Clinical (Week 5 - Calcium and Reproduction) Flashcards
1
Q
Where are oestrogens synthesised?
A
Ovaries:
- Granulosa
- Theca cells
Corpus luteum
2
Q
What does LH stimulate the granulosa cells to produce?
A
Pregnenolone
3
Q
What diffuses from the granulosa cells to the adjacent theca cells and what does this cause?
A
Pregnenolone
Causes theca cells to express:
- 17,20-lyase (also known as 17α-Hydroxylase)
- 3β-HSD
4
Q
What happens when the theca cells express the enzymes in response to pregnenolone?
A
Pregnenolone is converted to DHEA:
- By 17α-hydroxylase
DHEA is converted to androstenedione:
- By 3β-HSD
5
Q
What other function does 3β-HSD have?
A
Converts pregnenolone to progesterone
6
Q
What are the three types of naturally occurring oestrogen in the body?
A
Oestrone (E1)
Oestradiol (E2)
Oestriol (E3)
7
Q
What happens to most androstenedione?
A
Returns to granulosa cells:
- Converted to oestrone (E1) by aromatase
8
Q
What function does 17β-HSD have?
A
Converts oestrone (E1) to Oestradiol (E2) (Also converts Androstenedione to testosterone)
9
Q
What enzymes does FSH increase the expression of?
A
Aromatase
17β-HSD
(Both from the granulosa cells)
10
Q
Where else can oestrogens be synthesised?
A
Aromatase is expressed in fat and bone:
- Peripheral production of Oestrone (E1)
11
Q
Where is progesterone synthesised and by what enzyme?
A
Made from pregnenolone by 3β-HSD in:
- Corpus luteum - Placenta (during pregnancy) - Adrenal glands
12
Q
Why is progesterone made in the adrenal glands?
A
Step in androgen and mineralocorticoid production
13
Q
During the following stages, what products are mainly made from pregnenolone:
- Follicular maturation
- Following ovulation (Luteal phase)
A
Follicular maturation:
- Oestradiol (E2)
Luteal phase:
- Progesterone
14
Q
What is oligomenorrhoea?
A
Reduced period frequency to less than 9/year
OR
Having a menstrual cycle > 35 days
15
Q
What is primary amenorrhoea?
A
Failure of menarche by 16 years of age
16
Q
What is secondary amenorrhoea?
A
Cessation of periods for >6 months:
- In a woman who previously menstruated
17
Q
What are the two physiological causes of amenorrhoea?
A
Post-menopausal state
Pregnancy
18
Q
What can cause primary amenorrhoea?
A
Turner’s Syndrome (45, XO)
Kallman’s Syndrome
19
Q
A 19 year old woman presents concerned that she hasn’t started menstruating. She has also noted that her breasts have hardly developed. On examination you notice she has no sense of smell (anosmia). You decide to test her pituitary hormones and discover a lack of LH and FSH.
A
Kallman’s Syndrome
20
Q
What ovarian problems may cause secondary amenorrhoea?
A
PCOS
Premature ovarian failure
21
Q
Which of these does not cause hypothalamic dysfunction and therefore does not cause secondary amenorrhoea:
- Weight loss
- Over exercise
- Poor sleep
- Stress
- Infiltrative disease
A
Poor sleep
22
Q
What pituitary problems can result in amenorrhoea?
A
Increased PRL
Hypopituitarism
23
Q
Flushing, reduced libido and dyspareunia are signs of what?
A
Oestrogen deficiency
24
Q
What is dysparenuia?
A
Difficult or painful sex
25
What are features of PCOS?
Acne
| Hirsutism
26
What blood tests should be done in oligo/amenorrhoea?
LH/FSH/Oestradiol
27
What additional investigations can be done if the following are suspected:
- Hirsutism
- Hypothalamic/Pituitary problem
- Primary amenorrhoea or Turner's
- PCOS
```
Hirsutism:
- Testosterone
Hypothalamic/Pituitary problem:
- Pituitary function tests
- MRI pituitary
Primary amenorrhoea or Turner's:
- Karyotype
PCOS:
- USS
```
28
What is primary hypogonadism and what can cause it?
