Endocrine infertility Flashcards by Karen Gao

What is the definition of infertility?

The inability to conceive after 1 year of regular unprotected sex

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How common is infertility?

Happens in 1 in 6 couples

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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

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What are causes of male hypogonadism?

Hypothalamic pituitary disease
Primary gonadal disease
Hyperprolactinaemia
Androgen receptor deficiency

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What are examples of hypothalamic pituitary diseases that can cause male hypogonadism?

hypopituitarism
Kallmans syndrome (anosmia and low GnRH)
Illness/underweight

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What are examples of primary gonadal diseases that can cause male hypogonadism?

Congential - kleinfelters syndrome XXY

Aquired - testicular torsion, chemotherapy

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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

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What is azoospermia?

Absence of sperm in ejactulate

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What is oligospermia?

Reduced number of sperm in ejaculate

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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

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What are endogenous sites of production of androgens

Interstitial leydig cells of the testes
Adrenal cortex in males and females
Ovaries
Placenta
Tumours

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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)

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How much of the circulating testosterone is protein bound?

98%

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How is dihydrotestosterone (DHT) made

by 5 alpha reductase via tissue specific processing

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How is 17b oestradiol (E2) made from testosterone?

Aromatase enzyme via tissue specific processing

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How does dihydrotestosterone act?

via the androgen receptor

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How does 17b oestradiol act?

via oestrogen receptor (ER) eg brain and adipose tissue

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What is the mechanism of action of DHT and E2 via?

Nuclear receptors

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What are nuclear receptors?

a class of proteins found within cells that are responsible for sensing steroid and thyroid hormones and certain other molecules.

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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

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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 >> 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