Pharmacology of Reproductive Hormones Flashcards
what are the most common uses of reproductive hormones?
- contraception/infertility
- hormone replacement therapy
- cancer (breast, prostata)
discuss the female hypothalamus-pituitary-gonadal axis
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
discuss the male hypothalmao-pituitary- gonadal axis
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
discuss the action of GnRH
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
Name the GnRH agonists
Gonadorelin
Leuprorelin
Nafarelin
what are the uses of GnRH receptor agonists
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)
name the GnRH antagonists
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
what is the use of GnRH antagonists
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
which hormone is detected in the pregnancy test
hCG
name the gonadotropin preparations
menotropins - hMG
urofollitropin/follitropin - rFSH
lutropin (rLH)
choriogonadtropin (rhCG)
Uses: - male infertility (pituitary insufficiency)
- ovulation induction - IVF
which structures produce oestrogen
follicle, Corpus luteum and the placenta
describe the oestrogen receptor
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
discuss the actions of oestrogen
- female development: in utero and at puberty
- feedback action: negative feedback action at low concentrations they have a positive feedback action
- 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 - metabolic - anabolic and retention of salt and water
what are the uses of oestrogen
Uses:
- contraceptions
- hormone replacement therapy
what is the oestrogen antagonist
clomiphene
what does clomiphene do
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
what is raloxifene
SERM: selective oestrogen receptor modulator
- antagonist in breast and uterus so doesnt cause cancer
- partial agonist in bones, vascular system - used in oesteoperosis
what is tamoxifen
SERM: selective oestrogen receptor modulator
- antagonist in breast
- partial agonist in bones, vascular system and UTERUS - slightly increases risk of endometrial cancer
what is the difference between raloxifene and tamoxifen
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
name an aromatase inhibitors
anastrazole
what is anastrazole used for
used for treatment of breast cancer as it suppresses oestrogen synthesis
what is progesterone produced by
and what receptor dies it use
corpus luteum and placenta
also a ligand activated transcritption factor receptor
what are the actions of progetsogens
Actions:
1. negative feedback action on FSH and LH release
- 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 - development of uterus and mammary glands in pregnancy
what are the pharmacological effects of progestogens?
USES:
- contraception (+/- oestrogen)
- hormone replacement therapy (+oestrogen)
Unwanted effect: weak androgenic action
what is mifepristone
emergency contraceptive
what does mifepristone do
favours degeneration of CL
and is used as emergency contraception and early pregnancy termination (+ prostaglandin)
discuss the combined oral contraceptive
Combined Oral Contraceptive
- Oestrogen + Progesterone
e. g. ethinyloestradiol + norethisterone
pills taken for 21 days followed by 7 drug free days
what are the mechanisms of action of the combined oral contraceptive
mechanisms of action:
1. oestrogen: suppression of FSH release - follicle fails to develop and so there is no endogenous oestrogen surge
- progestogen:
- inhibition of LH release - no ovulation - cervical mucus made hostile to sperm - oestrogen and progestogen
- abnormal endometrial development - makes conditions unfavourable for implantation
side effects of COC
increased hypertension
may be increased risk of thromboembolic disease
decreased risk of ovarian and endometrial cancer
may be increased risk of cervical cancer
what are the progestogen only contraceptives
Norethisterone
Levonorgestrel
Depot Medroxyprogesterone acetate - DMPA
pill taken/ drug released continuously
menstrual disturbances
what is mechanism of action of progestogen only contraceptive
mechanism of action:
- production of cervical mucus hostile to sperm
- only in higher preparations: inhibition of LH and FSH release - no ovulation
what is tibolone
used for HRT
prodrug metabolised to low potency oestrogen, progestogen and androgen
HRT can increase risk of cancers
