Pharmacology of Reproductive Hormones

Question 1

what are the most common uses of reproductive hormones?

Answer 1

• contraception/infertility
• hormone replacement therapy
• cancer (breast, prostata)

Question 2

discuss the female hypothalamus-pituitary-gonadal axis

Answer 2

The hypothalamus releases GnRH
Acts on anterior pituitary and releases FSH and LH

FSH released mainly in the first half of the cycle and LH mainly in the second half of the cycle
these cause the ovaries to produce oestrogen and progesterone

With progesterone it is a simple feedback loop so at relatively high concentrations you have a shutdown

for oestrogen it is more complicated. at low concentrations oestrogen also has negative feedback loop - shuts down secretion of LH and FSH but when levels of oestrogen are high for a relatively long period then positive feedback loop is present

Question 3

discuss the male hypothalmao-pituitary- gonadal axis

Answer 3

in the male the hypothalamus releases GnRH which acts on anterior pituitary which stimulates the secretion of FSH and LH

FSH stimulates gametogenesis
LH stimulates the synthesis of testosterone

the testosterone has a negative feedback action at hypothalamus and anterior pituitary - simple negative feedback loop

Question 4

discuss the action of GnRH

Answer 4

Action: stimulate gonadotropin release

Pulsatile: 
- low frequency: FSH release
- high frequency: LH release 
- Continuous: (non-physiological):
  desensitises GnRH receptors and inhibits FSH and LH release

Question 5

Name the GnRH agonists

Answer 5

Gonadorelin
Leuprorelin
Nafarelin

Question 6

what are the uses of GnRH receptor agonists

Answer 6

Pulsatile dosing:
- promotes ovulation in infertility (rare)

Continuous dosing: desensitises the receptors and suppresses the release of FSH and LH

• endometriosis - growth of endometrial tissue outside the uterine cavity
• breast and prostate cancer (these cancers are dependent on oestrogen in breast and testosterone dependent prostate)
• suppress FHS and LH release (IVF)

Question 7

name the GnRH antagonists

Answer 7

Ganirelix
Cetrorelix
Degarelix

have same use as continous dosage of GnRH - however - advantage is that you prevent the initial flair of FSH and LH release

Question 8

what is the use of GnRH antagonists

Answer 8

Uses:
- suppress FSH and LH release (IVF) - used in IVF clinics to suppress the endogenous synthesis of gonadotropins so as to be able to control the timings of various hormones to control ovulation very carefully

• antiandrogen therapy for prostate cancer

Question 9

which hormone is detected in the pregnancy test

Answer 9

hCG

Question 10

name the gonadotropin preparations

Answer 10

menotropins - hMG
urofollitropin/follitropin - rFSH
lutropin (rLH)
choriogonadtropin (rhCG)

Uses: - male infertility (pituitary insufficiency)
- ovulation induction - IVF

Question 11

which structures produce oestrogen

Answer 11

follicle, Corpus luteum and the placenta

Question 12

describe the oestrogen receptor

Answer 12

Nuclear Receptor
ligand activated transcriptional factors: receptor is intracellular, causes dimerisation of the activated receptor and therefore the receptor is able to translocate into the nucleus

Question 13

discuss the actions of oestrogen

Answer 13

1. female development: in utero and at puberty
2. feedback action: negative feedback action at low concentrations they have a positive feedback action
3. stimulate - edometrial proliferatuve phase in the first half of the cycle
   - fertilisation - favouring cervical secretion (increased volume, and decreased viscosity) - allows sperm to travel easily and allows penetration of sperm
4. metabolic - anabolic and retention of salt and water

Question 14

what are the uses of oestrogen

Answer 14

Uses:

• contraceptions
• hormone replacement therapy

Question 15

what is the oestrogen antagonist

Answer 15

clomiphene

Question 16

what does clomiphene do

Answer 16

clomiphene

• antagonist at anterior pituitary and hypothalamic receptors
• used to induce ovulation in infertility

prevents the negative feedback at anterior pituitary and hypothalamus and used in some cases of infertility - used to induce ovulation

so increases the synthesis of FSH and LH

Question 17

what is raloxifene

Answer 17

SERM: selective oestrogen receptor modulator
- antagonist in breast and uterus so doesnt cause cancer

• partial agonist in bones, vascular system - used in oesteoperosis

Question 18

what is tamoxifen

Answer 18

SERM: selective oestrogen receptor modulator

• antagonist in breast
• partial agonist in bones, vascular system and UTERUS - slightly increases risk of endometrial cancer

Question 19

what is the difference between raloxifene and tamoxifen

Answer 19

raloxifene is antagonist in breast and uterus

tamoxifen is anatagonist in breast but partial agonist in the uterus - so slightly increases the risk of breast cancer

Question 20

name an aromatase inhibitors

Answer 20

anastrazole

Question 21

what is anastrazole used for

Answer 21

used for treatment of breast cancer as it suppresses oestrogen synthesis

Question 22

what is progesterone produced by

and what receptor dies it use

Answer 22

corpus luteum and placenta

also a ligand activated transcritption factor receptor

Question 23

what are the actions of progetsogens

Answer 23

Actions:
1. negative feedback action on FSH and LH release

2. stimulate (in second half of cycle)
   - endometrial secretory phase
   - implantation-favouring cervical secretion (decreased volume and increased viscosity) - stimulates production of mucous that is implantation favourable and not favourable for sperm production
3. development of uterus and mammary glands in pregnancy

Question 24

what are the pharmacological effects of progestogens?

Answer 24

USES:

• contraception (+/- oestrogen)
• hormone replacement therapy (+oestrogen)

Unwanted effect: weak androgenic action

Question 25

what is mifepristone

Answer 25

emergency contraceptive

Question 26

what does mifepristone do

Answer 26

favours degeneration of CL

and is used as emergency contraception and early pregnancy termination (+ prostaglandin)

Question 27

discuss the combined oral contraceptive

Answer 27

Combined Oral Contraceptive

• Oestrogen + Progesterone
  e. g. ethinyloestradiol + norethisterone

pills taken for 21 days followed by 7 drug free days

Question 28

what are the mechanisms of action of the combined oral contraceptive

Answer 28

mechanisms of action:
1. oestrogen: suppression of FSH release - follicle fails to develop and so there is no endogenous oestrogen surge

2. progestogen:
   - inhibition of LH release - no ovulation - cervical mucus made hostile to sperm
3. oestrogen and progestogen
   - abnormal endometrial development - makes conditions unfavourable for implantation

Question 29

side effects of COC

Answer 29

increased hypertension
may be increased risk of thromboembolic disease

decreased risk of ovarian and endometrial cancer

may be increased risk of cervical cancer

Question 30

what are the progestogen only contraceptives

Answer 30

Norethisterone
Levonorgestrel
Depot Medroxyprogesterone acetate - DMPA

pill taken/ drug released continuously

menstrual disturbances

Question 31

what is mechanism of action of progestogen only contraceptive

Answer 31

mechanism of action:

1. production of cervical mucus hostile to sperm
2. only in higher preparations: inhibition of LH and FSH release - no ovulation

Question 32

what is tibolone

Answer 32

used for HRT
prodrug metabolised to low potency oestrogen, progestogen and androgen

HRT can increase risk of cancers