Flashcards in Clinical (Week 5 - Calcium and Reproduction) Deck (180):
Where are oestrogens synthesised?
- Theca cells
What does LH stimulate the granulosa cells to produce?
What diffuses from the granulosa cells to the adjacent theca cells and what does this cause?
Causes theca cells to express:
- 17,20-lyase (also known as 17α-Hydroxylase)
What happens when the theca cells express the enzymes in response to pregnenolone?
Pregnenolone is converted to DHEA:
- By 17α-hydroxylase
DHEA is converted to androstenedione:
- By 3β-HSD
What other function does 3β-HSD have?
Converts pregnenolone to progesterone
What are the three types of naturally occurring oestrogen in the body?
What happens to most androstenedione?
Returns to granulosa cells:
- Converted to oestrone (E1) by aromatase
What function does 17β-HSD have?
Converts oestrone (E1) to Oestradiol (E2)
(Also converts Androstenedione to testosterone)
What enzymes does FSH increase the expression of?
(Both from the granulosa cells)
Where else can oestrogens be synthesised?
Aromatase is expressed in fat and bone:
- Peripheral production of Oestrone (E1)
Where is progesterone synthesised and by what enzyme?
Made from pregnenolone by 3β-HSD in:
- Corpus luteum
- Placenta (during pregnancy)
- Adrenal glands
Why is progesterone made in the adrenal glands?
Step in androgen and mineralocorticoid production
During the following stages, what products are mainly made from pregnenolone:
- Follicular maturation
- Following ovulation (Luteal phase)
- Oestradiol (E2)
What is oligomenorrhoea?
Reduced period frequency to less than 9/year
Having a menstrual cycle > 35 days
What is primary amenorrhoea?
Failure of menarche by 16 years of age
What is secondary amenorrhoea?
Cessation of periods for >6 months:
- In a woman who previously menstruated
What are the two physiological causes of amenorrhoea?
What can cause primary amenorrhoea?
Turner's Syndrome (45, XO)
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.
What ovarian problems may cause secondary amenorrhoea?
Premature ovarian failure
Which of these does not cause hypothalamic dysfunction and therefore does not cause secondary amenorrhoea:
- Weight loss
- Over exercise
- Poor sleep
- Infiltrative disease
What pituitary problems can result in amenorrhoea?
Flushing, reduced libido and dyspareunia are signs of what?
What is dysparenuia?
Difficult or painful sex
What are features of PCOS?
What blood tests should be done in oligo/amenorrhoea?
What additional investigations can be done if the following are suspected:
- Hypothalamic/Pituitary problem
- Primary amenorrhoea or Turner's
- Pituitary function tests
- MRI pituitary
Primary amenorrhoea or Turner's:
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
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
How many times must FSH be high to suggest a diagnosis of premature ovarian failure? What must it be greater than
- 2 separate occasions -> Greater than 1 month apart
What age are patient's suffering from premature ovarian failure?
Women younger than 40
What chromosomal abnormalities can cause premature ovarian failure?
What gene mutations can cause premature ovarian failure?
LH/FSH receptor mutations
What autoimmune conditions are associated with premature ovarian failure?
APS1/1 (Autoimmune Polyendocrine Syndrome)
What iatrogenic causes are there of premature ovarian failure?
What are some hypothalamic causes of secondary hypogonadism?
Idiopathic Hypogonadotropic Hypogonadism (IHH)
What are some other causes of secondary hypogonadism?
Prader-Willi (Chromosome 15q11-13 mutations)
What are the most common causes of functional hypothalamic amenorrhoea?
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
What underlies IHH?
Inability to activate pulsatile GnRH secretion in puberty
What genetic defects may cause IHH?
GnRH neuron migration
What role does Kisspeptin have and how can this be linked to IHH?
- 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
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
No olfactory bulb -> Hypo-/Anosmia
What is the male:female ratio for Kallman's Syndrome?
What can cause pituitary dysfunction?
Non-functioning pituitary macroadenoma:
- Pressure -> Hypopituitarism
What can cause hyperprolactinaemia?
- Dopamine antagonists
- False hyperprolactinaemia
What are the Rotterdam criteria for PCOS?
- Menstrual irregularity
> Increased free testosterone
- Polycystic ovaries
What are some congenital causes of poor ovarian development?
Absence of uterus
What causes hirsutism?
Excess androgen at hair follicle:
- Due to excess circulating androgen
- Peripheral conversion to testosterone at follicle
In what populations is familial hirtuism common?
What are the features of these causes of hirsutism:
- Non-classical CAH
What can cause a short history of hirsutism with signs of virilisation?
What testosterone levels are seen in androgen-secreting tumours? What size do these tumours tend to be on MRI
How can PCOS be treated?
- Regulates cycle
- Reduces ovarian androgens
- Cyproterone acetate
- Efflornithine cream
- Laser phototherapy
How can late onset CAH be treated?