```
An ovarian problem:
- Increased LH/FSH
- Reduced response to gonadotropins
> Hypergonadotropic Hypogonadism
- eg. Premature Ovarian Failure
```
29
What is secondary hypogonadism and what can cause it?
Problem with hypothalamus and/or pituitary:
- Reduced/Inappropriately normal LH/FSH
> Hypogonadotropic Hypogonadism
- Can be due to
> High PRL
> Hypopituitarism
30
How many times must FSH be high to suggest a diagnosis of premature ovarian failure? What must it be greater than
FSH >30:
| - 2 separate occasions -> Greater than 1 month apart
31
What age are patient's suffering from premature ovarian failure?
Women younger than 40
32
What chromosomal abnormalities can cause premature ovarian failure?
Turner's
| Fragile X
33
What gene mutations can cause premature ovarian failure?
LH/FSH receptor mutations
34
What autoimmune conditions are associated with premature ovarian failure?
Addison's
Thyroid
APS1/1 (Autoimmune Polyendocrine Syndrome)
35
What iatrogenic causes are there of premature ovarian failure?
Radiotherapy
| Chemotherapy
36
What are some hypothalamic causes of secondary hypogonadism?
Functional disorders
Kallman's Syndrome
Idiopathic Hypogonadotropic Hypogonadism (IHH)
37
What are some other causes of secondary hypogonadism?
Prader-Willi (Chromosome 15q11-13 mutations)
| Haemochromatosis
38
What are the most common causes of functional hypothalamic amenorrhoea?
Weight change
Stress
Exercise
39
Which of the following is not a sign/symptome of IHH:
- Absent/Delayed sexual development
- Reduced gonadotropins
- Increased sex steroids
- Absence of hypothalamic-pituitary axis defects
Increased sex steroids:
| - They are reduced in IHH
40
What underlies IHH?
Inability to activate pulsatile GnRH secretion in puberty
41
What genetic defects may cause IHH?
GnRH neuron migration
GnRH secretion
GnRH action
42
What role does Kisspeptin have and how can this be linked to IHH?
```
Functions:
- Potent stimulator of GnRH release
- Gatekeeper of puberty
- Regulates male and female fertility
- Influences ovulation and menstruation
Mutations in the KISS1R receptor:
- Prevents Kisspeptin binding
> Reduces GnRH release
```
43
What would be seen on MRI of a patient with Kallman's syndrome and how does this reflect on one of the symptoms?
Normal pituitary gland
BUT
No olfactory bulb -> Hypo-/Anosmia
44
What is the male:female ratio for Kallman's Syndrome?
4:1
45
What can cause pituitary dysfunction?
Non-functioning pituitary macroadenoma:
- Pressure -> Hypopituitarism
Empty sella
Infarction (Apoplexy)
46
What can cause hyperprolactinaemia?
```
Prolactinomas
Pituitary pathology
Drugs:
- Antipsychotics
- Dopamine antagonists
Hypothyroidism
Macroprolactin:
- False hyperprolactinaemia
```
47
What are the Rotterdam criteria for PCOS?
```
2 of:
- Menstrual irregularity
- Hyperandrogenism
> Hirsutism
> Increased free testosterone
- Polycystic ovaries
```
48
What are some congenital causes of poor ovarian development?
```
Absence of uterus
Vaginal atresia
Turner's
Testicular feminisation
CAH
```
49
What causes hirsutism?
Excess androgen at hair follicle:
- Due to excess circulating androgen
- Peripheral conversion to testosterone at follicle
50
In what populations is familial hirtuism common?
Mediterranean
51
What are the features of these causes of hirsutism:
- PCOS
- Familial
- Idiopathic
- Non-classical CAH
Long histories
| Serum testosterone
52
What can cause a short history of hirsutism with signs of virilisation?
