(endo) reproductive treatments

Question 1

what are the symptoms are testosterone deficiency?

Answer 1

• low libido
• loss of early morning erections
• decreased energy
• reduced frequency dhaving

Question 2

how is testosterone deficiency diagnosed?

Answer 2

at least two low measurements of morning fasting testosterone (i.e. before 11am)

then investigate the cause

Question 3

how is testosterone replaced in deficient patients who do not desire fertility?

Answer 3

first treat symptoms then replace testosterone with:

1) daily gel (careful not to cross-contaminate parter)
2) 3-weekly IM injection
3) 3-monthly IM injection
4) implants, oral preparations

Question 4

what TWO safety considerations must be taken into account when replacing testosterone?

Answer 4

replacing testosterone will:

1) increase haematocrit (risk of hyperviscosity + stroke)
2) increase PSA levels (can stimulate growth of prostate cancers)

Question 5

how is primary hypogonadism treated?

Answer 5

difficult to treat

Question 6

how is secondary hypogonadism treated if fertility is desired?

Answer 6

(deficiency of gonadotrophins - i.e. hypogonadotrophic hypogonadism)

treat with gonadotrophins (i.e. LH + FSH) to induce spermatogenesis

Question 7

why is secondary hypogonadism treated with gonadotrophins?

Answer 7

(when fertility is desired)

give LH = to stimulate Leydig cells to increase intratesticular testosterone

give FSH = to stimulate seminiferous tubule development and spermatogenesis

Question 8

what treatment would you recommend in the following scenario?

35yr old man with hypogonadism due to opioid abuse

1) LH 3, FSH 5 iU/L
2) low morning testosterone 7 nmol/L (normal 9-30 nmol/L)
3) fatigue and reduced shaving frequency
4) trying to conceive with his partner for 2 years with no success
5) sperm sample: low sperm count ie ‘male factor’ infertility

Answer 8

opiates suppress GnRH (and therefore LH, FSH and T)

so, as patient desires fertility

1) do NOT give testosterone
2) give hCG injections (which will act on LH receptors)
3) if no response to hCG injections after 6 months, give FSH injections

Question 9

for a male patient with hypogonadism that desires fertility, why is testosterone NOT given?

Answer 9

giving T will via the negative feedback system, reduce LH + FSH further

= further reducing spermatogenesis, leading to infertility

Question 10

for a male patient with hypogonadism that desires fertility, why are hCG injections given?

Answer 10

1) the hCG injections will act on the LH receptors to stimulate Leydig cells to produce androgens
2) if no response after 6 months, add FSH injections (to stimulate Sertoli cells)

Question 11

what is the diagnosis in the following scenario?

• 30 year old woman
• unsuccessfully trying to conceive for 3 years
• lack of periods (amenorrhoea)
• hyperandrogenism (hirsutism and acne)
• ultrasound scan = polycystic ovarian (PCO) morphology
• LH 8.0 iU/L, FSH 4.5 iU/L

Answer 11

polycystic ovary syndrome (PCOS)

Question 12

what are the symptoms of polycystic ovary syndrome (PCOS)?

Answer 12

1) hyperandrogenism (clinical/biochemical)
2) PCO morphology (on ultrasound)
3) oligomenorrhoea OR anovulation

Question 13

what are the possible causes of hypothalamic amenorrhoea?

Answer 13

1) low body weight (BMI)
2) excessive exercise
3) stress
4) genetic susceptibilty

Question 14

what is the most common cause of irregular periods/infertility?

Answer 14

PCOS

Question 15

what is the purpose of ovulation induction in women experiencing infertility?

Answer 15

• aim to develop one ovarian follicle by giving a low dose of FSH (injections)

Question 16

why is a LOW dose of FSH given to women experiencing infertility during ovulation induction?

Answer 16

low dose to ensure only one follicle develops as

= > 1 follicle developing risks a multiple pregnancy = risks for mother + baby

Question 17

• PCOS is the commonest cause of anovulation -

in this scenario, how is ovulation restored?

