Endocrine infertility Flashcards
What is the definition of infertility?
The inability to conceive after 1 year of regular unprotected sex
How common is infertility?
Happens in 1 in 6 couples
What are the clinical features of hypogonadism in men?
Loss of libido - sexual interest/desire Impotence Small testes Decrease in muscle bulk Osteroporosis Basically all the features of low testosterone
What are causes of male hypogonadism?
Hypothalamic pituitary disease
Primary gonadal disease
Hyperprolactinaemia
Androgen receptor deficiency
What are examples of hypothalamic pituitary diseases that can cause male hypogonadism?
hypopituitarism
Kallmans syndrome (anosmia and low GnRH)
Illness/underweight
What are examples of primary gonadal diseases that can cause male hypogonadism?
Congential - kleinfelters syndrome XXY
Aquired - testicular torsion, chemotherapy
What are investigations for male hypogonadism?
If LH, FSH and testosterone are low - MRI pituitary
Prolactin levels - if high will switch off reproductive function
Sperm count
Chromosomal analysis eg kleinfelters
What is azoospermia?
Absence of sperm in ejactulate
What is oligospermia?
Reduced number of sperm in ejaculate
What is the treatment for hypogonadism?
Replacement testosterone for all patients
For fertility - if hypo/pituitary disease subcutaneous gonadotrophins LH and FSH
Hyperprolactinaemia - dopamine agonist
What are endogenous sites of production of androgens
Interstitial leydig cells of the testes Adrenal cortex in males and females Ovaries Placenta Tumours
What are the main actions of testosterone?
- development of male genital tract
- maintains fertility in adulthood
- control of secondary sexual characteristics
- anabolic effects (muscle, bone)
How much of the circulating testosterone is protein bound?
98%
How is dihydrotestosterone (DHT) made
by 5 alpha reductase via tissue specific processing
How is 17b oestradiol (E2) made from testosterone?
Aromatase enzyme via tissue specific processing
How does dihydrotestosterone act?
via the androgen receptor
How does 17b oestradiol act?
via oestrogen receptor (ER) eg brain and adipose tissue
What is the mechanism of action of DHT and E2 via?
Nuclear receptors
What are nuclear receptors?
a class of proteins found within cells that are responsible for sensing steroid and thyroid hormones and certain other molecules.
What are clinical uses of testosterone?
In adulthood it will increase: Lean body mass Muscle size and strength Bone formation and bone mass (in young men) Libido and potency
What is required to restore fertility?
Treatment with gonadotrophins to restore normal spermatogenesis
What is amenorrhoea?
Absence of periods
What is primary amenorrhoea?
Failure to begin spontaneous menstruation by age 16 years
What is secondary amenorrhoea?
Absence of menstruation for 3 months in a women who has previously had cycles
What is oligomenorrhoea?
Irregular long cycles
What are causes of amenorrhoea?
Pregnancy/lactation (high prolactin) Ovarian failure Gonadotrophin failure Hypoprolactinaemia Androgen excess: gonadal tumour
What are causes of ovarian failure that can lead to
amenorrhoea?
Premature ovarian insufficiency Ovariectomy/chemotherapy Ovarian dysgenesis (turners 45 XO) - lacking one chromosome
What are examples of causes of gonadotrophin failure?
Hypo/pit disease
Kallmann’s syndrome (anosmia, low GnRH)
Low BMI
Post pill amenorrhoea
What are investigations for amenorrhoea?
Pregnancy test LH, FSH, oestradiol levels day 21 progesterone Prolactin, thyroid function tests Androgens (testosterone, androstenedione, DHEAS) Chromosomal analysis (turners 45 XO) Ultrasound scan ovaries/uterus
What are treatment options for amenorrhoea?
Treat cause - eg low weight
Primary ovarian failure - infertile, HRT
Hypothalamic pituitary disease - specific treatment
What are the treatment options for hypothalamic/pituitary disease?
HRT for oestrogen replacement
Fertility: gonadotrophins (LH and FSH) - part of IVF treatment
What is PCOS (polycystic ovarian syndrome) associated with?
Increased cardiovascular risk and insulin resistance - don’t know why
What is the criteria to diagnose PCOS?
Need two of the following:
Polycystic ovaries on USS
Oligo-/anovulation
Clinical/biochemical androgen excess
What are clinical features of PCOS
Hirsuitism
Menstrual cycle disturbance
Increased BMI
What are the two drugs you can use to treat PCOS
Metaformin and clomiphene
What is clomiphene?
It is a fertility drug that is anti-oestrogenic in the hypopthalamo-pituitary axis
What is the action of clomiphene?
Binds to oestrogen receptors in the hypothalamus thereby blocking the normal negative feedback, resulting in an increase in secretion of GnRH and gonadotrophins
What are treatment options for PCOS
Metaformin
Clomiphene
Gonadotrophin therapy as part of IVF treatment
What are causes of hyperprolactinaemia?
Dopamine antagonist drugs Stalk compression due to pituitary adenoma PCOS Hypothyroidism Oestrogens (OCP), pregnancy, lactation Idiopathic
Examples of dopamine antagonist drugs?
antiemetics - metoclopramide and antipsychotics - phenothiazines
What are clinical features of hyperprolactinaemia?
Galactorrhoea
Reduced GnRH secretion/LH action»_space; hypogonadism
Prolactinoma - headache, visual field defect
What is the treatment of hyperprolactinaemia?
Treat the cause - eg stop the drugs and treat with dopamine agonist
Prolactinoma - dopamine agonist therapy
Pituitary surgery rarely needed
What are examples of dopamine agonists?
Bromocriptine
Cabergoline
What happens in the reproductive axis in men?
Hypothalamus secretes GnRH which stimulates the pituitary to secrete gonadotrophins which stimulates the testis to make the appropriate hormone - then neg feedback
What happens in the reproductive axis in females in the follicular phase?
Hypothalamus secretes GnRH which stimulates the pituitary to secrete gonadotrophins which stimulates the ovary to make the appropriate hormone - then neg feedback
What happens in the reproductive axis in females during ovulation?
High levels of estradiol produced cause positive feedback after the ovary is stimulated by gonadotrophins, causing an LH surge
What happens in the reproductive axis in females during luteal phase if implantation does not occur
Endometrium is shed - menstruation
What is primary gonadal failure?
When testes or ovaries have failed for some reason
How can primary gonadal failure be diagnosed
Low testosterone/oestradiol (end organ hormone secretion), less neg feedback and high GnRH and high LH and FSH
What happens in hypopituitary disease on endocrine infertility?
Failure of hypothalamus or pituitary leading to less trophic action on testes/ovary so low sex hormone and low LH or FSH and low testosterone/oestrodiol
Why do you have to give subcutaneous gonadotrophins if a male with hypogonadism wants to get pregnant?
Because just giving them testosterone will not produce sperm
