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gender affirming pharmacotherapies Flashcards

1
Q

what are the most commonly used puberty blockers

A

gonadotropin-releasing hormone (GnRH) agonists

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2
Q

what do gonadotropin-releasing hormone agonists do

A

inhibit release of sex hormones e.g. testosterone and oestrogen

prevent actions of luteinizing hormone (LH) and
follicle stimulating hormone (FSH)

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3
Q

where is gonadotropin-releasing hormone (GnRH) produced

A

cells in hypothalamus

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4
Q

gonadotropin-releasing hormone (GnRH) is a decapeptide. what is this

A

ten amino acids in size

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5
Q

when gonadotropin-releasing hormone (GnRH) is produced, where does it go

A

released into small blood vessels, carried to pituitary gland

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6
Q

how do gonadotropin-releasing hormone (GnRH) change throughout childhood

A

low in childhood
inc as puberty begins

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7
Q

what occurs when gonadotropin-releasing hormone (GnRH) reaches the pituitary gland

A

gonadotropin-releasing hormone (GnRH) activates its receptor, gonadotropin-releasing hormone receptor (GnRHR)

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8
Q

what is the gonadotropin-releasing hormone (GnRH) receptor called

A

gonadotropin-releasing hormone receptor (GnRHR)

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9
Q

what is the gonadotropin-releasing hormone receptor (GnRHR)

A

seven transmembrane GPCR

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10
Q

what does gonadotropin-releasing hormone receptor (GnRHR) activation lead to

A

release of:

luteinizing hormone (LH)
follicle stimulating hormone (FSH)

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11
Q

what function does luteinizing hormone (LH) and follicle stimulating hormone (FSH) have in males

A

signal for testes to produce testosterone and produce sperm

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12
Q

what does testosterone stimulate

A

secondary sex characteristics e.g. penis, scrotum, facial hair growth

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13
Q

what function does luteinizing hormone (LH) and follicle stimulating hormone (FSH) have in females

A

signal ovaries to produce oestrogen hormones e.g. oestradiol and regulate menstrual cycle

stimulate development of secondary sexual characteristics e.g. breast development/ hips broadening

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14
Q

what is an example of an oestrogen hormone

A

oestradiol

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15
Q

what are other examples of puberty blockers (4)

A

goserelin
histrelin
leuprolide
triptorelin

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16
Q

what are puberty blockers traditionally used in

A

treatment of breast or prostate cancers

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17
Q

how do gonadotropin-releasing hormone (GnRH) agonists work

A

diretly stimulating the gonadotropin-releasing hormone receptor (GnRHR) in the pituitary gland

do not quickly dissociate

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18
Q

what is the initial impact of the gonadotropin-releasing hormone (GnRH) agonist binding to the gonadotropin-releasing hormone receptor (GnRHR)

A

flare effect

up to 10 fold increase in luteinising hormone
up to 2 fold increase in follicle stimulating hormone

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19
Q

what is the impact of the gonadotropin-releasing hormone (GnRH) agonist binding to the gonadotropin-releasing hormone receptor (GnRHR) after continuous administration

A

decrease in luteinising hormone and follicle secreting hormone

via receptor downregulation by internalisation of receptors

gonadotropin-releasing hormone receptors (GnRHR) removed from cell surface in pituitary gland, cannot interact with agonist anymore

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20
Q

result of The Cass Review

A

NHS england - puberty blockers not routine treatment for children with gender dysphoria

BMA - disagreed, calling for ban to be lifted

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21
Q

other than as a puberty blocker, what other role does gonadotropin-releasing hormone (GnRH) have

A

supressing endogenous sex hormone production

switch off body’s sex hormone production, cross sex hormones can be administered

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22
Q

in MTF, which gonadotropin-releasing hormone (GnRH) are injected to reduce testosterone production 2

A

goserelin
leuprorelin

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23
Q

why does administration of oestrogen lower testosterone

A

negative feedback in hypothalamic pituitary gonadal axis

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24
Q

why do MTF require anti androgen medication after oestrogen admin

A

testosterone levels are decreased to be low for a male but above normal range for a female after oestrogen admin alone

further inhibits testosterone

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25
Q

examples of anti-androgen medication aka MTF (3)

A

spironolactone
finasteride
cyproterone

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26
Q

what is spironolactone

A

mild antiandrogen

androgen receptor (AR) competitive antagonist

competes with androgen

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27
Q

what is the androgen receptor a target for (2)

A

testosterone

more potent androgen dihydrotestosterone (DHT) - produced from testosterone

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28
Q

what other function does spironolactone have

A

reduce effects of androgens produced by adrenal glands as well as testes

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29
Q

what can a high dose of spironolactone induce

A

breast development, feminization, lack of spontaneous erections

30
Q

what is cyproterone

A

anti androgen

acts as an androgen receptor antagonist

helps counteract flare effect of gonadotropin-releasing hormone (GnRH) agonists, reduces testosterone surge

31
Q

what is finasteride

A

inhibitor of enzyme 5α-reductase

32
Q

what is the enzyme 5α-reductase responsible for

A

converstion of testosterone into DHT (more potent androgen)

33
Q

what gonadotropin-releasing hormone (GnRH) agonists are injected for FTM (2)

A

goserelin
leuprorelin

34
Q

examples of oestrogen blockers for FTM (2)

A

tamoxifen (oestrogen receptor antagonists)

anastrozole (aromatase inhibitors)

35
Q

what does endogenous oestrogen bind to

A

oestrogen receptor (ER)

