Sex Hormone Drugs

Question 1

List the following for: Oral contraceptives (COCP and POP)

• Use
• Example drugs
• Drug class
• Mechanism of action
• Adverse effects
• Warnings / contraindications
• Important drug reactions

Answer 1

Contraception

COCP and POP

Oral contraceptives

Oestrogen – prevent ovulation
Progesterone (low levels) – thicken cervical mucus

• Small risk of thromboembolism
• Smoking
• Thromboembolic event
• Obesity
• Hypertension
• Long-term use over 35 years

Metabolised by CYP 450 enzymes, following increase production of CYP 450

• Anti-epileptics e.g., Carbamazepine or Phenytoin
• Antibiotics e.g., Rifampicin and Rifabutin
• Natural products e.g., St John’s Wort
• Soya products

Question 2

List the following for: HRT

• Use
• Example drugs
• Drug class
• Mechanism of action
• Adverse effects

Answer 2

Relieve symptoms of the menopause and reduce osteoporosis risk

Oestradiol and Medroxyprogesterone

Hormone replacement therapy (HRT)

• Absorb oestrogen to maintain oestrogen levels
• Progesterone added to prevent actions of unopposed oestrogen
• Unopposed oestrogen – risk of endometrial and ovarian cancer
• Opposed oestrogen (with progesterone) – risk of breast cancer
• Risk of venous thromboembolism – stroke risk
• Risk of cardiovascular disease

Question 3

List the following for: Bisphosphonates

• Use
• Example drugs
• Drug class
• Mechanism of action
• Adverse effects

Answer 3

Osteoporosis (prophylaxis and treatment)

Alendronic acid

Bisphosphonates

Reduce bone turnover
Newer drugs – affects osteoclast membrane, can’t attach to bone
Older drugs – promote osteoclast apoptosis

Upper GI effects – oesophagitis
- Hypocalcaemia

Question 4

List the following for: Progesterone receptor antagonist

• Use
• Example drugs
• Drug class
• Mechanism of action

Answer 4

Termination of pregnancy

Mifepristone (RU-486)

Progesterone receptor antagonist

Normally, progesterone prevents contractility of myometrium in pregnancy

• Mifepristone acts as an anti-progesterone
• Sensitises the myometrium to prostaglandin-induced contractions

Question 5

List the following for: Selective oestrogen receptor modulators (SERM)

• Use
• Example drugs
• Drug class
• Mechanism of action
• Adverse effects

Answer 5

Breast cancer treatment (oestrogen receptor positive)
Osteoporosis treatment

Tamoxifen
Raloxifene

Selective oestrogen receptor modulators (SERM)

Breast cancer treatment (Tamoxifen)
- Pro drug – metabolised in the liver
- Active metabolites compete with oestrogen receptor, reduce oestrogen binding
- Inhibits growth and promotes apoptosis in oestrogen receptor positive tumours
Acts as both agonist (endometrium) and an antagonist (breast)
Osteoporosis treatment (Raloxifene)
- Bone selective oestrogen receptor modulator
- Has ‘oestrogen’ effects on the bone, without systemic negative effects of oestrogen

• Endometrial hyperplasia (agonist in endometrium)

Question 6

List the following for: Oestrogen receptor agonist

• Use
• Example drugs
• Drug class
• Mechanism of action

Answer 6

Anovulation

Clomiphene

Oestrogen receptor agonist

• Competes with oestrogen at the receptor, prevents oestrogen from binding
• Induces production of anterior pituitary hormones (low oestrogen has negative feedback effects)
• LH surge = ovulation

Question 7

List the following for: Selective progesterone receptor modulators

• Use
• Example drugs
• Drug class
• Mechanism of action
• Warnings / contraindications

Answer 7

Morning after pill (emergency contraception)
Uterine fibroid treatment

Ulipristal Acetate ‘morning after pill’

Selective progesterone receptor modulators

• Reversibly inhibits progesterone receptor
• Prevents rise in progesterone
• Severe liver disease (CYP metabolism)
• Established pregnancy