ORAL CONTRACEPTIVE

 

ORAL CONTRACEPTIVE

 

Drugs are available that decrease fertility by a number of different mechanisms, such as preventing ovulation, impairing gametogenesis or gamete maturation, and interfering with gestation. Currently, interference with ovulation is the most common pharmacologic intervention for preventing pregnancy.

Contraceptive means interception in the birth process at any stage ranging from ovulation to ovum implantation. An ideal contraceptive agent should not only be safe but provide reversible suppression of fertility.

Oral Contraceptive

(I) COMBINATION PILLS: containing a combination of Estrogen + Progestin in varying amounts or in phased regimens (Monophasic, Biphasic or Triphasic).

(ii) MINI PILLS (Progestin only pills)

(iii) POST COITAL (Morning after) Pills.

(iv) CENTCHROMAN: Non-Hormonal estrogen receptor antagonist.

1. Combination oral contraceptives:

Products containing a combination of an estrogen and a progestin are the most common type of oral contraceptives.

Monophasic combination pills

Monophasic combination pills contain a constant dose of estrogen and progestin given over 21 days.

ESTROGEN                         PROGESTERONE

1.Ethinyl Estradiol (30μg) + Norgestral (300μg)

2.Ethinyl Estradiol (30μg) +Levonorgestral(150μg)

3.Ethinyl Estradiol (50μg) + Norgestral (0.5mg)

4.Mestranol Estradiol(50μg) + Norethindrone(1mg)

5.Ethinyl Estradiol (30μg) + Desogestral (150μg)

 

These are called Monophasic combination pills. No Phasic ↑or↓ In the E/P content during 21 days of pill administration. The First pill is taken on the 5th day after starting of the menses. One Pill is to be taken each day consecutively for 21 days. Next 7 days are pill free period. Next course starts after the 5th day of menstruation. A regular cyclic menstrual bleeding on withdrawal of the pill (Progestogenic effect). If woman misses one pill some day she should take 2 pills next day & continue the pill as used. Pills that have been missed for 2-3days or at frequent days, the course should be stopped. Mechanical barriers like Condoms, Diaphragm or Jelly should be used & next course start from 5thday of menses as usual.

 

Biphasic combination pills

Biphasic & Triphasic pills Mimic the hormonal changes during the menstrual cycle.

Biphasic pills have a fixed dose of estrogen for 21days with ↑doses of progesterone during two successive phases i.e., from the day 1-10 & 11-21. Next 7days are pill free.

For Ex:

Ethinyl Estradiol(35μg) + Northindrone(0.5mg)

A pack of ten tablets from day1 to day10.

Then,

Ethinyl Estradiol(35μg) + Northindrone(1mg)

A pack of 11 tablets from day 11 – 21day.

 

Triphasic combination pills

Triphasic pills →Higher dose of Estrogen at near mid cycle but ↑doses of  Progesterone for three successive phases. i.e., for 1-6, 7-11 & 12- 21days.

By a gap of 7days of pill free period.

Example:

Ethinyl Estradiol 30μg + Norgestrel 0.05mg

                                                 (6Tab→day 1-6)

Ethinyl Estradiol 40μg + Norgestrel 0.07mg

                                              (5Tabs→day 7-11)

Ethinyl Estradiol 30μg + Norgestrel 0.125mg

                                         (10Tabs→day 12-21)

 

2. Progestin-only pills:

Products containing a progestin only, usually norethindrone (called a “mini-pill”), are taken daily on a continuous schedule. Progestin-only pills deliver a low, continuous dosage of drug. These preparations are less effective than the combination pill, and they may produce irregular menstrual

cycles more frequently than the combination product. The progestin only pill has limited patient acceptance because of anxiety over the increased possibility of pregnancy and the frequent occurrence of menstrual irregularities. The progestin-only pill may be used for patients who are breastfeeding (unlike estrogen, progestins do not have an effect on milk production), are intolerant to estrogen, are smokers, or have other contraindications to estrogen-containing products.

 

3. Postcoital contraception (‘MORNING AFTER PILL’):

Postcoital or emergency contraception reduces the probability of pregnancy to between 0.2 and 3 percent. Emergency contraception uses high doses of progestin (for example, 0.75 mg of levonorgestrel) or high doses of estrogen (100 μg of ethinyl estradiol) plus progestin (0.5 mg of levonorgestrel) administered within 72 hours of unprotected intercourse (the “morning-after pill”). For these regimens, a second dose of emergency contraception should be taken 12 hours after the first dose. A newer progestin-only regimen consists of a one-time dose of 1.5 mg levonorgestrel. For maximum effectiveness, emergency contraception should be taken as soon as possible after unprotected intercourse and preferably within 72 hours. The progestin-only emergency contraceptive regimens are generally better tolerated than the estrogen-progestin combination regimens. A single dose of mifepristone has also been used for emergency contraception.

 

4. CENTCHROMAN

It is a non steroidal antagonist And available as Tab containing 30mg of Centchroman in each Tab.

