COMBINED ORAL CONTRACEPTIVE PILLS AND NEWER ADVANCES IN CONTRACEPTION BY DR SHASHWAT JANI.

1. Combined Oral
Contraceptives
Dr Shashwat K. Jani.
M.S. ( Gynec )
Diploma in Endoscopy.
Assistant Professor, Smt. N.H.L. Medical College.
Sheth V. S. General Hospital, Ahmedabad.
( M ) : 99099 44160.
E- mail : drshashwatjani@gmail.com

2. Introduction
 World’s population expected to reach 9 billion by 2050.
 India accounts for 18% of World’s population… !!!
 Annually, 529,000 maternal deaths & 50 million
morbidity.
 In India, contraceptive prevalence is 48.3% .
 21% of all pregnancies resulting live births are
unplanned….!!!
 If unmet need for contraception was met, we can avoid
52 million unwanted pregnancies
25-50% of maternal deaths
( Hindin MJ, Lancet. 2007;370:1297-8 )
Dr Shashwat Jani. 9909944160 2

3. Dr Shashwat Jani. 9909944160 3

4. Dr Shashwat Jani. 9909944160 4

5.  1st Clinical trials of COC were
described by John Charles Rock &
Goodwin Pincus with approval of
marketing in USA in 1960.
Within 5 years it was used by 30
millions women all over the world.
At the moment , COC is used by over
100 million women worldwide.
Dr Shashwat Jani. 9909944160 5

6. Combined Oral Contraceptives ( COC )
 Commonly known as the “ Pill “
Widely Accepted & Most Effective
Reversible method of Fertility Control.
 In 1951, India was the 1st country in
world to introduce COC in National
programme of Family Planning.
Dr Shashwat Jani. 9909944160 6

7. COC : Estrogen + Progestogen
 Estrogen :
2 types : - Ethinyl Estradiol ( EE )
- Mestranol ( Not used )
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8. PROGESTOGENS :
( 4 Groups )
1 ) Norethisterone Group : ( 1st generation Pills )
Moderate Androgenic property ….
Norethisterone,
Norethisterone Acetate ,
Ethiynoidal diacetate ,
Lynestrenol
2 ) Norgestrel : ( 2nd generation pills )
Strong Progestogenic & Androgenic property….
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9. 3 ) 19 – nor testosterone derivatives :
( 3rd generation pills )
Anti ovulatory function by suppressing Gonadotropin…
Desogestrel,
Gestodene,
Norgestimate.
4 ) Spironolactone analogue :
Antiandrogenic & Anti mineralocorticoid …
Drosperinone ( DRSP )
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10. A comparison of various progestins…
Progestin Estro-genic
Anti-estrogenic
Andro-genic
Antiandro
-genic
Antimineralo
-corticoid
Progesterone - - - + +
Older progestins:
MPA
-
-
+
-
-
Norethisterone
-
+
+
-
-
Levonorgestrel
-
+
+
-
-
Newer progestins:
Desogestrel
Cyproterone
acetate
-
-
-
-
-
-
-
+
-
-
Drospirenone - - - + +

11. Types of COC
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12. 1) Monophasic
 Contains Estrogen & Progesterone in same
amount in Each pill .
 Divided in 2 subgroups :
- Low dose pills : EE 30 – 35 microgm
- Very low dose pills : EE 15 – 25 microgm.
Mala - N
• dl – NGL 0.15 mg
• EE 0.03 mg
Mala - D
• l – NGL 0.15 mg
• EE 0.03 mg
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13. 2 ) Multiphasic
 Contains low or variable amounts of E and P in 2
( biphasic ) or 3 ( triphasic ) phases of cycles.
 Biphasic : constant EE – 35 microgm
progestogens : low in first 10 days
higher in next 11 days .
NOT POPULAR – MORE FAILURE RATE .