Answer 17

1) lifestyle changes, weight loss, metformin
2) letrozole (aromatase inhibitor)
3) clomiphine (oestradiol receptor modulator)
4) FSH stimulation

Question 18

what is letrozole?

Answer 18

first line medication to treat anovulation/infertility in women

= aromatase inhibitor

Question 19

what is clomiphine?

Answer 19

medication to treat anovulation/infertility in women (second line after letrozole)

= oestradiol receptor modulator

Question 20

why are FSH injections given to women experiencing infertility?

Answer 20

to stimulate the development of one follicle

Question 21

explain the mechanism of action of letrozole

Answer 21

aromatase inhibitor

1) inhibits aromatase and so prevents the conversion or testosterone to oestradiol
2) less oestradiol results in less negative feedback to the hypothalamus + APG
3) less negative feedbakc stimulates more hypothalamic GnRH secretion and more pituitary LH/FSH secretion
4) results in more systemic LH + FSH = follicular development for ovulation

Question 22

what effect does oestradiol normally have on the HPG axis?

Answer 22

via negative feedback, reduces hypothalamic GnRH and pituitary LH/FSH secretion

Question 23

explain the mechanism of action of clomiphine

Answer 23

oestradiol receptor modulator

1) binds to the oestradiol receptor and antagonises it
2) blocks the oestradiol receptor and so less oestradiol activates the negative feedback system
3) decreased negative feedback causes increased hypothalamic GnRH and pituitary LH/FSH secretion
4) increased systemic FSH causes follicular development for ovulation

Question 24

summarise the steps of IVF

Answer 24

IVF = in vitro fertilisation

1) give a large dose of FSH to stimulate many follicles to grow
2) oocyte retrieval from ovary
3) fertilisation in vitro = either IVF or ICSI
4) embryo incubation
5) embryo transfer (of strongest embryo and wait for implantation)

Question 25

when is ICSI used over IVF?

Answer 25

in cases of male factor infertility - low sperm count - abnormally-shaped sperm - low sperm motility

Question 26

what essential step must be done prior to oocyte retrieval in IVF?

Answer 26

must give a large, pharmacological dose of FSH = to stimulate multiple follicles to grow (i.e. superovulation)

Question 27

what must be done following administration of the FSH injection in IVF?

Answer 27

after FSH injection-induced superovulation, must give a hormone that prevents the LH surge = to prevent ovulation from actually taking place

Question 28

why is the premature ovulation prevented in IVF?

Answer 28

give hormone to prevent the LH surge that stimulates ovulation = so the oocyte is not lost from the follicle when it is retrieved

Question 29

what are two possible ways by which premature ovulation is prevented in IVF?

Answer 29

prevent the LH surge either by 1) SHORT protocol (GnRH antagonist) 2) LONG protocol (GnRH agonist)

Question 30

what is the GnRH SHORT protocol?

Answer 30

give a GnRH antagonist = inhibits GnRH secretion and therefore LH/FSH secretion, preventing the LH surge - start FSH from day 2. give GnRH antagonist from day 6

Question 31

what is the GnRH LONG protocol?

Answer 31

give a GnRH agonist = inhibits GnRH secretion and therefore LH/FSH secretion, preventing the LH surge - give GnRH agonist from before the end of the last cycle and then FSH from day 2 of next cycle

Question 32

compare how the SHORT protocol compares to the LONG protocol to prevent premature ovulation

Answer 32

1) SHORT = give FSH from day 2 and GnRH antagonist from day 6 2) LONG = give GnRH agonist from end of last cycle and then FSH from day 2 of next cycle

Question 33

explain how the GnRH SHORT protocol works

Answer 33

give a GnRH antagonist = inhibits GnRH secretion = inhibits LH/FSH secretion = prevents LH surge

Question 34

explain how the GnRH LONG protocol works

Answer 34

give a GnRH agonist = continuous administration of GnRH desensitises the GnRH receptor = so excess GnRH inhibits LH secretion from gonadotrophs

Question 35

what is the function of the GnRH receptor and where is it found?

