Endocrine Disorders Affecting Reproduction

Question 1

Describe the pattern of GnRH release.

What is the consequence of this?

Answer 1

• GnRH is released in a pulsatile manner throughout the day.

- This results in pulsatile FSH and LH release.

Question 2

What is the consequence of continuous GnRH release?

Answer 2

Continuous GnRH release decreases release of FSH and LH.

Question 3

List the 3 categories of causes of HPG axis dysfunction.

Answer 3

1 - Central pathology.

2 - Gonadal damage.

3 - PCOS.

Question 4

What is the most common cause of secondary amenorrhoea?

Answer 4

Pregnancy.

Question 5

List 3 symptoms of oestrogen deficiency.

Answer 5

1 - Hot flushes.

2 - Poor libido.

3 - Dyspareunia.

Question 6

List 7 factors to consider when assessing the function of the HPG axis in females.

Answer 6

1 - Menstrual history (oligomenorrhoea / amenorrhoea).

2 - Oestrogen deficiency.

3 - Hirsutism.

4 - Acne.

5 - Androgenic alopecia.

6 - Weight changes.

7 - Galactorrhoea.

Question 7

List 3 central causes of amenorrhoea.

Answer 7

1 - Hypothalamic responses due to anorexia excessive exercise and stress.

2 - Pituitary tumours.

3 - Hypogonadotropic hypogonadism (failure of FSH / LH secretion).

Question 8

List 2 ovarian causes of amenorrhoea.

Answer 8

1 - Turner’s syndrome.

2 - Premature ovarian failure.

Question 9

List 2 miscellaneous causes of amenorrhoea.

Answer 9

1 - PCOS.

2 - Thyrotoxicosis.

Question 10

When does leptin secretion increase?

Why?

Answer 10

• Following weight gain.

- Because there is more adipose tissue secreting it.

Question 11

List the anterior pituitary hormones.

Answer 11

1 - ACTH.

2 - TSH.

3 - GH.

4 - LH.

5 - FSH.

6 - Prolactin.

Question 12

Which cells release prolactin?

Answer 12

Lactotrophs.

Question 13

How is prolactin release controlled?

Answer 13

It is constantly negatively regulated by dopamine.

Question 14

What effect does prolactin have on other anterior pituitary hormones?

Answer 14

Prolactin negatively regulates FSH and LH.

Question 15

What is the effect of thyrotropin-releasing hormone on prolactin?

Answer 15

Thyrotropin-releasing hormone stimulates the release if prolactin from the anterior pituitary (as well as thyroid-stimulating hormone).

Question 16

What is the average upper limit of prolactin concentration?

Answer 16

500mu/L.

Question 17

Why is hyperprolactinaemia difficult is diagnose in postmenopausal women?

Answer 17

• Because prolactin inhibits FSH and LH, therefore oestrogen production.
• The effects of a lack of oestrogen are normally the indicators of hyperprolactinaemia.
• In postmenopausal women, oestrogen isn’t being released anyway.

Question 18

List the symptoms of hyperprolactinaemia in premenopausal women.

Answer 18

1 - Oligo/amenorrhoea.

2 - Vaginal dryness.

3 - Flushes.

4 - Sweats.

5 - Galactorrhoea.

Question 19

List 4 causes of hyperprolactinaemia.

Answer 19

1 - Prolactinomas.

2 - Space-occupying lesions.

3 - Dopamine antagonists.

4 - Secondary hypothyroidism.

Question 20

Why might a space-occupying lesion cause hyperprolactinaemia?

Answer 20

Because the pituitary stalk might become compressed / disconnected, causing loss of inhibitory signalling by the hypothalamus.

Question 21

Define premature ovarian insufficiency.

Answer 21

Elevated LH and FSH (menopause) <45 years of age.

Question 22

List 4 causes of premature ovarian insufficiency.

Answer 22

1 - Turner’s syndrome.

2 - Fragile X syndrome.

3 - Autoimmune disease against the ovaries.

4 - Iatrogenic (chemotherapy, radiotherapy, surgery etc.).

5 - Mutations in the FSHR.

Question 23

Summarise the pathophysiology of Addison’s disease, Hashimoto’s disease, Cushing’s disease and Grave’s disease.

Answer 23

• Addison’s disease is hypoadrenalism due to an autoimmune response to the adrenal cortex.
• Hashimoto’s disease is hypothyroidism due to an autoimmune response to the thyroid gland.
• Cushing’s disease is hyperadrenalism due to an adrenal tumour or a pituitary tumour.
• Grave’s disease is hyperthyroidism due to autoantibodies that stimulate the TSH receptor.

Question 24

Describe the mechanism of autoimmune premature ovarian insufficiency.

Answer 24

Antiovarian antibodies cause inflammatory infiltration of the ovaries, leading to apoptosis and atrophy.

Question 25

Why is there a link between autoimmune premature ovarian insufficiency and Addison's?

Answer 25

Because the autoantibodies might target the same autoantigens in the adrenal gland as in the ovaries.

Question 26

What is the treatment of premature ovarian insufficiency?

Answer 26

Oestrogen replacement.

Question 27

List 5 signs and symptoms of polycystic ovary syndrome.

Answer 27

1 - Oligo/ amenorrhoea. 2 - Hirsutism. 3 - Obesity. 4 - Infertility (due to anovulation). 5 - Polycystic ovaries on ultrasound.

