combined oral contraceptive pills and newer advances in contraception by dr shashwat jani
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COMBINED ORAL CONTRACEPTIVE PILLS AND NEWER ADVANCES IN CONTRACEPTION BY DR SHASHWAT JANI.TRANSCRIPT
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 : [email protected]
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 )
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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.
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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.
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COC : Estrogen + Progestogen
Estrogen :
2 types : - Ethinyl Estradiol ( EE )
- Mestranol ( Not used )
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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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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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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 - - - + +
Types of COC
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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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2 ) Multiphasic
Contains low or variable amounts of E and P in 2 ( biphasic ) or 3 ( triphasic ) phases of cycles.
Biphasic : constant EE – 35 microgmprogestogens : low in first 10 days
higher in next 11 days .NOT POPULAR – MORE FAILURE RATE .
NOT AVAILABLE IN INDIA …
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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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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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2 ) Endometrial Hyperplasia :
stromal oedema , decidual reaction & regression of glands making endometriumnonreceptive to embryo.
3 ) Cervical mucus :
thick , viscid , scanty .
impaired sperm transport & penetration.
4 ) May affect tubal motility & alter tubal transport.
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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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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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AdministrationNew 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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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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• 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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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
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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Effectiveness…
Failure rate : 0.1%Failure rate are mainly due to missed pills.
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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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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 StabilisationGreat social advantage. Withdrawl bleeding is predictable & postponed safely by taking more low dose pills contineously .
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• 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 preventingpregnancy.
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• Protection against benign tumors1) 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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• Protection against diseases 1) Ectopic Pregnancy 2) PID 3) Anaemia and Malnutrition 4) Endometriosis 5) Acne and Hirsutism6) DUB7) Osteoporosis
• Simplicity and Attractiveness• No Affection on Future fertility ( 3 months )
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Emergency Contraception…
1) Yuzpe regimen –0.1mg EE + 1 mg dl-Norgestrel1st dose Within 72 Hrs of ContactRepeated after 12 Hrs.
2) Ovral1st 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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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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Major Side Effects…
• Cardiovascular Diseases1) MI – Increased Risk in heavy smokers 2) Ischaemic Stroke - 1.5 times more3) Haemorrhagic Stroke – double risk4) Venous Thromboembolism – Risk increases with age, recent surgery and thrombophilia
• Hypertension - In women more than 35 Yrs.• Carcinogenecity
1) Breast Cancer2) Cervical Cancer
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Interaction With Drugs…
1) Barbiturates , Sulphonamides, Rifampicinand 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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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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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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NEWER
CONTRACEPTIVES
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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, hypokalamicparalysis.
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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
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.
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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.
RISUG : - “Reversible Inhibition of Sperm Under
Guidence . “
- Developed by IIT & AIIMS.
- clear polymer gel made of Styrene maleicanhydrate ( SMA ) mixed with DimethylSulphoxide ( 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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Intra Vas Device ( IVD ) – Shug :- 2 devices inserted in to each Vas .
- Needs special surgical skill.
- wider trials needed.
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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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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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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…
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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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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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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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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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PATH Women’s Condom
• Polyurethane condom pouch
• Foam dots improve adherence to vaginal walls
• Soft outer ring
• Dissolving capsule
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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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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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Non contraceptive uses …
• DUB
• Endometrial Hyperplasia
• Endometriosis
• Breast cancer
• HRT
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Combined InjectableContraceptives
• 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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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”
Transdermal delivery system
• Nestorone ( newer progestin ) :
- Available as Cream & Patch.
- Patches used like pills : 3 weeks ON 1 week OFF.
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VAGINAL RINGS
• LNG ring covered by silastic tube .
• Delivers 20 microgm / day
• Replaced every 3 months.
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Combined Ring – NUVA RING :
• Soft, transperent, ethinylvinyl 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
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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.
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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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Quinacrine pellet
• It acts as Sclerosing agent
• Inserted transcervically through hysteroscopein proliferative phase.
• Repeated in next cycle.
• Long term results are awaited.
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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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Gynefix
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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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