4.2 Sex Steroid Pharmacology

Question 1

What are sex steroids synthesised from?

Answer 1

Cholesterol

Question 2

How do steroid hormones exert their effects?

Answer 2

Classic nuclear receptors

Exerts effects through gene transcription

But also a membrane receptors

Question 3

What are the major effects of oestrodiol?

Answer 3

Stimulates growth of the endometrium and breast

Stimulates production of progesterone

Actions

• mild anabolic
• sodium and water retention
• raised HDL, lower LDL
• decreased bone resorption
• impaired glucose tolerance
• increase blood coagulability

Question 4

What are the major effects of progesterone?

Answer 4

Stimulates growth of the endometrium and breast

Maintains pregnancy

Inhibits production of ER

actions

• secretory endometrium
• anabolic
• increase bone mineral density
• fluid retention
• mood changes
• maintain pregnancy

Question 5

What are the major roles of testosterone?

Answer 5

Stimulates male characteristics

Hairy body

Deep voice

Anabolism

Aggression

acne

Question 6

what are the side effects of oestrogen?

Answer 6

breast tenderness
nausea, vomiting
water retention
increased blood coagulability
thromboembolism 
impaired glucose tolerance
endometrial hyperplasia and cancer
ovarian metaplasia and cancer
breast hyperplasia and cancer

Question 7

what are the side effects of progesterone?

Answer 7

weight gain
fluid retention
anabolic
acne
nausea/vomiting
irritability depression, PMS 
lack of concentration

Question 8

what are the side effects of testosterone?

Answer 8

metabolic - adverse effects on lipid profiles, particularly the HDL-C/LDL-C ratio, hence increased risk of atherosclerotic disease in males

Question 9

what are the main pharmacokinetic points of oestrogen?

Answer 9

• natural and synthetic oestrogen well absorbed in the GI tract
• also readily absorbed from skin and mucous membranes
• metabolism = liver
• excretion = in the urine as glucuronides and sulphates

Question 10

what are the main pharmacokinetic points of progesterone?

Answer 10

injected progesterone is bound to albumin with some stored in adipose tissue

metabolised by the liver

metabolites excreted in the urine conjugated to glucuronic acid

Question 11

what are the adverse effects of the combined pill?

Answer 11

• risk of thromboembolism is small
• smoking increases this risk substantially
• also for long term use in women over 35
• consider other risk factors e.g obesity and hypertension

Question 12

what are the COCP and POP contraceptives metabolised by? what can effect their efficacy as a result?

Answer 12

COCP and POP are metabolised in the liver by CYP 450

Therefore, efficacy is reduced by enzyme inducing drugs

e. g anti-epileptics such as carbamazepine or phenytoin
e. g antibiotcs such as rifampicin and rifabutin
e. g some natural products such as St johns wort

because they all INCREASE the production of hepatic CYP450

Question 13

how do soya protein products effect oestrogen absorption?

Answer 13

enhance oestrogen absorption and reduce its storage in adipose tissue and muscle

as a result, cause the half life to be reduced from 15 to 7 hours

Question 14

why would you prescribe hormone replacement therapy to a menopausal woman?

Answer 14

symptom management e.g hot flushes/sweats and dyspareunia

osteoporosis prevention

HOWEVER: not good for the prevention of heart disease and shouldn’t be prescribed for that

Question 15

what steroid can be used in hormone replacement therapy and how is it administered?

Answer 15

oestrodial

administered

• orally
• transdermally
• implant
• transvaginally
• nasally

Question 16

what are the risks of hormone replacement therapy?

Answer 16

• (ERT) unopposed oestrogen = increased risk of developing endometrial and ovarian cancers
• (HRT) opposed oestrogen = increased risk of developing breast cancer
• increased risk of venous thromboembolism
• cardiovascular disease
• increased risk of stroke

Question 17

how does hormone replacement therapy have adverse effects on the thromboembolism profile?

Answer 17

increased activated protein c resistance

increased thrombin activation

decreased anti thrombin III activity

decreased protein S levels

Decreased factor VII levels

decreased tissue factor pathway inhibitor

Question 18

how does hormone replacement therapy have a beneficial effect on the lipid profile?

Answer 18

increased HDL-c
decreased oxoLDL-c
decreased triglyceride
decreased lipoprotein (a)

Question 19

what is Mifepristone (RU486)?

Answer 19

progesterone (and glucocorticoid) receptor antagonist

acts as a anti-progesterone

sensitising the myometrium to prostaglandin-induced contractions

used for termination of pregnancy

Question 20

what is a SERM?

Answer 20

a selective oestrogen receptor modulator

consists of pure agonists and pure antagnoists that act on oestrogen receptors

are distinct in having varying effects in differing tissues

drugs in this class have important clinical usage 
e.g tamoxifen, raloxifene

Question 21

give an example of three Selective oestrogen receptor modulators

Answer 21

clomiphene
Tamoxifen
Raloxifene

Question 22

what is clomiphene?

Answer 22

a selective oestrogen receptor modulator (SERM)

used in the treatment of anovulation

competes with oestrogen for ER binding

leads to ovulation induction through increased production of anterior pituitary hormones

Question 23

what is tamoxifen and how does it act?

Answer 23

It is a selective oestrogen receptor modulator (SERM)

has little affinity for oestrogen receptor

metabolised in liver to active derivatives which then compete with oestrogen for binding to the ER

in endometrium, acts as an ER agonist
in breast, acts as ER antagonist (causes cells to arrest in the cell cycle)

Question 24

what is ulipristal acetate?

Answer 24

a selective progesterone receptor modulator

when used for emergency contraception, the primary mode of action is thought most likely to be delay or inhibition of ovulation

also effective for the treatment of uterine fibroids