Question 28

What proportion of premenopausal women have PCOS?

Answer 28

10%.

Question 29

List 3 hormonal changes in women with PCOS.

Answer 29

1 - Increased testosterone. 2 - Increased androstenedione. 3 - Increased LH. * Not oestrogen deficient.

Question 30

Why is LH increased in PCOS? What is the effect of LH hypersecretion?

Answer 30

- It is increased as a result of increased frequency of hypothalamic gonadotropin-releasing hormone pulses. - Increased LH leads to an increase in androgen production by the theca cells within the ovary.

Question 31

What is the cycle of clinical features causing PCOS? How is this used to treat PCOS?

Answer 31

Each of these factors upregulate each other: 1 - Anovulation. 2 - Insulin resistance. 3 - Androgen excess. 4 - Obesity. - Treatment involved breaking this cycle, usually by losing weight.

Question 32

List 2 risks of PCOS regarding pregnancy.

Answer 32

1 - The risk of gestational diabetes is ten times increased in pregnant women with PCOS. 2 - The risk of pregnancy-related hypertension is equally high in women with PCOS. 3 - There is an increased risk of ovarian hyperstimulation syndrome, and subsequently fertilisation of more than one egg.

Question 33

Describe the mechanism of action of Dianette as an oral contraceptive.

Answer 33

- It contains ethinyl oestradiol, a synthetic oestrogen. | - It also contains cyproterone acetate, an anti-androgen that acts on the endometrium like progesterone.

Question 34

Describe the mechanism of action of Yasmin as an oral contraceptive.

Answer 34

- It contains ethinyl oestradiol, a synthetic oestrogen. | - It also contains drospirenone, a synthetic progesterone.

Question 35

What is androgen insensitivity syndrome?

Answer 35

A spectrum of disorders due to mutations in the androgen receptor, where patients are genetically male but have female characteristics. This can include: 1 - Complete androgen insensitivity syndrome. 2 - Incomplete androgen sensitivity syndrome. 3 - Reifensteins syndrome.

Question 36

List 5 symptoms of complete androgen insensitivity syndrome.

Answer 36

1 - Female external genitalia. 2 - Short vagina. 3 - No uterus. 4 - Absent prostate. 5 - Gynaecomastia.

Question 37

Why might androgen insensitivity syndrome present as an inguinal hernia?

Answer 37

Because undescended testes cause inguinal bulging.

Question 38

Why do patients with androgen insensitivity syndrome have high LH?

Answer 38

Because there is no negative feedback mechanism as LH cannot stimulate androgen production at the ovaries.

Question 39

Why do patients with androgen insensitivity syndrome have high oestrogen?

Answer 39

1 - Due to LH-driven gonad secretion. 2 - Due to aromatisation of testosterone, which is also high in androgen insensitivity syndrome.

Question 40

What is 5-alpha-reductase deficiency?

Answer 40

A condition in which genetic females are unable to convert testosterone to dihydrotestosterone, resulting in slightly masculine characteristics.

Question 41

Is testosterone decrease with age pathological or physiological?

Answer 41

Physiological - decrease is normal.

Question 42

List 6 causes of male primary hypogonadism (hypergonadotropic hypogonadism where the problem is in the testes).

Answer 42

1 - Trauma. 2 - Cancer treatment. 3 - Undescended testes. 4 - Infections. 5 - Chromosomal abnormalities such as Klinefelter's syndrome. 6 - Systemic diseases such as liver cirrhosis.

Question 43

List 6 causes of male secondary hypogonadism (hypogonadotropic hypogonadism where the problem is in the brain).

Answer 43

1 - Pituitary tumours. 2 - Hyperprolactinaemia. 3 - Hypothalamic disorders such as craniopharyngioma pituitary tumour and Kallmann syndrome. 4 - Systemic diseases such as liver cirrhosis. 5 - Obesity. 6 - Androgen abuse.

Question 44

List 8 symptoms of hypogonadism in males.

Answer 44

1 - Delayed puberty. 2 - Reduced libido. 3 - Gynaecomastia. 4 - Loss of body hair. 5 - Decreased muscle mass. 6 - Female fat distribution. 7 - Osteoporosis. 8 - Infertility.

Question 45

If FSH and LH are high, is this indicative of primary or secondary hypogonadism? Why?

Answer 45

- Primary hypogonadism. - Because the brain is able to release signals to the testes, but a signal is not being relayed back to the brain, so the problem is with the testes.

Question 46

What is the karyotype of Klinefelter's syndrome?

Answer 46

47 XXY.

Question 47

List 6 symptoms of Klinefelter's syndrome.

Answer 47

1 - Small testes. 2 - Azoospermia. 3 - Gynaecomastia. 4 - Reduced sexual hair. 5 - Osteoporosis. 6 - Tall stature.

Question 48

Give an example of a genetic cause of primary male hypogonadism other than Klinefelter's syndrome.

Answer 48

Myotonic dystrophy.

Question 49

What is the treatment for hypergonadotropic hypogonadism?

Answer 49

Testosterone replacement.

Question 50

Why does androgen abuse cause hypogonadism?

Answer 50

Because the exogenous testosterone blocks FSH and LH production.

Question 51

List 5 symptoms of androgen abuse.

Answer 51

1 - Psychological changes. 2 - Prostate cancer. 3 - Atrophy of the testes. 4 - Azoospermia. 5 - Polycythaemia.