HORMONAL CONTRACEPTIVES

"The only remedy against hunger is reasonable birth control"

-Friedrich Durrenmatt

Even-though 2nd in the world's population list, India’s total fertility rate may have declined significantly over the years by adapting various contraceptive methods, but there remain significant challenges in family planning. The limited choices and access to family planning services, poor quality of available services, cultural and religious opposition, fear of adverse effects and gender-based barriers are responsible for the very high rate of unmet need for contraception in low-resource countries such as India.

Definition of Contraception: Interception in the birth process at any stage ranging from OVULATION to OVUM IMPLANTATION. Designed to prevent pregnancy due to coital act either temporary or permanent measure.

NEED FOR CONTRACEPTION AROSE FROM FAMILY PLANNING

• To bring down population growth.
• To reduce infant &maternal mortality rate.
• To prevent pregnancies that are too early, too frequent & too many.

METHODS OF CONTRACEPTION

1. Non Hormonal

A. Natural methods-Lactational Amenorrohoea, Calender based methods, Symptom based methods

B. Barrier methods- Condoms, Diaphragms

C. Intrauterine devices

D. Permanent methods- Tubectomy and Vasectomy

2. Hormonal

A. Female Hormonal Contraceptives

B. Male Hormonal Contraceptives

HORMONAL CONTRACEPTION IN FEMALES

ORAL.

1. Combined Oral contraceptives

2. Minipills
3. Postcoital/Emergency contraceptive pills
4. Centchroman

PARENTERAL

1. Injectable

        DMPA

        Norethindrone enanthate

        Combined

2. Implants

        Norplant

        Implanon

3. Transdermal patch

DEVICES

1. Progestasert
2. Vaginal ring

ORAL HORMONAL CONTRACEPTIVES

COMBINED ORAL CONTRACEPTIVE (COC) PILLS

• Most popular
• 99%-99.5% of success rate 
• Most effective
• Preparations contain judiciously balanced formulations of low doses of Estrogens (E) and Progestins (P)
• Most of the preparation provide pocket of 21 + 7 pills
• 21 pills are- COCs & 7 are -Lactose or Iron tablets

 

Examples of Combinations :

• Ethinyl estradiol (30μg) + Norgestrol (0.3mg)
• Ethinyl estradiol (50μg) + Norgestrol (0.5mg)
• Ethinyl estradiol (50μg) + LevoNorgestrol (0.25mg)
• Ethinyl estradiol (30μg) + LevoNorgestrol (0.15mg)
• Ethinyl estradiol (20μg) + LevoNorgestrol (0.1mg)
• Ethinyl estradiol (30μg) + Desogestrol (0.3mg)
• Mestronol (50μg) + Norethindrone (1mg)

A. MONOPHASIC PILLS- Same/constant amount of E & P in each pill in one pocket

B. BIPHASIC PILLS -Same amount of E each pill and Level of P is increased about halfway through cycle

• Day 01 -11à  Ethinyl estradiol (35μg) + Norethindrone (0.5mg)
• Day 12- 21à  Ethinyl estradiol (35μg) + Norethindrone (1mg)

C. TRIPHASIC PILLS-Contain high dose of E in midcycle with increase doses of P given over 3 successive phases

• Day 01- 06à  Ethinyl estradiol (30μg) + Norgestrol (0.05mg)
• Day 07- 11à  Ethinyl estradiol (40μg) + Norgestrol (0.075mg)
• Day 12- 21à  Ethinyl estradiol (30μg) + Norgestrol (0.125mg)

Timing of initiation of COC

• 1^st pill on 5^th day after start of menses. Then one pill on each day for 21 days
• Next 7 days are “pill free period”
• Next course start again 5th day of menses
• If women misses one pill on some day, she should takes 2 pills next day and then continue one pill a day as usual.
• If pills have been missed foe 2-3 days or frequent days, then course should stopped. Mechanical barrier should be used & next course should start from 5th day of menses as usual.

