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Year 2 - endocrine > Causes of Fertility Issues > Flashcards

Causes of Fertility Issues Flashcards

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1
Q

What are the 3 groups of ovulation disorders?

A
  1. hypothalamic-pituitary failure
  2. hypothalamic-pituitary dysfunction
  3. ovarian failure
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2
Q

What is the typical hormonal profile for Group I: Hypothalamic-pituitary failure?

A
  1. Low levels of FSH and LH
  2. Leading to oestrogen deficiency
  3. Negative progesterone challenge test
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3
Q

What is the most common cause of ovulatory disorders?

A

Group II - Hypothalamic-pituitary dysfunction (85% of ovulatory disorders)

= most commonly associated with PCOS

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4
Q

What are the features of Group II: Hypothalamic-pituitary dysfunction?

A
  1. Normal gonadotropins
  2. excess LH
  3. Normal oestrogen levels
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5
Q

How is ovarian failure (Group III) diagnosed?

A
  1. high gonadotrophins (FSH >30 IU/l on two samples)
  2. low oestrogen levels
  3. symptoms of menopause in an amenorrhoeic patient
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6
Q

Why can high GnRH levels lead to low oestrogen levels?

A

(1) High or irregular GnRH pulses cause the pituitary to release more LH but less FSH.

(2) Since FSH stimulates the ovaries to produce oestrogen, low FSH results in decreased oestrogen production, leading to low oestrogen levels

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7
Q

What is considered premature ovarian failure?

A

Premature ovarian failure is defined as menopause before 40 years.

Causes include
1. genetic factors
(eg, Turner syndrome)

  1. autoimmune ovarian failure
  2. bilateral oophorectomy - removal of ovaries
  3. pelvic radio/chemotherapy
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8
Q

What does a negative progesterone challenge test indicate?

A

A negative test (no withdrawal bleed) suggests

  1. low oestrogen levels
  2. possible uterine/endometrial abnormality
  3. cervical stenosis
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9
Q

What test is used to assess if a woman has ovulated?

A

The midluteal serum progesterone test (D21), where progesterone levels >30 nmol/l indicate ovulation

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10
Q

Which test is commonly used to diagnose PCOS in women with ovulatory disorders?

A

Transvaginal ultrasound, which checks for follicular growth and signs of PCOS

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11
Q

What is the first-line treatment for PCOS if a woman wants to conceive?

A

Clomifene citrate (oral medication), which increases GnRH and LH/FSH levels to stimulate ovulation

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12
Q

What is the recommended management for anovulation due to hypothalamic-pituitary failure
(Group I)?

A
  1. Stabilise weight
  2. Pulsatile GnRH therapy or gonadotropin (FSH + LH) injections with ultrasound monitoring
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13
Q

What is the management for premature ovarian failure?

A
  1. Hormone replacement therapy (HRT)
  2. Egg/embryo donation
  3. Cryopreservation of eggs or embryos before chemotherapy or radiotherapy
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14
Q

What are the risks associated with gonadotrophin therapy for ovulation induction in PCOS?

A

There is an increased risk of multiple pregnancies and ovarian hyperstimulation

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15
Q

What is the management of type II anovulation (PCOS)

A

Lifestyle - 90% of women with PCOS are obese; ovulation induction only if BMI <30

1st line (for conception)
= Clomifene citrate (PO)
This prevents negative feedback to the hypothalamus and increases GnRH, LH, and FSH

If they do NOT want conception
= Combined oral contraceptive pill (COOP).

2nd line
= Metformin
Reduces insulin resistance, restores ovulation, and improves clomifene sensitivity

3rd line
= Gonadotrophin therapy (FSH injections) - risk of multiple pregnancy.

4th line
= Laparoscopic ovarian diathermy Risks: ovarian destruction, surgery complications

5th line
= IVF

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16
Q

What eating disorder is characterised by a fear of gaining weight and a distorted body image?

A

Anorexia nervosa

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17
Q

What are common clinical features of anorexia nervosa?

A
  1. Low BMI (<18.5)
  2. Hair loss
  3. Increased lanugo
  4. Low pulse and BP
  5. Anaemia
  6. Dehydration
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18
Q

What are the key endocrine features of anorexia nervosa?

A

Low FSH, LH, and oestradiol which leads to hypoestrogenism

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19
Q

What is PCOS?

A

A condition where women have high levels of male hormones, irregular periods, and/or cysts on their ovaries

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20
Q

What is the pathophysiology of PCOS?

A

Raised testosterone
Raised LH
Normal FSH
Low (SHBG)

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21
Q

What are the key clinical features of PCOS?

