Drugs affecting Reproduction

Question 1

List 3 locations whereby oestrogen is produced

Answer 1

• Ovary
  
- Placenta
  
- Adrenal cortex
  
- Testis

Question 2

List the 3 main endogenous oestrogens in humans.

Answer 2

• Oestradiol (most potent and 1º secreted from ovaries)
  
- Oestrone
  
- Oestriol

Question 3

Outline the MOA by which oestrogens induce their effect.

Answer 3

Oestrogens bind: 1) nuclear receptor (ERa/ERß) to ∆ gene transcription ; 2) GPER membrane receptors to mediate rapid vascular actions 


Question 4

Give 3 therapeutic uses of Oestrogen

Answer 4

HRT

Contraception

Prostate/Breast Ca

Feminisation

Question 5

List 3 ways Oestrogen can be administered.

Answer 5

• Oral
• Transdermal
• Intramuscular
• Implantable
• Topical

Question 6

What is a SERM?

Answer 6

Competitive antagonists or partial agonists of oestrogens

Question 7

Give an example of a SERM.

Answer 7

Tamoxifen: Oestrogen-dependent breast Ca with anti-oestrogenic effect on tissue

Raloxifene: Post-menopausal OP, anti-oestrogenic effects on breast and uterus but oestrogen on bone

Clomiphene: Oestrogen antagonist at hypothalamus and pituitary to block negative feedback mediated by oestrogen = increase GnRH and FSH/LH causing ovulation

Question 8

Which enzyme converts cholesterol to pregnenolone?

Answer 8

CYP11A1

Question 9

Which enzyme converts pregnenolone to 17a-hydroxypregnenolone?

Answer 9

17a-hydroxylase

Question 10

Which enzyme converts 17a-hydroxypregnenolone to DHEAS/Andreostenediol?

Answer 10

17,20 lyase

Question 11

Which enzyme converts 17a-hydroxypregnenolone to 17a-hydroxyprogesterone?

Answer 11

3ß-HSD

Question 12

What enzyme converts DHEAS to Androstenedione?

Answer 12

3ß-HSD

Question 13

What enzyme converts Androstenediol to Testosterone?

Answer 13

3ß-HSD

Question 14

What enzyme can convert androstenedione or testosterone to estrone and estradiol ± estriol?

Answer 14

Aromatase

Question 15

What enzyme converts testosterone to Dihydrotestosterone?

Answer 15

5a-reductase

Question 16

What is the drug target in its MOA for Finasteride?

Answer 16

5a reductase

Question 17

What is the drug target in its MOA for Anastrazole?

Answer 17

Aromatase

Question 18

Which enzyme can convert deoxycorticosterone to corticosterone?

Answer 18

11ß-hydroxylase

Question 19

Which enzyme an convert 11-deoxycortisol to cortisol?

Answer 19

11ß-hydroxylase

Question 20

Which enzyme converts progesterone to deoxycorticosterone?

Answer 20

21a-hydroxylase

Question 21

Which enzyme converts 17a-hydroxyprogesterone to 11-deoxycortisol?

Answer 21

21a-hydroxylase

Question 22

Which enzyme converts progesterone to 17a hydroxyprogesterone?

Answer 22

17a-hydroxylase

Question 23

Outline 3 sources of Progesterone in the body.

Answer 23

Corpus luteum
Placenta
Testis
Adrenal cortex

Question 24

Outline the mechanism of action of Progesterone.

Answer 24

Acts on Progesterone Receptor (PR) to ∆ gene transcription in target tissues

Question 25

Give an example of a natural progesterone and a testosterone-derivative

Answer 25

Natural: Hydroxyprogesterone, medroxyprogesterone, dydrogesterone - Inactive orally b/c presystemic hepatic metabolism Administration: IM or topical Testosterone-derivatives: Norethisterone, norgestrel, ethynodiol 
 - Absorbed orally

Question 26

Give 3 effects of Progesterone

Answer 26

Inhibit oestrogen synthesis Maintenance of endometrium Stimulate glands in endometrium and mammary milk gland development

Question 27

Give 3 adverse effects of Progesterone Rx.

