ovulation disorders and male hypogonadism Flashcards
(87 cards)
1
Q
oestrogen synthesis
A
oestrogen are a class of steroid hormones which control the development and maintenance of female sex characteristics
2
Q
glandular oestrogen synthesis occurs in
A
the granulose and theca cells as well as in the corpus lute
3
Q
granulose cells are stimulated by
A
LH to produce pregnelone, pregneolne then diffuses into adjacent theca cells where it is converted to androstenedione via DHEA.
4
Q
the androstenedione
A
then returns to the granulose cells where it is converted to oestone via Aromatase and then to estradiol via 17-beta-HSD
5
Q
expression of aromatase and 17-beta- HSD is controlled by
A
FSH stimulation
6
Q
extra-glandular synthesis of oestrogen
A
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
7
Q
progesterone is synthesised from
A
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
8
Q
actions of progesterone are mediated by
A
an intra-cellular progesterone receptor which numbers are increased in the presence of oestrogen
9
Q
products of the follicular and luteal phase
A
oestradiol is the main production of the follicular phase and progesterone is the main product of the luteal phase
10
Q
oligomenorrhea
A
reduction in the frequency of an individuals period to less than 9 a year
11
Q
primary amenorrhoea
A
failure of menarche by the age of 16
12
Q
secondary amenorrhoea
A
cessation of menarche for more than 6 months in an individual who has previously had periods
13
Q
physiological causes of amenorrhoea
A
- physiological: pregnancy and post-menopausal
14
Q
causes of primary amenorrhoea
A
consider congenital causes such as turners syndrome and kallmans syndrome
15
Q
causes of secondary amenorrhoea
A
- 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
16
Q
investigating ammenorrhoea
A
- 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
17
Q
next step is too establish
A
if hypogonadism is present, in females hypogonadism is identified by low levels of oestrogen
18
Q
types of female hypogonadism
A
primar hypogonadism and seondary hypogonaism
19
Q
primary hypogonadism
A
- 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
20
Q
secondary hypogonadism
A
- 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
21
Q
premature ovarian failure is also known as
A
primary ovarian insufficiency
22
Q
defintion
A
amenorrhoea, oestrogen fedicient and elevated gonadotrophin in a female before the age of 40 caused by loss of ovarian function
23
Q
causes
A
- 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
24
Q
50% of females with premature ovarian failure
A
have intermittent ovarian function so may rarely get pregnant this would be impossible in actual menopause
25
symptoms of premature ovarian failure
- hot flushness
- night sweats
- vaginal dryness causing painful sex (dyspareunia)
- osteoporosis
26
diagnosis
FSH level greater than 30 on 2 occasions more than one month apart
27
management
hormone replacement therapy
28
turner syndrome is a cause of
primary ovarian failure
29
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)
30
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
31
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
32
causes of secondary hypogonadism
- hypothalamic problem
- pituitary problem
- trader will syndrome
- haemochromatosis
33
hypothalamic problems causing secondary hypogonadism
functional hypothalamic disorders
kallmans syndrome
idiopathic hypogonadotrophic hypogonadism
34
pituitary problem
- hyperprolactinaemia
| - hypopituitarism
35
functional hypothalamic amenorrhoea is a
diagnosis of exclusion
36
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
37
3 main types of functional hypothalamic amenorrhoea
- weight loss related (i.e. anorexia)
- stress related
- exercise related (extreme exercise)
38
other causes of functional hypothalamic amenorrhoea
anabolic steroid abuse, systemic illness, recreational drugs, sarcoidosis
39
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
40
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
41
mutation of what is linked to idiopathic hypogonadotrophic hypogonadism
kisspeptin
42
kallmans syndrome
genetic disorder characterised by loss of GnRH secreting and ansomia (loss os sense of smell) or hyposmia (reduced sense of smell)
43
kallamns syndrome is a type of
hypogonadotrophic hypogonadism
44