Answer 35

found on the surface membrane of gonadotrophs of the anterior pituitary gland = GnRH binds to the GnRH receptors and stimulates gonadotrophin secretion

Question 36

why is continuous administration of GnRH agonist an effective step in IVF?

Answer 36

continuous administration of GnRH agonist = act on the the GnRH receptors, desensitising them eventually = inhibiting LH (and FSH) secretion = preventing LH surge, and therefore premature ovulation

Question 37

what is the difference between pulsatile and non-pulsatile GnRH administration in IVF?

Answer 37

pulsatile = normal LH stimulation non-pulsatile (i.e. continuous) = initial LH flare as receptors are stimulated, but eventually they become desensitised (so inhibit LH secretion)

Question 38

when is pulsatile GnRH administration used as treatment?

Answer 38

in hypothalamic amenorrhoea = to restore hypothalamic (HPG) axis and normal LH/FSH levels

Question 39

what is done after preventing premature ovulation in IVF?

Answer 39

next step = LH exposure to mature eggs (oocyte maturation)

Question 40

why is oocyte maturation an important step of IVF?

Answer 40

need mature oocytes so they can be fertilised (!!) - after preventing premature ovulation, need the oocyte to mature from metaphase 1 (diploid) TO metaphase 2 (haploid) = maturation requires LH exposure

Question 41

what are two ways in which oocyte maturation can take place in IVF?

Answer 41

1) hCG is normally given that acts on the LH receptors = acts as an LH surge = to induce oocyte maturation 2) GnRH agonist (in a pulsatile manner) can also be given to initially stimulate LH surge

Question 42

how are oocytes converted from immature ones to mature ones in IVF?

Answer 42

immature oocytes = metaphase 1 (diploid) *LH exposure via GnRHa OR hCG* mature oocytes = metaphase 2 (haploidi)

Question 43

why do oocytes need to be mature in IVF?

Answer 43

after maturation, achieve competence for fertilisation = i.e. have half the genetic information (haploid) so can NOW, receive the other half of genetic material from the sperm

Question 44

what three steps must be taken before oocyte retrieval in IVF?

Answer 44

1) FSH administration for superovulation 2) prevention of premature ovulation 3) LH exposure to mature oocytes

Question 45

what steps follow oocyte retrieval in IVF?

Answer 45

1) oocyte retrieval 2) fertilisation 3) embryo incubation (3-5 days) 4) embryo transfer 5) pregnancy test/US scan

Question 46

how long do you wait before doing a pregnancy test after transferring an IVF embryo to the endometrium?

Answer 46

approx 11 days

Question 47

name possible methods of contraception

Answer 47

1) barriers = male/female condoms, diaphragm, cap w spermicide 2) combined oral contraceptive pill (OCP) 3) progesterone-only pill (POP) 4) long-acting reversible contraceptive (LARC) 5) emergency contraception 6) vasectomy, female sterilisation

Question 48

name the two permanent methods of contraception

Answer 48

1) vasectomy | 2) female sterilisation

Question 49

name possible barrier methods of contraception

Answer 49

1) male/female condom 2) diaphragm 3) cap w spermicide

Question 50

list the pros and cons of condoms as a form of contraception

Answer 50

pros - protect against STIs - easy to obtain (no need to see HCP) cons - can interrupt sex/ erections - can reduce sensation - require some skill to use

Question 51

explain the mechanism of action of the oral contraceptive pill

Answer 51

- OCP contains oestrogen + progesterone - increased O+P increases hypothalamic + pituitary negative feedback - reduced hypothalamic GnRH and pituitary LH/FSH secretion three effects: 1) anovulation 2) thickens the cervical mucus 3) thins the endometrial lining

Question 52

why is anovulation caused when taking the OCP?

Answer 52

OCP increases oestrogen and progesterone = increased -ve feedback = reduced hypothalamic GnRH + pituitary LH/FSH secretion = anovulation

Question 53

why does the cervical mucus thicken when taking the OCP?

