Reproductive Endocrinology Flashcards
(100 cards)
1
Q
What hormone is released by the hypothalamus and acts on the pituitary to control the sex hormones?
A
Gonadotrophin Releasing Hormone
2
Q
What does GnRH do?
A
Responsible for the release of FSH & LH from the anterior pituitary
3
Q
How is GnRH secreted?
A
In a pulsatile manner - different frequencies in women, constant frequency in men
4
Q
How does the GnRH frequency change over time in women?
A
High frequency - stimulates LH
Low frequency - stimulates FSH
5
Q
What controls the change in GnRH frequency in a menstrual cycle?
A
Oestrogen released by the follicle acts on kisspeptin neutrons to increase frequency driving LH
6
Q
What is the effect of progesterone on GnRH frequency?
A
Reduces frequency
7
Q
Name the two phases of the menstrual cycle
A
- follicular phase (variable length)
2. luteal phase (constant 14 days )
8
Q
What does release of FSH cause?
A
Stimulation in growth of ovarian follicles which in turn release oestrogen
9
Q
Describe the effect on the axis when oestrogen is increased
A
Exerts negative feedback to temporarily lower FSH levels
10
Q
At a certain (set) level of oestrogen what happens to the feedback loop?
A
It exerts positive feedback to increase FSH and cause an LH surge
11
Q
What is the effect of an LH surge?
A
Leads to ovulation (34-36 hours after) which turns the follicle to the corpus luteum `
12
Q
What colour is the corpus luteum and why?
A
Yellow due to the abundance of cholesterol the intermediate for progesterone
13
Q
Name the hormone produced by the corpus luteum what does it do?
A
Progesterone - exerts negative feedback & decreases LH secretion
14
Q
What is required for the developing embryo to survive in the absence of LH?
A
It needs replaced with HCG - produced by the developing embryo itself
15
Q
Describe the histology of a follicle
A
Oocyte surrounded by follicular cells - granulosa & theca cells with areas of fluid know as the antrum. Oocyte is surrounded by the zona pellucida (protein layer that prevents polyspermic fertilisation)
16
Q
What is the effect of progesterone on oocyte release?
A
The increase after LH surge stimulates expression of enzymes that help breakdown the follicular wall leading to release of the oocyte
17
Q
What happens to granulosa & theca cells under the influence of LH?
A
They transform into luteal cells
18
Q
State four functions of oestrogen
A
- increase thickness of vaginal wall
- regulate LH surge
- reduce vaginal pH (increase lactic acid)
- decrease viscosity of cervical mucus to help sperm penetrate
19
Q
State four functions of progesterone
A
- maintains thickness of endometrium
- relaxes myometrium (removal of progesterone = contractions)
- responsible for infertile thick mucus
- increases basal body temperature
20
Q
How can regular menstrual cycles be assessed?
A
midluteal serum progesterone >30nmol/l
21
Q
What is needed to assess ovulation in irregular menstrual cycles?
A
Further hormone evaluation
22
Q
What are the three groups of ovulation disorders?
A
- Hypothalamic pituitary failure
- Hypothalamic pituitary dysfunction
- Ovarian Failure
23
Q
Describe hypothalamic pituitary failure
A
Hypogonadotrophic hypogonadism - low levels of FSH and LH result in an oestrogen deficiency
24
Q
How can oestrogen deficiency be tested?
A
Negative progesterone challenge test
25
In group 1 what is the usual presenting complaint
amenorrhoea
26
State the causes of hypothalamic pituitary failure
- stress, anorexia, excessive exercise, tumours, trauma, drugs, kallman's
27
What is Kallman's Disease?
Delayed/absent puberty
28
How are all ovulation disorders initially managed?
stabilise weight, modify lifestyle, folic acid, rubella immunity, chalmydia test
29
How are group 1 ovulation disorders managed?
Pulsatile GnRH through a pump
Gonadotrophin daily injections
Both monitored using ultrasound to show response
30
Describe hypothalamic pituitary dysfunction
Normal gonadotrophin & oestrogen levels but other hormone levels abnormal
31
Name two disorders in group 2 ovulation disorders ``
- Polycystic Ovarian Syndrome
| - Hyperprolactinaemia
32
How is PCOS diagnosed?
2/3 of ;
oligo/amenorrhoea
US appearance (lots of underdeveloped follicles)
Clinical/biochemical signs of hyperandrogenism
33
What are the clinical signs of PCOS?