Adrenal/Ovarian tumour
53
What testosterone levels are seen in androgen-secreting tumours? What size do these tumours tend to be on MRI
>5nmol/L
| >1cm
54
How can PCOS be treated?
```
Oral contraceptive:
- Regulates cycle
- Reduces ovarian androgens
Anti-androgens:
- Cyproterone acetate
- Efflornithine cream
Cosmesis:
- Electrolysis
- Laser phototherapy
```
55
How can late onset CAH be treated?
Low does glucocorticoid (reduces ACTH drive)
56
What is the incidence of Turner Syndrome?
1 in 2000 women
57
How many spontaneous abortions is Turner Syndrome responsible for?
15%
58
What are some defining clinical features of Turner Syndrome?
```
Short stature
Webbed neck
Wide spaced nipples
Cubitus valgus:
- Forearm angled away from body
```
59
What are some CVS effects of Turner Syndrome?
Aortic coarctation
Bicuspid aortic valve
Hypoplastic left heart
60
What GI problems are patients with Turner Syndrome more likely to have?
Crohn's
| UC
61
If a patient has no chromosomal abnormalities, yet absent ovaries, what is this due to?
XX Gonadal Dysgenesis
62
A patient's karyotype is 46 XY, yet they are phenotypically female.
Testicular feminisation:
- Androgen Insensitivity Syndrome
- Pseudohermaphrodites
63
What biochemistry is seen in primary male hypogonadism?
Reduced testosterone
| Increased LH/FSH
64
What biochemistry is seen in secondary male hypogonadism?
Reduced testosterone
| Reduced/Inappropriately normal LH/FSH
65
What are some congenital causes of primary male hypogonadism?
Klinefelter's
| LH/FSH receptor mutations
66
What are some acquired causes of primary male hypogonadism?
Testicular trauma
| Haemochromatosis
67
What are some congenital causes of secondary male hypogonadism?
Kallman's
| Prader-Willi
68
What are some acquired causes of secondary male hypogonadism?
Hyperprolactinaemia
| Pituitary damage
69
What examination signs are relevant in diagnosing male hypogonadism?
Staging of puberty
Testicular volume
Visual fields
70
What level of total testosterone may suggest male hypogonadism?
71
If testosterone is low, what must be done next?
Repeat total testosterone
OR
If SHBG variation suspected:
- Measure free testosterone
72
What free testosterone level suggest male hypogonadism?
73
What does SHBG stand for?
Sex hormone-binding globulin
74
What is the incidence for Klinefelter's Syndrome?
1 in 500 men
75
What is the Karyotype in Klinefelter's?
47, XXY
76
What are the clinical features of Klinefelter's Syndrome?
```
Reduced testicular volume
Gynaecomastia
Eunuchoidism (Deficiency of sexual development)
Reduced intelligence (in 40%)
Azoospermia
```
77
What biochemical results are seen in Klinefelter's for each of the following:
- Testosterone
- LH/FSH
- SHBG
- Oestradiol
Testosterone is reduced
LH/FSH are raised
SHBG is raised
Oestradiol is raised
78
What functional causes of secondary male hypogonadism are there?
Exercise
Weight loss
Stress
Illness
79
What infiltrative diseases can cause secondary male hypogonadism?
Sarcoidosis
| Haemochromatosis
80
What drugs can cause secondary male hypogonadism?
Anabolic steroids
| Opiates
81
When is testosterone replacement offered?
If
82
Will testosterone restore fertility?
No
83
How does testosterone replacement affect the following:
- Sexual function
- Bone health
- Muscle strength
Sexual function:
- Erectile function improved in young men
Bone health:
- Increased hip + spine BMD (IM>Transdermal)
Muscle strength:
- Reduced fat mass
- Increased limb strength
84
What drugs can cause gynaecomastia?
Oestrogens
Testosterone
Spironolactone
Digoxin
85
Why can a germinoma cause gynaecomastia?
