Hormonal Contraceptives

&
Oral Contraceptive Pill
 Hormonal Contraceptives:

1. Oral contraceptives

2. Parenteral/ Injectable contraceptives:

• Medroxyprogesterone acetate
(Progestin depot provera)
• I/M injection at 3 months interval
3. Implanted contraceptives:
•Levonorgestrel (Norplant)
•Etonogesterol
•Contraception up to 5 years
Classification of oral contraceptives:
A.Combined pill (both estrogen & progesterone)
• According to combination:
1. Monophasic -Fixed dose of oestrogen and
progesterone throughout the cycle (Ethinyl
estradiol 0.02 mg + L-Norgestrel 0.1 mg)
2. Bi-phasic and Tri-phasic - Dose of oestrogen
is fixed but dose of progesterone vary to
mimic the natural cycle
• According to dose:
1. Low dose pill – Dose of oestrogen is 30 – 50 µg
2. Standard pill or high dose pill – oestrogen 100 µg
and progesterone 250 – 500 µg
B. Mini pill (Progesterone only pill) (0.35 mg
Norethindrone)
 Estrogen preparation used –
1. Ethinyl estradiol
2. Mestranol – Prodrug, converted to ethinyl
estradiol
3. Conjugated estrogen (premarin)
4. Stilbesterol
 Progesterone preparations used –
1. Levonorgestrel
2. Norethindrone
3. Ethinodiol
4. Norgestimate
 Mechanism of action of combined pill:
1. Prevention of ovulation:
•Estrogen inhibits secretion of follicular stimulating hormone
(FSH), so no follicular growth
•Progesterone inhibits secretion of luteinizing hormone
(LH), no mid-cycle LH surge occurs.
•So, there will be no ovulation
2. Prevention of fertilization:
Both combined pill and mini pill
•Thickening of cervical secretion
•Changes in ciliary motility of uterine tube
3. Prevention of implantation:
Balance between estrogen and progesterone required for
implantation is disturbed by combined pill leads to
endometrial thinning and prevention of implantation.
Pharmacological effects:
• Depression of ovarian function (chronic use)
• Decrease ovarian size and less follicular growth
• Cervical hypertrophy and polyp formation
• Breast enlargement and suppression of lactation
• Mild change in mood and behavior
• Inhibition of pituitary gonadotropin
• Weight gain due to salt and water retention by increased
renin-angiotensin activity
• Thromboembolic phenomenon due to estrogen
• Increase blood pressure and heart rate
• Decrease flow of bile and increase incidence of gall
bladder stone
• Increase serum triglyceride, HDL and LDL
• Decrease free and esterified cholesterol
• Increase pigmentation (chloasma) and Acne
Clinical uses:
1. Contraception
2. Post menopausal syndrome - To prevent hot
flush, urogenital atrophy, osteoporosis and
psychological disorder
3. Severe dysmenorrhea
4. Endometriosis
5. Failure of ovarian development
6. Post menopausal osteoporosis: Estrogen
7. Dysfunctional uterine bleeding (DUB)
8. Premenstrual symptoms
 Non-contraceptive benefits of OCP:
1. Decrease risk of ovarian cyst, ovarian
carcinoma, endometrial carcinoma, benign
breast disease
2. Lower incidence of
• Pelvic inflammatory disease
• Ectopic pregnancy
• Rheumatoid arthritis
• Hirsutism
• Iron deficiency anemia
• Osteoporosis
• Premenstrual symptoms
• Dysmenorrhoea
• Endometriosis
3. Menstrual regulation and prevention of DUB
Adverse effects:
A.Mild:
1. Nausea
2. Mastalgia, Edema
3. Headache, Migraine
4. Changes in serum protein
5. Increase ESR due to increase fibrinogen
6. Withdrawal bleeding sometimes fails to occur
B.Moderate:
1. Breakthrough bleeding due to progesterone
2. Weight gain and hypertension
3. Increase skin pigmentation
4. Acne & Hirsutism - Androgen like progesterone
5. Ureteral dilatation
6. Vaginal infection
7. Amenorrhea
C. Severe:
1. Moderate to severe hypertension
2. Increase incidence of thrombosis
3. Risk of Myocardial infarction
4. Risk of stroke and Subarachnoid hemorrhage
5. Cholecystitis, Cholangitis, Cholestatic jaundice
6. Increase incidence of hepatic adenoma and
ischemic bowel disease
7. Depression
8. Increase the risk of cervical and breast
carcinoma
9. Alopecia
10. Erythema multiforme, erythema nodosum
 Contraindications:
1. Thrombophlebitis
2. Thromboembolic phenomenon or past history
3. Cerebrovascular disorder or past history
4. Unknown vaginal bleeding
