Sex Steroid Hormone Pharmacology Flashcards
How are sex steroid hormones transported
Bound to SHBG and albumin
Binding protects against first pass metabolism
Progesterone does not bind to SHBG - majority undergo first pass metabolism
Oestrogen increases SHBG
What is enterohepatic recirculation of oestrogen
Oestrogen absorbed from GIT pass into liver
Conjugated and excreted into bile
Unconjugated by colonic flora
Absorbed from GIT pass into peripheral circulation
Thus antibiotics altering gut flora can affect oestrogen absorption
What type of receptors do sex steroid hormones act on
Intracellular receptors
Bind to DNA and alter gene transcription and protein synthesis
Give examples of sex steroid receptors
ER alpha, ER beta
PR A, PR B
AR 1, AR2
Why does progesterone activity require oestrogen to be present before
Oestrogen stimulates PR synthesis via ER binding
Action of progesterone requires presence of PR
What are the effects of oestrogen
Endometrial proliferation Breast proliferation PR synthesis Na and water retention Increased blood coaguability Improve lipid profile: high HDL, low LDL Reduce bone resorption Impaired glucose tolerance
What are side effects of oestrogen
Breast tenderness N+V Fluid retention and bloating Increased risk of VTE Endometrial hyperplasia and cancer Breast hyperplasia and cancer Ovarian metaplasia and cancer
What are effects of progesterone
Endometrial maturation and glandular formation Breast growth Inhibit ER synthesis Maintain pregnancy Anabolic Na and water retention Mood changes
What are side effects of progesterone
N+V
Weight gain
Depression/PMS
What are effects of androgens
Deepening of voice
Male pattern hair growth
Aggression
Anabolic
What are side effects of androgens
Poor lipid profile: low HDL, high LDL
Increased risk of atherosclerotic disease
Increased risk of stroke
What are formulations of COCP
Monophasic
Biphasic
Triphasic
Progesterone dose increase in phases during the cycle
What is mechanism of action of COCP
Inhibit ovulation
Progesterone at High dose inhibits positive feedback - thus inhibit LH surge
What are side effects of COCP
Impaired glucose tolerance Hypertension Increase risk of VTE Increased risk of IHD and stroke Increased risk of breast cancer Increased risk of cervical cancer
What are drug interactions of COCP
CYP450 inducers: causes contraceptive failure
Soya proteins: decreases T1/2 by increasing oestrogen absorption and decreasing storage in adipose
What is mechanism of action of POP
Thicken cervical mucus
Low dose progesterone
Give examples of IM progesterone injection
Medroxy Progesterone Acetate
What is mechanism of action of IM progesterone injection
Inhibit ovulation
Thicken cervical mucus
12 weeks
Give examples of intradermal progesterone depot
Etonogestrel
What is mechanism of action of etonogestrel
Inhibit ovulation
Thicken cervical mucus
What is levonorgestrel
Progesterone receptor modulator
What are indications of levonorgestrel
Emergency contraceptive - 72hrs UPSI
Intrauterine system
What is mechanism of action of levonorgestrel
Emergency: inhibit ovulation and implantation
IUS: inhibit endometrial proliferation, thicken cervical mucus
What is Ulipristal acetate
Selective progesterone receptor modulator
What are indications of ulipristal acetate
Emergency contraception - within 120hrs UPSI
What is mechanism of action of Ulipristal acetate
Inhibit ovulation
What are the types of hormone replacement therapy
HRT: oestrogen and progesterone
ERT: oestrogen only
What is mechanism of action of HRT
Relieve post menopausal symptoms:
Flushing
Atrophic vaginitis
Osteoporosis
What are side effects of HRT
ERT: Increased risk of endometrial cancer
Increased risk of breast cancer
Increased risk of VTE (oral admin only)
Increased risk of stroke
Improved lipid profile (but NOT used for purpose of preventing CVD)
What are contraindications of HRT
ERT in women wo hysterectomy
Give examples of oestrogen receptor blockers
Clomiphene
Tamoxifen
Raloxifene
What is mechanism of action of Clomiphene
ER Antagonist at hypothalamus and pituitary
Inhibit negative feedback
Increase GnRH and LH/FSH release
Increase oestrogen and progesterone release
What are indications of clomiphene
Infertility
Induce ovulation
What is mechanism of action of tamoxifen
Selective oestrogen receptor modulator
ER Agonist at bone and endometrium
ER Antagonist at Breast
Inhibit proliferation of myoepithelial cells in breast
What are indications of Tamoxifen
Oestrogen receptor positive breast cancer
What is mechanism of action of Raloxifene
Selective oestrogen receptor modulator
Agonist at bone and endometrium
Antagonist at Breast
What are indications of Raloxifene
Osteoporosis
Breast cancer
What are examples of anti-progestins
Mifepristone
What is mechanism of action of Mifepristone
Progesterone receptor Partial agonsist
Acts as an antagonist in high levels of progesterone
What are indications of Mifepristone
Terminate pregnancy
Induce labour
Give examples of anti-androgens
Cyproterone
What is mechanism of action of cyproterone
Act as partial agonist at Progesterone receptor
Have weak progesteronergic effect
What are indications of cyproterone
In COCP
Give examples of testosterone replacement therapy
Finasteride
What is mechanism of action of Finasteride
5alpha reductase inhibitor
Inhibit breakdown of testosterone to 5alpha-DHT
What are indications of Finasteride
Male hair loss
BPH
