Ovulatory disorders, hormone release and fertilisation Flashcards
What hormone does the hypothalamus release that causes the anterior pituitary to release gonadal hormones?
Gonadotrophic releasing hormone.
What are the gonadal hormones?
Luteinising hormone and follicle stimulating hormone.
What action does follicle stimulating hormone have and where does it act?
Follicle stimulating hormone acts on the ovaries to cause maturation of the primary follicles to secondary follicles.
What hormone is released as the primary follicle becomes the secondary follicle?
Oestrogen.
In low concentrations, oestrogen has…..effect
An inhibitory effect on LH.
A stimulatory effect on FSH.
In high concentrations, oestrogen has…. effect
A stimulatory effect on LH.
An inhibitory effect on FSH.
Name the two phases of menstruation
Follicular phase and luteal phase.
Describe the follicular phase
Follicle develops from the primary follicle to a secondary follicle releasing oestrogen. This causes LH to be suppressed and FSH to slightly rise at first. As levels of oestrogen increase, FSH concentration falls and LH increases. The spike in LH causes ovulation of the most mature follicle.
Describe the luteal phase
After ovulation, LH levels dip. The follicle is now a dead follicle known as a corpus luteum. The corpus luteum secretes several hormones as it is converted to the corpus albicans. These include progesterone, oestrogen and inhibin. Progesterone inhibits the release of GnRh from the hypothalamus, inhibin prevents the release of FSH and oestrogen levels are still detectable. Once the corpus luteum becomes the corpus albicans- these hormones are no longer released allowing GnRH to rise again and a new cycle to start.
What are the actions of progesterone in the luteal phase of menstruation?
Stimulates endothelial growth.
Inhibits GnRH release.
What is the function of theca cells
During the follicular phase of growth- these cells are recruited around the follicle. They release androgens.
What is the relationship between theca cells and granuloma cells?
Granuloma cells produce aromatase which converts the androgen produced by theca cells to oestrogen.
When is HCG released?
The follicle will release this if it has been fertilised.
What does HCG do?
Maintains the corpus luteum- after 6 weeks the placenta takes over this role.
What is amenorrhoea?
Absent menstruation
What is oligomenorrhoea?
Cycle greater than 35 days
Less than 9 periods per year
Primary causes of amenorrhoea
Failure of menarche by the age of 16
Causes include- congenital issues e.g. Turners syndrome, Kallmann’s syndrome
Secondary causes of amenorrhoea
Cessation of periods for >6 months in an individual who has already menstruated.
Causes include- PCOS, POF, uterine problems, hypothalamic dysfunction (weight loss, excessive exercise, stress), hypopituitism, high prolactin.
What does prolactin do?
Stimulates formation of breast milk. Often seen in pregnant women.
WHO classification of amenorrhoea
Group 1- hypothalamic pituitary failure
Group 2- hypothalamic pituitary dysfunction
Group 3-ovarian failure
Hypothalamic pituitary failure is also known as
Hypogonadal hypogonadism.
What is hypogonadal hypogonadism
Means the hypothalamic pituitary axis is not produced the gonadal hormones meaning the gonads themselves (ovaries, testes) cannot produce the appropriate hormones (oestrogen, testosterone)
What would the levels of FSH, LH, prolactin and oestrogen be like in a patient with hypogonadal hypogonadism
Low FSH and LH
Meaning low oestrogen
Normal prolactin
Causes of hypogonadal hypogonadism?
Stress Excessive exercise Anorexia Brain/pituitary tumours Head trauma Kallmanns syndrome Drugs (steroids/opiates)
Management of hypogonadal hypogonadism?
Stabilise weight
Pulsatile GnRH release if hypo hypo
Or gonadotrophin daily injections (FSH and LH)
Ultrasound monitoring
Describe hypothalamic pituitary dysfunction
Normal gonadotrophin levels
Normal LH and FSH
Normal oestrogen however oligo/amenorrhoea
What causes hypothalamic pituitary dysfunction?
Empty sella- small or absent pituitary
PCOS
Describe ovarian failure
High levels of gonadotrophins (FSH, LH)
Low oestrogen levels
Causes of ovarian failure
Premature ovarian failure
In females, what characterises hypogonadism?
Low levels of oestrogen
In males, what characterises hypogonadism?
Low levels of testosterone.
Primary hypogonadism
Problem at the ovaries/testes. No issue at the hypothalamus therefore called hypergonadal hypogonadism (hypothalamus producing more hormones yet the gonads still not working)
Secondary hypogonadism
Problem at the hypothalamic pituitary axis. Therefore called hypogonadotrophic hypogonadism.
What investigations should you do into a patient with oligo/amenorrhoea
LH, FSH, oestradiol
Thyroid function, prolactin
Additional investigations that may aid diagnosis in a patient with oligo/amenorrhoea
Ovarian ultrasound +/- endometrial thickness
Testosterone if hirsutism
Pituitary function tests + MRI of the pituitary
Karyotype if suspected congenital.
Premature ovarian failure is an example of what type of failure/dysfunction
Hypergonadal hypogonadism
What would you expect the levels of oestrogen, LH and FSH to be in POF?
Low oestrogen
High FSH and LH.
What symptoms would you have with POF?
Amenorrhoea
Hot flushes
Night sweats
Atrophic vaginitis- dry vagina and inflammation due to thinning and shrinking of the tissues.
What causes premature ovarian failure?
Chromosomal abnormalities e.g. Turners syndrome, fragile X
Gene mutations e.g. LH/FSH receptors
Autoimmune conditions such as Addison’s.
Iatrogenic (chemotherapy or radiotherapy)
Treatment of POF
Hormone replacement therapy
Egg or embryo donation
What causes secondary hypogonadism?