Low does glucocorticoid (reduces ACTH drive)
What is the incidence of Turner Syndrome?
1 in 2000 women
How many spontaneous abortions is Turner Syndrome responsible for?
What are some defining clinical features of Turner Syndrome?
Wide spaced nipples
- Forearm angled away from body
What are some CVS effects of Turner Syndrome?
Bicuspid aortic valve
Hypoplastic left heart
What GI problems are patients with Turner Syndrome more likely to have?
If a patient has no chromosomal abnormalities, yet absent ovaries, what is this due to?
XX Gonadal Dysgenesis
A patient's karyotype is 46 XY, yet they are phenotypically female.
- Androgen Insensitivity Syndrome
What biochemistry is seen in primary male hypogonadism?
What biochemistry is seen in secondary male hypogonadism?
Reduced/Inappropriately normal LH/FSH
What are some congenital causes of primary male hypogonadism?
LH/FSH receptor mutations
What are some acquired causes of primary male hypogonadism?
What are some congenital causes of secondary male hypogonadism?
What are some acquired causes of secondary male hypogonadism?
What examination signs are relevant in diagnosing male hypogonadism?
Staging of puberty
What level of total testosterone may suggest male hypogonadism?
If testosterone is low, what must be done next?
Repeat total testosterone
If SHBG variation suspected:
- Measure free testosterone
What free testosterone level suggest male hypogonadism?
What does SHBG stand for?
Sex hormone-binding globulin
What is the incidence for Klinefelter's Syndrome?
1 in 500 men
What is the Karyotype in Klinefelter's?
What are the clinical features of Klinefelter's Syndrome?
Reduced testicular volume
Eunuchoidism (Deficiency of sexual development)
Reduced intelligence (in 40%)
What biochemical results are seen in Klinefelter's for each of the following:
Testosterone is reduced
LH/FSH are raised
SHBG is raised
Oestradiol is raised
What functional causes of secondary male hypogonadism are there?
What infiltrative diseases can cause secondary male hypogonadism?
What drugs can cause secondary male hypogonadism?
When is testosterone replacement offered?
Will testosterone restore fertility?
How does testosterone replacement affect the following:
- Sexual function
- Bone health
- Muscle strength
- Erectile function improved in young men
- Increased hip + spine BMD (IM>Transdermal)
- Reduced fat mass
- Increased limb strength
What drugs can cause gynaecomastia?
Why can a germinoma cause gynaecomastia?
How long does a normal menstrual cycle last?
Where is GnRH synthesised?
What kind of release does GnRH have and what doe sit stimulate the release of?
- Low frequency pulses -> FSH
- High frequency pulses -> LH
What functions does FSH have?
Stimulates follicular development
What functions does LH have?
Its peak stimulates ovulation
Stimulates corpus luteum development
What does an ovulation predictor kit detect? How correct is it?
When does progesterone peak and why?
After ovulation (Day 21 of cycle)
Produced by corpus luteum
When does oestradiol peak?
Before ovulation (Day 12 of cycle)
Where is Oestrogen secreted from?
Placenta during pregnancy
What functions does oestrogen have?
Produces fertile cervical mucous
- Inhibit FSH and PRL secretion (-ve feedback)
- Stimulates LH secretion (+ve feedback)
What is the main function of progesterone?
Helps maintain early pregnancy
What other functions does progesterone have?
Inhibits LH secretion
Produces infertile/thick cervical mucous
Maintains endometrial thickness
Increases basal body temperature
Relaxes smooth muscles
How can we confirm ovulation has occurred?
Mid-luteal (Day 21) serum progesterone:
- 2 samples
What is the WHO classification of Hypothalamic Pituitary Failure?
What test can prove oestrogen deficiency?
Negative progesterone challenge test:
- ie No menstruation 5 days after progesterone
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
FSH/LH daily injections
- Increase multiple pregnancy rate
What is WHO group 2?
Hypothalamic Pituitary Dysfunction
What WHO group does PCOS belong to?
How are polycystic ovaries defined?
More than twelve 2-9mm follicles
Increased ovarian volume >10ml
How many PCOS patients are insulin resistant
What effects does insulin have
Co-gonadotropin to LH:
- Increases LH
Reduces SHBG -> Increased free testosterone
What criteria must be met before treatment for PCOS?
Folic acid (400μg/5mg daily)
Patent fallpoian tube
What is the 1st line treatment for inducing ovulation in PCOS?
- 50 to 100 to 150mg
- Days 2-6
If a patient is resistant to the 1st line PCOS treatment, what can be tried?
What scan findings indicate dichorionic twins and monochorionic twins?
Dichorionic - Lamba Sign
Monochorionic - T Sign
What is the pathophysiology behind Twin-Twin Transfusion Syndrome (TTTS)?
Unbalanced vascular connections to placenta
Recipient -> Polyhydramnios
- Growth restriction
How can TTTS be treated?
Laser division of placental vessels
What are some long-term problems with prematurity?