NOT AVAILABLE IN INDIA …
Dr Shashwat Jani. 9909944160 13

14.  Triphasic :
Triquilar –
- 0.03 EE +0.5mg l-norgestrel (1 - 6)
- 0.03 EE +0.75mg l-norgestrel (7-11)
- 0.03 EE +0.125mg l-norgestrel (12 - 21)
Total monthly intake – 0.68mg EE +1.92mg progesterone
• Adv. – high efficacy rates
- few side effects
- less break through bleeding
- does not affect s.cholesterol & LIPIDS
• Disadv. – high pregnancy rates if errors in pill intake .
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15. Mechanism of action:
1 ) Inhibition of Ovulation :
 both hormones act on Hypothalamo pituitary
axis , suppress release of FSH & LH from Ant.
Pituitary.
E – inhibits FSH.
P – inhibits preovulatory LH Surge , less effect
on FSH.
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16. 2 ) Endometrial Hyperplasia :
 stromal oedema , decidual reaction &
regression of glands making endometrium
nonreceptive to embryo.
3 ) Cervical mucus :
thick , viscid , scanty .
impaired sperm transport & penetration.
4 ) May affect tubal motility & alter tubal
transport.
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17. Selection of the patient
 Detail history ( headache , migraine , etc…)
 Thorough general examination
( Breast , blood pressure… )
 Pelvic examination to exclude cervical
pathology.
 Cervical cytology
 Rule out any other contraindications.
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18. Checklist for Prescribing COC…
Last menstrual period, rule out pregnancy
Less than 6 months postpartum & lactating?
Age, Cigarette smoking, h/o migraine
Known case of diabetes or hypertension
History of stroke, MI or thrombosis
h/o jaundice/ liver disease
h/o breast/ genital tract malignancies
h/o drug intake: Antitubercular, antiepileptic
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19. Administration
New User :
- 1st day of Cycle .
- Daily 1 tab. Preferably at night for consecutive 21 days.
- Continued for 21 days and then 7 days break ( with
iron tablets ) .
- Next pack of Pill should be started on 8th day ,
IRRESPECTIVE OF BLEEDING ( same day of the week , pill
finished ).
- Simple Regimen of “ 3 WEEKS ON & 1 WEEK OFF “
- No break between packs.
 Can start pill up to 5 days of bleeding with extra
precaution with condom for next 7 days.
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20. Missed Tablets :
1 missed – Take 2 tablets next day .
2 or 3 missed – Take 2 tablets on two consecutive
days and continue the rest of the pack.
+Another Contraceptive for 1 week.
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21. • Lactating Women – Progestogen only pills /
Combined pills after 6 months
• Non Lactating Women – Combined oral pills
after 3 to 6 weeks or after menstruation
• 1st / 2nd Trimester abortion – during first 7
days.
• Amenorrhea : At any time after excluding
pregnancy + barrier method for 7 days.
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22. Extended Use of COC…
(Seasonale)
Available since 2003
150μg of LNG + 30μg of EE
Only Active Pills taken continuously for 84 days,
then break for 7 days.
Fewer periods (4 in a year)
Pearl index- 0.78
Breakthrough bleeding/ spotting – First few
cycles

23. Follow up …
 Examined after 3 months , then after
6 months and then yearly .
 Ask for any symptoms…
 Examination for breast , pelvis, BP & weight &
cervical cytology.
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24. Effectiveness…
Failure rate : 0.1%
Failure rate are mainly
due to missed pills.
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25. How long can be continued …???
In properly selected patient without
any risk factor , benefits are more ,
and so can be continued up to age of
50 with careful monitoring. Offers
dual advantage of Contraception and
HRT.
For spacing of birth : 3 – 5 years.
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26. Advantages…
• Prevention of pregnancy
India - MMR 1per 57 i.e. 400 in 1,00,000
2/5th of these deaths can be prevented by use
of OCs
• Cyclical Stabilisation
Great social advantage.
Withdrawl bleeding is predictable &
postponed safely by taking more low dose pills
contineously .
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27. • Cure of Menstrual Disorders
Dysmenorrhoea & Ovulation pain – By inhibiting
ovulation & production of PG .
Menorrhagia & Metrorrhagia - Norgestrel High dose oral
pills more useful.
Lessens PMT.
• Protection against Cancer
a) Endometrial cancer- Reduction by 50 %
effect persists for 15 yrs.
b) Ovarian Cancer – Reduction by 40 %
effect persists for 10 yrs.
c) Choriocarcinoma – Indirectly prevention by preventing
pregnancy.
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28. • Protection against benign tumors
1) Fibrocystic and Fibroadenomatous disease
2) Ovarion Functional Cysts
1) Follicular Cyst – 50 %
2) Corpus Luteum Cyst – 80 %
3) Fibroid Uterus - Reduction by 30%
Low Dose OC’s reduce fibroid ( WHO 1996)
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29. • Protection against diseases
1) Ectopic Pregnancy
2) PID
3) Anaemia and Malnutrition
4) Endometriosis
5) Acne and Hirsutism
6) DUB
7) Osteoporosis
• Simplicity and Attractiveness
• No Affection on Future fertility ( 3 months )
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30. Emergency Contraception…
1) Yuzpe regimen –
0.1mg EE + 1 mg dl-Norgestrel
1st dose Within 72 Hrs of Contact
Repeated after 12 Hrs.
2) Ovral
1st dose 2 tablets within 72 hrs.
2nd dose 2 tablets after 12 hrs.
3) Overal – L
1ST dose 4 tablets within 72 hrs.
2nd dose 4 tablets after 12 hrs.
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31. Minor Side Effects…
• Nausea, Vomiting and Lack of appetite
• Break through bleeding
• Menorrhagia and irregular bleeding
• Oligomenorrhoea and Amenorrhoea
• Breast changes – Heaviness and Tenderness
• Vaginal Discharge – Cx -erosion, dysplasia causes
leucorrhoea
• Headache and Migraine
• Chloasma
• Wt. Gain
• Psychosexual Trouble – Depression, Loss of Libido
• Others - Leg Cramps, Dimness of Vision
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32. Major Side Effects…
• Cardiovascular Diseases
1) MI – Increased Risk in heavy smokers
2) Ischaemic Stroke - 1.5 times more
3) Haemorrhagic Stroke – double risk
4) Venous Thromboembolism – Risk increases
with age, recent surgery and thrombophilia
• Hypertension - In women more than 35 Yrs.
• Carcinogenecity
1) Breast Cancer
2) Cervical Cancer
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33. Interaction With Drugs…
1) Barbiturates , Sulphonamides, Rifampicin
and Anticonvulsant interfere with OC’s and
failure rate increases
2) Interaction with antidiabetic drugs
3) Vit. C aggravates the effect of COC.
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34. Absolute Contraindications…
(WHO Category IV)
• Migraine, with focal Neurological Symptoms
• Pregnancy and breast feeding ( 6 Months)
• Severe Hypertension
• Complicated valvular heart disease
• D.M. with vascular complications
• Active hepatitis, liver tumors
• Major Surgery
• Prolonged Immobilization .
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35. Indications of Withdrawal :
 Severe migraine
Visual or speech disturbances
Sudden chest pain
Unexplained fainting attack or acute vertigo
Severe leg cramps
Excessive weight gain
Severe depression
Prior to surgery ( Atleast 6 weeks )
Patient wants pregnancy … 
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36. NEWER
CONTRACEPTIVES
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37. MALE
 GOSSYPOL :
- A Chinese drug … !!!

