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RB Y2 Endocrine - 6 Reproductive > Ovulation Disorders > Flashcards

Ovulation Disorders Flashcards

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1
Q

erectile dysfunction in overweight men

A

oestrogen plays a role in fat storing and is naturally present in small amounts in men, when you gain weight, oestrogen levels rise

this inhibits GnRH production and testosterone

results in erectile dysfunction etc

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2
Q

what is the rate limiting step for the production of steroids

A

the conversion of cholesterol to pregnenolone

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3
Q

synthesis of progesterone

A

synthesised from pregnenolone by the action of 3ß-HSD in the corpus luteum, by the placenta during pregnancy and by the adrenals (as a step in the androgen and mineralocorticoid synthesis)

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4
Q

oligomenorrhoea

A

reduction in frequency of periods to less than 9 a year

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5
Q

primary amenorrhoea

A

failure of menarche by the age of 16

think anatomical/congenital (Turner’s/Kallmann) cause?

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6
Q

secondary amenorrhoea

A

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

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7
Q

physiological causes of amenorrhoea

A

pregnancy

post menopause

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8
Q

causes of secondary amenorrhoea

A

Ovarian problem: PCOS, premature ovarian failure

Uterine problem: uterine adhesions

Hypothalamic dysfunction: weight loss (BMI <18.5), over exercise, stress, infiltrative

Pituitary: high PRL, hypopituitarism

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9
Q

symptoms of oestrogen deficiency

A

flushing, libido, breast tenderness, vaginal atrophy causing dyspareunia (painful sex)

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10
Q

vaginal atrophy

A

inflammation of the vagina due to thinning and shrinking of the tissue

can be due to oestrogen deficinecy

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11
Q

investigations of amenorrhoea

A

LH, FSH, Oestradiol (main oestrogen)

ovarian US ± endometrial thickness

testosterone if there is hirsutism

pituitary function tests and MRI pituitary if indicated

karotype if it is primary amenorrhoea/Turner’s symptoms

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12
Q

what is female hypogonadism identified by

A

low levels of oestrogen

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13
Q

primary hypogonadism

A

problem with ovaries - high FH/LSH = hypergonadotrophic hypogonadism

eg premature ovarian failure

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14
Q

secondary hypogonadism

A

problem with the hyothalamus/pituitary axis - low LH/FSH = hypogonadotrophic hypogonadism

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15
Q

WHO group 1 definition of anovulation

A

hypothalamic pituitary failure

  • low LSH, FH, oestrogen deficiency, normal PRL, amenorrhoea
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16
Q

progesterone challenge test

A

used to evaluate a patient who is experiencing amenorrhoea

progesterone administered as an IM injection

if the patient has sufficient oestradiol, withdrawal bleeding should occur - indicating that the patients amenorrhoea is due to anovulation

if no bleeding occurs it is likely to be due to low serum oestradiol, HPA dysfunction etc

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17
Q

progesterone challenge test in WHO group 1 anovulation

A

negative

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18
Q

WHO group 2 definition of anovulation

A

hypothalamic pituitary dysfunction

  • normal gonadotrophins/excess LH
  • normal eostrogen levels - positive progesterone test
  • oligo/amenorrhoea

PCOS

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19
Q

WHO group 3 definition of anovulation

A

ovarian failure

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20
Q

which WHO group of anovulation is PCOS classified into

A

2

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21
Q

premature ovarian failure

A

amenorrhoea, oestrogen deficiency and elevated gonadotrophins occuring <40 as a result of loss of ovarian function

there is a low likelihood of conception

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22
Q

biochemistry of premature ovarian failure

A

FSH >30 on 2 separate occasions more than one month apart

LH high

oestradiol low

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23
Q

causes of premature ovarian failure

A

autoimmune disease (eg associations with Addison’s, thyroid, APS1/2)

chromosomal abnormalities (e.g. Turner, Fragile X, XX gonadal agenesis)

gene mutations (eg in FSH/LH receptor)

iatrogenic - radio/chemo, bilateral oophorectomy

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24
Q

clinical features of premature ovarian failure

A

features of low oestrogen:

