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Oral Contraceptive Pills

Combined Pills


These are of two types: monophasic pills and multiphasic pills.


Monophasic Pills


These pills contain estrogen and progestogen in the same amount in each pill.


They are divided into three subgroups:

  1. Standard dose containing ethinyl estradiol (EE) 0.05 mg/day (50 Jig/day).
  2. Low-dose pills containing EE 0.03-0.035 mg in each pill
  3. Very low-dose containing 0.020 mg EE in each pill

Each pill contains a progestogen such as levonorgestrel 0.015 mg or other newer varieties such as desogestrel, gestodene, norgestimate, norethisterone, and drospirenone (DRSP).


Multiphasic Pills


These phasic formulations employ low doses and variable amounts of estrogen and progestogen in two (biphasic) or three (triphasic) periods within the menstrual cycle. The dose of progestogen is low at the beginning and higher at the end, while the estrogen remains either constant or rises slightly in mid-cycle. The total doses of steroids in a whole cycle are less in these pills.


Very rarely used today.


Four groups of progestogens are used nowadays in oral contraceptives (OCs):

  1. Norethisterone group
    Pills containing these drugs are called first-generation pills.
  2. Norgestrel
    Pills containing norgestrel are called second-generation pills.
  3. 19-Nortestosterone Derivatives
    1. Three progestogens, namely desogestrel, gestodene, and norgestimate-have been developed for contraceptive use.
    2. iThey have minimal androgenic and anabolic effects, indeed virtually none. The decreased androgenicity of the new products is reflected in increased sex-hormone-binding globulin and decreased free testosterone concentration.
    3. This effect has the potential to decrease acne, hirsutism and promote favorable lipid changes.
    4. OCs containing desogestrel or gestodene produce less break through bleeding (BTB) and do not increase body weight in most cases. On the other hand, OCs containing desogestrel or gestodene probably carry a small extra risk of venous thromboembolism (VTE) beyond that attributable to OCs containing LNG.
  4. A new progestin called drospirenone (DRSP) is derived from 17-alpha spironolactone, an analog of spironolactone. It has antiandrogenic and antimineralocorticoid activities. The USFDA in May 2001 approved "Yasmin," containing 0.03 mg of EE and 3 rug of DRSP, as a monophasic birth control pill for women. OCs containing DRSP /EE have been found to be highly effective and provide a safety level equivalent to that of other pills. These DCs lessen acne, hirsutism, seborrhea, and premenstrual syndrome. Cs containing desogestrel, gestodene, and DRSP are called third-generation pills.
  5. Mala-N (30μg EE + 0.30 mg norgestrel per pill) is supplied free in India through family planning (welfare) clinics. Mala-D (30 μg EE + 0.15 mg levonorgestrel per pill) is sold at a subsidized rate (1/10th or 1/30th the price of other preparations).
    How to take
    One OC pill is to be taken during the first cycle from the first d or any of the next 4 days and should be continued daily for 21 days, stopped and restarted after a gap of 7 days, irrespective of onset or stoppage of menstruation during these pill-free days.
    In lactating women, it is preferable to use progestogen-only pills, if they are available, and the women choose to use them. Otherwise, combined oral contraceptives (COCs) should be used after breast feeding is stopped fully or COCs should be started 3-6 weeks after childbirth or if menstruation starts, whichever is earlier.

Management if Missed Pills


Missed Pill

What to do

One Missed

Take as soon as possible

Two / Three Missed

Carry on & finish the packet as usual but back up contraception for next one week.

More than Three missed

Carry on & finish the packet as usual but back up contraception for rest of the cycle

Pill and elective surgery


Stop 4 weeks before to avoide TE

Pill with Pregnancy


Risk of CMF tetus is some as general rate (2-3%), there for continue the pregnancy if required.

Mechanism of Action

  1. Inhibition of ovulation: The combined pills inhibit ovulation by suppressing hypothalamic-releasing factors, which in turn leads to inappropriate secretion of FSH and LH: these hormones are maintained at constant low levels similar to those seen in the proliferative phase of the cycle. As a result, no LH surge occurs and ovulation is suppressed.
  2. Alteration of endometrium: OCs alter maturation of the endometrium, rendering it unsuitable for implantation of the fertilized ovum.
  3. Changes in cervical mucus: Cervical mucus becomes scanty, viscous, and cellular with low spinnbarkeit and no ferning; these changes impair sperm transport and penetration.
  4. Pearl index: Combined pills are very effective. The failure rate when correctly and consistently used is only 0.1 % or 1 per 1000 in the first year of use, but the typical failure rate, as is commonly used, is 1.8%.
  5. The failures are mostly due to missed pills, delay in starting the next course, and stoppage of the drug due to side effect or fear complex without taking other contraceptive measures.