Acne, hirtirsm, olio/amenorrhoea ...
34
Why is insulin resistance more common in women with PCOS?
LOOK UP ANSWER
35
How is PCOS infertility managed?
Depends on symptoms/needs of patients
1. Clomifere citrate tablets
2. Gonadotrophin therapy
3. Laparoscopic ovarian diathermy
36
Describe the mechanism of action of clomifere citrate
Anti-oestrogen, stimulates LH & FSH
37
What drug can be added to clomifere citrate?
Metformin
38
What is the main risk for gonadotrophin therapy?
Multiple pregnancy
39
What is the difference between monozygotic & dizygotic twins?
dizygotic - come from two fertilised ova
| monozygotic - come from an egg splitting
40
Describe monochorinic twins
Twins that share a placenta - three times increased risk of perinatal mortality
41
What signs indicate chrionicity?
Lambda sign - dichorionic
| T sign - monochorionic
42
Describe twin - twin transfusion syndrome
Unbalanced vascular communication within placenta bed - one big baby & one small baby. Most successful treatment is intra-uterine surgery
43
What long term consequences are linked to prematurity?
- ADHD
- Lower IQ
- Language problems
44
After what length of time on IVF is there a risk of ovarian cancer?
12 months
45
How does hyperprolactinaemia often present?
amenorrhoea, galactorrhoea, visual field problems
46
What is the treatment for hyperprolactinaemia?
Dopamine agonist
47
Describe ovarian failure
High gonadotrophin & low oestrogen - menopause
48
What causes ovarian failure?
- genetic (turner's syndrome, fragile X, XX gonadal agenesis)
- autoimmune
- oophorectomy
- chemotherapy/radiotherapy
- family history
49
How is ovarian failure managed?
Hormone Replacement Therapy (OCP)
Assisted conception
Counselling
50
Where do FSH and LH act on in the male reproductive tract?
FSH - Sertoli cells
| LH - Leydig cells
51
What do sertoli cells do?
Produce androgen binding protein leading to local testosterone production & spermatogenesis
Produce Inhibit which exerts negative feedback on the hypothalamus to decrease GnRH
52
What do leydig cells do?
produce testosterone from cholesterol leading to local production, release into the body & spermatogenesis
53
Describe the function of the blood testes barrier
Separates the immune cells from stem cells to stop the immune cells attacking the new cells
54
State two functions of testosterone
- maintains the integrity of the blood testes barrier
| - releases mature spermatozoa from sertoli cells by influencing peritubular myeloid cells
55
What proteins does testosterone bind to?
SHBG & Albumin
56
Define hypogonadism
clinical syndrome comprising of signs, symptoms & biochemical evidence of testosterone deficiency
57
What is meant by primary hypogonadism?
Testes are primarily affected, decreased testosterone results in a decrease in negative feedback.
58
State the biochemistry of primary hypogonadism
Low testosterone, anterior pituitary secretes higher amounts of LH/FSH
'hypergonadotrophic hypogonadism'
59
What is meant by secondary hypogonadism?
hypothalamus/pituitary affected despite testes being capable of normal function
60
State the biochemistry of secondary hypogonadism
Low FSH/LH and low testosterone
| 'hypogonadotrophic hypogonadism'
61
Name three congenital causes of primary hypogonadism
- klinefelter's syndrome
- cryptorchidism (undescended testes)
- Y-chromosome micro deletions (lack of male characteristics)
62
What causes klinefelter's syndrome?
Nondisjunction - unequal division of chromosomes between cells
63
How is klinefelter's syndrome diagnosed?
Karyotyping
64
Name some clinical features of klinefelter's syndrome
Infertility, small firm testes, cryptorchidism, learning difficulties, 'female' like body structure, little chest hair & breast development
65
State some acquired causes of primary hypogonadism
trauma, chemotherapy/radiation, varicocele, mumps, infiltrative disease, certain medications
66
Name two congenital causes of secondary hypogonadism
Kallmann's Syndrome
| Prader Willi Syndrome
67
Describe Prader Willi Syndrome
Excessive appetite, increased consumption, loss of GnRH & lack of sexual development
68
Describe Kallmann's Syndrome
Genetic disorder characterised by GnRH deficiency & hypo/anosmia (reduced/no sense of smell)
69
What are the signs & symptoms of hypogonadism in pre-pubertal onset?