Answer 27

``` Acne Fluid retention Weight gain Depression Change in libido Breast discomfort Menstrual cycle irregularity Increased VTE % ```

Question 28

What is anti-progestogen?

Answer 28

Progestogen antagonist

Question 29

Give an example of an anti-progesterone used in medical ToP.

Answer 29

Mifepristone

Question 30

In the COCP, what two elements are involved?

Answer 30

Oestrogen Progesterone E.g. Drospirenone/Ethinylestradiol

Question 31

What is the standard regime of COCP.

Answer 31

21 days + 7 day break

Question 32

Outline the MOA of COCP

Answer 32

Oestrogen: negative feedback at Hyp and Ant. Pituitary to reduce GnRH and FSH/LH thus reduced development of ovarian follicle and ovulation; Build up of endometrium 
 Progestin: Inhibit LH secretion and prevent ovulation; Maintenance of endometrium + endometrium glands; mucous plug at cervix

Question 33

Give 3 adverse effects of the COCP.

Answer 33

``` Mild nausea Flushing Dizziness Bloating Weight gain Skin changes (acne or pigmentation) Depression Amenorrhoea or variable duration ``` VTE

Question 34

Give an example of a Progesterone Only Pill (POP)

Answer 34

Norethisterone Levonorgestrel Ethynodiol diacetate

Question 35

Outline the regime of a POP.

Answer 35

Daily | No disruption

Question 36

Which form of contraception is more effective, COCP or POP?

Answer 36

COCP

Question 37

A 21 year old girl presents after an UPSI 48 hours ago and seeks a form of contraception. What would you give? When would you need to give it by? How would this be administered

Answer 37

Levonorgestrel ± oestrogen < 72 hours Oral

Question 38

State 3 forms of LARCs and explain what is given for each

Answer 38

1) IUS: Levornogestrel from T-shaped tube in uterus releasing progestogen to prevent implantation + thicken cervical mucous + thin endometrium to prevent implantation 2) IUD: Copper Plastic and Copper device implanted in uterus presenting sperm survival 3) IM Injection: Medroxyprogesterone acetate to prevent ovulation and thicken cervical mucus plug 4) SC Implant: Levornorgestrel administration via flexible subcutaneous rod in upper arm releasing progesterone to stop ovulation and thicken cervical mucus and thinning of uterus to prevent implantation

Question 39

Give 5 Sx of the Menopause

Answer 39

``` Hot flushes Headaches Drier mucosal membranes Body and pubic hair become darker Bone loss mass and more fragile Vaginal dryness, itching and shrinking Nipples smaller and flatten Breasts droop and flatten Risk of CVD Teeth loosen and gums recede ```

Question 40

Give 3 sites of production of Androgens in the body.

Answer 40

Leydig cells Adrenal glands Ovaries 


Question 41

Outline the MOA of Androgens

Answer 41

Bind nuclear receptors to ∆ gene expression

Question 42

Give 3 therapeutic uses of Androgens and where they may be used.

Answer 42

Male hypogonadism: IM testosterone injections Prostatic cancer (anti-androgens): Flutamide, cyproterone Benign prostatic hypertrophy (Dihydrotestosterone synthesis inhibitors - 5a-reductase): Finasteride Aplastic anaemia: Anabolic steroids such as nandrolone

Question 43

What are anabolic steroids?

Answer 43

Modified androgens e.g. nandrolone = increase protein synthesis and muscle development

Question 44

Give 3 side effects for anabolic steroids.

Answer 44

Infertility Salt and water retention Coronary heart disease Liver disease

Question 45

What is a GnRH analogue?

Answer 45

GnRH decapeptide analogue to manipulate reproductive axis

Question 46

Give an example of a GnRH analogue

Answer 46

GnRH pump Gonadotropin Gonadorelin Nafarelin

Question 47

What regime would you administer GnRH analogues in?

Answer 47

Pulsatile to stimulate gonadotropins (FSH + LH) and induce ovulation