This document discusses the history, present use, and future of combined contraceptives or "the pill". It describes how the pill was developed in the 1950s-60s using synthetic hormones like norethindrone and norethynodrel. Newer progestins were later introduced with fewer side effects. The document outlines the pharmacology of estrogen and progestin components, mechanisms of action, drug interactions, and medical eligibility criteria for pill use. It reviews cycle benefits, possible health benefits like cancer reduction, and newer contraceptive options including pills containing drospirenone and vaginal rings. The conclusion discusses decreasing estrogen content and developing new delivery methods as future prospects.

1. Combined ContraceptivesCombined Contraceptives
Past, Present And FuturePast, Present And Future
Dr. Mamdouh SabryDr. Mamdouh Sabry
MD. Ain Shams, Ph.D Paris V Un. FranceMD. Ain Shams, Ph.D Paris V Un. France
Consultant Ob. & Gyn.Consultant Ob. & Gyn.
EL Mataria Teaching Hospital, Nasser InstituteEL Mataria Teaching Hospital, Nasser Institute
Cairo, EgyptCairo, Egypt

2. 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.

3. The Pill
1955-58 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.

4. Pharmacology
Estrogen 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.
 Estradiol valerate and 17-Beta estradiol show minimal
effect on liver enzymes, which means no DVT .

5. Progesterone component
Synthetic Progesterone
Progestins

6. II. Progestin Content

7. New Progestins
• Include desogestrel, gestodine and
norgestimate. Newer are norelgestromin,
etenogestrel and drospirenone ( DPN ).
• New progestins increase SHBG, decrease
free testosterone ( acne and hirsutism ),
do not affect cholesterol. They may even
improve the lipid profile.
• Families X generations.

9. 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.

11. Drug Interactions with Pills
• Drugs that stimulate liver metabolism can
decrease the contraceptive efficacy ( FSH,
LH level ).
Carbamazepine Felbamate Nevirapine
Oxcarbamazepine Phenobarbital Phenytoin
Topiramate Rifampicin Vigatarabin
Primidone Rifabutin
And possibly ethoximide, griseofulvin and
troglitazone.

12. 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.

13. Medical Eligibility Criteria
( WHO )
4 Categories

14. Category 1
(no restriction of use)
• Menarche to <40yrs
• Nulliparous/ parous
• Postpartum >21 days
• Post-abortion
• Past ectopic pregnancy
• h/o hypertension,
varicose veins, minor
surgery
• Family h/o breast cancer
• Endometriosis, fibroid
• Ov. cancer
• 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

15. 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 without
immobilization
• Unexplained amenorrhea
• Valvular heart disease
uncomplicated
• Diabetes with no vascular
disease
• Hyperlipidemias with no
risk factors
• Sickle cell disease
• Symptomatic gall bladder
disease treated surgically

16. 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

17. 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

18. 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.

19. Cycle Related Benefits
• Decreased blood loss.
• Scheduled bleeding episodes.
• Minimize or eliminate menstrual period.

20. 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.

21. 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. )

22. 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 ).

23. 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.

24. 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.

25. Benefits of the Pill: risk reduction in %
• Ectopic pregnency 90%
• Cancer
Ovary 40%
Endometrium 40%
Benign breast disease 40%
• Ovarian Cysts
Solid 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%

26. “ It is safer for a young woman to be on
the Pill than to become pregnant “
- 2 per 10 000 risk for VTE of users in age
rep. period X 20 per 10 000 during
pregnancy.

27. Recent Contraceptive Options
1) Pills containing (Drospirenone)
2) 24/4- day regimen.
3) Nova Ring
4) Ortho Evra

28. New Contraceptive Options
Cont’d
Yasmin, Norocarmina:
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.

29. New Contraceptive Options
Cont’d
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 ( Norocarmina
and Yaz……. 3 mg drospirenone ).
They decrease the amount and duration of
bleeding and inhibit folliculogenesis .

30. New Contraceptive Options
Cont’d
Vaginal Ring ( Nuva Ring, Organon ):
The flexible ring polymer……( 5mcg of EE/day
+ 120 mcg etenogestrel, active metabolite of
desogestrel ).
3 weeks use and one week free.

31. New Contraceptive Options
Cont’d
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.

32. Future Prospects
• Decrease Estrogen content
• Apply new estrogens
• Anti androgens
• Natural progesterone or similar
• Patching
• Nasal
• Post-coital ( local or patching )
• Libido

33. Thank you