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x 2nd Year Medicine > Reproductive Endocrinology > Flashcards

Reproductive Endocrinology Flashcards

1
Q

What are primordial germ cells?

A

earliest recognisable germ cells

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2
Q

What is oogonia?

A

Structure formed after the completion of the last pre-meiotic division before they become oocytes

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3
Q

Secondary oocytes have gone through how many meiosis cycles?

A

2

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4
Q

When is the first polar body formed in female germ cells?

A

One of the 2 products of the first stage of meiosis

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5
Q

How is the 2nd polar body formed?

A

When sperm enters the oocyte and the 2nd meiotic division is complete

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6
Q

What are the 2 phases of the ovarian cycle?

A

Follicular

Luteal

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7
Q

What happens in the follicular phase of the ovarian cycle?

A

Maturation of egg until it’s ready for ovulation at midcycle

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8
Q

What happens in the luteal phase of the ovarian cycle?

A

Development of the luteum

Induces preparation of the reproductive tract for pregnancy (if fertilisation occurs)

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9
Q

What are the primary follicles?

A

A layer of granulosa cells which surrounds the primary oocyte before birth

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10
Q

How many primary follicles are present in a female when she is born?

A

~2 million

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11
Q

Does the number of primary follicles in a females ovaries increase or decrease as she gets older?

A

Decrease

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12
Q

How is the secondary follicle formed?

A

The oocyte grows around 1000x its size and the follicle expands and becoems differentiated under the influence of hormones

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13
Q

How many eggs will be ovulated within a woman’s lifetime?

A

~400

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14
Q

What happens to the follicular cells after ovulation?

A

They undergo luteinisation to transform into the corpus luteum

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15
Q

What hormone does the corpus luteum secrete?

A

Progesterone

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16
Q

What hormone is secreted in the follicular phase?

A

Oestrogen

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17
Q

After ovulation for how long does the corpus luteum grow before reaching its maximum size?

A

8-9days

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18
Q

If the egg has not become fertilized then what will happen to the corpus luteum?

A

Lasts for ~14 days post-ovulation and then degenerates signalling a new ovarian cycle

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19
Q

If the egg DOES become fertilized then what happens to the corpus luteum?

A

It persists in teh ovary and produces progesterone and oestrogen in increasing amounts until after pregnancy

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20
Q

The hypothalamus secretes GnRH which acts next on which part of the body?

A

Anterior pituitary gland

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21
Q

Once acted upon by GnRH, what does the anterior pituitary release?

A

FSH

LH

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22
Q

What does FSH do in the ovarian cycle?

A

Acts on the ovary to stimulate follicle development

FSH and LH stimulate oestrodiol secretion and ovulation

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23
Q

What is the role of LH in the ovarian cycle?

A

Acts on the ovary to stimulate follicle maturation, ovulation and development of the corpus luteum

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24
Q

What do FSH and a little LH cause to happen in the ovary in the follicular phase?

A

Upto 15 follicles begin to mature i.e. their granulosa and theca cells develop

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25
Q

What do the theca cells cause to happen in the follicular phase?

A

Produce androgen which is converted by the granulosa to oestradiol which thickens the endometrium and thins the cervical mucous

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26
Q

What does the dominant follicle possess so that it can continue along the cycle?

A

LH receptor

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27
Q

At mid cycle, high levels of oestrogen are produced, the hypothalamus does what in response to this?

A

Release GnRH thus FSH and LH are released in a surge from the ant. pituitary

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28
Q

What happens to the FSH and LH levels during ovulation?

A

They begin to fall

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29
Q

after ovulation what happens to the remaining granulosa cells from the dominant follicle?

A

Proliferate to form the corpus luteum and secrete progesterone

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30
Q

What does hCG stand for?

A

Human chorionic gonadotrophin

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31
Q

What happens to the corpus luteum if it does not detect hCG after 12 days post-ovulation?

A

It degenerates and becomes the corpus albicans

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32
Q

When the corpus luteum becomes the corpus albicans progesterone and oestrogen levels fall, what can now happen?

A

A new cycle can recommence

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33
Q

If the corpus luteum does detect levels of hCG then what will it do?

A

Produces progesterone until ~6weeks into the pregnancy when the placenta takes over this role.

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34
Q

What hormones stimulate spermatogenesis?

A

FSH

Testosterone

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35
Q

What decreases FSH secretion in men?

A

Inhibin

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36
Q

What is the name of the cells which secrete androgen-binding globulin (ABG) and inhibin, and where are they found?

A

Sertoli cells in the seminiferous tubules

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37
Q

LH stimulates secretion of what other hormone?

