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

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 )

Dr Shashwat Jani. 9909944160 2



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.


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.

6Dr Shashwat Jani. 9909944160

COC : Estrogen + Progestogen

Estrogen :

2 types : - Ethinyl Estradiol ( EE )

- Mestranol ( Not used )


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….


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 )


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


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


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 …


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 .


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.


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.


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.


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


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.


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.


• 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.


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.


Effectiveness…

Failure rate : 0.1%Failure rate are mainly due to missed pills.


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.


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 .


• 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.


• 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)


• 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 )


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.


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


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


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.


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 .


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 …


NEWER

CONTRACEPTIVES


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.


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.


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.


Intra Vas Device ( IVD ) – Shug :- 2 devices inserted in to each Vas .

- Needs special surgical skill.

- wider trials needed.


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. ”

• .


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.


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…


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.


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…


Other Ongoing trials…

• Use of following as Male Contraceptives…

1 ) Neem extracts.

2 ) retinoic receptor antagonist

3 ) papaiya seed extracts

4 ) olealonic acid


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.


PATH Women’s Condom

• Polyurethane condom pouch

• Foam dots improve adherence to vaginal walls

• Soft outer ring

• Dissolving capsule


SILCS Diaphragm

• Cervical barrier device

• One-size-fits most

• Developed with input from women and men in multiple countries

• Regulatory application in Europe & US.


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.


Non contraceptive uses …

• DUB

• Endometrial Hyperplasia

• Endometriosis

• Breast cancer

• HRT


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.


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.


VAGINAL RINGS

• LNG ring covered by silastic tube .

• Delivers 20 microgm / day

• Replaced every 3 months.


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


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.


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.


Quinacrine pellet

• It acts as Sclerosing agent

• Inserted transcervically through hysteroscopein proliferative phase.

• Repeated in next cycle.

• Long term results are awaited.


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.


Gynefix


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.



Health & Medicine

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