5. Suspected breast tumour or other estrogen dependent
neoplasm
6. Adolescent whose epiphysial closure is not yet
completed
 Drug interactions:
• Rifampicin, phenytoin, carbamazepine - Therapeutic
failure
• Alcohol, Tobacco
• Antibiotics: Decreased efficacy of OCP as because
normal flora of GIT that increase enterohepatic recycling
of estrogen are inhibited
Cautions:
1. Liver disease
2. Asthma
3. Eczema
4. Migraine
5. Diabetes
6. Hypertension
7. Optic neuritis
8. Convulsive disorder
9. CCF
10.Fibroid uterus
Guideline of prescription of ocp:
1. Age – over 35 years
2. Obesity – BMI > 39 Kg/m2
3. History of smoking, alcoholism
4. Family history of thrombophlebitis
5. History of diabetes mellitus
6. History of hypertension
7. Long term immobility
8. Breast feeding
9. Pregnancy
10. Any cardiac disease
11. Jaundice
12. History of breast and genital tract cancer
13. Undiagnosed vaginal bleeding
14. History of taking drugs like rifampicin
 Post coital contraceptives
• These drugs should be taken within 72 hours of
coitus
1.Levonorgestrel 1.5 mg once or 0.75mg twice daily
for 1 day
2.Ethinyl oestradiol (100 µg) + Levonorgestrel (0.5mg)
1 tab stat then another tab after 12 hours.
3.Conjugated oestrogen -10 mg thrice daily for 5 days
4.Ethinyl estradiol – 2.5 mg twice daily for 5 days
5.Diethyl Stilbesterol – 50 mg daily for 5 days
6.Mifepristone – 600 mg once in day 1 + Misoprostol
400 µg – once on day 3.
 Mini pill
• Progesterone only (Norethindrone)
• Less effective, higher failure rate
• Should be taken everyday (28 days)
• Mainly acts by changing cervical mucosa
• Administered when there is absolute
contraindication of estrogen – lactating mother,
risk of estrogen dependent carcinoma
• No effect on coagulation
• May decrease chance of breast carcinoma
• Breakthrough bleeding can occur
• Increase incidence of ectopic pregnancy
 Parenteral contraceptives
 Medroxy progesterone:
• Long acting, sustained release I/M preparation given every 3
months interval
• Can cause irregular bleeding, permanent sterility
• More failure rate
 Levonorgestrel implants (Norplant)
• Contraception up to 5 years
• 6 flexible silastic capsules containing levonorgestrel
implanted subcutaneously inside the upper arm.
• Disadvantages - Needs surgical procedures during insertion
and removal of capsules
• Adverse effects - Irregular bleeding, Sterility, Ectopic
pregnancy 1-3 per thousand
 Hormonal replacement therapy (HRT)
• HRT is a safe and effective treatment for
postmenopausal women with symptoms.
 Hormone Given:
1. Oestrogen: Conjugated oestrogen/ Micronized 17β
estradiol/ Ethynyl oestradiol
2. Progesterone: Progestin medoxyprogesterone/
Norethindrone acetate
3. Gonadomimetics: Tibolone containing synthetic
estrogen, progestogen and an androgen
 Dosage Forms:
Oral pill, Transdermal patch, Implants, Vaginal ring,
gel or spray.
Types of HRT:
1. Estrogen only HRT:
• Prescribed in women who have had a
hysterectomy (uterus and ovaries removed).
• Taken daily
2. Cyclical (sequential) HRT:
• Prescribed for women having menopausal
symptoms but are still have their periods.
• Daily estrogen along with progestogen for last
14 days of either each menstrual cycle or in
every 3 months
3. Continuous combined HRT:
• Prescribed for post-menopausal women
• Estrogen and progestogen are taken daily
Indications of HRT:
Usually given after menopause
• To relieve vasomotor symptoms - Hot flushes,
Sweating, Insomnia
• To improve urogenital symptoms - Atrophic vaginitis
• To prevent osteoporosis
Contraindications of HRT:
• History of breast cancer, endometrial cancer
• Severe active liver disease
• Hypertriglyceridemia
• Thromboembolic disorders
• Undiagnosed vaginal bleeding
• Endometriosis, Fibroids
 Adverse Effects
• Nausea, Bloating, weight gain, fluid retention
• Mood swings
• Breakthrough bleeding
• Breast tenderness
Potential risks of HRT in postmenopausal
women:
• Breast cancer - Use of combined HT after at least 5
years of continuous HT
• Endometrial cancer: Use of estrogen-only HT
because oestrogen builds up the lining of uterus.
The risk is reduced by adding progesterone with
oestrogen
• Thromboembolism