Answer 53

progesterone thickens the cervical mucus to prevent sperm entry into the uterus

Question 54

why does the endometrial lining thin when taking the OCP?

Answer 54

oestrogen = causes proliferation + growth of the endometrial lining progesterone = prevents endometrial hyperplasia by opposing the effects of oestrogen = overall, thinning of the endometrial lining occurs = reduces the risk of implantation

Question 55

list the pros and cons of the OCP as a form of contraception

Answer 55

pros - easy to take, effective - does not interrupt sex - can take several packets back to back to avoid withdrawal bleeds - reduce risk of endometrial + ovarian cancer cons - difficult to remember - no protection against STIs - possible interactions w other medication - side effects possible (spotting, nausea, mood/libido changes, DVT/PE)

Question 56

what are the three common non-contraceptive uses of the OCP?

Answer 56

1) menorrhagia = reduces period pain + makes periods lighter 2) endometriosis = making periods less painful + lighter reduces endometriosis symptoms 3) PCOS = reduces LH secretion and therefore, reduces overactivation of androgen production in theca cell, reducing hyperandrogenism

Question 57

why can the OCP not be prescribed for a women with PCOS desiring fertility?

Answer 57

OCP = reduces LH/FSH secretion and causes anovulation so patient is not fertile - - in this situation, treatment is either 1) letrozole, clomiphine, IVF for infertility 2) laser, waxing, creams for hyperandrogenism 3) metformin + lifestyle changes for impaired glucose tolerance 4) progesterone courses for risk of endometrial cancer --

Question 58

how does the OCP help with menorrhagia and endometriosis?

