Injectable hormonal contraceptives
By Prof. Dr. Saeeda Majeed
Types:
n4weekly Injectables
CYCLOFEM - 25mg medroxy progesterone acetate
§ 5mg estradiol cypionate.

MESIGYNA - 50mg norethisterone
§ 5mg estradiol valerate.

n8 weekly Injectables:
Noristerate two monthly injections
Norethindrone ennthate
Norethisterone enanthate NET-E-N

n12 weekly Injectables:
Depoprovera (medroxy progesterone acetate) MPA 150mg / 3 monthly injection.

Mode of action:
Ø Potent progesterone like activity
Ø Show activity
Ø Inhibit sperm transport
Ø Prevent implantation by producing endometrial changes.
Ø Anti-estrogenic, anti-androgenic and anti-gonadotrophic effect.
Ø No effect on lipid or liver metabolism.

Advantages of injectable contraceptives:

1. Protective against CA endometrium.
2. It is non carcinogenic
3. Effective, safest and reversible contraceptive
4. It has no harmful effect on lactation
5. Easy return to fertility
6. Less blood flow during menstrual cycle.
MIRENA
The intrauterine Levonorgesterol system.
Also called No-bleed contraceptive

Mode of action of IUCD
Local hormonal action
Rate of release is 20ug/daily/5years
Serum concentration of Levonorgesterol is low but concentration in uterus is 1000 fold higher than that in the circulation.
Pre-ovulatory estradiol and luteinizing hormone peak values are low
It causes atrophy of endometrial epithelium
Strong stromal decidual reaction
Glandular atrophy
Uterine atmosphere is hostile for sperm transport.

Effect on endometrium
Thin atrophic epithelium
Decreased blood flow so it is recommended for menorrhagia cases
Vascular changes include,
Thickening of arterial walls
Suppression of the spiral arteriols
Capillary thrombosis
Atrophy of the glands.

Hormone realeasing IUCD Mirena:
Advantages:

1. Strong local action
2. Reduce menstrual blood loss
3. Less menstrual discomforts
4. No dysmenorrhoea
5. Excellent contraceptive choice
6. Suitable for women having menorrhagia
7. For unwilling to use COCP
8. Low rate of ectopic pregnancy
9. Additional health benefit.


Advantages of (LNG-IUS)
1. Complete reversibility
2. Reduction in amount and duration of blood loss
3. Iron deficiency anaemias improve.
4. Dysmenorrhoea also improves
5. Provides many health benefits
6. Most of generalized effects due to ayatemic applications of levenorgestrel can be avoided in this method.
7. It can be used as an option for progestin treatment during estrogen replacement therapy in postmenopausal women.
8. Effective in cases of dysmenorrhoea
9. Best for perimenopausal women
10. Can be indicated for women not willing for COCP.
11.
Disadvantages of (LNG-IUS) Mirena/Levonova


Ø Expulsion
Ø Perforation
Ø Prolonged duration of post insertion intermenstrual bleeding/ spotting

Sub dermal implants

nINDICATIONS FOR USE:
For long term reversible contraception.

nDOSAGE AND ADMINISTRATION:

Types:
ü FIRST GENERATION NORPLANTS:

NORPLANT I

ØSIX silastic capsules
ØSize of each - 36mm x 2.4mm
- 36mg levonorgestrel

ü SECOND GENERATION NORPLANTS:

§ Norplant II:
· (Levonorgestrel + polydimethyle sioxane
· Two capsules
· Size 4cm x 2.4mm
· Release 30ugm / day
§ Implanon: (EVA)
· Single rod of ethylene vinyl acetate
· 60mg of 3-ketodesogestrel
· size 40mm x 2mm
· Release – 60mg / day
Mode of action:
v Inhibition of ovulation
v Production of thick, scanty cervical mucus which prevent sperm penetration
v Suppression of endometrial growth- hypotrophic changes
v Decrease in progesterone secretions during the leuteal phase
v Lack of follicular maturation
v It suppress LH necessary for ovulation.
Pharmacokinetics:
Progesterone only contraceptive
Five years contraceptive protection
Daily release rate of levonorgestrel is:
§ 85mcg/24hr initially
§ 50mcg/24hr 9 months
§ 35mcg/24hr 18 months
§ 30mcg/24hr rest of years
Proper action starts few days after insertion
After removal of implants the plasma levonorgestrel level becomes unremarkable within 40 hours.