hot flushes

night sweats

atrophic vaginitis

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25
treatment of premature ovarian failure
hormone replacement therapy egg/embryo donation counselling and support networks
26
secondary hypogonadism
hypogonadism as a result of hypothalamic or pituitary disease characterised by low oestradiol and low/inappropriately normal LH and FSH
27
causes of secondary hypogonadism
**hypothalamic problems:** - functional disorders: low weight (BMI \<18.5), stress, extreme exercise) - brain pituitary tumours - Kallman's syndrome - IHH **pitutiary problems** miscellaneous: Prader/Willi and haemachromatosis
28
management of hypothalamic anovulation
* stabilise weight * BMI \>18.5 * pulsatile GnRH if hypog hypog * -SC/IV, pulsatile administration every 90 minutes * LH and FSH daily injections * *require US monitoring of response*
29
what is the problem with gonadotrophin injections to treat secondary hypogonadism
higher multiple pregnancy rates
30
what is the ovulation rate with pulsatile GnRH treatment for secondary hypogonadism
90%
31
what are the 3 types of functional hypothalamic amenorrhoea
weight change stress extreme exercise
32
why does stress cause amenorrhoea
evolutionary mechanism to avoid conception during physiological stress
33
at which BMI does amenorrhoea tend to occur
\<18.5 normal ovulatory cycle unlikely \<16 cycle usually stops
34
what happens to GnRH secretion in functional hypothalamic amenorrhoea
aberrations in pulsatile GnRH secretion, causes impairement of LH and FSH there are complex hormonal changes manifested by profound **hypooestrogenism**
35
idiopathic hypogonadotrophic hypogonadism
* congenital absent/delayed sexual development associated with inappropriate low levels of gonadotrophic and sex hormones in the absence of anatomical/functional defects of HPA * **major defect is an inability to activate pulsatile GnRH secretion during puberty due to a genetic defect**
36
what additional phenotype features may be present in IHH
anosmia
37
what mutations have been identified as a cause of IHH
mutations in GPCR KISS1R (GPR54) gene the ligand for **KISS1R - 'Kisspeptin'** is a potent **stimulator of GnRH secretion** GnRH neurone has Kisspeptin receptors on it, pulsatile release of Kisspeptin causes pulsatile release of FH and LSH
38
name 3 functions of Kisspeptin
gatekeeper of puberty and GnRH secretion key regulator of male and female fertility influence positive and negative feedback of oestrogen and therefore influence ovulation and menstrual cycle
39
what are most of IHH cases
60% kallman's syndrome 40% normosmic IHH
40
kallman's syndrome
genetic disorder characterised by loss of GnRH secretion and anosmia/hyposmia causes primary amenorrhoea
41
why does kallman's syndrome cause anosmia
**absence of olfactory bulbs -** are in close proximity to the hypothalamus during embryogenesis
42
what is pituitary function and imaging like in kallman's syndrome
remainder of pituitary function normal and MRI imaging normal
43
inheritance of kallman's syndrome
family history variable patterns of inheritance genetic heterogenity is displayed (same phenotype casued by different alleles on the same gene)
44
hyperPRL
inhibits GnRH secretion - can be caused by a prolactinoma or drugs (eg dopamine antagonists)
45
what are some ovarian causes of amenorrhoea
ovarian failure (high gonadotrophins) congenital problem with ovarian development (absence of uterus, vaginal atresia, Turner, CAH) PCOS
46
PCOS
causes secondary oligo/amenorrhoea, infertility, obesity, acne and hirsutism most common endocrine disorder in women can be uni or bi lateral inherited condition
47
what exacerbates PCOS
weight
48
diagnosis of PCOS
Rotterdam criteria (2/3): - menstrual irregularity - hyperandrogenism - polycystic ovaries
49
what is acanthosis nigricans associated with
* Associated with obesity, insulin resistance, PCOS and adenocarcinoma of the stomach
50
what skin lesion is PCOS associated with
acanthosis nigricans
51
blood tests of PCOS
**increased testosterone (high free androgen)** **increased LH:FSH ratio** increased TSH and lipids impaired glucose tolerance
52
US of PCOS
53
insulin resistance in PCOS
this is seen in 50-80% of patients diminshed biological response to a given level of insulin, however as the pancreatic reserve is normal **hyperinsulinaemia** occurs 20% of patients have glucose intolerance or non-insulin dependent DM exacerbated by obesity
54
what does hyperinsulinaemia in PCOS result in
**raised LH levels (altered LH:FSH ratio).** This leads to increased androgen synthesis and arrest of normal follicular development lowered FSH - insufficient to stimulate granulosa cells (infertility?) lowered SHBG levels, leading to **increased free testosterone**, leading to hyperandrogenism
55
management of PCOS
1. **weight loss** and **metformin** 2. **local measures**: shaving, wax, creams etc 3. **OCP** - acne and hirsutism respond to this. Can add **Crypoterone acetate** 4. cosmesis eg laser phototherapy, electrolysis
56
the risk of which 2 cancers is increased in PCOS
ovarian and endometrial
57
OCP action
suppresses ovarian androgen production and reduces free androgens by increasing SHBG levels - hirsutism benefit and regulates cycles
58
what local anti-androgen creams are available for treatment of PCOS
**elfornithine** cream (Vaniqa) inhibits hair growth
59
what is used in the management of PCOS if the OCP has not been of much benefit
**cyproterone acetate** (steroidal anti-androgen of co-cyprindiol) often combined with OCP as Dianette
60
use of Metformin in PCOS
to restore cycles and fertility, helps insulin resistance and so reduces androgen production helps all aspects of PCOS
61
what cosmetic management can be performed in PCOS
electrolysis and laser phototherapy
62
pre-fertility treatment
