8 - Sex Steroid Pharmacology Flashcards
outline the 3 key sex related drug groups and what drugs exist within them
Drug groups
• Sex steroid hormones
• Oestrogens, progestagens, androgens
- Inhibitors & antagonists
- RU486, finasteride
• Mixed agonists/antagonists
• Selective estrogen receptor modulators (SERMs)
and
selective progesterone receptor modulators (SPRMs)
what are sex steroid hormones synthed from?
cholesterol
will become testoreone then estradiol (oestrogen)
via a series of conversion reactions
oestrogen is the more potent androgen than testoterone
how do sex steroid hormones excert change ?
they do this via nuclear receptors and then affect gene transcription
what are the major effects of
oestradiol, progesterone, testostrone
oestradiol - Stimulates growth of the
endometrium and breast; stimulates production of Prog - which then inibits the effects of estradiol.
progesterone - Stimulates growth of the
endometrium and breast;
maintains pregnancy
Testosterone - Stimulates male characteristics;
hairy body; deep voice; anabolism; aggression.
Oestrogen action and side effects
one or two
Actions • Mild anabolic • Sodium and water retention • Raises HDL, lowers LDL • Decrease bone resorption • Impair glucose tolerance • Increase blood coagulability
Side effects • Breast tenderness • Nausea, vomiting • Water retention • Increased blood coagulability • Thromboembolism • Impaired glucose tolerance • Endometrial hyperplasia & cancer • Ovarian metaplasia & cancer • Breast hyperplasia & cancer
Progesterone / progestin action and side
effects
one or two of each
Actions • Secretory endometrium • Anabolic • Increases bone mineral density • Fluid retention • Mood changes • Maintains pregnancy
side effects • Weight gain • Fluid retention • Anabolic • Acne • Nausea/vomiting • Irritability Depression, PMS • Lack of concentration
testosterone action and side effects
one or two
Actions/Side effects • Male secondary sex characteristics • Anabolic • Acne • Voice changes • Increases aggression • Metabolic - adverse effects on lipid profiles particularly the HDLC/LDL-C ratio hence increased risk of atherosclerotic disease in males
quick revision : try draw/outline hormones roles in the menstrual cycle
give it a go
outline how hormonal contraception works
broadly - specifics are in repro
- Interruption of physiological control of the menstrual cycle
- Endometrial and cervical mucus effects
- Inhibition of ovulation
COCP - tablet, patches and other methods
Progesterone Depot/IMplant - LARC
POP - low dose progesterone - specifics are in repro lecs
oestrogen and prog
metabolised where ?
absorbtion?
both the liver
Oest - absorbed well in the GI or via skin
Prog - Injected and bound to albumin
what are the ADR’s of the COCP
risk of a DVT or thromboembolism but v small
smoking will increase risk alot, so will long term use over 35 years
take into account other risks such as obesity or hypertension
what are the DDI’s of COCP and POP (the same)
name 3 classes of drugs that have the key effect
COCP and POP contraceptives are metabolised in the liver by CYP 450 enzymes
• Therefore oral contraceptive efficacy is reduced by enzyme inducing drugs
– anti-epileptics such as carbamazepine or phenytoin;
– some antibiotics such as rifampicin and rifabutin and
– some natural products such St John’s Wort
• because they all increase the production of hepatic CYP450
• Soya protein products enhance oestrogen absorption and reduce its storage in adipose and muscle and so cause the T1/2 to be reduced from ~15
to 7 hours
what is HRT, why prescribe it ?
The Menopause
• Ovarian follicle supply depleted
• Consequently ovarian sex steroid production stops
• End of female reproductive capacity
• ALSO
Loss of oestrogen and progesterone leads to a range of systemic effects as symptoms of menopause
so Hormone replacement therapy can reduce symptoms of menopause such as hot flushes, sweats and dyspareunia (painful sex)
and reduce osteoporosis risk and hence dangerous broken bones in older ladies
HRT is NOT effective at reducing heart disease, DONT use for
what steroids are used in HRT
dont need to know this
Oestradiol: e.g. valerate, enanthate, micronised
oestradiol, ethinyl estradiol, etc.
(1-2 mg/day)
Premarin® (0.625-1.25 mg/day)
Medroxyprogesterone acetate (Provera®) (2.5 mg/day)
Norethisterone (1 mg/day)
Levonorgestrel (1.5 mg/day)
what are the risks of HRT
Unopposed oestrogen (ERT): increases risk of developing endometrial and ovarian cancers Opposed oestrogen (HRT): increases risk of developing breast cancer
Increase risk of venous thromboembolism
▪ Cardiovascular disease
Beneficial effect on lipid profile – increased HDL-C, decreased oxoLDL-C, decreased triglyceride, decreased
lipoprotein
▪ Increased risk of stroke
Use of oral but not transdermal oestrogen is associated with a small increase in the risk of stroke