nEFFECTIVENESS:

nPregnancy rate is 3.9%
nIt is high in obese women
nEctopic pregnancy rate is very low i.e. 0.13/100 women
Time of insertion:

nDuring menses
nImmediately post abortion
nSix weeks after delivery.

Risk factors:
nHypertension
nClotting defect
nLiver disease
nDiabetes
nSmoking
nPregnancy
nCA breast, CA cervix and endometrium
Pre-requisite for insertion:
A. Only specially trained clinicians should perform insertions and removals of norplants.
B. Informed consent should be taken after proper counseling.
C. Selection and exclusion criteria should be followed.
D. Careful technique to minimize tissue trauma correct subdermal placement of the implants and aseptic technique should be followed.
E. Pregnancy should be excluded
F. Pelvic examination must be done to exclude any pelvic pathology.
G. Instructions to patient for proper follow-up and for removal must be given.
H. Smoking should be avoided.
I. Breast examination.
Base line investigations:
nClotting profile
nLFT
nRFT
nAllergy test
nPelvic USG/ folliculometry
nDetailed endocrine study
nCervical/ vaginal mucus study
nSerum progesterone level
nSperm penetration test
Undesirable effects:
I. Irregular menstrual loss
II. Intermenstrual bleeding
III. Continous bleeding
IV. Prolong period of amenorrhoea
V. Ectopic pregnancy
VI. Allergic reactions
VII. Lower abdominal pain.
VIII. Follicular cysts
IX. Hypertension
X. Headache
XI. Visual disturbances
XII. Signs of thromboembolic phenomena
XIII. Nervousness
XIV. Nausea, vomiting
XV. Ovarian enlargement
XVI. Dermatitis
XVII. Acne
XVIII. Mastalgia
XIX. Weight gain
XX. Hair loss
XXI. Hirsutism


Advantages of Norplant:
Safe
Effective
Reversible
Reliable
Longterm method of contraception
Acceptable
Low removal rate
Quick return of fertility so patient can become pregnant within one year
Disadvantages:
High discontinuation rate
Very costly
Removal is difficult in some cases
Menstrual pattern changes
Prolonged bleeding episode
Irregular bleeding
Ammenorrhoea
High pregnancy rate in late years of total duration
Delayed return to fertility
Indications of removal:
Ø At the end of five years
Ø If preganacy occurs
Ø If patients complains of heavy, contineous vaginal bleeding
Ø Prolonged episodes of headaches and visual disturbance
Ø If patients develop arterial or venous thromboembolic phenomenon
Removal procedure:
1. Facilities should be available anytime to remove the implants on request of the patient or discontinuation cases.
2. Same procedure should be adopted for removal as for insertion.
3. A non hormonal contraceptive method should be advised until all implants are removed
4. A second attempt can be done for complete removal of implants.
5. Reimplantation should be done through the same incision at the same time.
6. Same equipment, position of the patients and the same aseptic technique is required
7. Removal is more difficult and will take more time than the insertion.
8. In difficult cases we can locate implants by ultrasound and x-ray.
Contraindications:
A. Known or suspected pregnancy case.
B. Undiagnosed abnormal genital bleeding
C. Known or suspected breast cancer
D. Other hormone dependent tumors
E. Acute liver disease
F. Benign or malignant tumor
G. Active thrombophlebitis or thromboembolic disorders.
Drug interaction:
o Phenytoin sodium
o Carbamazepine
o Barbiturates
o Rifampacine