Endocrine Infertility Flashcards

1
Q

Which cells within the testes does LH stimulate and what does it make these cells produce?

A
Leydig Cells
Produce testosterone (secondary sexual characteristics + aids spermatogenesis)
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2
Q

Which cells within the testes does FSH stimulate and what does it makes these cells produce?

A
Sertoli cells (in seminiferous tubules)
Produce sperm + inhibin A + B
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3
Q

What does inhibin inhibit?

A

Pituitary FSH secretion

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4
Q

What are the 3 phases of the menstrual cycle?

A

Follicular Phase
Ovulation
Luteal Phase

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5
Q

What does LH stimulate in the ovaries?

A

Oestradiol + progesterone production

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6
Q

What does FSH stimulate in the ovaries?

A

Follicular development + inhibin production

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7
Q

What effect does oestrogen have on the HPG axis in the follicular phase of the menstrual cycle?

A

It has a negative feedback effect: inhibits FSH + LH

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8
Q

What does the leading follicle develop into by around day 10?

A

Graffian Follicle

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9
Q

Once oestrogen reaches a certain level it switches to positive feedback. How does it do this?

A

It increases GnRH secretion
It increases LH sensitivity to GnRH
Causes mid cycle LH surge leading to ovulation

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10
Q

Define infertility.

A

Inability to conceive after 1 year of regular unprotected sex

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11
Q

What is primary gonadal failure and what effects does it have on the HPG axis?

A

A problem with the gonads
Testes/ovaries don’t produce enough testosterone/oestrogen so there is no negative feedback on the HPG axis resulting in high GnRH, LH + FSH.

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12
Q

Describe the levels of the different hormones in the HPG axis in the case of hypothalamic/pituitary disease causing infertility.

A

Low GnRH
Low FSH
Low LH

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13
Q

State 5 clinical features of male hypogonadism.

A
Loss of libido 
Impotence  
Small testes  
Decreased muscle bulk 
Osteoporosis (testosterone has anabolic action in the bone)
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14
Q

State 6 causes of male hypogonadism.

A
Hypopituitarism 
Kallmann’s Syndrome (anosmia + low GnRH) 
Illness/underweight 
Primary gonadal disease
Hyperprolactinaemia 
Androgen receptor deficiency (RARE)
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15
Q

State congenital and acquired causes of primary gonadal disease.

A

Congenital: Klinefelter’s Syndrome (XXY)
Acquired: Testicular torsion, chemotherapy

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16
Q

What are the main investigations for male hypogonadism?

A

LH, FSH + testosterone (if all low- MRI to check pituitary problem)
Prolactin
Sperm count (azoospermia: absence of sperm in ejaculate; oligospermia: reduced number of sperm in ejaculate)
Chromosomal analysis (Klinefelter’s= XXY)

17
Q

What is given to all patients with hypogonadism?

A

Testosterone to increase muscle bulk + protect against osteoporosis

18
Q

How do you restore fertility in someone with hypothalamic/pituitary disease?

A

Subcutaneous gonadotrophin injections to stimulate testosterone release

19
Q

What is the treatment for hyperprolactinaemia?

A

Treat cause- stop drugs
Dopamine agonists – bromocriptine + cabergoline
Pituitary surgery (rarely used because drugs normally works well)

20
Q

State 5 endogenous sites of production of androgens.

A
Interstitial leydig cells in the testes  
Adrenal cortex
Ovaries  
Placenta  
Tumours
21
Q

What are the 4 main actions of testosterone?

A
Development of the male genital tract 
Maintains fertility in adulthood  
Control of secondary sexual characteristics 
Anabolic effects (muscle, bone)
22
Q

Testosterone is heavily plasma protein bound and it can be converted to other hormones in various tissues. State 2 products that testosterone can be converted to and the enzymes responsible for these conversions.

A

Converted by 5-alpha-reductase to dihydrotestosterone (DHT), which acts on androgen receptors
Converted by aromatase to 17-beta-oestradiol, which acts on oestrogen receptors

23
Q

What type of receptors does DHT and E2 act on?

A

Nuclear receptors

24
Q

What are the clinical uses of testosterone?

A
Increase lean body mass 
Increase muscle size + strength 
Bone formation + bone mass  
Libido + potency  
(Does NOT restore fertility)
25
What is the difference between primary and secondary amenorrhoea?
``` Primary= failure to begin spontaneous menstruation by age 16 Secondary= absence of menstruation for 3 months in a woman who has previously had cycles ```
26
What is oligomenorrhoea?
Irregularly long cycles
27
List 9 causes of amenorrhoea.
``` Pregnancy Lactation Ovarian failure: Premature ovarian insufficiency, Ovariectomy, Chemotherapy, Ovarian dysgenesis (Turner’s Syndrome (45 X)) Hypothalamic/pituitary disease Kallmann’s syndrome Low BMI Post-pill amenorrhoea (long use of pill, then go off it, it could take a while for the periods to return) Hyperprolactinaemia Androgen excess (gonadal tumour) ```
28
State 3 features of Turner’s syndrome.
Short statue Cubitus valgus (forearm is angled away from the body to a greater degree than normal when fully extended) Gonadal dysgenesis
29
State 8 investigations for amenorrhoea.
Pregnancy test LH, FSH + Oestradiol Day 21 Progesterone: (high levels indicate ovulation has occurred) measure at day 18, 21 + 24 Prolactin Thyroid function test (both hyper- + hypothyroidism can cause problems) Androgens (testosterone, androstenedione, DHEAS) Chromosomal analysis Ultrasound scan ovaries/ uterus
30
What are the implications on health of polycystic ovarian syndrome (PCOS)?
``` Increased cardiovascular risk Insulin resistance (diabetes) ```
31
What are the criteria for diagnosing PCOS?
> 2 of the following: Polycystic ovaries on ultrasound scan Clinical/ biochemical signs of androgen excess Oligoovulation/ anovulation
32
List 3 clinical features of PCOS
Hirsuitism Menstrual irregularities Increased BMI
33
Describe the treatment for PCOS.
METFORMIN: insulin sensitiser CLOMIPHENE: anti-oestrogenic effects in the hypo-pit axis – binds to oestrogen receptors in the hypothalamus thereby blocking negative feedback, increases GnRH + gonadotrophin secretion GONADOTROPHIN THERAPY as part of IVF treatment
34
What hypothalamic hormone has a stimulatory effect on prolactin release?
Thyrotrophin releasing hormone (TRH)
35
What effect does hyperprolactinaemia have on the HPG axis?
Reduces GnRH pulsatility so that it is released basally all the time rather than in regular pulses It will switch off gonadal function via LH actions on the ovaries + testes
36
State 9 causes of hyperprolactinaemia.
``` Dopamine antagonists (anti-emetics + anti-psychotics) Prolactinoma Stalk compression due to pituitary adenoma (so dopamine can’t get to adenohypophysis) PCOS Hypothyroidism Oestrogens (OCP) Pregnancy Lactation Idiopathic ```
37
What are 3 clinical features of hyperprolactinaemia?
Galactorrhoea Reduced GnRH + gonadotrophin secretion: HYPOGONADISM Prolactinoma: Visual field defect + Headache
38
Describe treatment of amenorrhoea
``` Treat cause (e.g. low weight) Primary ovarian failure (Infertile, HRT) Hypothalamic/ pituitary disease (HRT for oestrogen replacement, fertility- gonadotrophins) ```