Combined Hormonal Contraception

“Combination of synthetic progestogen and oestrogen”

Method of Action

• Combination of synthetic progestogen (progestin) and oestrogen (oestradiol valerate- prodrug or ethinyloestradiol)
  • Low oestrogen conc and high progesterone suppress gonadotrophin release
    • Gonadotrophin is responsible for follicular releasing hormone and luteinising hormone release from anterior pituitary
  • Progestins bind to progesterone receptors
    • Induce thick viscid mucous and inhibit LH surge
    • Bind to other receptors e.g. gonadotrophin, androgen, oestrogen, glucocorticoid and mineralocorticoid
      • Anti-gonadotrophin binding is desirable
      • Other receptor binding produces S/E
  • Synthetic oestrogen allows better cycle control and bleeding profile by stabilising endometrium, inhibiting FSH release

Effects

• Fallopian tube
  • Reduced cilia beating, contractions
• Ant pituitary and hypothalamus
  • Progestin inhibits LH surge
  • Oestrogen inhibits FSH release
  • Both: inhibit GnRH release
• Endometrium
  • Thick viscid mucous induction
  • Increase PR receptors
  • Asynchronous development
• Cervix
  • Progestin causes the thick viscid mucous plug
• Ovary
  • Progestin stops ovulation
  • Oestrogen stops follicular development

Side Effects

• Blood vessels: ↑­ clotting and ↓ antithrombin so ­↑ risk of MI/stroke/DVT
• CNS: nausea, mood changes
• Water and sodium retention: oedema, weight gain, breast tenderness
• Hypertension
• Androgenic effects: oily skin, acne, hirsutism, weight gain
• Possible association with breast cancer in short term

Examples

• COCP
  • Monophasic e.g. Zoely 24 days active, 4 days placebo
  • Biphasic, triphasic and quadriphasic e.g. Qlaria preparations
• CTP: Evra patch weekly then patch free week, release hormones every 24hrs
• Combined vaginal ring: NuvaRing stays in situ for 3 weeks

Contraindications

• CVD
• Obesity
• >35
• Smoking
• Migraines
• Liver disease
• Breast cancer

Protection

• Ovarian
• Endometrial and colorectal cancer

Other Uses

• Reduce menstrual symptoms
• Menorrhagia
• Acne