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Year 2 Collin > Endo 9 - Causes of endocrine infertility > Flashcards

Endo 9 - Causes of endocrine infertility Flashcards

1
Q

What do Sertoli cells secrete that inhibits FSH and GnRH secretion from APG and Hypothalamus?

A

Inhibin

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2
Q

What are the 3 phases of the 28 day menstrual cycle

A
  1. Follicular phase - oestradiol and progesterone (-ve feedback present) secreted by ovaries, follicles in ovary growing
  2. Ovulation - big increase in Oestradiol, causing +ve feedback which causes big increase in LH (especially) and FSH secretion
  3. Luteal phase:
    - If implantation doesn’t occur - endometrium is shed
    - if implantation does occur - pregnancy
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3
Q

What is infertility

A

Inability to conceive after 1 year of regular unprotected sex

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4
Q

What is primary gonadal failure and what are the consequences of it

A
  1. Testes or ovaries dont work

2. Means that there are high levels of GnRH and LH/FSH, as no negative feedback from testosterone/oestradiol

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5
Q

Describe hypothalamic/pituitary disease?

A

Secondary gonadal failure

Problem with hypothalamus/pituitary so not enough LH/FSH secreted, and so low testosterone/oestradiol levels

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6
Q

What is hypogonadism (M)

What are the clinical features

A

Low functioning testes (in males)

  1. Loss of libido
  2. Impotence
  3. Small testes
  4. Decreased muscle bulk
  5. Osteoporosis
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7
Q

What are the 2 causes of male hypogonadism

A
  1. Hypothalamic-pituitary disease (secondary gonadal failure)
    Can be caused by:
    -Hypopituitarism
    - Kallmans syndrome (improper development of GnRH neurones - causes anosmia and low GnRH).
    - Illness/underweight (low leptin levels switch off GnRH neurones)
  2. Primary Gonadal disease
    Can be caused by:
    - Congenital: Klinefelters syndrome (XXY)
    - Acquired: Testicular torsion, chemotherapy
  3. Hyperprolactinaemia
  4. Androgen receptor deficiency
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8
Q

Why might infertility be linked with an inability to smell (anosmia)

A

In hypothalamic-pituitary disease, Kallmans syndrome is a cause. This is an inability of the GnRH neurones to project fully. The GnRH neurones grow with the olfactory neurones, so sometimes the olfactory neurones are also not developed

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9
Q

What investigations should be done if male presents with hypogonadism

A
  1. LH/FSH/Testosterone - if all low, MRI pituitary
  2. Prolactin
  3. Sperm count - (azoospermia/oligospermia?)
  4. Chromsomal analysis (for Klinefelters)
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10
Q

What is the treatment for male hypogonadism

A
  1. Replacement testosterone for all patients
  2. If patient wants a child - and has Hypo/pit disease, can give LH/FSH
  3. If hyperprolactinaemia, can give dopamine agonist
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11
Q

Name 5 sites of endogenous androgen production

A
  1. Leydig cells (testes)
  2. Adrenal cortex - zona reticularis
  3. Ovaries
  4. Placenta
  5. Tumours
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12
Q

4 main actions of testosterone?

A
  1. Development of male genital tract
  2. Fertility in adulthood
  3. Controls secondary sexual characteristics
  4. Anabolic effects (muscle and bone)
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13
Q

98% of circulating Testosterone is PPB. The free plasma testosterone has 2 possibilities, which are

A
  1. Can be converted into DHT by 5a-reductase. DHT works via androgen receptor (AR)
  2. Can be converted into 17B-oestradiol (E2) via aromatase. E2 works via oestrogen receptor (ER).