  1. Cure of menstrual disorders: OCs cure dysmenorrhea and ovulation pain. Menorrhagia and metrorrhagia can always be controlled by the use of COCs. OCs also lessen premenstrual tensions such as nervousness, irritability, depression, etc., during 7-10 days before menses. Also the cycles become regular.
  2. Protection against cancer: It has been conclusively proved that OCs directly prevent two common types of genital cancer: endometrial cancer and ovarian cancer; it also indirectly prevents choriocarcinoma by preventing pregnancy.
    COCs decrease the ovarian cancer by about 40% and the effect persists for at least 10 years. COCs also lower the risk of endometrial cancer by about 50%, the effect lasts for up to 15 years.
    They also decrease the risk of colon cancer.
  3. Protection against benign tumors and related diseases:
    1. Benign breast diseases (BBDs); It is well documented that BBDs, such as fibrocystic and fibroadenomatosis diseases, are reduced by 50-70% in pill users.
    2. Ovarian functional cysts: Various studies have shown that low-dose OCs lower the risk of developing functional ovarian cysts. The risk of follicular cysts goes down by 50% and that of corpus luteum cysts by about 80%.
    3. Fibromyoma of the uterus: The risk of uterine fibroid is reduced by about 30% in women who have used OCs for 10 years. Low-dose OCs help reduce fibroids and lessen menstrual flow.

Friends, in the previous question I have goven a list of conditions in which OCP’s are beneficial. Here I would like to mention in brief.


Tumors associated

Provides protection

Cervical cancer

Hepatic cancer

Pituitary adenoma

Breast cancer+/-

Ovarian tumors.cysts

Uterine tumor

Benign breast disease


OCP’s are protective against benign breast diseases, but as far as carcomp,a breast is concerned their role is controversial.


OCP’s are considered in the etiology of Ca breast.

  1. Protection against diseases:
    1. Ectopic pregnancy: Chance of ectopic pregnancy with its grave consequences is lowered by 50% in low- dose courses.
    2. Pelvic inflammatory diseases: Several studies have shown that regular pill users are protected from PIDs to the extent of 50%. OCs reduce PIDs by hindering the ascent of STD bacteria (including chlamydia) from the vagina upward by thickening the cervical mucus and lessening uterine motility, as well as by obviating illegal abortions and delivery of unwanted children.
    3. However, barrier contraceptives protect women better against STDs and HIV / AIDS than OCs do.
    4. Anemia and malnutrition: Pills reduce iron deficiency anemia by reducing menstrual flow in 60-80% of pill users; they improve nutrition of women by preventing repeated and frequent pregnancies.
    5. Endometriosis: Combined high-dose pills control endometriosis to a good extent when used continuously with increasing doses to produce pseudopregnancy.
    6. Acne and hirsutism: OCs are effective in treating acne and hirsutism by increasing sex-hormone-binding globulin and significantly decreasing free testosterone levels. Formulations with desogestrel, DRSP and cyproterone are specially effective in this respect.
  2. Premenstrual syndrome: OCs and pills containing DRSP reduce premenstrual syndrome.
    Side Effects and Risks
    1. Breakthrough bleeding: This is slightly more common with the lower-dose pills.
    2. The women should have two pills a day for 2 or 3 days, which usually controls BTB; if not, EE 0.02 mg may be taken for 7 days along with the pills.
    3. Oligomenorrhea happens sometimes with low-dose pills. The women should be reassured that oligomenorrhea is not harmful but rather good for health. But if they are not convinced, EE 0.02 mg may be added in the last 7 days for a few cycles.
    4. Amenorrhea is usually temporary and not harmful.
    5. Change to triphasic pills or supplementation with EE for two to three cycles usually cures amenorrhea.
    6. Stroke and myocardial infarction: Women who do not smoke, have their blood pressure checked, and do not have hypertension or diabetes are at no increased risk of myocardial infarction if they use low-dose COCs, irrespective of their age and duration of OC use.
    7. The risk of hemorrhagic stroke does not increase in women below 35 years of age who do not smoke and are not hypertensive.
    8. Current users of low-dose COCs have a low absolute risk of VTE mainly because incidence of VTE is very low in nonpregnant women. Nevertheless, this risk is three to six times more than nonusers. The absolute risk of VTE attributable to OC use rises with increasing age, recent surgery, and some forms of thrombophilia. Progestogens are associated with the increase of low-density lipoprotein cholesterol and a decrease of high-density cholesterol, which enhance the risk of atherosclerosis, coronary heart disease and cerebral thrombosis; but estrogens have the opposite effect, and these actions seem relatively balanced in low-dose COCs.
    9. Breast and cervical cancer: There is a small increase in risk of current users of the pill (relative risk 1.24), and the risk reduces gradually over the 10 years after discontinuing use.
    10. Breast cancer in current or past OC users is largely localized in the breast-a condition that usually has a better prognosis.
    11. The risk of breast cancer is due to the progestogen component of the pills, as the risk is same among users of progestogen-only methods.
    12. Studies in developed and developing countries have shown a modest increase in the risk of cervical cancer (1.3-1.8-fold) among women who have used COCs for more than 5 years. However, it is not clear whether the increased risk is due to direct effect of the pill or some characteristics of the pills' users such as age at first intercourse, number of sexual partners, parity, and smoking status.
    13. Liver tumor: OCs increase the incidence of a rare benign liver tumor, namely, primary hepatocellular adenoma.
    14. Vitamin B6 (pyridoxine) may help curing depression after OC use.