Secretes hCG
86
How long does a normal menstrual cycle last?
28-35 days
87
Where is GnRH synthesised?
Hypothalamus
88
What kind of release does GnRH have and what doe sit stimulate the release of?
Pulsatile:
- Low frequency pulses -> FSH
- High frequency pulses -> LH
89
What functions does FSH have?
Stimulates follicular development
| Thickens endometrium
90
What functions does LH have?
Its peak stimulates ovulation
Stimulates corpus luteum development
Thickens endometrium
91
What does an ovulation predictor kit detect? How correct is it?
LH
| 97%
92
When does progesterone peak and why?
```
After ovulation (Day 21 of cycle)
Produced by corpus luteum
```
93
When does oestradiol peak?
Before ovulation (Day 12 of cycle)
94
Where is Oestrogen secreted from?
Ovaries
Adrenal cortex
Placenta during pregnancy
95
What functions does oestrogen have?
Thickens endometrium
Produces fertile cervical mucous
High concentrations:
- Inhibit FSH and PRL secretion (-ve feedback)
- Stimulates LH secretion (+ve feedback)
96
What is the main function of progesterone?
Helps maintain early pregnancy
97
What other functions does progesterone have?
```
Inhibits LH secretion
Produces infertile/thick cervical mucous
Maintains endometrial thickness
Increases basal body temperature
Relaxes smooth muscles
```
98
How can we confirm ovulation has occurred?
Mid-luteal (Day 21) serum progesterone:
- >30nmol/L
- 2 samples
99
What is the WHO classification of Hypothalamic Pituitary Failure?
Group 1
100
What test can prove oestrogen deficiency?
Negative progesterone challenge test:
| - ie No menstruation 5 days after progesterone
101
How can hypothalamic anovulation be managed?
```
Stabilise weight (BMI>18.5)
Pulsatile GnRH is hypog. hypog.:
- S/C or IV pump (worn continuously)
- Pulse every 90 minutes
OR
FSH/LH daily injections
- Increase multiple pregnancy rate
```
102
What is WHO group 2?
Hypothalamic Pituitary Dysfunction
103
What WHO group does PCOS belong to?
Group 2
104
How are polycystic ovaries defined?
More than twelve 2-9mm follicles
Increased ovarian volume >10ml
Uni/Bilateral
105
How many PCOS patients are insulin resistant
50-80%
106
What effects does insulin have
Co-gonadotropin to LH:
- Increases LH
Reduces SHBG -> Increased free testosterone
- Hyperandrogenism
107
What criteria must be met before treatment for PCOS?
```
Weight loss
Smoking cessation
Folic acid (400μg/5mg daily)
Rubella immune
Semen analysis
Patent fallpoian tube
```
108
What is the 1st line treatment for inducing ovulation in PCOS?
Clomifene citrate:
- 50 to 100 to 150mg
- Days 2-6
109
If a patient is resistant to the 1st line PCOS treatment, what can be tried?
Metformin
FSH injections
Diathermy
IVF
110
What scan findings indicate dichorionic twins and monochorionic twins?
Dichorionic - Lamba Sign
| Monochorionic - T Sign
111
What is the pathophysiology behind Twin-Twin Transfusion Syndrome (TTTS)?
```
Unbalanced vascular connections to placenta
Recipient -> Polyhydramnios
Donor:
- Oliguria
- Oligohydramnios
- Growth restriction
```
112
How can TTTS be treated?
Laser division of placental vessels
Amnioreduction
Septostomy
113
What are some long-term problems with prematurity?
```
6 times risk of CP
Impaired sight
Congenital heart disease
Reduced IQ
ADHD
```
114
What investigation results are seen in hyperprolactinaemia?
```
Normal FSH/LH
Reduced oestrogen
High PRL:
- >1000iU/L on more than 2 occasions
TFTs normal
MRI
```
115
How is hyperprolactinaemia treated?
