Reproductive Hormones/Drugs

Question 1

GnRH released from hypothalamus stimulates

Answer 1

Acts via Gq receptor
FSH release at low frequency pulses
LH at higher freq pulses
Continuous release (from administration) causes initial flare of both then down-regulation of receptors

Question 2

GnRH agonists uses (pulsatile dosing)

Answer 2

E.g. gonadorelin, leuprorelin

Pulsatile dosing for male infertility from hypothalamic hypogonadism (and very rarely for female)

Question 3

GnRH antagonist uses

Answer 3

E.g. ganirelix, degarelix

Used for prostate cancer treatment for more immediate effect, and used with gonadotropins for ART

Question 4

Gonadotropin types, release sites and receptor type

Answer 4

FSH and LH from anterior pituitary
hCG by placenta
Act on Gs receptors

Question 5

FSH actions females

Answer 5

Increases aromatase expression (in granulosa cells), follicle development, and LH receptor expression in follicle in females

Question 6

LH actions females

Answer 6

Stimulates androgen precursor synth in follicles (theca cells), ovulation and directs steroid production in 2nd half of cycle by converting ruptured follicle to corpus luteum

Detected in ovulation kits

Question 7

hCG actions

Answer 7

Acts on LH receptor as very similar

Maintains corpus luteum in first trimester of pregnancy

Question 8

Oestrogens production sites

Answer 8

Ovaries (follicles and corpus luteum) and placenta

Question 9

Oestrogen actions (reproductive)

Answer 9

Reproductive:
Female development (in utero + puberty)
Negative feedback on GnRH production at hypothalamus
Endometrial proliferative phase
Stimulates high-pH mucous production so favourable for sperm in fertilisation

Question 10

Oestrogen uses

Answer 10

Contraception (suppress GnRH secretion therefore ovulation) with progestogen
HR therapy (±progestogen)

Question 11

Oestrogen antagonists and uses

Answer 11

Clomifene and tamoxifen used to induce ovulation by reducing oestrogen neg feedback on hypothalamus in infertility, first step in treatment

Question 12

SERM uses

Answer 12

SERM acts as agonist in some tissues and antagonist in others
Raloxifene to prevent osteoporosis in menopause (antagonist in breast and uterus so doesn’t inc cancer risks and partial agonist in bones/liver)
Tamoxifen is antagonist in breast (some cancers oestrogen dependent) (and partial agonist in bones/liver/uterus so slight inc risk of endometrial cancer)
Clomifene to induce ovulation, prevents oestrogen feedback to hypothalamus

Question 13

Aromatase inhibitor use

Answer 13

Anastrazole in breast cancer, suppresses local oestrogen synth

Question 14

Progestogens production (endogenous)

Answer 14

Produced endogenously by corpus luteum and placenta

Question 15

Progestogen actions

Answer 15

Feedback to reduce GnRH release in hypothalamus
Prevents proliferation and inc differentiation in endometrium during luteal phase (decreased volume secretion, inc viscosity)
Development of uterus + breast and suppression of uterine contractility in pregnancy

Question 16

Progestogen uses

Answer 16

Contraception (±oestrogen)
HR therapy (+ oestrogen)
Suppressing ovulation long term (e.g. dysmenorrhoea, endometriosis, hirsutism and bleeding disorders when oestrogens) contraindicated
Levonorgestrel high dose used to prevent implantation in morning after pill

Question 17

Progestogen antagonist uses

Answer 17

Mifeprestone for early stage pregnancy termination (+prostaglandin), mimics drop at end of cycle to result in menstruation and blastocyst ejection

Question 18

Combined oral contraceptive MOAs

Answer 18

Can be ethylenoestradiol and norethisterone
Oestrogen reduces FSH release: follicle fails to develop + no surge in endogenous oestrogen
Progestogen makes unfavourable mucous for fertilisation + inhibits LH surge so no ovulation
Progestegon + oestrogen result in abnormal endometrial development

Question 19

Combined oral contraceptive SEs

Answer 19

Small inc risk of cervical cancer, dec ovarian/endometrial cancer risk
Inc risk of thromboembolic disease, and stroke and MI for women already with risk factors

Question 20

Progestogen only contraceptive MOA

Answer 20

Can be continuous (regular bleeding), oral or in patches/implants
MOA: cervical mucus unsuitable for fertilisation, no normal endometrium development, some preps cause no LH surge so no ovulation

Question 21

HRT treatments (often in menopause)

Answer 21

Oestrogen + Progestogen to mimic premenopausal
Oestrogen in women w/out endometrium so no endometrial cancer risk
Raloxifen (SERM, agonist in bone, antagonist in breast + uterus)
Tibolone (prodrug metabolised to low potency oestrogen/progestogen/androgen)

Question 22

HRT SEs

Answer 22

inc breast+ CVD risk
dec CVD risk in perimenopausal women
small inc risk of ovarian cancer

Question 23

GnRH agonists uses (continuous dosing)

Answer 23

E.g. gonadorelin, leuprorelin
Continuous dosing: induce ovulation, endometriosis, precocious puberty and given with anti-androgen in prostate cancer to prevent initial flair but down regulate GnRH receptors as tumours use GnRH for growth

Question 24

If clonifene treatment unsuccessful:

Answer 24

Menotrophin (FSH/LH combo) or follitropin (FSH) then chorionic gonadotrophin administered in large doses if clomifene infertility treatment unsuccessful

Question 25

FSH effects males

Answer 25

In males stimulates Sertoli cells to nourish sperm

Question 26

LH actions males

Answer 26

In males stimulates testosterone production

Question 27

Oestrogen actions (non-reproductive)

Answer 27

Non-Reproductive:
Anabolic + retains salt/water
Reduces fragility of vessels
Increases coagulability of blood (so no haemorrhage in birth) and inc HDL/dec LDL so cardioprotective
Reduces bone resorption - stronger bones

Question 28

Progestogen synthetics

Answer 28

Synthetics: levonorgestrel, norethisterone, desogestrel, MPA

Question 29

Progestogen contraceptive pill SE

Answer 29

SE: irregular bleeding, possibly reversible bone resorption due to neg feedback of oestrogen production but not accepted theory