36
Q

what occurs once the ER-oestrogen receptor complex is formed

A

translocates to nucleus

activates gene transcription and translation of oestrogen-regulated genes

37
Q

tamoxifen mechanism of action

A

selective oestrogen receptor modulator - certain tissues e.g. dec breast tissue

oestrogen receptor antagonist, prevents oestrogen binding/ activating

reduces oestrogen effects

38
Q

what is anastrozole FTM mechanism of action

A

aromatase enzyme inhibitor

aromatase coverts androgens to oestrogens

inhibitor thus reduces oestradiol and inc testosterone levels

39
Q

what GnRH agonists are used MTF

A

goserelin
leuprorelin

40
Q

what GnRH agonists are used FTM

A

goserelin
leuprorelin

41
Q

what cross sex hormones are used MTF

A

oestrogens

42
Q

what cross sex hormones are used FTM

A

testosterone

43
Q

what hormone receptor antagonists are used MTF

A

spironolactone
cyproterone

44
Q

what hormone receptor antagonists are used FTM

45
Q

what hormone production inhibitors are used MTF

A

finasteride

46
Q

what hormone production inhibitors are used FTM

A

anastrozole

47
Q

risks/ side effects of testosterone therapy

A

polycythaemia - inc rbc in blood

48
Q

risks/ side effects of oestrogen therapy

A

venous thromboembolisms (VTE)

49
Q

risks/ side effects of both oestrogen and testosterone therapy

A

inc cvd risk

inc development of type 2 diabetes

impaired fertility

50
Q

what is aromatase

A

enzyme

converting androgens (male sex hormones) into estrogens (female sex hormones)

51
Q

MTF effects

A

redistrubution of body fat

dec muscle mass

softer less oily skin

testicular atrophy

breast development

52
Q

FTM effects

A

vaginal atrophy

cessation of menses

clitoral enlargement

increased muscle mass

deepening of voice

53
Q

world professional association for transgender health (WPATH)

A

advocates for informed consent prior to hormone therapy

encourages puberty blockers before surgical change in childhood as puberty blockers are reversible

54
Q

how is goserelin administered

A

subcutaneous implant in abdominal wall

55
Q

histrelin

A

gonadotropin-releasing hormone analog

suppresses sex steroid production

56
Q

oestradiol administration vs oestrogen administration

A

serum estradiol is easier monitored

but, more expensive than oestrogen admin

57
Q

oestradiol administration side effects

A

inc. insulin resistance

inc. weight gain

58
Q

transdermal oestradiol

A

bypasses hepatic 1st pass metabolism, avoids liver reduces clotting, so reduces thromboembolic risk

59
Q

ethinylestradiol

A

oral synthetic estrogen

inc first pass metabolism, inc thromboembolic risk

60
Q

oral testosterone

A

inc liver toxicity risk due to inc liver enzyme levels

transdermal/ parenteral admin preferred

61
Q

monitoring

A

continuous screening and monitoring of hormone levels

cervical cancer screening if cervical tissue present

62
Q

summarise puberty blockers

A

GnRH agonists - safe, efficacious way to inhibit development of secondary sex characteristics

anti-androgens - facilitate development of feminising characteristics - less cost effective than GnRH and also is more commonly used comcomitantly with estrogen therapy

cross sex hormones - induce secondary sexual characteristics after piberty blockers used

63
Q

ethical considerations - 4

A

informed consent, esp in minors as side effects may occur, esp long term ones

avoids gender affirming surgeries later in life e.g. chest reconstruction

Pediatric Health, Medicine, and Therapeutics journal - GRH agonist histrelin is effective, checking serum hormone level monitoring vital/access is limited - expensive, relevant as gender dysphoria inc risk of anxiety, depression

Journal of Health ethics article - treatment be initiated when the patient is in the stage where a child has had some
experience of his/her biological gender and can therefore make a logical decision

64
Q

Leuprolide admin

A

intramuscular injection

65
Q

Supprelin or Histrelin admin

A

implant under dkin, releases agent over period of one year

66
Q

GnRH Agonists mechanism of action

A

gonadotropin-releasing hormone (GnRH) produced in hypothalamus, carried via blood vessel to GnRHR

GnRH agonist stimulating the gonadotropin-releasing hormone receptor (GnRHR) in the pituitary gland, same effect

downregulation

decrease in luteinising hormone and follicle secreting hormone

suppress release of gondotropins LH FSH from pituitary gland

dec in sex hormones (testosterone or estrogen)

(GnRHR) removed from cell surface in pituitary gland, cannot interact with agonist anymore

in MFT, usually used before estrogen therapy

67
Q

anti androgen spironolactone mechanism of action

A

aldosterone antagonist, also blocks androgen receptors

dec testosterone

68
Q

how are cross sex hormones admin

A

basically estrogen therapy is usually with anti androgens

testosterone therapy is usually after GnRH agonist to suppress endogenous oestrogen production

69
Q

main types of med classes we gaf about - 4

A

cross sex hormones

puberty blockers - gonadotropin-releasing hormone (GnRH) agonists

anti androgen medication post oestrogen admin aka testosterone blockers and antag

oestrogen blockers and antag

70
Q

meds for each class we gaf about - 11

A

cross sex hormones - oestradiol, oestrogen, testosterone

puberty blockers - goserelin, histrelin, leuprolide, triptorelin

anti androgen med - spironolactone, cyproterone ( aldosterone and androgen receptor antag)

oestogen blockers - tamoxifen (oes antag), anastrozole (aromatase inhibitors)

71
Q

extra we gaf about

A

ethinylestradiol

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