·         Centchroman →taken twice in a week for first 3 months & then once a week subsequently to be continued irrespective of the following menstrual cycles, as long as contraception is desired.

·         The 1st Tab →should be taken on the first day of menstrual cycle (Eg. Sunday)

·         2nd Tab → on 4th day of the cycle (i.e.,Wednesday)

·         Subsequent Tab →taken on every sun & wed for 1st 3 months.

·         Followed by once a week on the same day every week.

·         The missed Tab →taken as soon as possible & the normal schedule should be adhered to.

 

If the dose is missed by 2-7days, the normal dose schedule is maintained. But mechanical barrier contraception (Eg .condoms) are used as preventive measure additionally. Till the next menstrual period. If the dose is missed for more than 7days, reinitiate by weekly schedule for 3months & weekly schedule there-after. Centchroman is a potent competitive antagonist at peripheral estrogen receptors & suppress proliferative stage of endometrium.

 

 

Mechanism of action

Hormonal birth control medications prevent pregnancy through the following ways:

Ø  By blocking ovulation (release of an egg from the ovaries), thus preventing pregnancy

Ø  By altering mucus in the cervix, which makes it hard for sperm to travel further

Ø  By changing the endometrium (lining of the uterus) so that it cannot support a fertilized egg

Ø  By altering the fallopian tubes (the tubes through which eggs move from the ovaries to the uterus) so that they cannot effectively move eggs toward the uterus

Adverse effects

Most adverse effects are believed to be due to the estrogen component, but cardiovascular effects reflect the action of both estrogen and progestin. The incidence of adverse effects with oral contraceptives is relatively low and is determined by the specific compounds and combinations used.

1. Major adverse effects: The major adverse effects are breast fullness, depression, fluid retention, headache, nausea, and vomiting.

2. Cardiovascular: Although rare, the most serious adverse effect of oral contraceptives is cardiovascular disease, including thromboembolism, thrombophlebitis, hypertension, increased incidence of myocardial infarction, and cerebral and coronary thrombosis. These adverse effects are most common among women who smoke and who are older than age 35 years, although they may affect women of any age.

3. Carcinogenicity: Oral contraceptives have been shown to decrease the incidence of endometrial and ovarian cancer. The incidence of cervical cancer may be increased with oral contraceptives, because women are less likely to use additional barrier methods of contraception that reduce exposure to human papilloma virus (the primary risk factor for cervical cancer). The ability of oral contraceptives to induce other neoplasms is controversial. The production of benign tumors of the liver that may rupture, and hemorrhage is rare.

4. Metabolic: Abnormal glucose tolerance (similar to the changes seen in pregnancy) is sometimes associated with oral contraceptives.Weight gain is common in women who are taking the nortestosterone derivatives. Weight gain may be less with oral contraceptives containing drospirenone.

5. Serum lipids: The combination pill causes a change in the serum lipoprotein profile: Estrogen causes an increase in HDL and a decrease in LDL (a desirable occurrence), whereas progestins may negate some of the beneficial effects of estrogen. Therefore, estrogen- dominant preparations are best for individuals with elevated serum cholesterol.

 

Contraindications:

 Oral contraceptives are contraindicated in the presence of cerebrovascular and thromboembolic disease, estrogen dependent neoplasms, liver disease, and pregnancy. Combination oral contraceptives should not be used in patients over the age of 35 who are heavy smokers.

 

Drug Interaction:

v  The effectiveness of COC, POP and EHC will be reduced by interaction with drugs that are enzyme inducers

v  Broad spectrum antibiotics may reduce effectiveness of COC by altering the bacterial flora of the bowel.

v  Certain drugs can decrease the effectiveness of combination-type birth control pills by decreasing the drug concentration in your system (impaired enterohepatic recirculation or hepatic induction). This can result in pregnancy.

v  Drugs that may cause this effect include: many antibiotics (e.g., cephalosporins, chloramphenicol, macrolides, penicillins, tetracyclines, sulfas), aprepitant, bexarotene, bosentan, dapsone, griseofulvin, certain HIV protease inhibitors (e.g., amprenavir, nelfinavir, ritonavir), modafinil, nevirapine, rifamycins (e.g., rifampin), many seizure medications (e.g., barbiturates, carbamazepine, phenytoin, primidone, topiramate), St. John's wort.

v  Before using this medication, tell your doctor or pharmacist of all prescription and non-prescription/herbal medications you may use, especially of: thyroid hormone drugs, certain benzodiazepines (e.g., diazepam, chlordiazepoxide), prednisone-like drugs, certain antidepressants (e.g., tricyclics), beta-blockers (e.g., metoprolol), "blood thinners" (anticoagulants such as warfarin), insulin.

v  This product can affect the results of certain lab tests (e.g., thyroid). Inform all laboratory personnel that you use this drug.

v  Birth control pills may significantly intensify the effects of alcohol.

v  Consult your doctor or pharmacist about this. Do not start or stop any medicine without doctor or pharmacist approval.