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Lecture Notes - Endocrinology > Male reproductive physiology and hypogonadism > Flashcards

Male reproductive physiology and hypogonadism Flashcards

1
Q

What 2 structures do the testes contain

A

seminiferous tubules composed of Sertolli cells and germ cells
Interstitial containing Leydig cells that produce testosterone

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2
Q

What stimulates the secretion of GnRH

A

hypothalamic neurones

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3
Q

What stimulates the release of LH and FSH

A

Pulsatile GnRH

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4
Q

How does GnRH stimulate the release of LH and FSH

A

it binds to receptors on the plasma membrane of pituitary gonadotrophs and stimulates their release by a calcium-dependent mechanism that may involved diacyclglycerol

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5
Q

What are LH and DSH composed of

A

two glucoprotein chains

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6
Q

What do LH and FSH do

A

They interact with cell membrane receptors and stimulate adenylate cyclase

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7
Q

What does LH stimulate in males

A

The production of testosterone by Leydig cells
The synthesis of testoereon by actin gone the steroidogenic acute regulatory protein which delivers cholesterol to the inner mitochondrial membrane where it is converted to pregnenolone

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8
Q

Sperm are produced under the stimulation of what

A

testosterone and FSH

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9
Q

What inhibits FSH secretion

A

inhibin B as well as testosterone and estradiol

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10
Q

What modulate GnRH secretion

A

several hormones, neurotransmitters and cytokines

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11
Q

When might testosterone levels be reduced

A

acute and chronic illnesses and fasting

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12
Q

How much plasma testosterone is free (unbound)

A

2%

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13
Q

Some testosterone is bound to a hepatic glycoprotein. What is this called

A

sex hormone-binding globulin

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14
Q

What is the other protein that testoesterone can be bound to

A

albumin

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15
Q

What can cause an increase in SHGB

A 
Ageing 
antiepileptic agents 
liver disease 
oestrogens 
thyrotoxicosis 
growth hormone deficiency
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16
Q

What can cause a decrease in SHGB

A 
Diabetes mellitus 
Obesity 
corticosteroids, anabolic steroids 
hypothyroidism 
acromegaly
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17
Q

Why is it that changes in the SHBG levels do not affect free androgen levels

A

Hypothalamic-pituitary system responds to acute changes in the concentrations of bioavailable testosterone by altering testosterone synthesis

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18
Q

What are the physiological actions of tester one

A

The result of the combined effects of testosterone and its active metabolites

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19
Q

What are the major functions of androgens in males

A

regulation of gonadotrophin secretion from the hypothalamic-pituitary system

initiation and maintenance of spermatogenesis

formation of the male genital tract during embryogenesis
development of male secondary sexual characteristics and sexual potency at puberty and their maintenance there after

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20
Q

What is male hypogonadism

A

a syndrome of decreased testosterone production, sperm production or both

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21
Q

What might hypogonadism result from

A

disease of the testes (primary hypogonadism)

disease of the pituitary or hypothalamus (secondary hypogonadism)

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22
Q

Why is primary hypogonadism also sometimes known as hypergonadotrophic hypogonadism

A

reduced testosterone levels result in elevated gonadotrophin levels (negative feedback effect)

23
Q

What are some of the congenital causes of primary hypogonadism

A

Klinefelter’s syndrome
Cryptorchidism
Other chromosomal abnormalities

24
Q

What is the most common cause of primary hypogonadism

A

Klinefelter’s syndrome

25
Q

What causes Klinefelter’s syndrome

A

1 or more extra chromosome

This results in damaged seminiferous tubules and Leydig cells

26
Q

What is the most common Klinefelter’s genotype and what does it result from

A

47XXY

Non-disjunction of the sex chromosomes of either parent during meiotic division

27
Q

What are some other symptoms of Klinefelter’s syndrome

A

Intellectual dysfunction and behaviour abnormalities that cause difficulty in social interactions

Predisposition to developing chronic bronchitis, bronchiectasis and emphysema, breast cancer, non-Hodgkin’s lymphoma, varicose veins, leg ulcer,s diabetes mellitus

28
Q

What does Cryptorchidism refer to

A

unilateral or bilateral undescended tests (in the abdominal cavity or in the inguinal canal) that cannot be manipulated manually in the scrotum by the age of 1 year

