L05: Endocrine Disorders Affecting Reproduction Flashcards
What hormone does the anterior pituitary gland release to the ovaries
LH
FSH
Which cells in the ovaries produce androgen
Theca cells
What happens to the androgens that are produced by theca cells
Enter the follicles where the granulosa cells are and get converted to oestrogen
Which hormone has a negative feedback to the pituitary gland
Inhibin
What type of feedback does oestradiol give
Negative feedback
Positive feedback
When does oestradiol give negative feedback
In the early cycle when there is high moderate levels of it which suppresses LH/FSH
When does oestradiol give a positive feedback
In the mid cycle when there is high levels and this causes LH/FSH surge
What hormone from the hypothalamus causes the secretion of LH/FSH
GNRH
What type of secretion does GNRH have
Pulsatile secretion
If there is continuous secretion of GNRH what happens to the GNRH receptors
They become downregulated
So if there is continuous secretion of GNRH what happens to LH/FSH
Decreases
What are the 3 areas of problems that can arise in the HPG axis in females
1) central damage: lack of LH/FSH
2) gonadal damage: failure of germ cell production or lack of LH and FSH
3) PCOS: gonadal damage but high level of oestrogen
What does hypogonadal mean
Decreased gonadal function and decreased sex hormones
What makes you hypergonadal
High levels of FSH and LH due to a problem with the gonads so they are not responding to LH/FSH and the pituitary is secreting more to get a response
What does oligomennorhea mean
Less than 9 cycles in a year or periods that last more than 42 days
What is ammenorhhea
Absence of periods for more than 6 months
What are the 2 types of ammenorhhea
Primary
Secondary
What is primary ammenorhhea
Patient has never had periods before, indicated failure of menarche after age of 16
What is secondary ammenorhhea
Patient had periods but stopped for more than 6 months
What are the consequences of oestrogen deficiency
Hot flushes
Poor libido
Painful sex
What are the 3 categorical causes of ammenorhhea
Pregnancy
Central
Ovarian
If someone presents with ammenorhhea what do we first need to exclude
Pregnancy
What are the central causes of ammenorhhea
hypothalamic ammenorhhea
Hyperprolactinemia (lactation)
Pituitary tumours
Hypogonadotrohic hypogonadism (low FSH and LH)
What are the ovarian causes of ammenorhhea
Turners syndrome
Premature ovarian failure
PCOS
What are is hypothalamic ammenorhhea due to
Anorexia
Exercise
Bulimia
What is the treatment for hypothalamic ammenorhhea
Weight gain
What other hormones does the anterior pituitary gland release
ACTH GH TSH LH FSH Prolactin
What is prolactin involved in
Breast milk production
Which cells produce prolactin
Lactotrophs
What is prolactin suppressed by
Dopamine
What does prolactin inhibit
LH
FSH
What other hormone causes the increased release of prolactin
TRH
What are the clinical features of high prolactin in pre-menopausal women
Oligo/ammenorhhea Oestrogen deficiency- vaginal dryness Spontaneous galactorhhea (milk production)
What are the pathological causes of high prolactin (hyperprolactinaemia)
- prolactin secreting pituitary tumours (prolactinomas)
- loss of dopamine so loss of inhibitory effect by dopamine due to compression of infundibulum by a pituitary tumour
- dopamine antagonist drugs
- hypothyroidism
What are the 2 types of prolactin secreting pituitary tumour that you can get
Microadenoma
Macro adenoma
What is the difference between micro and macro adenoma
Microadenoma: less than 1cm in diameter
Macro adenoma: greater than 1cm in diameter
Why do you get high levels of prolactin when there is hypothyroidism
1) hypothyroidism means low TH
2) low thyroid hormone mean less negative feedback to the hypothalamus
3) hypothalmus therefore produces more TRH
4) high TRH causes high prolactin
What are the clinical features of premature ovarian insuffiency
Ammenorhhea
Oestrogen deficiency
High levels of FSH/LH- due to lack of negative feedback
What are the causes of premature ovarian insuffiency
Turners syndrome
Autoimmune such as graves, addition
Iatrogenic: Chemotherapy, Radiotherapy and surgery
Mutation in FSH receptor in ovary ( FMR1 gene)
What are the common features of turners syndrome (44 XO)
Short stature Low hairline Shield shaped thorax Widely spaced nipples Elbow deformity Gonadal streaks No menstruation
What is the autoimmune disease that cause premature ovarian insuffiency
Graves’ disease
Addisons
Diabetes
What is the likely mechanism for autoimmune disease causing premature ovarian insuffiency
Production of anti ovarian antibodies
Apoptosis
Atrophy
What mutations leads to changes in FSH receptor that leads to premature ovarian insufficiency
FMRI gene mutations (fragile X)