weight loss to optomise results (BMI \>30 has a poor treatment outcome) lifestyle modifications: smoking and alcohol folic acid 400mcg daily (5g if BMI \>30) check rubella immune normal semen analysis patent fallopian tube
63
what vaccine is given for rubella
MMR (live attenuated vaccine) UK VACCINATION SCHEDULE: given at 1 year and 3y4m
64
what are the 3 options for ovarian induction in PCOS
*metformin may induce conception alone* Clomifene citrate gonadotrophin therapy laparoscopy ovarian diathermy
65
clomifene citrate (*Ovulation Induction in PCOS* ) - possible AE
inhibits oestrogen receptors in the hypothalamus, inhibiting negative feedback of oestrogen on gonadotrophin release, leading to up-regulation of HPG axis may cause ovarian hyperstimulation syndrome
66
gonadotrophin therapy (Ovulation Induction in PCOS )
daily injections of recombinant FSH to stimulate the ovary directly
67
what are the risks with gonadotrophin therapy
multiple pregnancy and over stimulation
68
laparoscopic ovarian diathermy (Ovulation Induction in PCOS )
many singleton pregnancies
69
what is the risk with laparoscopic ovarian diathermy
destruction of ovaries
70
what are the risks of ovulation induction
ovarian hyperstimulation multiple pregnancy ovarian cancer
71
what happens in ovarian hyperstimulation
* Ovaries become swollen and painful. Ovarian enlargement, oedema, hypovolaemia, acute kidney injury * Ranges from mild to severe * There is an increased risk \<35 years, and in PCOS
72
what are the biggest risks in multiple pregnancies
prematurity (half of twins are born before 36 weeks) and low birth weight
73
problems associated with prematurity:
* Neonatal intensive care may be required * Breathing help * RDS * Long term: cerebral palsy, impaired sight, congenital heart disease * Still birth/neonatal death * Disability
74
hirsutism
excess hair, usually referring to women with male pattern hair distribution caused by excess androgen at the hair follicle, due to either excess circulating androgen or increased peripheral conversion at the hair follicle
75
long history causes of hirsutism
PCOS, familial (ethnic origin, especially Mediterranean population), idiopathic, CAH all present with a testosterone that is not dramatically elevated (\<5nmol/L) and no virilisation
76
causes of hirsutism with a short history
adrenal/ovarian tumour (frequently benign) high testosterone levels (\>5nmol/L), signs of virilisation (deepening of voice and clitoromegaly) MRI adrenal and ovaries for tumours (\>1cm)
77
what can exposure to exogenous testosterone cause
hyperandrogenism
78
turner's syndrome
affects women, 45X (one X chromosome missing) can uncommonly be mosaicism
79
ovarian function in Turner's syndrome
an early loss of ovarian function is common, a small percentage of females will retain normal ovarian function throughout young adulthood ## Footnote **most will be infertile**
80
puberty in female's with Turner's syndrome
most **fail to progress through puberty**, 30% have some pubertal development there is normal adrenarche and pubic hair development breast development depends on when the ovaries fail (there may be none if they fail before puberty) **failure to develop 2y sexual characteristics is typical**
81
how does Turner's present in paediatrics
short stature puberty abnormalities
82
how does Turner's syndrome present in adults
primary or secondary amenorrhoea infertility
83
clinical features of Turners
short stature webbed neck shield chest with wide spaced nipples cubitis valgus lymphoedema coarctation of the aorta
84
XX gonadal dysgenesis
a form of female hypogonadism, in which there are absent ovaries, without any chromsomal abnormality
85
testicular feminization (androgen insensitivity syndrome)
a genetic disorders that makes XY fetuses insensitive to androgen they are born externally looking like normal girls, and tend to identify with being female
86
define inferility
failure to achieve a clinical pregnancy after 12 months or more of regular unprotected sexual intercourse (in absence of known reason) in a couple who have never had a child.
87
define primary and secondary infertility
* primary - the couple have never conceived * secondary- the couple have previously conceived (may nothave been successful)
88
list factors that increase the likelihood of conception
* Women \<30 * Previous pregnancy * Less than 3 years trying to conceive * Intercourse occurring around ovulation * Woman’s BMI 18.5 – 30 * Both partners are non-smokers * Caffeine intake of less than 2 cups of coffee daily * No use of recreational drugs
89
what drug has a direct correlation to still birth
cocaine
90
define anovulatory infertility
ovaries do not release an occyte during the menstrual cycle
91
hydrosalpinx
* distally blocked fallopian tube withc lear/serous fluid - may become distended * can cause pain, discharge, infertility, menorrhagia and ectopic pregnancy
92
define endometriosis
the presence of endometrial glands otuside the uterine cavity
93
most common cause of endometriosis
retrograde menstruation - menstrual blood containing endometrial cells flows back out through fallopian tubes into pelvic cavity instead of out of the body
94
classical scan sign of endometriosis
chocolate cysts
95
examination of patient for infertility
* BMI * general - body hair distribution, galactorrhoea * pelvic - presence of vas deferens, varicocele (reduce sperm count)
96
investigation of female for infetility
* Endocervical swab for chlamydia * Cervical smear if due * Blood for rubella immunity * Midluteal progesterone * test of tubal patency
97
first line investigation for tubular assessment
Hysterosalpingiogram
98
when is laparoscopy first line for infertility
known pelvic disease/pathology

RB Y2 Endocrine - 6 Reproductive (4 decks)

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