Sex hormones Flashcards
What is the sex steroid synthesis pathway (for oestrogen’s & progesterone)
Cholesterol
- -> Progesterone (also converted to androstenedione)
- -> Androstenedione
Androstenedione
- -> Oestrone (via aromatase)
- -> Testosterone
Oestrone
- -> Oestrodial (reversible)
- -> Oestriol
Testosterone
- -> DHT (via 5alpha-reductase)
- -> Oestrone (via aromatase)
What are some uses for oestrogen therapies?
Hypogonadism in children - allows 2o sexual maturation
In combination with progesterone:
- Menopause - relief from many menopausal symptoms, atrophy & dryness of vagina, hot flushes, improved lipid function, reduced risk of colorectal cancer etc
- Oesteoporosis
- Contraception
- Amenorrhoea
What are some risks/adverse effects of oestrogen therapies?
Increased risk of cancer - breast & uterine due to increased proliferation of cels
Increased DVT
Nausea/vomiting
Breast tenderness
What is the molecular mechanism of action for oestrogen?
Steroid hormone = lipid soluble = nuclear receptor
Dimerisation upon receptor binding, acts as transcription factor
Binds to a DNA response element to upregulate gene transcription & translation
There are alpha & beta oestrogen receptors (ER) which are present on bone, CV, breast, uterine & CNS tissue
Binding to different sub-receptor elicits different effect
May also be membrane receptors for rapid effect
What is the action of tamoxifen?
What is its use?
Limitations?
Selective oestrogen receptor modulator (SERM)
Antagonist of breast tissue + CNS tissue
Partial agonist of uterine (++), bone & CV tissue
Metastatic breast cancer
Associated with increased risk of endometrial cancer, ocular toxicity, increased DVT risk & menopausal symptoms
What is Raloxifene?
What is its use?
Limitations?
Selective oestrogen receptor modulator (SERM)
Partial agonist of bone & CVS tissue
Antagonist at breast, uterine & CNS tissue
Used in osteoporosis
Increased risk of DVT ??
What is exemestane?
What is its use?
Limitations?
Aromatase inhibitor
Reduces the production of oestrogen’s by preventing conversion of androstenedione & testosterone to oestradiol
Used to improve disease free survival after tamoxifen
Reducing oestrogen without affecting receptor - therefore benefits are reduced risks associated with SERMs - reduced incidence of bilateral breast cancer, DVT, endometrial cancer
Risks associated with decreased oestrogen - osteoporosis/fracture, CVD (altered lipid profile), menopausal symptoms, hepatic steatosis
What are androgens generally used for?
Anabolic effects - senile osteoporosis
Androgenic effects - hypogonaism in children
Growth - dwarfism in children
Endometriosis
What are the functions of testosterone & DHT?
Testosterone - spermatogenesis, 2o sexual maturation, anabolic effects
DHT - external virilisation, prostate development, sexual maturation
How is testosterone converted to DHT?
Some testosterone is not converted and has direct effects via nuclear receptors
Some testosterone is bound to SHBG in the plasma and diffuses across the cell membrane
It is converted to DHT in the cytoplasm via 5a-reductase
DHT binds to a cytoplasmic receptor, dimerisers and enters the nucleus to bind a response element. Upregulates gene transcription & translation
What are the risks of androgen use?
Increased CVD - alters lipid profile
Females - hirutism, acne, menstrual irregularities, masculanisation
Males - prapism, impotence, decreased spermatogenesis, gynecomastia
Children - premature closing of growth plates
What are 3 anti-antrogeneric drugs?
5a-reductase inhibitors (finasteride)
Androgen receptor antagonist
Cyproterone
Flutamide
What is finasteride?
What is its use?
Limitations?
5a-reductase inhibitor
Prevents the conversion of testosterone to DHT in the cytoplasm
Used in benign prostatic hyperplasia
Reducing DHT, increases conversion to oestrogen - tender breasts, gynacomastia, breast cancer
Impotence, decreased libido, ejaculatory disorders
What is cyproterone?
What is its use?
Limitations?
Cyproterone is a synthetic progesterone
Used in OCP but also as androgen receptor antagonist
Used as a receptor antagonist for prostate cancer & androgenism in females
Cognitive changes, oedema, fatigue, decreased spermatogenesis
What is flutamide?
What is its use?
Limitations?
Non-steroidal androgen receptor antagonist
Metastatic prostate cancer
Diarrrhoea, anaemia, hepatic injury, dizziness, blurred vision