Mechanism of action of DHT/E2 is via nuclear receptors

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14
Q

What are the clinical uses of testosterone

A

Test will increase:

  1. Lean body mass
  2. Muscle size and strength
  3. Bone formation and mass (in young men)
  4. Libido and potency

NB. Testosterone will not restore fertility - fertility requires treatment with gonadotrophin (FSH/LH) to restore normal spermatogenesis - i.e. if primary gonadal failure, having a child is dependent on how much term is left

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15
Q

Which 3 disorders in females may cause infertility

A
  1. Amenorrhoea
  2. Polycystic Ovarian Syndrome (PCOS)
  3. Hyperprolactinaemia
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16
Q

What are the 3 types of amenorrhoea (absence of periods)

A
  1. Primary amenorrhoea - failure to begin spontaneous menstruation by 16
  2. Secondary amenorrhoea - absence of menstruation for 3 months in a F who has previously had cycles (p much rules out congenital causes)
  3. Oligomenorrhoea - irregular long cycles
17
Q

What are the causes of amenorrhoea?

A
  1. Pregnancy/lactation
  2. Ovarian failure - caused by:
    - Premature ovarian failure (early menopause)
    - Ovariectomy/chemotherapy
    - Ovarian dysgenesis (Turners 45 X0)
  3. Gonadotrophin failure (hypo/pit disease, Kallmans syndrome, low BMI (low leptin), post pill amenorrhoea)
  4. Hyperprolactinaemia (also switches off testosterone)
  5. Androgen excess, gonadal tumour
18
Q

What investigations can be done for amenorrhoea

A
  1. Pregnancy test
  2. LH, FSH, Oestradiol
  3. Day 21 progesterone - it should be high, if low then they haven’t ovulated in that cycle
  4. Prolactin, thyroid function tests
  5. Androgens
  6. Chromosomal analysis (Turners 45 XO)
  7. Ultrasound scan ovaries/uterus
19
Q

What is the treatment for amenorrhoea

A
  1. Treat cause (e.g. low weight)
  2. If primary ovarian failure - they are infertile - give HRT
  3. Hypothalamic/pituitary disease - give HRT for oestrogen replacement. If patient wants child, give gonadotrophins (LH + FSH), use as part of IVF treatment
20
Q

What is the criteria to diagnose PCOS

A

2 of the following:

  1. Polycystic ovaries on uterus upon ultrasound scanning
  2. Oligo-anovulation
  3. Clinical/biochemical androgen excess
21
Q

What are the clinical features of PCOS

A
  1. Hisutism
  2. Menstrual cycle disturbance
  3. Increased BMI
22
Q

What is the treatment for PCOS?

A
  1. Metformin - improves insulin sensitivity
  2. Clomiphene (antioestrogenic) - it works by binding to oestrogen receptors in hypothalamus - blocks normal negative feedback - more GnRH and FSH/LH secretion
  3. Gonadotrophin therapy as part of IVF treatment
23
Q

Prolactin secretion is regulated by?

A

Dopamine mainly (inhibitory effect) and TRH (thyrotrophin releasing hormone - stimulatory effect but small compared to DA)

24
Q

What 2 effects does high prolactin have on the reproductive axis?

A
  1. Switches off GnRH pulsatility

2. Inhibits LH actions on ovary/testis

25
Q

What can be the causes of hyperprolactinaemia?

A
  1. DA antagonist drugs (e.g. anti-emetics - metocopramide, anti-psychotics - phenothiazines)
  2. Prolactinoma
  3. Stalk compression due to pituitary adenoma

(Milder causes include:

  1. PCOS
  2. Hypothyroidism
  3. Oestrogens/pregnancy/lactation)
  4. Idiopathic)
26
Q

What are the clinical features of prolactinomas

A
  1. Galactorrhoea
  2. Reduced GnRH secretion = less LH action = hypogonadism
  3. Prolactinoma may cause headache and visual field defects
27
Q

How can hyperprolactinaemia be treated

A
  1. Treat the cause - stop drugs
  2. DA agonist - Bromocriptine/cabergoline
  3. If Prolactinoma- DA agonist, pituitary surgery very rarely needed
28
Q

Young woman with secondary amenorrhoea and galactorrhea. Prolactin levels = 4500 (very high). What would her blood results show?

A
  1. Low LH, Low FSH, Low estradiol

Year 2 Collin (114 decks)

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