Reproductive and post-reproductive health

Question 1

What are the different drug groups used in reproductive health?

Answer 1

Sex steroid hormones
Inhibitors and antagonists
Mixed agonist/antagonist

Question 2

Give examples of sex steroid hormones

Answer 2

Oestrogens, progestogens and androgens

Question 3

Give examples of inhibitors and antagonsists

Answer 3

RU486, finasteride

Question 4

Give examples of mixed agonists/antagonists

Answer 4

Selective oesterogen receptor modulators

Selective progesterone receptor modulators

Question 5

What are sex steroids synthesised from?

Answer 5

Cholestrol

Question 6

What is the difference between Estrone and Estradiol?

Answer 6

Estone is more prevalent in post menopausal women whereas Estradiol is the more potent oestrogen present in reproductive life for follicular maturation

Question 7

What are the receptors for steroid hormones? How do they exert their effects?

Answer 7

Classic nuclear receptors

Exert effects via gene transcription, as a transcription factor

Question 8

What additional type of receptor does it have?

Answer 8

Membrane receptor for oestrogen

Question 9

What are the major actions/effects of estradiol?

Answer 9

Stimulates growth of the endometrium and breast
Mild anabolic
Na and H20 retention 
Raises HDL and lowers LDL
Decreases bone reposition
Impairs glucose tolerance
Increased blood coagulability
Stimulates production of progesterone

Question 10

What are the major actions/effects of progesterone?

Answer 10

Stimulates growth of the endometrium and breast
Anabolic
Increases bone mineral density
Fluid retention
Mood changes
Maintains pregnancy
Inhibits production of oestrogen

Question 11

What are the major effects of testosterone?

Answer 11

Male characteristics
Body hair
Acne
Deep voice
Anabolism
Aggression

Question 12

What are the side effects of oestrogen?

Answer 12

Breast tenderness
Nausea/vomiting
Water retention
Increased blood coagulability 
Thromboembolism
Impaired glucose tolerance
Emdometrial hyperplasia and cancer
Breast hyperplasia and cancer
Ovarian metaplasia

Question 13

What are the side effects of progesterone?

Answer 13

Weight gain
Fluid retention
Anabolic 
Acne
Nausea/vomiting
Irritability, depression, PMS
Lack of concentration

Question 14

What are the side effects of testosterone?

Answer 14

Adverse effects of lipid profiles especially the HDL-c/LDL-c ratio
Increased risk of atherosclerotic disease in males

Question 15

Pharmacokinetics of oestrogen: What does it’s absorbability mean for administration?

Answer 15

Natural and synthetic oestrogen are well absorbed in the GI tract so can be given in oral root
OR via patches in skin because readily absorbed from skin and mucus membranes

Question 16

Where is oestrogen metabolised and by what?

Answer 16

Liver by CYP450

Question 17

How is oestrogen excreted?

Answer 17

In the urine as glucoronides and sulphates

Question 18

Pharmacokinetics of progesterone: How is it transported in blood and where is it stored?

Answer 18

Injected progesterone if bound to albumin with some stored in adipose tissue

Question 19

Where is progesterone metabolised and by what?

Answer 19

Liver by CYP450

Question 20

How is progesterone excreted?

Answer 20

In urine conjugated to glucuronic acid

Question 21

What are some adverse effects of the combined pill?

Answer 21

Risk of thromboembolism

Question 22

What risk factors increase the likelihood of the adverse effects?

Answer 22

Smoking
Long term use after 35 years of age
Obesity
Hypertension

Question 23

What enzyme is involved in COCP and POP metabolism

Answer 23

CYP 450 in the liver

Question 24

What reduces the contraceptive efficacy?

Answer 24

Enzyme inducing drugs which increase production of CYP450

Question 25

What are some examples of enzyme inducing drugs?

Answer 25

Anti-epileptics e.g. carbamazepine or phenytoin Antibiotics e.g. rifampicin and rifabutin Natural products e.g. St Johns Wort- anti-depressant

Question 26

What are the effects of soya protein on oral contraceptives?

Answer 26

Enhance oestrogen absorption and reduce its storage in adipose and muscle so cause the T1/2 to bee reduced from 15 to 7 hrs

Question 27

Why prescribe hormone replacement therapy?

Answer 27

To relieve systemic symptoms that are a result of loss of oestrogen and progesterone Osteoporosis

Question 28

What are the routes of HRT administration?

Answer 28

``` Oral Transdermal Implant Transvaginal Nasal ```

Question 29

Risks of taking unopposed oestrogen?

Answer 29

Increased risk of developing endometrial and ovarian cancers

Question 30

Risks of taking HRT: oestrogen and progesterone?

Answer 30

Increased risk of developing breast cancer

Question 31

Why is there an increased risk of venous thromboembolism?

Answer 31

``` Theres increased activated protein c resistance Increased thrombin activation Decreased anti thrombin 3 activity Decreased protein s levels Decreased factor 7 levels Decreased TF pathway inhibitor ```

Question 32

What is Mifepristone (RU486)?

Answer 32

Progesterone receptor antagonist so acts as an anti-progesterone

Question 33

What effect does RU486 have?

Answer 33

Sensitising the myometrium to prostaglandin induced contarctions

Question 34

What is the use of RU486?

Answer 34

For the termination of pregnancy

Question 35

What is a SERM?

Answer 35

Selective estrogen receptor modulator, have varying effects in different tissues

Question 36

What are examples of drugs in the SERM class?

Answer 36

Tamoxifen Raloxifene Clomiphene

Question 37

What is Raloxifene?

Answer 37

Management og post-menopasual osteoporosis- stops acceleration of bone resorption

Question 38

What is clomiphene, what is its use?

Answer 38

Used in the treatment go anovulation

Question 39

What is the mechanism of action of Clomiphene

Answer 39

Competes with oestrogen for ER binding Tricks the pituitary to think there is no oestrogen This increases oestrogen production, and thus increased follicular development

Question 40

What is Tamoxifen?

Answer 40

Pro drug

Question 41

How is Tamoxifen made functional?

Answer 41

Metabolised in the liver to make active derivatives

Question 42

What is the mechanism of action of active Tamoxifen?

Answer 42

Competes with oestrogen for bidding to the ER

Question 43

Why is there so much person to person variability in Tamoxifen effects?

Answer 43

Metabolising enzymes come in various isoforms and so have varying metabolisms

Question 44

Where does Tamoxifen have converse effects?

Answer 44

Breast tissue and endometrial tissue

Question 45

What effect does Tamoxifen have on the endometrium?

Answer 45

Acts as ER agonist

Question 46

What effect does Tamoxifen have on the breast?

Answer 46

Acts as ER antagonist, causes the cell to arrest cycle

Question 47

What is Ulipristal acetate?

Answer 47

Selective progesterone receptor modulator

Question 48

What is Ulipristal acetate?

Answer 48

Used for emergency contraception and used for uterine fibroids

Question 49

What does Ulipristal acetate bind to?

Answer 49

Progesterone receptor