Download - Oral Contraceptives, Up to date Overview

Oral ContraceptivesUp to date Overview

Dr. Mamdouh SabryMD. Ain Shams Uni. Cairo, Ph.D. Paris V Uni.

Mataria Teaching Hosp. & Nasser InstituteCairo, Egypt

History• Fertility control is as old as humankind.• Embryocide and abortion were the methods

of choice among primitive societies.• Condom appeared during the 16th century to

protect first from STD ( S ) which was epidemic at that time.

• Spermicides and occlusive pessaries introduced for commercial use in the 19th century.

• Richter introduced thread pessary and Grafenberg used copper made intrauterine ring, few years later, at the end of the 19th century.

The Pill1955-58 Field trails in Puerto Rico, Haiti and Mexico City.

1957 FDA approves norethindrone ( Norlutin; Syntex-Parke Davis ) and

norethynodrel ( Enovid, Searle ) for treatment of gynaecological disorders

1959 Searle applies FDA approval of Enovid as a contraceptive.

1960 Searle receives FDA approval for norethynodrel ( Enovid ) for

contraception; Syntex grants Ortho the right to market norethindrone.

1961 Schering introduces Anovlar ( norethisterone + ethinylestradiol ) in Europe.

1962 Ortho receives FDA approval for norethindrone for contraception.

( marketed as Ortho-Novum )

1965 Early US pill use has risen from half a million woman in 1961 to almost 4

million women in 1965.

PharmacologyEstrogen Component

Ethinyl estradiol ( EE ) developed by adding ethinyl group at 17th position of estradiol ( inactive orally ) orally active potent estrogen.

Mestranol ( 3-methyl ether of EE ) converted into EE in the body.

All low dose pills contain EE. Metabolism of EE varies from female to female and variable

in the same female at different times. This explains difference in side effects from case to case.

Thrombosis as a side effect is dose related.

II. Progestin Content

New Progestins

• Include desogestrel, gestodine and norgestimate. Also, newer are in development.

• New progestins increase SHBG, decrease free testosterone ( acne and hirsutism ), do not affect cholesterol. They may even improve the lipid profile.

• Families X generations.

Mechanism of Action• Progestitional agent primarily suppresses LH

secretion ( to prevent ovulation ).• Estrogen suppresses FSH secretion, preventing

the emergence of dominant follicle which contributes to contraception efficacy.

• Estrogen stabilizes endometrium ( minimizes irregular shedding and potentiates progesterone action )

• Progesterone endometrium non-receptive to ovum implantation. Also thick cervix mucus with decreased total sperm motility.

Drug Interactions with Pills

• Drugs that stimulate liver metabolism can decrease the contraceptive efficacy ( FSH, LH level ).

Carbamazepine Felbamate NevirapineOxcarbamazepine Phenobarbital PhenytoinTopiramate Rifampicin VigatarabinPrimidone RifabutinAnd possibly ethoximide, griseofulvin and

troglitazone.

Drug Interactions with Pills Cont’d

• Pills effect on other drugs:Pills potentiate the action of diazepam,

chlordiazepoxide (librium), tricyclic antidepressants and theophylline. Lower doses of these agents may be effective in pill users.

• Larger doses of acetaminophen and aspirin are needed in pill users due to influence on clearance rate.

Medical Eligibility Criteria (WHO)Category 1:

(no restriction of use)

• Menarche to <40yrs• Nulliparous/ parous• Postpartum >21 days• Postabortion• Past ectopic pregnancy• h/o hypertension,

varicose veins, minor surgery

• Family h/o breast cancer• Endometriosis, fibroid

• Unexplained vaginal bleeding after evaluation

• Hypo/hyperthyroidism• HIV, malaria,

T.B,shistosomiasis, hepatitis(non active)

• Iron deficiency anemia, thalassemia

• History of gestational diabetes

• Depressive disorders• PID, STDs• Endometrial, ovarian Ca

Category 2 (benefits outweigh risks)

• Age over40• Obesity BMI 30 or more• Family h/o DVT/PE• Superficial

thrombophlebitis• Cigarette smoking

<35years• Migraine headache

without localizing signs or aura <35years

• Undiagnosed breast mass

• Surgery withoutimmobilization

• Unexplained amenorrhea• Valvular heart disease

uncomplicated• Diabetes with no vascular

disease• Hyperlipidaemias with no

risk factors• Sickle cell disease• Symptomatic gall blader

disease treated surgically

Category 3(risks outweigh benefits)

• Cigarettes smoking <15/ day in>35 years

• Postpartum <21 days or <6 months in lactating women

• History of OC induced cholestatic jaundice or symptomatic gall bladder disease treated medically

