L5 - Disorders of Ovulation COPY

Question 1

MENSTRUAL CYCLE

i) between which two times is the follicular phase? what state is the endothelium in?
ii) how do estradiol levels change through the follicular phase? are progesterone levels high or low?
iii) which two hormones surge pre ovulation?
iv) when does the luteal phase begin?
v) which hormone peaks in the luteal phase? why?
vi) what type of endometrium is in the luteal phase?

Answer 1

i) follicular phase is from day 1 of menstrual cycle to ovulation
- endothelium is proliferative

ii) estradiol levels rise in the follicular phase then peak jusy before pre ov surge and proges levels are low
iii) LH and FSH
iv) luteal phase behings post ovulation
v) progesterone peaks in luteal phase as its produced by the corpus luteum
vi) luteal phase = secretory endothelium

Question 2

label the diagram

Answer 2

A = progesterone

B = estradiol

C = LH

D = FSH

Question 3

CENTRAL MEDIATOR: KISSPEPTIN

i) which hormone does it promote secretion of? where is it secreted from?
ii) which hormone are KISS1 neurons highly responsive to? which hormone does this feed back to?
iii) name two ways kisspeptin has metabolic influences on reproduction
iv) what effect can oestrogen have on kisspeptin? what does this depend on?

Answer 3

i) promotes secretion of GnRH from the hypothalamus
ii) KISS1 neurons are highly responsible to oestrogen which can feedback to GnRH production

iii) kisspeptin interacts with leptin to signal fat stores
- has a permissive effect on puberty and reproduction

iv) oestrogen can have pos and neg feedback on kiss neruons depending on their location in the hypothal and stage of dev

Question 4

DIAGNOSIS OF OVULATION

i) how long is a regular menstrual cycle?
ii) name two things that may signal to the woman that ovulation has occured
iii) how may ovulation be confirmed biochemically? why does this work? what may be done if a woman has a longer cycle?
iv) which kits can be bought over the counter?
v) what imaging method can be done from day 10 to look at follicle size and the corpus luteum
vi) name four things that are not reliable sources of whether ovulation has occured?

Answer 4

i) 28 days
ii) mid cycle pain and thicker vaginal discharge

iii) using day 21 progesterone blood test
- progesterone is produced by the corpus luteum if someone has ovulated
- do this 7 days before start of next period of periods are longer

iv) LH detection kits
v) transvaginal pelvic ultrasound
vi) dont use basal body temperature, cervical mucus change, vaginal ep change or endometrial biopsies

Question 5

MENSTRUAL PATTERN TERMINOLOGY

i) what is amenorrhoea?
ii) what is primary and secondary amenorrhoea?
iii) what is oligomennorhea?
iv) what is polymenorrhoea?

Answer 5

i) amenorrhora = no period for more than 6 months

ii) primary = never had a period
secondary = did have periods but have stopped (has menstruated before)

iii) oligo = irregular periods usually more than 6 weeks apart
iv) polymenorrhoea = periods occuring less than 3 weeks apart

Question 6

CAUSES OF OVULATION PROBLEMS - BRAIN

i) name two main hypothalamic causes?
ii) which hormone may not be produced from the hypothalamus? what symptom can this be associated with?
iii) which hypothalamic cause does not involve a structural abnormality? name four possible causes of this
iv) lack of which two hormones from the pituitary gland can cause ovulat problems? name two causes of this

Answer 6

i) hypothalamic = lack of GnRH or functional hypothalm amenorrhoea
ii) GnRH may not have pulsatile secretion from the HT aka Kallmanns syndrome and may be assoc with ansomia

iii) func HT amenorrhea does not have a struc abnorm
- excess exercise, stress, weight loss, ED eg anorexia/bullimia

iv) lack of LH and FSH from PG can affect ovulation
- caused by pit tumours eg prolactinoms or post op/RT

Question 7

CAUSES OF OVULATION PROBLEMS - OVARY

i) what is the name of the condition associated with the ovary that prevents ovulation?
ii) name three possible causes of this
iii) name two conditions that have hyperandrogenism which can also prevent ovulation? which is the most common cause?

Answer 7

i) premature ovarian insuffieiency
ii) caused by chromo abnorms eg Turner syndrome (XO), autoimmune or iatrogenic (chemo/RT)
iii) PCOS (most common) and congenital adrenal hyperplasia

Question 8

HIRSUTISM

i) what is it?
ii) what does it depend on?
iii) what is it not?
iv) what causes 95% of hirtuism?
v) name three rare causes
vi) name three worrisome situations in the history?