Answer 58

``` OCP = contains oestrogen + progesterone = inhibits LH/FSH secretion = anovulation (+ thins endometrial lining) = makes periods lighter and less painful (reducing symptoms of endometriosis) ```

Question 59

how does the OCP help with PCOS?

Answer 59

a symptom of PCOS is hyperandrogenism = OCP inhibits LH secretion and therefore inhibits theca cell androgen production

Question 60

explain the mechanism of action of the progesterone-only pill

Answer 60

1) inhibit LH/FSH secretion and therefore inhibit ovulation | 2) thicken the cervical mucus to prevent sperm penetration

Question 61

list the pros and cons of the progesterone-only pill (POP)

Answer 61

pros - suitable if patient cannot take oestrogen - easy to take - doesn't interrupt sex - useful in menorrhagia cons - difficult to remember - no protection against STIs - side effects (spotting, mood/libido changes) - SHORTER-ACTING (needs to be taken at the same time each day)

Question 62

why is the OCP preferred in some cases to the POP?

Answer 62

POP has to be taken at the same time every day to ensure efficacy = shorter-acting (!!) compared to OCPwho

Question 63

which is more suitable for women who are breastfeeding: OCP, or POP?

Answer 63

POP - can be used when breastfeeding

Question 64

give examples of the most common long-acting reversible contraceptives (LARCs)

Answer 64

1) intra-uterine devices (i.e. copper coils) 2) intra-uterine systems 3) progesterone-only injectables or subdermal implants

Question 65

which is the most suitable contraceptive for nulliparous (no previous children) women and why?

Answer 65

copper coil - prevent implantation - rarely cause ectopic pregnancy - good emergency contraception

Question 66

what must be done before copper coil insertion?

Answer 66

exclude STIs and do a cervical screening test

Question 67

explain how an IUD (intra-uterine device) works

Answer 67

i.e. Copper coil = works by mechanically preventing implantation + decreasing sperm & egg survival

Question 68

how long do IUDs last and what are the implications of it?

Answer 68

last approx 5-10 years implications - can cause heavy periods - can come out in the first three months w periods (5%)

Question 69

explain how IUS (inttra-uterine systems) work

Answer 69

e.g. Mirena coil = secrete progesterone that will 1) thin the uterine lining 2) thicken the cervical mucus (can also help w heavy periods)

Question 70

how long do IUS last and when can they also be used, apart from contraception?

Answer 70

last 3-5 years (fewer years compared to IUDs) can also be used to treat heavy periods (as IUS secrete progesterone)

Question 71

what is the most effective form of emergency contraception and how?

Answer 71

copper coil (i.e. intra-uterine device - IUD) - can be fitted up to 5 days after unprotected sex

Question 72

what two emergency contraceptive pills are available?

Answer 72

1) ulipristal acetate 30mg | 2) levonorgestrel 1.5mg

Question 73

how does ulipristal acetate work as an emergency contraceptive?

Answer 73

30mg tablet - must be taken within FIVE days of unprotected sex - stops progesterone from working normally and prevents ovulation

Question 74

how does levonorgestrel work as an emergency contraceptive?

Answer 74

1.5 mg tablet - must be taken within THREE days of unprotected sex - synthetic progesterone that prevents ovulation

Question 75

which is less effective: ulipristal acetate or levonorgestrel?

Answer 75

levonorgestrel 1.5mg | = least effective (esp if BMI > 27kg/m2)

Question 76

what are the side effects of emergency contraceptive pills?

Answer 76

abdominal pain, nausea, headache | other medication an interfere w this

Question 77

what factors must be considered when choosing a form of contraception?

Answer 77

1) risk of VTE/stroke/CVD 2) comorbidities 3) other conditions that may benefit form contraception choice (menorrhagia, endometriosis, PCOS) 4) need to prevent STIs 5) concurrent medication (interactions, teratogenic drugs)

Question 78

in which scenarios are OCPs avoided?

Answer 78

- stroke/CVD history - heavy smokers - diabetes w complications - liver cirrhosis

Question 79

what are the symptoms of menopause?

Answer 79

hot flushes sweating disturbed sleep + mood low libido vaginal dryness joint & muscle aches absent/irregular periods

Question 80

define peri-menopausal

Answer 80

within 12 months of last menstrual period (LMP)

Question 81

define post-menopausal

Answer 81

after 12 months of LMP

Question 82

summarise the main risks of hormone-replacement therapy

Answer 82

1) risk of VTE 2) hormone-related cancers (breast, endometrial, ovarian) 3) risk of CVD 4) risk of stroke

Question 83

what can HRT increase the risk of in terms of VTE?

Answer 83

1) DVT (deep vein thrombosis) | 2) PE (pulmonary embolism)

Question 84

in which two forms can oestrogen HRT be taken?

Answer 84

oral or transdermal

Question 85

for patients at an increased risk of VTE, are oral or trasndermal oestrogens better and why?

Answer 85

oral = oestrogen ingested + undergoes first pass metabolism in the liver transdermal = delivered directly into circulation so transdermal > oral, as latter interferes w clotting factors in the liver and so increases the risk of vte

Question 86

what do oral oestrogens increase and when should they be avoided in particular?

Answer 86

increase SHBG (binds to oestrogen inactivating it), triglycerides and CRP = should be avoided in patients w BMI > 30kg/m2