A
  1. Obesity (high BMI)
  2. Hirsutism or acne
  3. Menstrual cycle abnormalities
  4. Infertility
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22
Q

What are the diagnostic criteria for PCOS (Rotterdam criteria)?

A

Diagnosis requires 2 out of 3 features
1. Oligo/amenorrhoea
= infrequent/ no periods

  1. Polycystic ovaries (on USS)
  2. hyperandrogenism
    = too much male hormones
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23
Q

What are the endocrine features of PCOS?

Study These Flashcards
A

(1) Normal gonadotrophins with excess LH
= FSH is low or normal, LH is high, they might still be within a “normal range” but they are imbalance

(2) Normal oestrogen levels
(3) Raised testosterone

(4) Insulin resistance

24
Q

What is the first-line treatment for managing PCOS symptoms?

Study These Flashcards
A

Weight loss and combined oral contraceptive pill (COCP) for management and symptom control

25
How does insulin resistance affect PCOS?
Insulin resistance contributes to hyperandrogenism and altered ovarian function in PCOS = too much male hormone (androgens) in the body
26
A 34-year-old woman attends the clinic feeling generally unwell. Her abdomen has become uncomfortable and distended over the last 2 days, and she is suffering from loose stools. She also feels dyspnoeic on exertion. On examination, all observations are within normal range and there is generalised abdominal tenderness with no guarding. The patient is undergoing fertility treatment and the previous week was injected with a gonadorelin analogue. Given the above history, which of the following is the most likely diagnosis?
Ovarian hyperstimulation syndrome (OHSS) = potential side-effect of ovulation induction
27
What is Premature Ovarian Failure?
Occurs when the ovaries stop functioning normally before age 40 from 1. Chemo/ radio 2. Turners syndrome or fragile X
28
What features of seen in premature ovarian failure?
- High FSH - High LH - Low oestradiol = female sex hormone also produced by males
29
What is Hypogonadotropic hypogonadism?
occurs when the testes fail to produce enough testosterone, causing the pituitary to release high levels of LH and FSH
30
What is the pathophysiology of primary hypogonadism? - hypergonadotropic
Testicular dysfunction causes decreased testosterone, leading to reduced negative feedback and increased LH/FSH production by the pituitary, causing hypergonadotrophic hypogonadism
31
What is the pathophysiology of secondary hypogonadism? - hypogonadotropic
Dysfunction of the pituitary gland or hypothalamus meaning they don't make enough LH and FSH, so the testes don’t get the signal to produce testosterone. This causes low testosterone with low or normal LH and FSH levelsresulting in hypogonadotrophic hypogonadism
32
What are the clinical features of pre-pubertal onset male hypogonadism?
1. Small sexual organs (testes <5 mL) 2. Decreased body hair 3. High-pitched voice 4. Low libido = reduced sex drive 5. Gynaecomastia = enlargement of breast tissue in males caused by an imbalance between male hormones (androgens) and female hormones (oestrogens) 6. Decreased bone/muscle mass
33
What investigations are done for male hypogonadism?
AM testosterone levels (x2) LH/FSH
34
When should testosterone be measured for male hypogonadism?
between 8-11am when levels are highest
35
What is Klinefelter's Syndrome?
The most common genetic cause of hypogonadism in men. Only occurs in MEN = caused by an extra X chromosome (47 XXY) = leading to infertility and small, firm testes
36
What is the incidence of Klinefelter's Syndrome?
approximately 1 in 600 men
37
What causes Klinefelter's Syndrome?
Caused by nondisjunction, resulting in a 47 XXY genotype though mosaic forms (46 XY/47 XXY) can occur
38
What are the common clinical features of Klinefelter's Syndrome?
1. infertile 2. have small firm testes 3. may present with learning disabilities and psychosocial issues
39
How is Klinefelter's Syndrome diagnosed?
karyotyping
40
A 17-year-old boy presents to the GP as he is yet to start puberty. On examination, he is taller than average but has gynecomastia and small firm testicles, with no secondary sexual characteristics What is the most likely diagnosis?
Klinefelter's syndrome
41
A 16-year-old female presents to the GP having not yet started periods. She is concerned that she has not started puberty. An early-morning blood sample is sent which reveals low serum follicle-stimulating hormone and luteinising hormone concentrations What condition is most likely the cause of her delayed puberty?
Kallmann syndrome
42
A 16-year-old boy presents to his GP complaining that he has not reached puberty like his peers. On examination, he is short and has small testes and no pubic or axillary hair. At what age are boys with no pubertal development classed as having delayed puberty?
14
43
A 14-year-old boy presents with concerns about his lack of development compared to his peers. He has not experienced any growth spurts, his voice has not deepened and he has minimal pubic hair. Which hormone should be assessed first to investigate the cause of his delayed puberty?