Answer 8

i) androgen dependent hair growth in a male distribution
ii) depends on excess androgens

iii) is not androgen independent or due to race
(hypertrichosis = excess hair but not in male pattern)

iv) 95% caused by PCOS or is idiopathic
v) rare = congenital adrenal hyperplasia, cushings, adrenal/ovarian tumour

vi) 1) sudden onset of severe symptoms
2) virilisation = front balding, deepened voice, clitoromegaly (growth of clitoris)
3) cushings syndrome

Question 9

CLINICAL FEATURES OF PCOS

i) how may androgens be altered? name two accompanying symptoms
ii) how may periods be implicated? how many periods may happen per year?
iii) what other metabolic factor increases risk of PCOS
iv) what are the three overlapping ways to diagnose PCOS?

Answer 9

i) increased androgens leading to hirtuism and acne

ii) chronic oligo/amenorrhea
- <9 periods per year or subfertility

iii) obesity can increase risk
iv) polycysctic ovaries, sparse periods (oligo/anovulation), androgen excess (inc testos)

Question 10

USS APPEARANCE OF POLYCYSTIC OVARIES

i) does a person with PCOS always have polycystic ovaries?
ii) how many immature follicles of 2-8 mm diameter are seen to be PCOS?
iii) what is the appearance of the stroma around the follicles?
iv) is US always necessary?

Answer 10

i) no
ii) >10 subcapsular immature follicles
iii) thickened ovarian stroma
iv) no - can use biochem tests to confirm

Question 11

HORMONAL ABNORMALITIES IN PCOS

i) what levels of LH and FSH are seen compared to normal? how is the LH:FSH ratio affected?
ii) what levels of androgens/free testos are seen
iii) what level of sex hormone binding globulin (SHBG) is seen?
iv) is oestrogen usually normal or abnormal?

Answer 11

i) raised LH and normal FSH
- increased LH:FSH ratio (3:1)

ii) raised androgens and free testos
iii) reduced SHBG
iv) oestrogen is usually normal

Question 12

SEX HORMONE BINDING GLOBULIN

i) which organ produces it?
ii) which two hormones does it bind?
iii) what happens to testosterone when it is bound to SHBG?
iv) which hormone increases it? what drug can increase its levels
v) what decreases SHBG? what does this lead to in the blood?

Answer 12

i) produced by the liver
ii) binds testosterone and oestrogen
iii) when testos is bound it is not converted to active DHT (not free)

iv) oestrogen increases SHBG
- seen in high levels in women on the pill

v) testosterone decreases SHBG which leads to more free testos in the blood

Question 13

PCOS AND METABOLIC SYNDROME

i) what can high levels of insulin cause in a person that is insulin resistant? (2)
ii) how can glucose tolerance be affected by PCOS? what two things does this increase risk of?
iii) how may lipids be affected in PCOS? what can this lead to?

Answer 13

i) high insulin can cause decreased SHBG and therefore increased free testosterone
ii) glucos tol can be impaired by PCOS which increases risk of T2DM and gestational diabetes
iii) dyslipidaemia can be increased which leads to vasc dysfunction

Question 14

REPRODUCTIVE EFFECTS/CANCER IN PCOS

i) what % of lack of ovulation infertility is caused by PCOS?
ii) does it affect likelihood of miscarriage?
iii) does it affect likelihood of gestational diabetes?
iv) what do the irregular periods and high oestrogen levels cause at a cellular level in the endometrium? what is this a risk factor for?
v) lack of which hormone on the endometrium can predispose to cancer
vi) name two other things that can increase risk of endometrial cancer

Answer 14

i) 80% of lack of ov is caused by PCOS
ii) increased likelihood of miscarriage
iii) increased risk of gestational diabetes
iv) can cause hyperplasia in the endometrium which is a risk factor for cancer
v) lack of progesterone on the endometrium
vi) also assoc with T2DM and obesity

Question 15

TREATMENT OF PCOS

i) name three lifestyle factors that can be changed? how may these affect insulin resis, SHBG and free testos?
ii) which eating disorder is assoc with PCOS?
iii) name three ways which combined oral contraceptives can treat PCOS
iv) name three negative side effects the COCP may cause
v) which type of drug may also be used in conjunction with COCP? why?

Answer 15

i) diet, exercise and smoking
- decreases insulin resis, increases SHBG and decreases free testos

ii) bullimia

iii) 1) increase SHBG therefore decrease free testos
2) decrease LH and FSH = stimulate ovaries
3) regulate cycle and decrease endomet hyperplasia

iv) weight gain, VTE, adverse effects on metabolic RFs
v) may add anti-androgens to contraception as can be teratogenic

Question 16

TX OF PCOS - ANTI ANDROGENS/INSULIN RESIS

i) name two anti-androgen drugs and the mech of action of each
ii) which drug may be given to target insulin resistance?
iii) which drug may also be added to this to increase ovulation? is this safe in pregnancy?
iv) which two conditions is this drug less helpful for?