Question 87

does HRT increase the risk of breast cancer? | explain

Answer 87

- combined HRT increases risks more than oestrogen only - continuous administration worse than sequential doses (risk related to duration of treatment and reduces after stopping) *assess risk in each individual before prescribing*

Question 88

does HRT increase the risk of ovarian cancer?

Answer 88

small increase in risk after long-term use

Question 89

does HRT increase the risk of CVD?

Answer 89

- no increased risk if started before the age of 60 years | - only increased risk if started 10 years after menopause

Question 90

does HRT increase the risk of stroke?

Answer 90

only small increase in risk when 1) oral oestrogen > trajsdermal oestrogen 2) combined HRT > oestrogen HRT

Question 91

what are progestogens

Answer 91

any substance that will successfully bind to and interact with the progesterone receptors in the body including: 1) the natural hormone, progesterone 2) synthetic progestins

Question 92

what precautions must be taken to reduce the risk of endometrial cancer and why?

Answer 92

if oestrogen is prescribed (HRT) = causes growth and proliferation of the endometrium = can lead to endometrial hyperplasia and endometrial cancer to prevent this, must prescribe PROGESTOGENS (!!) = will act to oppose the proliferative actions of oestrogen and thin the endometrial lining, reducing endometrial hyperplasia

Question 93

how often does HRT safety need to be assessed?

Answer 93

assess HRT safety + efficacy at 3 months and then annually

Question 94

is bleeding normal in patients on HRT?

Answer 94

- unscheduled bleeding is common in the first 3 months | - post-menopausal bleeding could indicate endometrial cancer

Question 95

what are the benefits of HRT in menopause?

Answer 95

1) relieve the symptoms of low oestrogen (i.e. disturbed sleep/mood, hot flushes, sweating, decreased libido) 2) less osteoporosis-related fractures

Question 96

define cisgender

Answer 96

same sex and gender (both align)

Question 97

define gender non-conforming

Answer 97

when sex and gender do not both align | when this causes stress = gender dysphoria

Question 98

define non-binary

Answer 98

gender does not match to traditional binary gender understanding = includes agender, bigender, pangender, gender fluid

Question 99

define transgender

Answer 99

transitioning physical appearance from one gender to another

Question 100

define transgender man

Answer 100

female sex at birth, but male gender now

Question 101

what is more common: transgender men or transgender women?

Answer 101

transgender women x3 more common than transgender men

Question 102

how are prepubertal young people wanting to transition gender managed?

Answer 102

1) GnRH agonist (continuous administration) for pubertal suppression THEN 2) administration of sex steroids THEN (after hormonal therapy for 1-2 years) 3) gender reassignment surgery

Question 103

how are hormones masculinised for trasngender men?

Answer 103

1) testosterone injection + gels (but SIDE EFFECTS: OSA, low HDL, polycythaemia) 2) progesterone to suppress menstrual bleeding if required

Question 104

how do patients respond to hormone masculinisation for transgender men?

Answer 104

- balding - deeper voice - acne - coarser, more facial + body hair - changes in the distribution of body fat - menstrual cycle stops - increased muscle mass + strength - enlargement of the clitoris

Question 105

how are hormones feminised for trasngender women?

Answer 105

1) oestrogen (transdermal, oral, IM) | 2) reduce testosterone (GnRH agonists, anti-androgen medication)

Question 106

how is oestrogen given when feminising hormones for transgender women?

Answer 106

high dose oestrogen e.g. 4-5mg per day to aim for oestradiol levels of 734 pmol/L

Question 107

what are the side effects of giving oestrogen when feminising hormones for transgender women?

Answer 107

risk of - VTE - stroke - CVD - high triglycerides - hormone-sensitive cancers (breast, ovarian, endometrial)

Question 108

how is testosterone reduced when feminising hormones for transgender women?

Answer 108

either 1) GnRH agonist (to desensitise the HPG axis and inhibit LH/FSH secretion) OR 2) anti-androgen medication (spironolactone)

Question 109

how do patients respond to hormone feminisation for transgender women?

Answer 109

** height, voice and Adam's apple don't change ** - softer skin - changes in body fat distribution - breast development - decrease in testicular size - hair may become softer and finer

Question 110

how is oocyte count tested for?

Answer 110

test AMH (anti-Mullerian hormone) = fewer eggs, fewer follicles, lower AMH levels

Question 111

how can non-endocrine causes of infertility be investigated in women?

Answer 111

hysterosalpingogram | = X-ray scan to look at the uterus and fallopian tubes

Question 112

explain the link between weight gain and androgen production

Answer 112

weight gain = increased adipose tissue = increased insulin resistance = increased compensatory insulin secretion = hyperinsulinaemia = causes excess testosterone production in the ovaries

Question 113

explain the link between weight gain and androgen production

Answer 113

weight gain = increased adipose tissue = increased insulin resistance (can lead to further weight gain) = increased compensatory insulin secretion = hyperinsulinaemia = causes excess testosterone production in the ovaries