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Lecture Notes - Endocrinology > Female reproductive physiology, amenorrhoea and premature ovarian failure > Flashcards

Female reproductive physiology, amenorrhoea and premature ovarian failure Flashcards

1
Q

What are the 2 phases of the menstrual cycle

A

Follicular (onset of mess and ends on the day of LH surge

Luteal (begins on the day of the LH surge and ends at the onset of the next menses

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2
Q

How long is the average adult menstrual cycle

A

28 days - 15 days in each phase

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3
Q

What is the first day of the cycle

A

the first day of menses

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4
Q

What are longer menstrual cycles normally associated with

A

anovulation

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5
Q

In terms of oocytes, what happens during each normal menstrual cycle

A

a single mature oocyte is released from a pool of hundred of thousands of primordial oocytes

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6
Q

What hormone levels are low during the follicular stage

A

serum oestradiol and progesterone

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7
Q

What does a low serum estradiol and progesterone result in

A

Negative feedback which results in increased GnRH pulse frequency

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8
Q

What is the effect of an increased GnRH pulse frequency

A

Increases serum FSH levels and LH pulse frequency

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9
Q

What does the increase in FSH stimulate

A

the recruitment and growth of a cohort of ovarian follicles

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10
Q

What do ovarian follicles consist of

A

oocytes surrounded by granulosa cells and theca cells

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11
Q

What enzyme does FSH stimulate

A

Aromatase (in the granulosa cells of the dominant follicle)

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12
Q

What is the function of aromatase

A

It converts androgens (synthesised in the theca cells) to oestrogen

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13
Q

What does the increase in estradiol production initially do

A

suppresses serum FSH and LH levels

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14
Q

What else plays a role in suppressing FSH

A

Serum inhibin B

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15
Q

What happens to the rest of the growing follicles

A

They undergo atresia after a single dominant follicle is selected

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16
Q

How does the LH surge arise

A

The negative feedback effect of ovarian steroids (particularly oestradiol) switches to a positive feedback effect

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17
Q

What is the LH surge associated with

A

an increased frequency of FnRH secretion and enhanced pituitary sensitivity to GnRH

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18
Q

What happens to estradiol secretion just before ovulation

A

It reaches a peak and then falls

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19
Q

How long does it take for the oocyte to be released following the LH surge

A

36 hours

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20
Q

What do the granulosa cells begin to produce and what do they develop into post oocyte release

A

Progesterone

Corpus luteum

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21
Q

What starts to rise towards the end of the luteal phase and why

A

FSH starts to rise to stimulate the development of the next follicle usually in the contralateral ovary.
This occurs due to the progesterone and oestrogen levels falling

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22
Q

Describe the levels of Inhibin A during the menstrual cycle

A

Low in the follicular phase and increased in the luteal phase

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23
Q

What happens to the corpus luteum and progesterone production if the oocyte becomes fertilised

A

The corpus luteum is maintained and progesterone production is also maintained

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24
Q

What is the effect of the serum estradiol concentrations during the follicular phase on the endometrium

A

Proliferation of the uterine endometrium and glandular growth occurs

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25
Q

What happens to the arterioles supplying the endometrium as the function of the corpus luteum declines

A

The arterioles undergo vasospasm (caused by locally synthesised protaglandins) causing ischaemic necrosis, endometrial desquamation (shedding) and bleeding

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26
Q

What is the principal and most potent oestrogen secreted by the ovary

A

Oestradiol

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27
Q

What do oestrogens promote

A

Development of secondary sexual characteristics (breast development etc.)
cause uterine growth
play an important role in regulation of menstrual cycle

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28
Q

How do oestrogens act

A

They bind to a nuclear receptor which binds to specific DNA sequences and regulates the transcription of various genes

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29
Q

What is the principle hormone secreted by the corpus luteum

A

Progesterone

30
Q

What is progesterone responsible for

A

Pro gestational effects - including induction of secretory activity in the endometrium in preparation for the implantaion of a fertilised egg
Inhibition of uterine contractions
increased viscosity of cervical mucus
glandular development of the breasts

31
Q

Describe the change in temperature during the menstrual cycle

A

It increased by 0.3-0.5 degrees after ovulation and persists during the luteal phase and returns to normal after the onset of menses

32
Q

What is inhibit

A

a glycoprotein consisting of two disulphide-linked subunits, alpha and beta

33
Q

Why are there two forms of inhibit

A

The beta subunit can exist in 2 forms

34
Q

Where is inhibin B secreted and what is its function

A

secreted by the follicle and inhibits the release of FSH from he pituitary

35
Q

Where is inhibin A secreted and what is its function

A

Secreted by the Corpus luteum of the last cycle

levels are low in follicular phase and increased i the luteal phase

36
Q

What is amenorrhoea

A

the absence of menstrual periods in a woman during her reproductive year
It can be primary or secondary

37
Q

What is primary amenorrhoea

A

The absence of menstrual periods by age 14 in a girls without breast development or by age 16 in a girl with breast development

38
Q

What is secondary amenorrhoea

A

The absence of menstrual periods for more than 3 months in a woman who has previously had an established menstrual cycle

39
Q

What has a higher incidence, primary or secondary amenorrhoea

A

Secondary

40
Q

What are some of the causes of amenorrhoea

A

Functional - street, weight loss, excessive exercise, eating disorders
Pituitary and hypothalamic tumours - adenomas, craniopharyngiomas, haemochromatosis
Hyperprolactinomas - cause pituitary stalk compression
Kallmann’s syndrome
Premature ovarian failure - chromosomal abnormalities, autoimmune, iatrogenic,
Uterine and vaginal outflow - congenital anatomical abnormalities
Thyroid dysfunction - Hypothyroidism or thyrotoxicosis
Hyperandrogenism- congenital adrenal hyperplasia, PCOS
Imperforate hymen
transverse vaginal septum between the cervix and the hymenal ring (prevents the egress o menses)