A

Testosterone

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38
Q

What effect does testosterone have on the secretion of GnRH?

A

It decreases the rate of secretion

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39
Q

Testosterone goes on to form dihydrotestosterone, what does this do?

A

enlarges the male sex organs
given males their secondary sexual characteristics
anabolism

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40
Q

What is oligomenorrhoea?

A

A decrease in the frequency of periods to <9/year

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41
Q

What is primary amenorrhoea?

A

Failure of menarche by 16

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42
Q

What is secondary amenorrhoea?

A

Cessation of periods in an individual for >6months in an individual who has previously menstruated

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43
Q

What are the physiological causes of amennorhoea?

A

Pregnancy

Post-menopausal

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44
Q

What can cause primary amenorrhoea?

A

Congenital problems (Turner’s syndrome, Kallman’s syndrome)

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45
Q

What can cause secondary amenorrhoea?

A

Ovarian problems - PCOS, POF
Uterine adhesions
Hypothalamic dysfunction
Pituitary problems

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46
Q

What are the symptoms of oestrogen deficiency?

A

Flushing
Libido decreased
Dysparenuria

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47
Q

What are the features of PCOS/androgen excess?

A

Hirsutism

Acne

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48
Q

What is one of the main symptoms of hypopituitarism or a pituitary tumour?

A

Galactorrhoea

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49
Q

What investigations should be done in ALL woman presenting with amenorrhoea?

A

LH, FSH, Oestradiol

TFTs and prolactin

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50
Q

How is female hypogonadism identified?

A

Low levels of oestrogen

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51
Q

What are the signs/symptoms associated with primary hypogonadism?

A

Problem with the ovaries
High LH/FSH - hypergonadotrophic hypogonadism
e.g. POF

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52
Q

What are the signs/symptoms associated with secondary hypogonadism?

A

Problem with the hypothalamus or pituitary
Low FSH/LH - hypogonadotrophic hypogonadism
Low oestradiol

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53
Q

What happens in premature ovarian failure (POF)?

A

Amenorrhoea, low oestrogen and high gonadotrophins in women <40y/o as a result of loss of ovarian function

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54
Q

How is POF diagnosed?

A

FSH >40 on 2 separate occasions >1month apart

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55
Q

What can cause POF?

A

Chromosomal abnormalities
Gene mutations
AI disease
Iatrogenic (radio/chemo)

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56
Q

What are the symptoms of functional hypothalamic amenorrhoea?

A

Weight change
Stress
Exercise (too much)
Eating disorders

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57
Q

What are the causes of functional hypothalamic amenorrhoea?

A 
Anabolic steroids
Systemic illness
Iatrogenic
Recreational drugs
Head trauma
Infiltrative disorders
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58
Q

What happens within the body during functional hypothalamic amenorrhoea?

A

Abnormal hypothalamic GnRH secretion leading to decreased gonadotrophin pulsations
This leads to low LH and FSH and thus low oestradiol

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59
Q

What is Kallman’s syndrome?

A

A genetic disorder causing a loss of GnRH secretion +/- anosmia

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60
Q

Does Kallman’s syndrome affect males or females more?

A

Males (x4)

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61
Q

Why is anosmia found in 75% of Kallman’s syndrome sufferers?

A

There are no olfactory bulbs present

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62
Q

What pituitary disorders can lead to loss of LH/FSH stimulation?

A

Presence of a non-functioning pituitary macroadenoma (pressure mass effects lead to hypopituitarism)
Empty sella
Pituitary infarction

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63
Q

What pituitary disorders can lead to hyperprolactinaemia?

A

Presence of a micro- or macro-prolactinoma

Some drugs e.g. dopamine agonists

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64
Q

Other than hyperprolactinaemia and a loss of LH/FSH stimulation, what other signs can indicate a pituitary disorder?

A

low FSH/LH

Low oestradiol

65
Q

What are the ovarian causes of amenorrhoea?

A

PCOS
Ovarian failure - high gonadotrophins
Congenital problem with ovarian development

66
Q

What are the Rotterdam criteria, of which 2/3 must be present for a diagnosis of PCOS to be given?

A

Menstrual irregularity
Hyperandrogenism (hirsutism and high free testosterone)
Polycystic ovaries

67
Q

What congenital problems of the ovaries can lead to amenorrhoea?

A 
Absence of uterus
Vaginal atresia (absence of normal opening)
Turner's syndrome
Testicular feminisation
Congenital adrenal hyperplasia
68
Q

What can a genetic predisposition to excess ovarian androgen secretion cause?

A

Polycystic ovaries

69
Q

What can cause increased testosterone in a female?

