaries or the adrenal glands
rarer causes pof amennorhoea
XX gonadal dysgenesis
androgen insensitivity syndrome
XX gondal dysgenesis
there is no chromosomal abnormality but the female has no functional ovaries
androgen insensitivity syndrome
individuals who are genetically male (XY) but phenotypically they are female
male hypogonadism
primary or secondary
primary male hypogonadism
- caused by a problem within the testes
- also known as hypergonadotrophic hypogonadism
- low testosterone levels with high FSH and LH levels
- acquired and congenital causes
secondary male hypogonadism
- low levels of testosterone with inappropriately low LH and FSH levels
- causes are hypothalamic and pituitary disorders
congenital causes of male primary hypogonadism
- klinefelters syndrome
- Y chromosomal micro deletions
- mutations in Lh and FSH receptors
- myotonic dystrophy (most common type of muscular dystrophy occurring in adults)
- cryptorchidism (absence of one or both testes from the scrotum)
acquired causes of primary hypogonadism
- testicular trauma/ torsion/ irradiation
- autoimmune testicular failure
- haemachromatosis
- varicocele
congenital causes of male secondary hypogonadism
- kallmans syndrome
- prader willi syndrome
- mutation in beta subunit of LH and FSH
acquired causes of male secondary hypogonadism
- hyperprolactinaemia
- hypopituatatrism
- hypothalamic dysfunction
- idiopathic hypogonadotrophic hypogonadism
klinefelters syndrome is the
most common congenital cause of primary hypogonadism
klinefelters syndrome only affects
male
klinefelters syndrome is a
chromosomal abnormality when there is an extra chromosome: 47 XXY
the extra X chromosome results
dysfunction of
- leydig cells: normally LH stimulates the leydig cells convert cholesterol to testosterone
- sartoli cells: normally FSH and testosterone stimulate the sartoli cells to produce sperme
normally due to negative feedback
testosterone from the leydig cells acts on the hypothalamus to reduce the release of gonadotrophin releasing hormone and LH secretion and inhibit produced by the sartoli cells inhibits the release of FSH
in klinefelters syndrome
testosterone is not produced by the leydig cells and inhibit is not produced by the sartoli cells so there is no negative feedback resulting in excessive production of gonadotrophin releasing hormone, FSH and LH
low levels of testosterone results in
supressed testes maturation and sperm reduction and inhibits the development of male secondary sex characteristics
clinical features of klinefelters syndrome
- small penis and testes
- gynaecomastia
- infertility
- intellectual dysfunction
- reduced secondary sex characteristics
secondary male hypogonadism is
hypogonadism as a result of hypothalamic or pituitary dysfunction
secondary hypogonadism test results
low 9am testosterone, low FSH and Low LH
hypothalamic causes of male hypogonadism
- idiopathic hypogonadotrophic hypogonadism
- kallmans syndrome
- functional hypothalamic disorders
pituitary causes of male hypogonadism
- hyperprolactinamia
- hypopituatatrism
- haemachromatosis
- prader will syndrome
testosterone replacement
in young men with clear evidence of hypogonadism testosterone replacement is indicated
benefits of testosterone replacement
- in young men helps with erectile dysfunction
- decreases fat mass and improves limb strength