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
45
kallmans syndrome is
4x more common in males
46
lows levels of
sex hormones (testosterone in males ad oestrogen and progesterone in females) leads to failure to start or complete puberty
47
male presentation of kallmans
- small penis and testes
- improper testicualr descent
- lack of facial hair
- low sperm count
- no deepening of voice
48
female presentation of kallmans
- amenorrhoea or oligomenorrhoea
| - lack of breasts and pubic hair
49
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
50
pituitary causes of secondary hypogonadism
- any case of hypopituitarism
| - hyperproalctinaemia
51
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
52
causes of hyperprolactinaemia causing secondary hypogonadism
- micro or macro prolactinoma
- drugs: dopamine antagonists SSRIS
- hypothyroidism
53
congenital adrenal hyperplasia most common type
deficiency of 21-alpha-hydroxylase enzyme
54
steroid biosynthesis pathway
draw out diagram
55
congenital adrenal hyperplasia is inherited
autosomal recessively
56
in baby girls congenital adrenal hyperplasia presents as
ambiguous genitalia caused by virilization
57
in baby boys congenital adrenal hyperplasia presents
wishin around one week with salt wasting with dehydration, hyponatrameia, hyperkalaemia and a metabolic acidosis
58
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
59
diagnosis of congenital adrenal hyperplasia
serum cortisol levels are always low
| the levels of 17-alpha- hydoxyprogesterone are elevated especially after synachtne test
60
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
61
androgen secreting tumours
tumours secreting male sex steroids that arise in females and cause virilization
62
levels of testosterone in androgen secreting tumours
very high usually greater than 5nmol/l
63
androgen secreting tumours can be of the
ovaries or the adrenal glands
64
rarer causes pof amennorhoea
XX gonadal dysgenesis
| androgen insensitivity syndrome
65
XX gondal dysgenesis
there is no chromosomal abnormality but the female has no functional ovaries
66
androgen insensitivity syndrome
individuals who are genetically male (XY) but phenotypically they are female
67
male hypogonadism
primary or secondary
68
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
69
secondary male hypogonadism
- low levels of testosterone with inappropriately low LH and FSH levels
- causes are hypothalamic and pituitary disorders
70
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)
71
acquired causes of primary hypogonadism
- testicular trauma/ torsion/ irradiation
- autoimmune testicular failure
- haemachromatosis
- varicocele
72
congenital causes of male secondary hypogonadism
- kallmans syndrome
- prader willi syndrome
- mutation in beta subunit of LH and FSH
73
acquired causes of male secondary hypogonadism
- hyperprolactinaemia
- hypopituatatrism
- hypothalamic dysfunction
- idiopathic hypogonadotrophic hypogonadism
74
klinefelters syndrome is the
most common congenital cause of primary hypogonadism
75
klinefelters syndrome only affects
male
76
klinefelters syndrome is a
chromosomal abnormality when there is an extra chromosome: 47 XXY
77
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
78
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
79
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
80
low levels of testosterone results in
supressed testes maturation and sperm reduction and inhibits the development of male secondary sex characteristics
81
clinical features of klinefelters syndrome
- small penis and testes
- gynaecomastia
- infertility
- intellectual dysfunction
- reduced secondary sex characteristics
82
secondary male hypogonadism is
hypogonadism as a result of hypothalamic or pituitary dysfunction
83
secondary hypogonadism test results
low 9am testosterone, low FSH and Low LH
84
hypothalamic causes of male hypogonadism
- idiopathic hypogonadotrophic hypogonadism
- kallmans syndrome
- functional hypothalamic disorders
85
pituitary causes of male hypogonadism
- hyperprolactinamia
- hypopituatatrism
- haemachromatosis
- prader will syndrome
86
testosterone replacement
in young men with clear evidence of hypogonadism testosterone replacement is indicated
87
benefits of testosterone replacement
- in young men helps with erectile dysfunction
| - decreases fat mass and improves limb strength