Dopamin agonist:
- Cabergoline twice weekly
- Bromocriptine is conventional
116
Can dopamine agonists be continued during pregnancy?
No
117
What are the FSH levels in ovarian failure?
>30iU/L on more than 2 occasions
118
What WHO group is ovarian failure?
Group 3
119
What are some causes of premature ovarian failure?
```
Genetic:
- 45, XO
- XX Gonadal agenesis
- Fragile X
Autoimmune
Oophorectomy
Pelvic radiotherapy
```
120
How is premature ovarian failure treated?
HRT
| Egg/Embryo donation
121
When is progesterone tested for?
Day 21 of the menstrual cycle
122
What hormones are tested for on days 2-6 of the menstrual cycle?
FSH/LH/Oestradiol
Testosterone + SHBG
PRL
TSH
123
What is the normal result to a progesterone challenge test?
Menstrual bleed after 5 days:
| - Indicated normal oestrogen levels
124
Why is the incidence of infertility increasing?
Older women
Chlamydia infections
Obesity
Male factor infertility
125
What is the definition of infertility?
Failure to achieve a clinical pregnancy after 12 months or more of regular unprotected sex (in absence of known reason) in a couple who has never had a child (WHO definition)
126
What is primary infertility?
Couple has NEVER conceived
127
What is secondary infertility?
Couple previously conceived:
- Pregnancy not successful
> Miscarriage OR
> Ectopic pregnancy
128
At what age are women more likely to conceive?
Younger than 30
129
At what point in the menstrual cycle is conception most likely to occur?
During the 6 days prior to ovulation (particularly two days before)
130
What BMI range is best for conception?
20-30
131
What other lifestyle factors affect the likelihood of conception?
Smoking
Caffeine intake
Use of recreational drugs
Alcohol
132
What are some hypothalamic causes of anovulation?
Anorexia/Bulimia
| Over-exercising
133
What are some pituitary causes of anovulation?
High PRL
Tumours
Sheehan Syndrome
134
What is Sheehan Syndrome?
Postpartum hypopituitarism:
| - Caused by ischemic necrosis due to blood loss and hypovolemic shock during and after childbirth
135
Loss of hair, increased lanugo hair, low bulse, hypotension and anaemia are signs of what?
Anorexia nervosa
136
What are endocrine features of anorexia?
Low FSH
Low LH
Low oestradiol
137
How does weight affect PCOS?
Exacerbates it
138
What are endocrine features of PCOS?
High free androgens
High LH
Impaired glucose tolerance
139
What are some clinical features of premature ovarian failure?
Hot flushes
Night sweats
Atrophic vaginitis
140
What are endocrine features of premature ovarian failure?
High FSH
High LH
Low oestradiol
141
What are some infective causes of tubal disease?
```
Pelvic inflammation:
- Chlamydia
- Gonorrhoea
- Other (Anaerobes, Syphilis, TB)
Transperitoneal spread:
- Appendicitis
- Intra-abdominal abscess
Following surgical procedure:
- IUCD
- Hysteroscopy
- HSG
```
142
What are some non-infective causes of tubal disease?
```
Endometriosis
Surgical (sterilisation)
Fibroids
Polyps
Congenital
Salpingitis Isthmica Nodosa
```
143
What is Salpingitis Isthmica Nodosa?
Diverticulosis of the Fallopian tube:
| - Nodular thickening of the narrow part
144
What is hydrosalpinx?
Fallopian tube dilated with water
145
How does hydrosalpinx present?
```
Abdominal/pelvic pain
Fever
Vaginal discharge -> Dyspareunia
Cervical excitation
Menorrhagia
Dysmenorrhoea
Infertility
Ectopic pregnancy
```
146
What is endometriosis?
Presence of endometrial glands outside uterine cavity
147
What can cause endometriosis?
Retrograde menstruation (commonest)
Altered immunity
Abnormal cellular adhesion molecules
148
How can the uterus appear in endometriosis?
