Sex Steroids Flashcards
Outline the basic pathway of Sex steroid synthesis
- Cholesterol-> Pregnenolone
- Pregnenolone -> Progesterone-> Testosterone
- Pregnenolone-> Androstenedione-> Estrone OR Testosterone
- Estrone and Testosterone can both-> Estradiol
With Steroid hormone- nuclear receptor binding, why is there a lag before seeing cellular effect?
Lag is due to time taken for gene transcription to occur
Does oestrogen bind to a nuclear or membrane receptor?
Both
Name the 3 types of sex steroid hormones
- Oestrogens
- Progestagens
- Androgens
List the major effects of Oestradiol and Progestrone
Oestradiol;
- Stimulates endometrium and breast growth
- Stimulates Progesterone production
Progesterone;
- Stimulates endometrium and breast growth
- Maintains pregnancy
- Inhibits Oestradiol production
List the major effects of Testosterone
Stimulates male characteristics
hair, voice, aggression, anabolism
What 3 tissues can have hyperplasia or cancer due to Oestrogen side effects
List 3 other side effects of Oestrogen
- Breast
- Endometrial
- Ovarian
- Fluid retention
- Increased coagulability-> Embolism
- Impaired glucose tolerance
List 3 actions and some side effects of Progesterone
Not an exhaustive list
Actions;
- Anabolic (just like Oestrogen)
- Mood changes
- Secretory endometrium
Side effects;
- Weight gain, Acne
- Fluid retention
- Irritability, depression, PMS, lack of concentration
Why are men more at risk of atherosclerotic disease?
Due to metabolic effects of Testosterone, we get adverse effects on HDL/ LDL ratio
List 4 Pharmacokinetic features of Oestrogen drugs
Natural & Synthetic Oestreogens are well absorbed;
- In GI tract, so can give ORALLY
- From Skin & Mucous membranes, so can give TRANSDERMALLY
- Metabolised in liver
- Excreted in urine as Sulphates and Glucuronides
List 3 Pharmacokinetic features of Progesterone drugs
- Bound to albumin, with some stored in adipose (so good for long acting preparations)
- Metabolised in liver
- Excreted in urine, conjugated to Glucuronic acid
COCP and POP are metabolised in the liver by what enzymes?
List 3 types of drugs/ substances that INDUCE these enzymes, leading to reduced contraceptive efficacy
- CYP 450s
- Anti-epileptics (Carbamazepine or Phenytoin)
- Some antibiotics (Rifampicin or Rifabutin)
- Some natural products (St Johns Wort)
How do Soya protein products alter Oestrogen’s effects
- Enhance oestrogen absorption and reduce its storage in adipose & muscle
- Thus half-life reduced from 15 to 7 hours
Suggest 2 reasons for prescribing HRT
- Reduce menopausal symptoms
- Protect against osteoporosis
(Protecting against heart disease is NOT a valid reason, as it is not effective)
List 5 routes of administering HRT
- Oral
- Transdermal
- Implant
- Nasal
- Transvaginal
List some risks of HRT
Risks associated with length of treatment, so risk drops when treatment stops
- Unopposed oestrogen (ERT)= Increased risk of Endometrial and ovarian cancers
- Opposed Oestrogen (HRT)= Increased risk of Breast cancer
- Increased risk of Venous Thromboembolism
- Increased risk of Stroke
What are Bisphosphonates?
How do they work?
- Drugs that reduce bone resorption used to treat and prevent osteoporosis
- Control osteoclast activity (prevent them from binding to bone)
List 3 pharmacokinetic features of HRT drugs?
- Long half life
- Poor gut absorption
- Absorption affected by food, so take on empty stomach
List some ADRs of Bisphosphonates
- Upper GI effects (Oesophagitis, stay seated or standing for 30mins after taking)
- Hypocalcaemia (Check Ca and Vit D levels before treatment)
Which enzyme converts Testosterone to Dihydrotestosterone?
Name a drug that inhibits this enzyme
Suggest a condition that this drug can be used to treat
- 5-Alpha-Reductase
- Finasteride
- Enlarged prostate
List some features of Mifepristone/ RU486
- Progesterone + Glucocorticoid receptor antagonist
- Anti progesterone
- Sensitises myometrium to prostaglandin-induced contractions (progesterone prevents contractions)
- Used to terminate pregnancy
Name 3 SERMS (Selective Oestrogen Receptor Modulators)
- Tamoxifen
- Clomiphene
- Raloxifene (Bone selective, does not increase risk of endometrial cancer)
List 3 features of Clomiphene
- Used to treat an ovulation
- Competes with oestrogen for binding to Oestrogen Receptor
- Increases production of Ant. Pit. hormones to induce ovulation
Describe the Pharmacokineitcs of Tamoxifen
- Is a Pro-drug itself, so has little affinity for the Oestrogen receptor
- Metabolised in liver-> Active derivatives
- Active derivatives compete with Oestrogen for binding to Oestrogen Receptor)
Compare the action of Tamoxifen in the breast and endometrium
- Endometrium: Acts as agonist
Breast;
- Acts as antagonist
- Causes cell cycle arrest
What type of drug is Ulipristal Acetate?
Suggest 2 uses
- A Selective Progesterone Receptor Modulator
- Emergency contraception
- Treatment of Uterine fibroids
How does Ulipristal Acetate work as Emery you contraception
Thought to be due to delay/ inhibition of ovulation
