Oral Contraceptives

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Methods of Contraception

1.       Direct inhibition of spermatogenesis

2.       Indirect inhibition of spermatogenesis

3.       Immunological techniques (vaccine)

4.       Inhibition of ovulation

5.       Prevention of fertilization

6.       Anti-zygotic drugs

7.       Inhibition of implantation

8.       use of spermicidal in vagina

9.       IUCD

OCS: History

·         1950: Pincus et al (progesterone prevents ovulation)

·         1959: 1^stpill appeared in USA

·         1960: mini pill (progesterone alone)

·         1970: Introduction low dose or                                                                                  second generation of OCS

·         1980: biphasic or triphasic regimens

·         1990: 3^rdgeneration OCS

§  (O + P has less androgenic activity,

§  e.g, norgestimate 0.25mg or desogestrel 0.15 mg)

INHIBITION OF OVULATION

Oral

• Combined pill
• Sequential pill
• Phased regimen
• Mini pill
• Post-coital pill

Injectable

•   Long acting  :  Progesterone . alone

•     Long acting   : Progestrone . +  Oestrogen

        Implants:

·      Norplant

Inhibition of ovulation

1.       Sequential Pills:    16 (O) + 5 (O+P) + 7 (DF)

2.       Mini pills :  Low dose progesterone  , Less effective

                     Mifepristone 600mg

                      Low dose OE (100 mcg) + norgestrel (1mg)  taken twice  12 hr  apart; 90 – 98 %

                         effective

                     In case of failure: abortion

3.      Phased Regimens:

A)      Biphasic:

10     O+P) + 11 (O+PP) + 7 (DF)

B)      Triphasic:

                I     6 ( E.O 30 µg + Levonorg. 50 µg)

                 II   5  (E.O 40 µg + Levonorg. 75 µg)

                III 10 (E.O 30 µg + Levonorg. 125 µg)

4.       Combined preparations:

                      21 days (O+P) + 7 days (DF)

                     99 – 100% effective

Combined Pills

Oestrogen		Progestin
Mestranol	50 µg	Norethindrone	5 mg
Ethinyl oestradiol	50 µg	Norethindrone	1 mg
Ethinyl oestradiol	20 µg	Norethindrone	1 mg
Ethinyl oestradiol	50 µg	Norgestrel	0.5 mg
Ethinyl oestradiol	20 µg	Norgestrel	0.3 mg
Ethinyl oestradiol	50 µg	Lynestrenol	1.0 mg

OCS: MECHANISM OF ACTIONS

·               Gn release from pituitary

·               Absence of FSH & LH peaks

·               Follicular development & ovulation

·               Thick cervical mucus

·               Implantation of blastocyst in

·               endometrium

·               Contractions of uterus & F.tubes are modified

   

OCS: Practical problems

1      Missing a pill?

2      Critical period

3      Short delay

4      h or more late

5      More than 1-2 tablets missed

6      If pregnancy occurs during OCS intake

7      Female with acne & hirusitism

8      Female with excessive menstrual loss

9      If OCS is discontinued

OCS: Adverse effects

Most serious:

1.       CVS side effects:

Ø         Thrmobophlebitis (due to O & P)

Ø         Thromboembolism ( due to oestrogen)

Ø     Hypertension

Ø         Cerebral & coronary thrombosis

Ø         Increased incidence of M.I. and stroke

2.       Cancer: Ca. breast, vagina and cervix ?

3.       Benign hepatoma:

4.       Gall stones:   biliary cholesterol secretion

Less serious:

Ø    Wt. gain

Ø    Pigmentation of cheeks, nose and forehood

Ø    Pruritus vulvae

Ø    Diabetes?

Ø    Mood swings, abdominal discomfort

Non- serious:

Ø    Nausea, vomiting

Ø    Breakthrough bleeding

Ø    Breast discomfort

Ø    Suppression of lactation (very rare)

OCS: Drug Interactions

A. Enzyme Inducers

     e.g., phenytoin, phenobarbitone, primidone, carbamazepine, rifampicin

B. Suppression of intestinal microflora

                               

          e.g., tetracylcine, ampicillin

OCS: Contraindications

•         Thrombo-embolic, coronary & cerebrovascular disease or history of above

•          Hypertension (moderate to severe)

•          Hyperlipidemia

•         Active liver disease, hepatoma or history of jaundice

•         Suspected / overted malignancy of genitals / breast

•          Porphyria

•         Impending major surgery (post-operative thromboembolism)

OCS: Relative contraindications

•         Diabetes

•         Obesity

•         Smoking

•         Undiagnosed vaginal bleeding

•         Uterine leiomyoma

•         Mentally ill

•         Above 35 years age

•         Mild hypertension

•         Migraine

•         Gall bladder diseases

OCS: Other health benefits

       Reduced risk of:

Ø  ovarian cysts

Ø  ovarian & endometrial cancer

Ø  benign breast diseases

Lower incidence of ectopic pregnancy

Less common:

Ø  Iron deficiency

Ø  Rheumatoid arthritis

       Benefits in:

Ø   pre-menstrual tension

Ø   dysmenorrhea

Ø   endometriosis

Ø   Acne & hirusitism

CENTCHROMAN

·      Non-steroidal oral contraceptive (CDRI, Lucknow)

·      Oestrogen antagonist

·      Anti-implantation agent

·      Safer free from OCS side effects; menstrual cycle not disturbed – may be lengthened in 6-10% women

·      For all age group of women

·      Failure rate: 1 - 3 %

·      Side effects: enlargement of ovary

·      C/I: polycystic ovarian disease, cervical hyperplasia,

·      renal or hepatic disease, tuberculosis & lactating mother

·      Dose: 30mg tablet twice a week; 30mg once a week till needed

Injectable preparations

·      Long acting P + O: once a month, i.m.

·      Long acting P only: higher dose, i.m. once in several month

          e.g., Depot medroxyprogesterone acetate (DMPA) – 150-400 mg / 3-6 months

§  Norethindrone enanthate (NEE, 200 mg / 2-3 months)

·      Mech. Actions: inhibit pituitray LH, suppression of ovulation + act on endometrium, fallopian tube and cervcial secretion

·      Side effects:  complete disruption of menstrual bleeding pattern & total amenorrhea;  in some people permanent sterility

·      When to start? Any time you are certain that the patient is not pregnant

·      WHO study:  combination of DMPA (25 mg) + oestradiol cypionate (5mg)

                      – has high efficacy & regular menstrual bleeding

Implants: Levonorgestrel implant

·         Consists of 6 flexible silastic capsules containing levonorgestrel (36mg/capsule)

·         Inserted under L.A. under the skin

·         Effective for 5 years, to be replaced afterwards                

·         Mech. Actions: antioestrogenic action on the endometrium &  cervical secretion; LH peak & ovulation suppressed

·         Side effects: irregular bleeding in 70% women & few pregnancy –some ectopic (1^styr), headache, nervousness, nausea, skin rash, acne, hirusitism, breast tenderness, wt. gain, enlarged ovarian follicles