Small male sexual organs, decreased body hair, high pitched voice, low libido, gynaecomastia, 'enuchoidal' habitus, decreased muscle & bone mass
70
What are the signs & symptoms of hypogonadism in post-pubertal onset?
Normal skeletal proportions but decreased sexual characteristics (libido, pubic hair, testicular volume, gynaecomastia, bone/muscle mass)
71
How is hypogonadism diagnosed?
AM testosterone
| LH/FSH Measurements
72
How is testosterone calculated?
By measuring total testosterone & SHBG to work out free testosterone
73
What are the three methods of testosterone replacement therapy?
- Gel
- Long-acting injection
- Short-acting injection
74
Describe the testosterone gel
Applied daily, mimics circadian rhythm but can cause skin irritation & risk of inter-personal contact
75
Describe the long acting testosterone injection
'nebido'
Given c. every 10 weeks, difficult to withdraw side effects if they are experienced, coughing post injection may occur but it maintains steady testosterone levels
76
Describe the short acting testosterone injection
'sustanon'
Variable testosterone levels, coughing may occur post injection but can be self administered, easier to withdraw if side effects experienced
77
What are the contraindications for testosterone replacement therapy?
Hormone responsive cancer
Possibility of prostate cancer
Haematocrit >50%
Severe sleep apnoea/heart failure
78
What three things should be monitored throughout testosterone replacement treatment?
- testosterone concentration
- PSA & DRE (cancer markers)
- Haematocrit
79
Why is the incidence of infertility increasing?
Older women, chlamydia, obesity, awareness of treatment, change in attitude
80
Define infertility
Failure to achieve a clinical pregnancy after 12 months or more of regular unprotected intercourse in a couple who have never had a child
81
What is the difference between primary and secondary infertility?
Primary - couple never conceived
| Secondary - couple have conceived but pregnancy was unsuccessful
82
Name some factors that affect fertility
- age
- previous pregnancies
- less than 3 years trying
- intercourse around ovulation
- BMI
- alcohol/smoking
- recreational drugs
83
Describe the implications of a hydrosalpinx
Damage causes accumulation of fluid which inhibits the cilia & leads to complete obstruction/ectopic pregnancy
84
What are the features of a hydrosalpinx?
Abdominal pain, discharge, excitation, dysmenorrhoea
85
What test could be done in a male who is suspected to be infertile?
Semen analysis, hormone biochemistry, chromosome analysis, biopsy/Ultrasound
86
What tests are done on women at the infertility clinic?
- swab for chlamydia
- cervical smear
- blood test for rubella immunity
- midluteal progesterone
- tubal patency test
87
What are the two types of tubal patency tests?
- hysterosalpingiogram
| - laparoscopy
88
Describe a hysterosalpingiogram
Visualisation of the tube by radiography & dye used if no known risk factors or laparoscopy contraindicated
89
When is laparoscopy used?
Possible tubal/pelvic disease, known pathology/suggestive history or abnormal HSG
90
What other tests can be used to investigate infertility in women?
Hysteroscopy
Pelvic Ultrasound
Endocrine profile
Chromosome Analysis
91
What is the very first aspect of infertility management?
Lifestyle Advice
92
What lifestyle advice is given to infertile couples?
- Lose weight
- Stop smoking, drugs & methadone
- Drink alcohol & caffeine in moderation
- Folic acid 400 micrograms/day
- Vitamin D 10 micrograms/day
- Need tested for chlamydia & rubella immunity
93
What are the two different aims of reproductive surgery?
- Treat infertility
| - Enhance IVF treatment
94
What can be done surgically to treat infertility?
- correction of adhesions
- removal of chocolate cysts in ovary
- unblock tube
- treat grade 1 & 2 endometriosis
95
How is proximal tubal obstruction treated?
Selective salpingography & catheterisation/cannulation to improve chances of pregnancy
96
What is removal of tissue (fibroids & polyps) called?
Measure
97
How is a uterine septum treated?
Resection
98
What are the four types of fibroid?
- pendunculated
- submucous
- subserous
- intramural
99
Do all fibroids need removed?
No - it is very patient dependent. Submucosal fibroids should be treated as they are impacting uterine cavity.
100
What are the seven steps of IVF?
1. Ovarian stimulation
2. Monitoring
3. Ovulation induction
4. Oocyte retrieval (in theatre)
5. Preparation of sperm
6. IVF - to produce blastocyst
7. Embryo transfer & luteal support