Functional hypothalamic disorders Kallmann's syndrome Idiopathic hypogonadal hypogonadism Pituitary problems Miscellaneous- Prader Willi, Haemochromatosis.
What is Kallmann’s syndrome?
Genetic disorder characterised by loss of GnRH release +/- anosmia.
Describe the function of the hypothalamus, pituitary and ovaries in Kallmann’s syndrome in a women
Hypothalamus- doesn’t produce GnRH
Pituitary- normal however won’t produce FSH and LH without the stimulation from the hypothalamus
Ovaries- normal however won’t produce oestrogen without FSH and LH.
Describe the function of the hypothalamus, pituitary and testes in Kallmans syndrome in a man
No release of GnRH from the hypothalamus
No release of FSH and LH because no stimulation gets to the pituitary
Therefore the testes don’t produce testosterone.
Describe idiopathic hypogonadal hypogonadism
Identified by the absent or delayed sexual development with low levels of gonadotrophin and sex hormones without an anatomical/functional defect in the hypothalamic pituitary axis.
What can patients with idiopathic HH not do?
Cannot activate the pulsatile release of GnRH. Possible anosmia (can't smell)
What is idiopathic HH associated with?
Genetic defect in the Kisspeptin.
What is the role of Kisspeptin?
Normally stimulates GnRH secretion. Known as the ‘gatekeeper of puberty’. Also influences oestrogen and therefore the menstrual cycle.
What is the mutation in the Kisspeptin gene?
GPCR KISS1R
What are functional hypothalamic disorders?
Stress, weight change, exercise
What are functional hypothalamic disorders due to?
Anabolic steroids Systemic illness Iatrogenic Recreational drugs Head trauma Infiltrative disorders e.g. sarcoidosis.
What pituitary issues can cause secondary hypogonadism?
Loss of LH and FSH secretion
- non functioning pituitary macro adenoma (pressure of them leads to hypopituitism)
- Empty sella
- Pituitary infarction
Or could be due to hyperprolactinaemia
- Micro or macro prolactinoma
- Drugs (dopamine antagonists)
What is polycystic ovarian syndrome?
Genetically predisposition to excess androgen production causing polycystic ovaries.
The excess androgen production causes an increase in testosterone accounting for some of the clinical features.
Clinical features of polycystic ovarian syndrome
Hirsutism (generally in male pattern but on females- caused by androgen excess at the hair follicle) Obesity Acne Cycle abnormalities Infertility
Treatment of PCOS
Oral contraceptive pill- decreases ovarian androgens and regulates the cycle.
Anti-androgens- cyproterone acetate (often used in conjunction with OCP-Dianette)
Local anti-androgens-Efflornifine cream
What else causes hirsutism?
PCOS- biggest contributor Familial esp- meditarranean Idiopathic Non-classical congenital adrenal hyperplasia Adrenal or ovarian tumour
How will hirsutism differ in someone with PCOS than it would in someone with an adrenal or ovarian tumour?
Long term hirsutism will occur in PCOS. Along with the testosterone not being dramatically elevated and no virilisation.
In people with ovarian or adrenal tumours- the onset of symptoms will be rapid and they will experience virilisation (development of male characteristics e.g. muscle bulk, hair growth, deep voice)
What is congenital adrenal hyperplasia?
Inherited group of disorders characterised by a deficiency in one of the enzymes that makes cortisol.
Which enzyme is most commonly deficient in congenital adrenal hyperplasia?
21 alpha-hydroxylase.
How does congenital adrenal hyperplasia present?
Varied- classical presents in infancy with virilisation and salt washing
Non-classical presents in adolescence/adulthood and only has a partial deficiency in the enzyme. Presents with hirsutism, menstrual disturbance and infertility.
Treatment of non classical congenital adrenal hyperplasia
Low dose glucocorticoid to suppress ACTH secretion.
Presentation of androgen secreting tumours
Rapid onset of symptoms
Frequently associated with signs of virilisation.
High testosterone levels (>5nmol/l)
MRI will show tumours on either the adrenals or ovaries.
Name some rarer causes of secondary hypogonadism
XX gonadal dysgenesis- absent ovaries but no chromosomal abnormalities
Testicular feminisation- androgen insensitivity syndrome- genetically XY male with testes however phenotypically female.
What is Turners syndrome?
Single X chromosome. Only occurs in females.
Describe a patient with turners syndrome
Short stature, webbed neck, shield chest with widespread nipples.
Lymphadaema, infertility and amenorrhoea.
How would primary hypogonadism present in a boy?
Low testosterone
High FSH and LH.
How would secondary hypogonadism present in a boy
Low FSH and LH
Low testosterone.
What is Klinefelters syndrome?
Most common congenital form of hypogonadism.
Clinical features of Klinefelters syndrome
Reduced testicular volume Gynaecomastia Eunuchoidism- deficiency of sexual development Intellectual dysfunction (in about 40%) Azoospermia (low sperm count)
When would you use testosterone replacement therapy
Young men you would probably use it. Not necessarily in older men (greater than 50)
What does testosterone therapy do?
Does not increase fertility
Improves sexual function
Improves bone health
Improves body composition and muscle strength by decreasing fat mass and improving limb strength.
Why does gynaecomastia occur?
Increased oestrogen action on breast tissue.
What causes gynaecomastia?
Physiological Drugs-spiranolactone, digoxin, oestrogen Hypogonadism Tumours- oestrogen secreting ones Endocrine disorders-thyrotoxicosis Systemic illness Hereditary disorders
Investigations into gynaecomastia
Testosterone, LH and FSH Oestradiol Prolactin LFT's Breast imaging Testicular/adrenal imaging
Treatment of gynaecomastia
Address underlying cause
surgery (cosmetic)
Medication (anti-oestrogen)