A

Polycystic ovaries
Pituitary gland overproduction
Insulin resistance and hyperinsulinaemia

70
Q

What can excess testosterone do in a female?

A

Increases LH
Causes insulin resistance and hyperinsulinaemia
Hirsutism

71
Q

What is hirsutism?

A

Excess hair when referring to women with male pattern hair distribution

72
Q

What causes hirsutism?

A

Androgen excess at the hair follicle

73
Q

What conditions can cause hirsutism?

A

PCOS
Familial
Idiopathic
CAH

All of the above have long histories with not dramatically high testosterone levels and no signs of virilisation. All those below have a short history and deepening of voice and clitoromegaly

Adrenal or ovarian tumours

74
Q

What is CAH?

A

An inherited group of disorders characterised by a deficiency in one of the enzymes necessary for cortisol synthesis.

75
Q

What is 90% of CAH caused by?

A

21-alpha-hydroxylase deficiency causing excess testosterone

Autosomal recessive disorder with a varied clinical presentation

76
Q

When is classic CAH diagnosed?

A

Diagnosed in infancy with virilisation and salt-wasting

77
Q

When is non-classic (partial) CAH diagnosed?

A

In adolesence/ early adulthood with hirsutism, menstrual disturbance, infertility due to anovulation

78
Q

What are androgen secreting tumours associated with?

A

Rapid onset of symptoms
Signs of virilisation
Increased testosterone
MRI showing adrenal and ovarian tumours >1cm diameter.

79
Q

If hirsutism is caused by PCOS then how is it treated?

A

Oral contraceptive pill
Anti-androgens (local and general)
Cosmesis

80
Q

If hirsutism is caused by late onset CAH, then what is it treated by?

A

low dose glucocoticoid to suppress ACTH drive

81
Q

What is different about the genetic makeup of an individual with Turner’s syndrome?

A

A female with only 1 X chromosome

82
Q

How common is Turner’s syndrome?

A

1 in 2000 live births

83
Q

How does Turner’s syndrome present in paediatrics?

A

Short stature

Failure to progress through puberty

84
Q

How does Turner’s syndrome present in adults?

A

Primary or secondary amenorrhoea

Infertility

85
Q

What other signs or symptoms can affect the CVS in Turner’s syndrome?

A

Coarctication of the aorta
Bicuspid aortic valve
Hypoplastic left heart

86
Q

What other signs or symptoms can affect the GI system in Turner’s syndrome?

A

GI bleeds

Increased incidence of Crohns and UC

87
Q

What other signs or symptoms can affect the body in Turner’s syndrome?

A 
Lymphoedema
Hypothyroidism
Osteoporosis
Scoliosis
1/3 have renal abnormalities
Otitis media
88
Q

What is XX gonadal dysgenesis?

A

Absent ovaries but no chromosomal abnormality

89
Q

What is testicular feministaion?

A

Androgen insensitivity syndrome

Genetically XY male (with testes) but in the complete form, phenotypically female

90
Q

How long does a normal menstrual cycle last?

A

28-35 days

91
Q

How long do oligomenorrhoea cycles last for?

A

> 35 days

92
Q

The surge of what hormone triggers ovulation?

A

LH

93
Q

What hormone peaks before ovulation?

A

Oestrodiol

94
Q

What hormone peaks after ovulation?

A

Progesterone

95
Q

How can ovulation be confirmed in an individual with regular cycles?

A

Midluteal (day21) serum progesterone (>30nmol/L) x 2 samples
Basal body temperature changes
Cervical mucous changes

96
Q

If a cycle lasts longer than 28 days, which phase of the cycle is likely to be the one which lasts longer?

A

Follicular

97
Q

How can you confirm ovulation in an individual with irregular cycles?

A 
Midluteal progesterone (day 21)
Early follicular phase (day 2-5)
 - Serum FSH/LH, oestradiol
 - Serum prolactin, TSH
 - Free androgen index
Progesterone challenge test
98
Q

What is the progesterone challenge test?

A

If a patient bleeds a week-10days after a 5 day course of progesterone then this indicates normal oestrogen levels

99
Q

What radiological investigations can be done to assess ovulation?

A

Transvaginal USS ovaries to look for ovarian morphology and serial scans to look for follicular growth and ovulation
If required:
MRI pituitary fossa
Bone density scan

100
Q

What is hypothalamic pituitary failure?

A

Where the hypothalamus does not release adequate GnRH.

101
Q

What are the effects of hypothalamic pituitary failure?

A

Hypogonadotrophic hypogonadism
Oestrogen deficiency
Normal proclatin
Amenorrhoea

102
Q

What can cause hypothalamic pituitary failure?