Follicle-stimulating hormone (FSH) and luteinizing hormone (LH)
44
What is Kallmann Syndrome?
A genetic condition where the body doesn't make enough of a hormone called GnRH. This hormone helps control puberty and periods. Because of this, people with Kallmann syndrome don't go through puberty normally and may not have periods. They also have trouble smelling things (anosmia or hyposmia)
45
Is Kallmann Syndrome more common in males or females?
Both males and females but is more common in males
46
How does Kallmann Syndrome affect periods in females?
Causes delayed puberty, with absent or very irregular periods due to low GnRH = which leads to low levels of FSH and LH, preventing normal ovarian function
47
What are the clinical features of Kallmann Syndrome?
(1) Hypogonadism = body produces too little sex hormones (eg, small testes in males, absent menstruation in females) (2) Hyposmia/anosmia (impaired sense of smell) (3) Possible associated abnormalities like 1. unilateral renal agenesis 2. red-green colour blindness 3. cleft lip/palate 4. bimanual synkinesis
48
What is the management for Kallmann Syndrome?
Hormone replacement therapy to stimulate puberty, maintain secondary sexual characteristics, and regulate periods. = In males : testosterone = In females : oestrogen and progesterone
49
What is the main difference between Kallmann syndrome and Klinefelter's syndrome?
Kallmann syndrome is caused by low GnRH, leading to delayed puberty and loss of smell whilst Klinefelter's syndrome is due to an extra X chromosome, causing infertility, small testes and sometimes learning difficulties
50
A 17-year-old man presents to the clinic with his parents. They report that he has always been tall for his age but has shown little development of secondary sexual characteristics compared to his peers. On examination, he is noted to have small testes and gynecomastia. Genetic testing reveals a karyotype of 47 XXY. What lab findings would be expected in this patient?
High LH, low testosterone, High FSH because: (1) Testes don’t work well → low testosterone (2) Pituitary tries to compensate → high LH and FSH
51
A 19-year-old male presented to the andrology clinic with a failure to gain secondary sexual characteristics. His height is 186 cm and his weight is 65 kg with a body mass index of 18.7 kg/m² Investigation results are as follows: Testosterone 6.2 nmol/L (8.7 - 29) FSH 0.3 u/L (0.3 - 10.0) LH 1.6 u/L (1.7 - 8.6) What is the most likely diagnosis and why?
Kallman's syndrome (1) Low LH and FSH because the hypothalamus doesn’t produce enough GnRH (2) Low testosterone due to lack of stimulation from LH and FSH
52
A 28-year-old man presents to his general practitioner with difficulty conceiving. He and his wife have been trying to conceive for one year through regular unprotected intercourse without success. His past medical history is notable for autism spectrum disorder. On examination, he is tall, standing at 1.9 metres, with disproportionately long limbs and breast enlargement; however, his sense of smell is intact. What additional feature might you expect in this man given the likely diagnosis and why?
Raised luteinising hormone (LH) and low testosterone = Man has Klinefelter's syndrome
53
What is GnRH and why is it important in the reproductive hormone system?
(1) GnRH (Gonadotropin-releasing hormone) is produced by the hypothalamus and signals the pituitary gland to release LH and FSH. (2) These hormones then stimulate the gonads to produce sex hormones like testosterone and oestrogen. (3) GnRH is crucial because it controls the whole reproductive hormone system and keeps hormone levels balanced
54
A 25-year-old woman presents with irregular periods, acne, and excess facial hair. Blood tests show normal levels of LH and FSH, but the LH: FSH ratio is elevated. What is the most likely diagnosis, and why is the LH: FSH ratio important?
(1) The most likely diagnosis is Polycystic Ovary Syndrome (PCOS). In PCOS, the LH: FSH ratio is often elevated (usually >2:1), even if the absolute levels of LH and FSH are within normal limits. (2) This relative increase in LH stimulates the ovaries to produce excess androgens, causing symptoms like irregular periods, acne, and hirsutism. (3) The disrupted ratio is key to the hormonal imbalance seen in PCOS
55
Are GnRH and gonadotrophins the same thing?
No = they are different but part of the same hormonal pathway. GnRH (Gonadotropin-Releasing Hormone) is released by the hypothalamus and stimulates the pituitary gland to release gonadotrophins = FSH and LH Gonadotrophins then act on the ovaries or testes to produce sex hormones like oestrogen or testosterone
56
What is raised in anorexia nervosa?
growth hormones, glucose, salivary glands, cortisol, cholesterol Starvation is a physical stress → The body releases more cortisol via the HPA axis Vomiting or use of laxatives/diuretics causes potassium loss

Year 2 - endocrine (37 decks)

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