29
Q

What are some acquired causes of primary hypogonadism

A 
Infections 
Testicular trauma or torsion 
chemotherapy 
radiotherapy 
autoimmune damage 
chronic illness e.g. COPD 
congestive cardiac failure 
Crohn's disease 
coeliac disease
chronic liver disease 
RA 
chronic kidney disease
AIDS
30
Q

What is secondary hypogonadism due to

A

Impaired secretion of hypothalamic GnRH or pituitary gonadotrophins

31
Q

What might congenital secondary hypogonadism be associated with

A

anosmia in Kallmann’s syndrome

32
Q

What is Kallmann’s syndrome sometimes associated with

A

red-green colour blindness
midline facial abnormalities (e.g. cleft palate)
urogenital tract abnormalities
synkinesis (mirror movements of the hands)
hearing loss

33
Q

What might secondary hypogonadism be caused by

A

Any pituitary or hypothalamic disease such as pituitary adenoma, craniopharyngioma, pituitary surgery, infarction, infection, infiltrative disorders such as haemochromatosis, sarcoidosis, histiocytosis, TB and fungal infections

34
Q

What can suppress gonadotrophin secretion

A 
chronic systemic illness
diabetes mellitus 
hyperprolactinaemia 
androgen excess 
cortisol excess 
oestrogen excess 
chronic opiate administration 
GnRH analogues
35
Q

What does the clinical presentation depend on

A

whether the onset of hypogonadism is before or after puberty

36
Q

What are the clinical presentation of hypogonadism before the onset of puberty

A

Delayed puberty

Testes

37
Q

What are the clinical presentation of hypogonadism after the onset of puberty

A

Fatigue, reduced energy and lowered physical strength
low mood, irritability and poor concentration
reduced libido and/or sexual function. loss of spontaneous morning erections and infertility
osteoporosis and fragility fractures
Soft tests

38
Q

What is the major action of testosterone on male sexuality

A

libido

39
Q

What is primary hypogonadism more likely to be associated with

A

gynaecomastia - due to the stimulation of testicular aromatase activity by the increased serum FSH and LH resulting in increased conversion of testosterone to estradiol and also increased testicular secretion of estradiol relative to testosterone

40
Q

How can a diagnosis of hypogonadism be confirmed

A

by finding low serum testosterone and or decreased sperm in the semen

41
Q

Describe the variation in levels of serum testosterone

A

Diurnal variation - maximum at about 9 am and lower levels in the evening

42
Q

What levels of LH and FSH indicate testicular damage (primary hypogonadism)

A

High concentrations

43
Q

What levels of LH and FSH indicate pituitary or hypothalammic disease

A

Low or inappropriately normal

44
Q

What should men with primary hypogonadism have done

A

A peripheral leukocyte karyotype to determine whether Klinefelter’s syndrome is present

45
Q

What is the treatment for hypogonadism

A

Directed at any underlying disorders
Relieve symptoms and preserve bone density
Pre-puberty boys should be started on low doses of testosterone that are gradually increased

46
Q

Where is testosterone gel applied

A

Should and upper arm

47
Q

What are some advantages of and disadvantages of the gel

A

Advantages - self-administration, avoidance of painful injections, dries quickly
Disadvantages - could be transferred to partner through skin contact , patients should not shower for 6 hours

48
Q

What are some disadvantages of IM testosterone

A

Pain at injection site
More mood swings
Only every 2-3 weeks

49
Q

What are some advantages and disadvantages of subcutaneous testosterone implants

A

Only every 6 months
Minor surgery
Complications include infection, bleeding, extrusion and scarring

50
Q

What are some side effects of testosterone replacement

A 
Acne on the upper trunk 
Prostate enlargement 
Polycythaemia 
Gynaecomastia 
Fluid retention 
Sleep apnoea 
mood fluctuations
51
Q

What are some contraindications of testosterone replacement

A 
Prostate cancer 
Polycythaemia 
breast carcinoma
sleep apnoea 
conditions in which fluid retention may be harmful
52
Q

How are men with secondary hypogonadism who desire fertility treated?

A

With gonadotrophin replacement or pulsatile GnRH therapy

53
Q

What should be asked about in a follow up appointment

A 
Improvements in symptoms 
Weight gain
peripheral oedema 
gynaecomastia 
In men over 40, PR exam
54
Q

What lab tests should be measured in follow up

A

Haemoglobin
Prostate -specific antigen (PSA)
LFT and fasting lipid profile
Testosterone levels

Lecture Notes - Endocrinology (40 decks)

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