A 
Stress
Exercise
Anorexia
Brain/Pituitary tumours
Head Trauma
Kallman's syndrome
Drugs (steroids/Opiates)
103
Q

How is hypothalamic pituitary failure managed?

A

Stabilise weight - BMI >19
Give pulsatile GnRH every 90 mins SC or IV (pump worn continuously)
Gonadotrophin daily injections
Need to monitor response with USS

104
Q

How does hypothalamic pituitary dysfunction manifest itself?

A

Normal gonadotrophins and oestrogen levels
Anovulation
PCOS

105
Q

How often is insulin resistance seen in individuals with PCOS?

A

50-80% of patients

106
Q

Why does compensatory hyperinsulinaemia occur in individuals with insulin resistance due to PCOS?

A

There is a normal pancreatic insulin reserve

107
Q

What do 20% of patients with PCOS and insulin resistance also have?

A

Frank glucose intolerance and Non-insulin requiring DM

108
Q

Insulin increases sex hormone binding globulin, what does this do to free testosterone levels?

A

Increases them and leads to hyperandrogenism

109
Q

Before any treatment is given for anovulation associated with PCOS, what management should be implemented?

A 
Weight loss
Stop smoking + drinking alcohol
Go on Folic acid 400mcg/5mg daily
Check rubella immunity
Check partners semen analysis
Check fallopian tube is patent
110
Q

What is the 1st line treatment for induction of ovulation in a woman with PCOS?

A

Clomifene citrate - an anti-oestrogen
50-100mg tab given on days 2-6 of the ovarian cycle
Only prescribable for 6-9months

111
Q

Other than Clomifene citrate, what other treatments exist for ovulation induction in individuals with PCOS?

A

Gonadotrophin therapy
Laproscopic ovarian diathermy
Metformin - with lifestyle modification (reduces androgen production)

112
Q

What are the features of ovarian failure?

A

Increased gonadotrophins

Decreased Oestrogen

113
Q

What are the causes of ovarian failure?

A

Premature - Turner syndrome, XX gonadal agenesis, premature menopause
AI ovarian failure
Pelvic radio/chemo

114
Q

What are the signs and symptoms of premature ovarian failure?

A

Menopause 30IU/L

Low oestradiol

115
Q

How is premature ovarian failure treated?

A

HRT - hormone replacement therapy
Egg or embryo donation
Ovary/egg/embryo cryo-preservation prior to potentially POF causing treatments
Counselling/ support network

116
Q

What questions should be asked in a history of somebody being investigated for hyperprolactinaemia?

A

Amenorrhoea?
Galactorrhoea?
Current medications?

117
Q

What examination is it important to do when investigating hyperprolactinaemia and why?

A

Visual fields - Invading tumour on optic chiasm

118
Q

What investigations should be done when investigating hyperprolactinaemia?

A 
FSH/LH (normal)
Oestrogen (low)
Serum prolactin (high)
TFTs (normal)
MRI to diagnose micro/macro prolactinoma
119
Q

How is hyperprolactinaemia treated?

A

Dopamine agonists
- Cabergoline - longer acting
- Bromocriptine - conventional
Should be stopped when pregnancy occurs

120
Q

What are the risks of ovulation induction and ART?

A

Ovarian hyperstimulation
Multiple pregnancy
Potential risk of ovarian cancer if used for >12 months

121
Q

How common is infertility?

A

Affects 1 in 6 couples

122
Q

How is infertility defined?

A

Failure to achieve a clinical pregnancy after >12 months of regular unprotected sexual intercourse - in absence of any known reason

123
Q

What is primary infertility?

A

Infertility in a couple who have never concieved a child

124
Q

What is secondary infertility?

A

Infertility is a couple who have previously concieved (pregnancy may not have been successful)

125
Q

What factors increase the chance of a successful pregnancy?

A

Woman <2 cups coffee daily

No recreational drugs

126
Q

What factors decrease the chance of a successful pregnancy?

A 
Woman >35
No previous pregnancy
>3 years trying
Intercourse mistimed
Woman's BMI 30
1 or both partners smoke
Caffeine intake = > 2 cups of coffee/day
Regular recreational drugs
Excess alcohol in either partner
127
Q

What disorders other than those involved in the gynecological system can cause infertility?

A

CKD
testosterone secreting tumours
CAH
Drugs: depo-provera, explanom, OCP

128
Q

What are the infective causes of tubal disease in women?

A

Pelvic inflammatory disease (STIs etc.)
Transperitoneal spread of appendicitis or an intra-abdominal abscess
Following invasive procedures or surgery of that area

129
Q

What are the non-infective causes of tubal disease?