- extract from Cotton seed.
- Oral 10 – 20 mg daily for 3 months then 20 mg
twice weekly.
- Inhibit Spermatogenesis by acting on
seminiferous tubules.
- S/E : fatigue, decrease libido, hypokalamic
paralysis.
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38. Polyurethane Male Condom
• Stronger and thinner than
latex condoms
• Better heat transmission
• Can safely be used with oil-based
lubricants
• Can be used by those with
latex allergies

39.  GnRH Analogues :
- decline in sperm density , sperm motility,
decrease in testosterone level.
- Marked loss of libido makes it unacceptable .
Add back therapy with Testosterone is given.
Dr Shashwat Jani. 9909944160 39

40. Male Hormonal Contraception
• Recent trials at Andrology Clinic,
Concord Hospital
• Depo Provera plus testosterone
implants 3 monthly.
• Very low sperm count (less than 1
million per ml) in all men on trial -
80% had no sperm.
• Few side-effects
• Similar regime using an oral
progestogen and testosterone
implants being trialed in UK
• Implants and testosterone also
being trialled.

41. RISUG :
- “Reversible Inhibition of Sperm Under
Guidence . “
- Developed by IIT & AIIMS.
- clear polymer gel made of Styrene maleic
anhydrate ( SMA ) mixed with Dimethyl
Sulphoxide ( DMSO ) injected in to Vas
deferens  partially blocks Vas , preventing
sperm from coming in to ejaculate.
- Phase I & Phase II trials cleared.
- VASALGEL is similar to it.
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42. Intra Vas Device ( IVD ) – Shug :
- 2 devices inserted in to each Vas .
- Needs special surgical skill.
- wider trials needed.
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43. Voegeli’s Heat Method
• A small increase in the temperature of the testes has a
large negative impact on the production of sperm
(spermatogenesis).
• Voegeli’s program for temporary sterilization is as
follows:
“A man sits in a [shallow or testes-only] bath of 116
degrees Fahrenheit for forty-five minutes daily for
three weeks.
Six months of sterility results, after which normal
fertility returns.
For longer sterility, the treatment is repeated. ”
• .
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44. Artificial Cryptorchidism/ Suspensories
(a) testes in normal position;
(b) testes raised to near inguinal canal; testes held in
place with
(c) briefs with ring of soft rubber or (d) ring alone.
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45. Gendarussa
• First nonhormonal male contraceptive pills.
• Developed by Indonesia.
• Active ingredient in Gendarussa disrupts an
enzyme in the sperm head, which weakens
the ability of the sperm to penetrate the
ovum.
• The effect is short term and reversible –
having no effect on male hormones.
• Still under clinical trials…
Dr Shashwat Jani. 9909944160 45