• Mild compensated cirrhosis

• History of hypertension including PIH -cannot be monitored-SBP=140-159 & DBP=90-99

• Hypertriglyceridemia• Migraine without aura

over 35years• Previous breast cancer

with no evidence for 5yrs• Antibiotics &

anticonvulsants

Category 4(not to be used)

• Valvular heart disease with thrombogenic complications

• Stroke & CAD• Diabetes with vascular

disease & for >20 years• Hypertension( SBP>160

& DBP> !00)• Cigarette smoking in

women with >35years• High risk & personal

history of thrombosis• Suspected pregnancy

• Multiple risk factors for atherosclerosis

• Migraine headaches with localizing neurological signs

• Acute or chronic liver disease

• Major surgery with prolonged immobilization

• Breast cancer• Hypersensitivity to any

component of pill

Overview OCs• Highly effective : failure rate expected

0.1% and typical 7.6% in the first year of use.

• Convenient : most common method.• Reversible : actually, it preserves fertility.• Safety : ( DVT/PE ), ( VTE )• Few intolerable side effects.• Limited Contraindications.• Pills have a lot of non-contraceptive

values.

Cycle Related Benefits

• Decreased blood loss.

• Scheduled bleeding episodes.

• Minimize or eliminate menstrual period.

Possible Health Benefits

• Less salpingitis ( PID ).• Less anaemia• Less symptoms of PCO.• Less benign breast distension.• Decreased functioning ovarian cysts.• Less benign ovarian neoplasia.• Possible fewer myomas.• Less Rheumatoid arthritis.

Possible Health Benefits Cont’d

• Stop ovulation in patients with bleeding tendency to prevent intra-peritoneal bleeding at ovulation.

• Most of this evidence is based on studies using higher amounts of estrogen ( 30-35 mcg. )

Cancer

• Pills protect against:

Endometrial Cancer ( 50-60% risk )

Ovarian Cancer ( 40-80% risk )

Cervical ( with long term use only in women infected with HPV ).

Bone• Increased evidence that OCs use

preserve BMD.• 3.3% increase in BMD in premenopausal

females using OCs.• Moderate smoking related loss of BMD.• Decreased risk of postmenopausal hip

fracture.Some studies showed no beneficial effect

on BMD.

Specific Symptoms & Conditions

• Acne: many combinations improve acne.• Hirsutism• DUB: improve in 3 cycles ( 87% ),placebo ( 45% ).• Menstrual associated symptoms: - Premenstrual syndrome ( PMS ), 20-40%

improve. - Premenstrual dysphoric disorders ( PMDD ), 3-8% improve. - Dysmenorrhoea, 40% improve.

Benefits of the Pill: risk reduction in %• Ectopic pregnency 90%• CancerOvary 40%Endometrium 40%Benign breast disease 40%• Ovarian CystsSolid tumors 20%Follicular Cysts 49%Luteal Cysts 78%• Fibroids ( after 5 years COC’s use ) 15%• Pelvic inflammatory disease 50%• Menorrhagia 50%• Iron deficiency anaemia 50%• Dysmenorrhea 40%• Hgic. disorders ( Ovarian bleeding ) 100%

“ It is safer for a young woman to be on the Pill than to become pregnant “

New Contraceptive Options

1) Yasmin, Berlex, (Drospirenone)

2) 24/4- day regimen.

3) Nova Ring

4) Ortho Evra

New Contraceptive Options Cont’d

Yasmin, Berlex:

Contains 30 mcg of EE and 3 mg of a novel progestin – Drospirenone.

Similar effectiveness to low dose OCs with mild mineralocorticoid and diuretic effect.

It can be used in patients with chronic NSAID users, and in renal disease.


24/4 day Regimen:

Two recent pills with 24/4 day regimen that differs from 21/7 regimen, both deliver 20 mcg EE ( Luestrin 24 Fe …… 1 mg norethindrone acetate ) and ( YAZ, Scherring……. 3 mg drospirenone ).

They decrease the amount and duration of bleeding and inhibit folliculogenesis better.


Vaginal Ring ( Nuva Ring, Organon ):

The flexible ring polymer……( 5mcg of EE/day + 120 mcg etonogestrel, active metabolite of desogestrel ).

3 weeks use and one week free.


Contraceptive Weekly Patch ( Ortho Evra, Janssen-Cilag ):

Delivers 20 mcg EE and 150 mcg norelgestromin ( active metabolite of norgestimate ) each day ( steady state level ).

One patch every week for 3 weeks and one patch free week.

Future Prospects

• Decrease Estrogen

• Anti androgens

• Patching

• Nasal

• Post-coital ( local or patching )

• Libido

Thank you