A 
Endometriosis
Surgical (sterilisation, ectopic pregnancy)
Fibroids
Polyps
Congenital
130
Q

What are the clinical features of tubal disease in women?

A 
Abdo pain
Febrile
Cervical excitation
Dysmenorrhoea
Ectopic pregnancy
Vaginal discharge
Dyspareunia
Menorrhagia
Infertility
131
Q

What is the prevalence of endometriosis?

A

approx 20%

132
Q

What is endometriosis?

A

Presence of endometrial glands outside the uterine cavity

133
Q

What are the clinical features of endometriosis?

A 
Dysmenorrhoea
Dysparenuia
menorrhagia
painful defecation
chronic pelvic pain
'chocolate' cysts on ovary
134
Q

What is a varicocele?

A

Varicose veins next to the testis (abnormal enlargement of pampiniform venous plexus in the scrotum)

135
Q

What are the non-obstructive causes of male infertility?

A

Genetic - Klienfelters syndrome
Chemo/radio
undescended testes
idiopathic

136
Q

What clinical features can arise from non-obstructive male infertility?

A 
decreased testicular volume
decreased secondary sexual characteristics
Vas deferens present
high LH/FSH
Low testosterone
137
Q

What are the obstructive causes of male infertility?

A

Congenital absence (CF)
Infection
Vasectomy

138
Q

What clinical features are typical of obstructive male infertility?

A

Normal testicular volume
Secondary sexual characteristics
Vas deferens may be absent
Normal FSH, LH and testosterone

139
Q

What endocrine disorders can cause male infertility?

A 
Acromegaly
Cushings Disease
Hyperprolactinaemia
Anorexia
Hyper or hypothyroidism
140
Q

What are the causes of erectile difficulties?

A

Diabetes
Spinal cord injury
Psychosexual

141
Q

What disorders can affect the sperm?

A

Rare defects e.g. globospermia, Kortagne’s syndrome

142
Q

When investigating infertility what examinations should be done of the female?

A

BMI
Body hair distribution and galactorrhoea
Pelvic exam - uterine and ovarian abnormalities/tenderness/mobility

143
Q

When investigating infertility what examinations should be done of the Male?

A

BMI

Gential exam - size/position of testes, penile abnormalities, presence of vas deferens, presence of varicoceles

144
Q

What investigations should be performed for an infertile woman?

A

Endocervical swab for chlamydia
Cervical smear if due
Blood for rubella immunity
Midluteal progesterione

145
Q

What are 2 tests for tubal patency?

A

hysterosalpingiogram

Laparoscopy

146
Q

What are the risk factors for a hysterosalpingiogram?

A

Tubal/pelvic pathology

147
Q

When is laparoscopy indicated?

A

In possible tubal/pelvic disease

148
Q

When is laparoscopy contraindicated?

A

Obesity
Previous pelvic surgery
Crohns

149
Q

When would a hysteroscopy be necessary for testing tubal patency?

A

Suspected or known pathology e.g. uterine septum, adhesions, polyps

150
Q

When would a pelvic ultrasound be indicated in testing for tubal patency?

A

When an abnormality is found on pelvic exam

151
Q

When would an endocrine profile and chromosomal analysis be necessary for testing of tubal patency?

A

Anovulatory or infrequent periods
Hirsute
Amenorrhoea

152
Q

What measurements should be taken when performing a semen analysis?

A 
Volume
pH
Concentration
Motility
Morphology
WBC
153
Q

If semen analysis is abnormal what other tests should be done when investigating the infertile male?

A

LH/FSH
Testosterone
Prolactin
TFTs

154
Q

If semen analysis is severely abnormal/azoospermic then what tests should be performed in the infertile male?

A

Endocrine profile
Chromosome analysis
Screen for CF (associated with absent vas deferens)
Testicular biopsy

155
Q

If an abnormality is found on a genital exam of a male then what test should be done next?

A

Scrotal USS

156
Q

What are the first line agents used in ovulation induction?

A

Antioestrogens - Clomifene citrate + tamoxifen

Aromatase inhibitors - Letrozole/Anastrozole (not in UK)

157
Q

What are the 2nd line agents for ovulation induction?

A

Clomifene citrate + metformin
Gonadotrophin therapy - daily injections
Laproscopic ovarian diathermy (drilling)

158
Q

How is male infertility treated?

A

Surgery for obstructed vas deferens
Intrauterine insemination in mild disease
Intracytoplamic sperm injection into egg (ICSI)
ICSI combined with surgical sperm aspiration from epididymis or testicle
Donor insemination

x 2nd Year Medicine (10 decks)

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