Fixed and retroverted
149
What characteristic cysts are seen on the ovaries in endometriosis?
'Chocolate' cysts
150
What is a varicoele?
Abnormal enlargement of the pampiniform venous plexus in the scrotum
151
What can cause vas deferens obstruction?
```
Congenital absence (CF)
Vasectomy
```
152
What can cause erectile dysfunction?
DM
Spinal cord injury
Psychosexual
153
What are some causes of semen disorders?
Globospermia
| Kartagener's Syndrome
154
What can cause testicular failure?
47, XXY
Chemotherapy/Radiotherapy
Undescended testes
155
What are some other endocrine causes of male infertility?
Hyperprolactinaemia
Acromegaly
Cushing's
Thyroid disease
156
What are some clinical features of obstructive male infertility?
Normal testicular volume
Normal secondary sexual characteristics
+/- vas deferens absence
157
What investigations results are seen in obstructive male infertility?
Normal LH
Normal FSH
Normal testosterone
158
What are some clinical features of non-obstructive male infertility?
Low testicular volume
Reduced secondary sexual characteristics
Vas deferens present
159
What investigations results are seen in non-obstructive male infertility?
High LH
High FSH
Low testosterone
160
Why would we carry out an endocervical swab in investigating female infertility?
To test for chlamydia
161
What blood tests do we do in an infertile woman?
Rubella immunity
| Progesterone level
162
How can we test tubal patency?
Hysterosalpingiogram
| Laparoscopy
163
When is a hysterosalpingiogram preferred?
If no know tubal/pelvic problems
| Laparoscopy contraindicated
164
What are some contraindications for laparoscopy?
Obesity
Previous pelvic surgery
Crohn's
165
When is laparoscopy preferred for investigating the fallopian tubes?
```
If history suggests pathology:
- Dysmenorrhoea
- Dyspareunia
If previous pathology:
- Ectopic pregnancy
- Endometriosis
- Appendix rupture
```
166
Whe is a hysteroscopy carried out?
If suspected/known endometrial pathology:
- Uterine septum
- Adhesions
- Polyps
167
When is a pelvic USS used?
If abnormality felt on examination/seen on HSG
168
How do we carry out semen analysis?
Two samples
| Over 6 weeks apart
169
What are the normal levels for each of the following in a semen sample:
- Volume
- pH
- Concentration
- Motility
- Morphology
- WBC
```
Volume >1.5ml
pH 7.2-7.8
Concentration >15,000,000/ml
Motility >50%
Morphology >4% are normal
WBC
```
170
If a woman is anovulatory, what should we test?
Early follicular bloods (Days 2-5):
- LH
- FSH
- E2
- Testosterone
- FAI
- PRL
- Thyroid hormones
171
What indicates non-rubella immune?
Rubella IgG antibodies 6U/L
172
If a mother becomes infected with rubella during pregnancy, what can happen to the child?
Microcephaly
PDA
Cataracts
173
What are some short-term complications of chlamydia infection?
Tubo-ovarian abscess
Peritonitis
Fitz-Hugh-Curtis Syndrome
174
What are some long-term complications of chlamydia infection?
Chronic pelvic pain
Infertility
Ectopic pregnancy
175
What are findings in Group 1 WHO ovulatory disorders?
Low FSH
Low oestrogen
Normal prolactin
Negative progesterone challenge
176
What disorders are normogonadotrophic and normoestrogenic?
WHO Group 2 (PCOS)
177
What findings are seen in all variants of ovarian failure and resistant ovary?
High FSH/LH
| Low oestrogens
178
How do Letrozole and Anastrozole work? What are they used to treat?
Inhibit ovarian aromatase
| PCOS
179
How does Tamoxifen work?
It is an anti-oestrogen
180
How can male infertility be treated?
Surgery to obstructed vas deferens
Intrauterine insemination
Intracytoplasmia sperm injection (ICSI)
Donor insemination