Mechanism of Action:

• Prevent ovulation by inhibiting Gn secretion via Pituitary & Hypothalamic inhibition
• P-suppress LH secretion
• E-suppress FSH secretion 

Benifits:

A. CONTARACEPTIVE- To prevent pregnancy

B. NON CONTRACEPTIVE 

• Improvement in menstrual abnormalities- a.Cycle Stabilization, b.Reduction in dysmenorrhea, c.Reduction in PMT synd., d.Protecton against IDA
• Protection against cancer- Endomerial & Ovarian cancer
• Protection against health diseases- PID, Endometriosis, Fibroid uterus, Hirsutism, Acne, Benign breast disease

Adverse Effects:

A. Non serious S/E (Change the Preparation or Method)

• Nausea, vomiting
• Headache
• Breakthrough bleeding
• Breast discomfort

B. S/E that appear later (May require discontinuation of therapy)

• Weight gain
• Acne, Chloasma
• Pruritis vulvae
• CHO intolerance
• Mood swings
• Amennorrohea
• Abdominal distension

C. Serious complications 

• Leg vein thrombosis
• Pulmonary embolism
• Coronary & Cerebral thrombosis à MI or stroke
• Rise in BP
• Increase in HDL/LDL ratio
• Genital carcinoma
• Benign hepatomas
• Gall stones

Contraindications:

A. Absolute

    1. Thromboembolic, coronary & CVD

    2. Moderate to severe HTN

    3. Active liver disease, Hepatoma

    4. Suspected/overt malignancy of genitals

    5. Porphyria

B. Relative

    DM, Obesity, Smoking, Mentally ill

    Mild HTN, Migraine etc..

MINI PILLS (Progestin only pills)

• To those cases where estrogens are contraindicated
• 96-98% efficacy
• Low dose of progestin pill to be taken daily without gap

Eg.: Norethindrone- 350 μg or Norgestreol- 75 μg

Mechanism of Action:

• Thinning of endometrial lining
• Thickening of cervical mucus
• Decreases tubal motility
• Inhibition of ovulation

Adverse Effects:

• Acne, hirsutism & amenorrhoea
• Unpredictable spotting & breakthrough bleeding

Contraindications:

• Pregnacy
• Breast cancer

EMERGENCY CONTRACEPTION/ POST COITAL/ MORNING AFTER PILL

• Emergency contraceptive pills à use within 72 hours
• Intrauterine devices à use within 5 days

• High doses of E &/or high doses of P
• Given immediately after unprotected coitus (Rape or Condom rupture)

Mechanism of Action:

• Ovulation inhibited or delayed
• Alterations in endometrial receptivity for implantation
• Dislodges an implanted blastocyst
• Alterations in tubular transport of sperms, eggs or embryo

METHODS:

1. LEVONORGESTREL

• 0.75mg, 2 doses 12 hours apart Or 1.5mg, single dose within 48 hours of coitus

2. MIFEPRISTONE

• 600mg single dose- within 72 hours

3. YuZpe method

• Levonorgestrel 0.5mg + Ethinylestradiol 0.1mg.....2 doses at 12 hour interval within 72 hours
• Low success rate
• Severe Nausea & Vomiting

4. ULIPRISTAL ACETATE (SPRM)

• 30mg single dose- within 120 hours
• S/E: Abd. pain, Menstrual disorder.

If these measures fail & pregnancy occurs, medical termination of pregnancy is advised to avoid teratogenic deformities of the fetus.

CENCHROMAN (Ormeloxifene)

NonSteroidal SERM developed at CDRI India.

Distributed under the name "SAHELI"

Dose & Schedule:

• Available as 30mg tablet.
• To be taken twice in a week for 1^st 3 months, then once a week subsequently continued irrespective of the Menstrual cycles.
• The first tab. to be taken on the first day of menstrual cycle, then second on 4th day.
• Contraceptive effect is rapidly reversible within 6 months & subsequent pregnancy is normal

Mechanism of Action:

Asynchrony between ovulation & development of uterine lining

Speeds transport of egg through fallopian tube,so implantation is not possible.

DOESN'T CAUSE: Nausea, vomiting, Vertigo, HTN, Breakthrough bleeding (as seen in steroidal OCs)

• No Risk of cancer, No A/E on lipid profile, No Thrombotic episodes.
• Doesn't exhibit androgenic, antiandrogenic or progestational properties.
• Pituitary, ovarian and other endocrine functions remain practically unaffected.

Side effects:

• Fluid retention
• Headache
• Weight gain
• Prolonged menstrual cycles

Contraindications:

• Hepatic dysfn. & Renal d/s
• PCOD
• TB
• Cervical hyperplasia

INJECTABLE HORMONAL CONTRACEPTIVES

• These have been developed to obviate the need for daily ingestion of pills.
• Given i.m. as oily solution
• Highly effective

LONG ACTING PROGESTIN ONLY INJECTIONS

1. Depot Medroxy Progesterone Acetate (DMPA)

• 150 mg at 3 months interval. Injection during first 5 days of menstrual cycle. 