46. Nifedipine – CCB
• CCBs also partially block the calcium channels
within the cell membranes of sperm. This
affects sperm function rather than production.
• A man taking nifedipine produces a normal
amount of sperm, and the sperm appear
functional when viewed through a
microscope. But in vitro tests show that these
sperm cannot fertilize an egg.
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47. Male Vaccines …
• Scientists are trying to isolate, identify, and
produce Anti sperm surface antigens which
will hinder sperm – egg without side effects.
• Will take long time…
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48. Other Ongoing trials…
• Use of following as Male Contraceptives…
1 ) Neem extracts.
2 ) retinoic receptor antagonist
3 ) papaiya seed extracts
4 ) olealonic acid
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49. FEMALE
Many researches are going
on for development of newer
Contraceptives for females which are
either Non Hormonal OR having low
dose of Estrogen and newer
Progestogens.
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50. PATH Women’s Condom
• Polyurethane condom
pouch
• Foam dots improve
adherence to vaginal
walls
• Soft outer ring
• Dissolving capsule
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51. SILCS Diaphragm
• Cervical barrier device
• One-size-fits most
• Developed with input
from women and
men in multiple
countries
• Regulatory application
in Europe & US.
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52. Centchroman ( Saheli )
• Ormeloxifene .
• research product of CDRI , Lucknow
• Non steroidal , potent anti estrogenic , weak
estrogenic.
• Prevent implantation of fertilized ovum .
• Orally 30 mg twice weekly for first 3 months
then once a week.
• Avoided in PCOD, liver , kidney disease.
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53. Non contraceptive uses …
• DUB
• Endometrial Hyperplasia
• Endometriosis
• Breast cancer
• HRT
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54. Combined Injectable
Contraceptives
• CYCLOFEM :
- DMPA 25 mg + Ostradiol cypionate 5 mg.
• MESIGYNA :
- NET- EN 50 mg + Oestradiol valerate 5 mg.
• Given within first 5 days of menstruation
• Next dose on same date of each month.
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55. New formulation of Depo-Provera:
Depo-subQ Provera 104, for delivery with Uniject
Depo-subQ Provera 104:
 New formulation for subQ injection
 30% lower dose (104 mg vs. 150 mg)
 Rapid onset of action
 Same effectiveness, same length of protection (>3 months)
 Approved by USFDA (2005) and UK
 Potential for home- and self-injection
 Available for roll-out in 2011; Acceptability studies to begin in
mid-2010
Uniject:
 Single dose, single package
 Prefilled, sterile, non-reusable
 Short needles for subQ injection (easier use by non-clinical
personnel/CHWs)
 Compact; easy to use and store
Potential “home
run”

56. Transdermal delivery system
• Nestorone ( newer progestin ) :
- Available as Cream & Patch.
- Patches used like pills : 3 weeks ON 1 week OFF.
Dr Shashwat Jani. 9909944160 56

57. VAGINAL RINGS
• LNG ring covered by silastic tube .
• Delivers 20 microgm / day
• Replaced every 3 months.
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58. Combined Ring – NUVA RING :
• Soft, transperent, ethinyl
vinyl ring
• Releases EE 15 microgm
+ Etonogestrel daily over
a period of 21 days.
• Then removed , after 1
week ( bleeding ) new
ring inserted.
• S/E : headache,
leucorrhea, vaginitis
Dr Shashwat Jani. 9909944160 58

59. LNG ROD
• Implant with total 150 mg of LNG
( 75 mg / rod ) is found effective for 5 years.
UNIPLANT
• Single rod implant
• Nomegestrol 38 mg.
• Releases 100 microgm / day.
• For 1 year.
Dr Shashwat Jani. 9909944160 59

60. Biodegradable
• Cipronor ( Single Capsule) – IMPLANTS :
- LNG 26 mg
- begins to disappear after 12 months.
• INJECTABLE :
- Microsphere of 0.06 – 0.1 mm diameter with
Norethindrone with or without EE.
- Given over Gluteal muscle.
- Once injected , can’t be removed.
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61. Quinacrine pellet
• It acts as Sclerosing agent
• Inserted transcervically through hysteroscope
in proliferative phase.
• Repeated in next cycle.
• Long term results are awaited.
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62. Frameless IUD - Gynefix
• Made of 6 copper beads ( 330 sqmm of Cu )
on monofilament polypropylene thread.
• Thread is knotted at one end , embeded in to
fundal myometrium up to 1 cm.
• Reduced risk of Expulsion, Dysmenorrhoea,
Bleeding , Infection.
• Can be used in Nulliparous.
• Removed with Hook.
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63. Gynefix
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64. ESSURE
• Transcervical
sterilisation
• 4 cm long , 2 mm
diameter microcoil
• Spring like device
• Inserted in each
fallopian tube through
hysteroscope.
• Tube is blocked
permanently when scar
tissue grow inside.
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