Health & Medicine
Oral ContraceptivesUp to date Overview
Dr. Mamdouh SabryMD. Ain Shams Uni. Cairo, Ph.D. Paris V Uni.
Mataria Teaching Hosp. & Nasser InstituteCairo, Egypt
HistoryFertility 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.
1955-58 Field trails in Puerto Rico, Haiti and Mexico City.
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.
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 )
Early US pill use has risen from half a million woman in 1961 to almost 4 million women in 1965.
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 ProgestinsInclude 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 ActionProgestitional 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 PillsDrugs 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 ContdPills 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 21 daysPostabortionPast ectopic pregnancyh/o hypertension, varicose veins, minor surgeryFamily h/o breast cancerEndometriosis, fibroid
Unexplained vaginal bleeding after evaluationHypo/hyperthyroidismHIV, malaria, T.B,shistosomiasis, hepatitis(non active)Iron deficiency anemia, thalassemiaHistory of gestational diabetesDepressive disordersPID, STDsEndometrial, ovarian Ca
Category 4(not to be used)Valvular heart disease with thrombogenic complicationsStroke & CADDiabetes with vascular disease & for >20 yearsHypertension( SBP>160 & DBP> !00)Cigarette smoking in women with >35yearsHigh risk & personal history of thrombosisSuspected pregnancy
Multiple risk factors for atherosclerosisMigraine headaches with localizing neurological signsAcute or chronic liver diseaseMajor surgery with prolonged immobilizationBreast cancerHypersensitivity to any component of pill
Overview OCsHighly 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 BenefitsDecreased blood loss.Scheduled bleeding episodes.Minimize or eliminate menstrual period.
Possible Health BenefitsLess salpingitis ( PID ).Less anaemiaLess symptoms of PCO.Less benign breast distension.Decreased functioning ovarian cysts.Less benign ovarian neoplasia.Possible fewer myomas.Less Rheumatoid arthritis.
Possible Health Benefits ContdStop 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. )
CancerPills protect against:Endometrial Cancer ( 50-60% risk )Ovarian Cancer ( 40-80% risk )Cervical ( with long term use only in women infected with HPV ).
BoneIncreased 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 & ConditionsAcne: many combinations improve acne.HirsutismDUB: 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 COCs 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 Yasmin, Berlex, (Drospirenone) 24/4- day regimen. Nova Ring Ortho Evra
New Contraceptive Options ContdYasmin, 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.
New Contraceptive Options Contd24/4 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.
New Contraceptive Options ContdVaginal 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.
New Contraceptive Options ContdContraceptive 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 ProspectsDecrease EstrogenAnti androgensPatchingNasal Post-coital ( local or patching )Libido