2. Norethindrone enanthate (NEE)

• 200mg at 2 months intervals. Injection during first 5 days of menstrual cycle.

These are useful in patients where compliance is a problem or in patients with heavy menstrual bleeding or estrogen contraindicated.

Mechanism of Action: Same as Minipills.

Side effects:

• Irregular bleeding ending up in Amenorhoea.
• Anovulation
• Osteoprosis on prolonged use.
• Weight gain
• Increase risk of Breast cancer
• Not suitable for adolescent girls and lactating mother

NUVA RING

Releases 15microgram EE  & 120 microgram Etonorgestrel over 24 hours

Used for 21 days followed by 7 day hormone free interval

COMBINED ESTROGEN- PROGESTIN INJECTED CONTRACEPTIVES

1. “Number-1”

• Estrogen valerate + 17-hydroxyprogesterone caproate.
•  i.m. every month

2. Estradiol cypionate + DMPA

• i.m. once a month

Advantages:

• They provide a single defined & predictable bleeding
• High contraceptive efficacy

SUBCUTANEOUS DMPA INJECTION

• FDA approved 2004
• Sustained absoprtion of progestin
• Low dose of progestin (104 mg)
• Injections every 3 months

 IMPLANTS

• These are drug delivery systems implanted under skin, from which the steroid is released slowly over 1-5 years.
• Consists either biodegradable polymeric matrices or Non biodegradable rubber membrane

NORPLANT

• 6 capsules each containing 36mg of LNG (total 216 mg)
• For S/C implant
• Usually upper arm
• Works up to 5 years
• Contraceptive effects are readily reversible with removal of implants

IMPLANON

• Single flexible rod 4cm long
• 68mg of Etonorgestrel
• Releases 60 μg/day for 3 years
• Inhibits ovulation within 8 hours of insertion & provides contraception for 3 years

UNIPLANT

• 55mg of Normestrel acetate in a 4cm silicone capsule with 100 μg release/day

TRANSDERMAL CONTRACEPTIVES

1. PATCH

• OrthoEvra patch- 3 patch system
• 1 patch for 1 week & 1 week is patch free.

2. Spray on contraceptive: Nestrone-Meterd dose transdermal system (MDTS) in phase1 trail.

INTRAUTERINE INSERTS

1. PROGESTASERT

• Progesterone impregnated intrauterine insert.
• 52 mg of LNG which primarily acts locally on endometrium

2. MIRENA/LNG-IUD

• Effective for 5 years
• Releases LNG at rate of 20 μg/day into uterine cavity
• 

3. FIBROPLANTS

• LNG released @ 14 μg/day.
• Suitable for perimenopausal women
• Effective for 3 years.

Complications of IUDs:

Expulsion
Uterine perforation
Irregular bledding
Pelvic infeection
Ectopc pregnency
Failure rate-3% in first year

CONTRACEPTIVE RINGS

NUVA RING

• Releases 15microgram EE  & 120 microgram Etonorgestrel over 24 hours
• Used for 21 days followed by 7 day hormone free interval

HORMONAL CONTRACEPTION IN MALES

Only way to supress male fertility by drugs is to INHIBIT SPERMATOGENESIS

Drugs & Approaches tried are:

ü  Antiandrogens

ü  Estrogens & Progestins

ü  Androgens

ü  Superactive GnRH analogues

ü  Cytotoxic drugs

GOSSYPOL

• Orally effective Nonsteroidal drug
• Obtained from Cotton Seed

Suggested dose:

• 20mg/day for initial 2-3 months followed by 50-60mg/week as maintenance
• But not more than 2 years at a stretch

Mechanism of Action:

Destroys the elements of the seminiferous epithelium but doesn't alter the endocrine function of testis significantly

Decrease sperm count & reduces sperm motility

ü  Infertility develops after couple of months, but recovery is restored after several months after discontinuation.

ü  Recovery possible if sperm count has not gone too low or the drug has not been continued for over 2 years.

Side effects:

• Hypokalemia
• Muscle weakness & transient paralysis
• Diarrhoea
• Breathlessness
• Neuritis

THANK YOU.......!!!!!!!