Answer 16

i) cyproterone acetate - inhibits bidning of testos and 5aDHT to androgen receptors
- spironolactone - anti mineralocorticoid and anti androgen properties

ii) metformin

iii) clomifene can increase ovulation
- safe in pregnancy

iv) metformin is less helpful for hirsutism and oligomenorrhoea

Question 17

PRIMARY OVARIAN INSUFFICIENCY

i) how may it present (2) which presentation can be associated with hot flushes and sweats?
ii) name four possible causes
iii) how will LH and FSH levels be implicated? why?
iv) which three other tests may be considered?
v) name four ways to manage it

Answer 17

i) with primary or secondary amenorrhoea
- hot flushes and sweats = secondary amenorrhea

ii) autoimmunity (may be assoc with other AI conds), X chromo abnorms (Turner/Fragile X), genetic predispos, iatrogenic (sx/RT)
iii) high levels of LH and FSH are seen due to lack of negative feedback by oestrogen
iv) may also do karyotype, pelvic US or AI/endocrine disease screen
v) manage by psych support, HRT (until 52), monitor bone density (DEXA), fertility (egg donor)

Question 18

TURNER SYNDROME

i) what % of cases will be XO (one X)? what will the rest have?
ii) does it affect males or females?
iii) name three ways it can present
iv) what may growth hormone treatment be useful for?
v) how may they CV system be implicated? (3)
vi) which other system may abnormalities be seen in?
vii) name one syndrome, thyroid disease, and bone problem that may also occur

Answer 18

i) 50% no X and the rest will have partial X or mosaicism
ii) only affects females
iii) present as a neonate, short stature in childhood or primary/secondary amennorhea
iv) GH treatment for short stature
v) CV system = coarctation of aorta, biscuspid aortic valve, aortic dissection, hypertension
vi) renal abnorms eg horseshoe kidney
vii) metabolic syndrome, hypothyroidism and osteoporosis may be seen (also see hearing loss)

Question 19

CONGENITAL ADRENAL HYPERPLASIA

i) which hormone has disordered biosynthesis?
ii) which pattern of inheritance do most patients have?
iii) what is the cause of 95% of CAH?
iv) how does this deficiency affect aldosterone, androgens and cortisol? why does this happen?
v) which two hormones may be raised due to lack of negative feedback? what does this drive?
vi) what test can confirm a diagnosis?

Answer 19

i) cortisol
ii) most patients are compound heterozygotes eg different mutations in two alleles
iii) 95% caused by 21 hydroxylase enzyme deficiency
iv) deficienct in 21 hydrox causes reduced aldo levels, cortisol deficiency and aexcess androgens as 21AH is not req for andreogen biosynth so production shifts in this direction
v) raised CRH and ACTH dye to lack of neg feedback and this drives excess adrenal androgen produc
vi) dx by confirming high levels of 17 hydroxyprogesterone (step before 21AH) with a synacthen test

Question 20

CAH PRESENTATION

i) which two ways can it present in childhood?
ii) what % of childhood presentations are salt losing? what is this due to deficiency of? name two ways this presents
iii) name three other signs in childhood
iii) which two ways can it present in adults?
iv) name four things seen in mild presentation in adults - what condition are these signs similar to?

Answer 20

i) classic or severe

ii) 66% are salt losing due to aldosterone deficiency
- can present with hypovolaemia and shock

iii) childhood signs - virilisation (amig genitalia in girls or early dev in boys), precocious puberty and abnormally accelerate growth
iii) adults - non classic/mild or late onset

iv) hirsutism, oligo/amennorhea, acne and subfertility
- similar to PCOS

Question 21

TREATMENT OF CAH

i) which two things can be replaced? name two drugs that can do this? what may be given if the patient is an infant?
ii) which drug can be given that supresses CRH and ACTH? what may this inhibit in children therefore needs to be monitored?
iii) how may ambiguous genitalia be manged?
iv) how may non classical CAH in adult women be treated? (think what cond its sim to)

Answer 21

i) replace GCs and MCs
- hydrocortisone and fludrocortisone
- give salt in infancy

ii) GCs can suppress CRH and ACTH but may inhibit growth in children so need to monitor
iii) mx ambig genitalia by surgery
iv) non classical CAH in adults is similar to PCOS so treat with COCP with out without an anti androgen