41
Q

Amenorrhoea may be due to a defect at what levels

A 
Hypothalamus 
Pituitary 
Ovaries
Uterus 
Vaginal outflow tract
42
Q

What is functional hypothalamic amenorrhoea characterised by

A

abnormal hypothalamic GnRH secretion, resulting in decreased gonadotrophin pulsations

43
Q

What might pituitary/ hypothalamic tumours cause

A

hypogonadotrophic hypogonadism and amenorrhoea

44
Q

What does hypoerprolactinaemia do

A

It can interrupt the transport of dopamine to the anterior pituitary which normally exerts an inhibitory effect on prolactin secretion

45
Q

What is Kallmann’s syndrome

A

Patients have congenital GnRH deficiency associated with anosmia

46
Q

How can congenital GnRH be inherited

A

Autosomal dominant
autosomal recessive or
X linked

47
Q

What is premature ovarian failure

A

Primary hypogonadism (lack of folliculogenesis and ovarian oestrogen production) before the age of 40

48
Q

What do the largest number of patients with primary amenorrhoea and ovarian failure have

A

turner’s syndrome

49
Q

What might acquired ovarian faker be cdue to

A

chemotherapy
radiotherapy
Autoimmune

50
Q

What is Mullein agenesis characterised by

A

congenital absence of the vagina with variable uterine development

51
Q

What is the most common cause of primary amenorrhoea with excess androgen production

A

congenital adrenal hypoerplasia (CAH)

52
Q

What does PCOS have a strong association with

A

insulin resistnace

53
Q

What are the features of Turner’s syndrome

A

lack of secondary sexual characteristics
short stature
widely spaced nipples
low posterior hairline
High arched palate, wide carrying angle, short 4th and 5th metacarpals
Cardio - congenital lymphoedema, aortic dissection, cortication of the aorta, hypertension
GI: angiodysplasia, coeliac disease
Renal: horseshoe kidneys, abnormal vascular supply
Endocrine: increased risk of hypothyroidism and Diabetes mellitus

54
Q

What are some areas to ask the patient about when presenting with amenorrhoea

A

Change in weight, stress, excessive dieting, exercise or illness
Drugs - contraceptive pill
Hypothalamic-pituitary disease e.g. headaches, visual field defects, fatigue, polyuria or polydipsia
Galactorrhoea (suggestive of hyperprolactinaemia
Symptoms of oestrogen deficiency e.g. hot flush, dry vagina, poor sleep or reduced libido
Hirsutism, acne or deepening of the voice
Hx of lower abdominal pain at the time of expected menses
History of dilatation and curettage or endometritis that might have caused scarring

55
Q

What should the physical exam for amenorrhoea include

A

Tanner staging for pubertal development
Measurements of height, weight and BMI
signs of associated underlying causes e.g. visual field defect, imperforate hymen, thyroid problems

56
Q

What is a sign of insulin resistance that patients with PCOS may have

A

Acanthosis nigricans (darkened areas of the skin) often in the armpits

57
Q

What are some of the initial tests for amenorrhoea

A 
Pregnancy test (serum or urine human chorionic gonadotrophin) 
Pelvic imaging (US or MRI) 
Serum FSH
serum prolactin 
serum TSH and T4 
Serum androgens
58
Q

Why are serum FSH levels tested in amenorrhoea

A

elevated in premature ovarian failure due to reduced inhibition due to ovarian oestradiol and inhibin

59
Q

What should patients have done if they have high FSH or are suggestive of primary ovarian failure

A

Karyotype to look for chromosomal abnormalities e.g. Turner’s

60
Q

When is a hypothalamic -pituitary MRI indicated

A

In women with hypogonadotrophic hypogonadism and no clear explanation
Those with visual field defects, headaches or any other signs of hypothalamic - pituitary dysfunction

61
Q

What should be included in the differential diagnosis for patients with hyperandrogenism

A

PCOS
CAH
androgen-secreting tumours

62
Q

What should also be tested for if a patient is suspected to have Turner’s syndrome

A 
Echocardiogram (congenital heart disease / aortic aneurysm) 
Renal US (renal anomalies) 
Thyroid function tests (a lot develop thyroid disease)
63
Q

Why should women with unexplained premature ovarian failure be screened for permutation in the FMR1 gene.

A

There is a risk that a patient with an FMR1 mutation would have a child with mental retardation and also has a link to fragile X syndrome

64
Q

How are the majority of women with prolactinomas successfully treated

A

Dopamine agonist

65
Q

What should patients with irreversible gonadotrophin deficiency receive

A

Oestrogen replacement therapy and progesterone if they have a uterus

66
Q

What should be started in girls with primary amenorrhoea and delayed puberty

A

Oral ethinylestradiol at a low dose to promote breast development and adult body habitus
Dose is gradually increased
Cyclical oral progesterone is added with the onset of breakthrough bleeding

67
Q

What can premature initiation of progesterone therapy cause

A

compromise ultimate breast growth

68
Q

What is required for the prevention of osteoporosis and coronary heart disease

A

Oestrogen-progestin replacement therapy

69
Q

What might adult women with premature ovarian failure be treated with

A

100ug of transdermal estradiol daily

70
Q

What must be performed in patients with Y chromosome material

A

gonadectomy - to prevent the development of gonadal tumours

Lecture Notes - Endocrinology (40 decks)

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