6 times risk of CP
Congenital heart disease
What investigation results are seen in hyperprolactinaemia?
- >1000iU/L on more than 2 occasions
How is hyperprolactinaemia treated?
- Cabergoline twice weekly
- Bromocriptine is conventional
Can dopamine agonists be continued during pregnancy?
What are the FSH levels in ovarian failure?
>30iU/L on more than 2 occasions
What WHO group is ovarian failure?
What are some causes of premature ovarian failure?
- 45, XO
- XX Gonadal agenesis
- Fragile X
How is premature ovarian failure treated?
When is progesterone tested for?
Day 21 of the menstrual cycle
What hormones are tested for on days 2-6 of the menstrual cycle?
Testosterone + SHBG
What is the normal result to a progesterone challenge test?
Menstrual bleed after 5 days:
- Indicated normal oestrogen levels
Why is the incidence of infertility increasing?
Male factor infertility
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)
What is primary infertility?
Couple has NEVER conceived
What is secondary infertility?
Couple previously conceived:
- Pregnancy not successful
> Miscarriage OR
> Ectopic pregnancy
At what age are women more likely to conceive?
Younger than 30
At what point in the menstrual cycle is conception most likely to occur?
During the 6 days prior to ovulation (particularly two days before)
What BMI range is best for conception?
What other lifestyle factors affect the likelihood of conception?
Use of recreational drugs
What are some hypothalamic causes of anovulation?
What are some pituitary causes of anovulation?
What is Sheehan Syndrome?
- Caused by ischemic necrosis due to blood loss and hypovolemic shock during and after childbirth
Loss of hair, increased lanugo hair, low bulse, hypotension and anaemia are signs of what?
What are endocrine features of anorexia?
How does weight affect PCOS?
What are endocrine features of PCOS?
High free androgens
Impaired glucose tolerance
What are some clinical features of premature ovarian failure?
What are endocrine features of premature ovarian failure?
What are some infective causes of tubal disease?
- Other (Anaerobes, Syphilis, TB)
- Intra-abdominal abscess
Following surgical procedure:
What are some non-infective causes of tubal disease?
Salpingitis Isthmica Nodosa
What is Salpingitis Isthmica Nodosa?
Diverticulosis of the Fallopian tube:
- Nodular thickening of the narrow part
What is hydrosalpinx?
Fallopian tube dilated with water
How does hydrosalpinx present?
Vaginal discharge -> Dyspareunia
What is endometriosis?
Presence of endometrial glands outside uterine cavity
What can cause endometriosis?
Retrograde menstruation (commonest)
Abnormal cellular adhesion molecules
How can the uterus appear in endometriosis?
Fixed and retroverted
What characteristic cysts are seen on the ovaries in endometriosis?
What is a varicoele?
Abnormal enlargement of the pampiniform venous plexus in the scrotum
What can cause vas deferens obstruction?
Congenital absence (CF)
What can cause erectile dysfunction?
Spinal cord injury
What are some causes of semen disorders?
What can cause testicular failure?
What are some other endocrine causes of male infertility?
What are some clinical features of obstructive male infertility?
Normal testicular volume
Normal secondary sexual characteristics
+/- vas deferens absence
What investigations results are seen in obstructive male infertility?
What are some clinical features of non-obstructive male infertility?
Low testicular volume
Reduced secondary sexual characteristics
Vas deferens present
What investigations results are seen in non-obstructive male infertility?
Why would we carry out an endocervical swab in investigating female infertility?
To test for chlamydia
What blood tests do we do in an infertile woman?
How can we test tubal patency?
When is a hysterosalpingiogram preferred?
If no know tubal/pelvic problems
What are some contraindications for laparoscopy?
Previous pelvic surgery
When is laparoscopy preferred for investigating the fallopian tubes?
If history suggests pathology:
If previous pathology:
- Ectopic pregnancy
- Appendix rupture
Whe is a hysteroscopy carried out?
If suspected/known endometrial pathology:
- Uterine septum
When is a pelvic USS used?
If abnormality felt on examination/seen on HSG
How do we carry out semen analysis?
Over 6 weeks apart
What are the normal levels for each of the following in a semen sample:
Morphology >4% are normal
If a woman is anovulatory, what should we test?
Early follicular bloods (Days 2-5):
- Thyroid hormones
What indicates non-rubella immune?
Rubella IgG antibodies 6U/L
If a mother becomes infected with rubella during pregnancy, what can happen to the child?
What are some short-term complications of chlamydia infection?
What are some long-term complications of chlamydia infection?
Chronic pelvic pain
What are findings in Group 1 WHO ovulatory disorders?
Negative progesterone challenge
What disorders are normogonadotrophic and normoestrogenic?
WHO Group 2 (PCOS)
What findings are seen in all variants of ovarian failure and resistant ovary?
How do Letrozole and Anastrozole work? What are they used to treat?
Inhibit ovarian aromatase
How does Tamoxifen work?
It is an anti-oestrogen