How do we diagnose for fragile X FRMI mutation
Karyotype and FRMI mutation analysis
How do we diagnose for autoimmune premature ovarian insuffiency
Screen for autoimmune disease such as anti ovarian antibodies
What is the management of Premature ovarian failure
Oestrogen replacement and progesterone (if there is a uterus)
What are the features of PCOS
Oligomennorhea Hirtusim Obesity Infertility Polycystic ovaries on ultrasound Hypernadrogenism
What are the levels of hormones like in PCOS
Increased testosterone, DHEA
Increase LH more than FSH
No oestrogen deficiency
What does PCOS increase the risk of during pregnancy
Gestational diabetes
What is the treatment for PCOS for obesity and oligo/amennorhea specifically
Metformin
Lifestyle changes
What is the treatment in PCOS for anovulatory infertility
Metformin and clomiphene or letrozole
Metformin and IVF
What is the treatment in PCOS for hirtusim
Yasmin or Dianette(contraceptive pill that reduces androgen)
Vaniqua cream
Cosmetic removal
Sprinolactone
What are the anti- and organic oral contraceptives
Yasmin
Dianette
What does diannete contain
35ug thinly estradiol
Cyproterone acetate
What does Yasmin contain
30ug ethinyl estradiol
Drospirenone
What does CAH stand for
Congenital adrenal hyperplasia
What are the 3 forms of CAH
Classical salt wasting CAH
Classical simple virilizing CAH
Non classical CAH
What is the cause of CAH
21 hydroxylase deficiency (enzyme)
Which 2 groups of hormone is 21 hydroxylase enzyme involved in producing
Aldosterone
Cortisol
When there is 21 hydroxylase deficiency i.e CAH what are the levels of hormone like
High androgen
Low cortisol
Low aldosterone
What is androgen insensitivity syndrome
A spectrum of disorder due to mutation in the androgen receptors
What does complete androgen insensitivity result in
poorly virilized infertile mean with complete testicular feminisation Female external genitalia Short blind ending vagina No uterus Absent prostate Breast development
What is the common presentation of androgen insensitivity
Inguinal hernia which is actually the testis
What doe blood test levels of androgen insensitivity show
High levels of testosterone
High LH
What is 5 alpha reductase involved in
Converting testosterone to DHT
Which is the most androgenic form: DHT or testosterone
DHT
If there is 5 alpha reductase deficiency what happens to testosterone
Unable to be converted to DHT
What happens to the patients with 5 alpha reductase deficiency
They are genetically male (46xy) but appear female
In males when LH is released what cell does it act on in the testis
Leydig cells
What does leydig cells produce
Testosterone
In males when there is FSH what cell does it act on in the testis
Sertoli cells cells within the seminiferous tubules
What does Sertoli cells produce in repsonse to FSH
Inhibin
What type of feedback does inhibin have to the pituitary gland
Negative feedback
What type of feedback does testosterone have on the pituitary gland and hypothalamus
Negative feedback
What happens to the levels of testosterone as you age
Decrease
What is the normal adult male testicular volume in ml
15-25ml
What are the 2 main categories of male hypogonadism
Primary causes of hypogonadism
Secondary causes of hypogonadism
What can cause primary hypogonadism in males
Trauma Chemotherapy Undescended testis Infections Klinefelters syndrome (chromosomal abnormality) Systemic disease
What can cause secondary gonadal failure
Pituitary tumour Hypothalamus disorders Hyperprolactinemia Systemic disease Obesity Androgen use and abuse
What does high levels of LH and FSH indicate
Primary gonadal failure as the testis are not responding to LH and FSH
What does low levels of FSH/LH indicate
Secondary gonadal failure as the higher centres are not producing LH/FSH for testosterone to be stimulated for production
What is klinefelters syndrome
When you have an extra X chromosome (47xxy)
What are the features of klinefelters syndrome
small testis No sperm No hair Osteoporosis Tall and slim
What is the treatment for primary and secondary gonadal failure
Testosterone replacement
Why can androgen use and abuse cause hypogonadism
Extra testosterone inhibits LH and FSH (negative feedback) so you do not get sperm production
To assess male infertility what do we look at
Seminal fluid
LH
FSH
Testosterone levels
If the FSH levels are high what does this indicate
Germ cell failure
Why does high FSH indicate germ cell failure
The testis are nor producing spermatocytes and you are not getting a feedback
What does a normal FSH indicate
Obstructive disease
What does low FSH, LH and testosterone indicate
Endocrine causes of pituitary and hypothalamus
What is the treatment for low FSH and low LH
Replacement therapy of LH and FSH