Drug Interactions


Barbiturates, sulfonamides, rifampicin, and anticonvulsant drugs interfere with the effect of OCs and increase failure rates. As such, it would be prudent to use high-dose formulations if other contraceptives prove unsuitable for patients taking those drugs.


Medical Eligibility Criteria for Initiation and Continuation of Combined OCs/Combined Injections/Transdermal Patches and Vaginal Rings.


WHO Category 4: Absolute contraindications for combined OC pills/ combined injections/ combined vaginal rings and patches

  1. Active liver disease (hepatitis/tumor)
  2. Postpartum: breast-feeding women <6 week postpartum
  3. Thrombophilia
  4. Ischemic heart disease
  5. Complicated migraine
  6. Pregnancy
  7. Complicated valvular heart disease
  8. Breast cancer (current or past history)
  9. Severe hypertension (systolic> 160 or diastolic> 100)
  10. DM with vascular complications
  11. Current history of thromboembolism/ stroke/ deep vein thrombosis

NOTE: Smoking, age more than 35 years, mild hypertension and uncomplicated DM are relative contraindications.

Progesterone-Only Pills/Mini Pills

Women who can use (indications) progestogen-only contraceptives safely and effectively include:

  1. Age: menarche to menopause
  2. Hypertension adequately controlled
  3. Thrombotic disorders
  4. Obesity
  5. Breast feeding >6 weeks onward
  6. DVT/PTE
  7. Non-breast-feeding before or after 21 days
  8. Valvular heart disease
  9. Smoking: any age

Category 4 for progesterone-only pills:

  1. Pregnancy
  2. Breast cancer
  3. Unexplained vaginal bleeding

Mechanism of action: same as COC.


They should be taken at the same time every day.


Pearl index for progesterone-only pills = 3%




To avoid bad effects of OCs, centchroman has been produced by the researchers of Central Drug Research Institute, Lucknow, India. It is a nonhormonal, chemical-synthetic, once-a-week Oe. "Centron" and "Saheli," contain 30 mg of centchroman.


Centchroman has a weak estrogenic and potent antiestrogenic effect-acting mostly on the endometrial target organs to suppress proliferation of the endometrium, thereby interfering with nidation of the embryo; it has no progestational, androgenic, or antiandrogenic properties.


Antiprogesterone RU-4S6 (Mifepristone)


This antiprogesterone compound, which prevents hormone action at the receptor level, produces a contraceptive effect at several points m the menstrual cycle. Given orally in mid-cycle, it can delay or inhibit the mid-cycle LH surge; administered in the late luteal phase, it induces menstruation or, when menses is delayed, very early abortion.


It has potential in future for use as a once-a-month pill during the luteal phase, however as of now it is not used for contraception.

Injectable Contraceptives

Progestogen-only injectable contraceptives:

  1. Depot-medroxyprogesterone acetate (DMPA)
  2. Norethisterone enanthate (NET EN or Noristerat)

One injection of Depo-Provera remains effective for 3 months. It is administered in the form of a 150 mg injection once every 3 months plus or minus 14 days.


One 200 mg NET EN injection is to be taken every 2 months


Both DMPA and NET EN are highly effective methods of contraception.

Pearl index: Typical failure rate of progestogen-only injectables, as commonly used, is 0.1-0.4%.

Mechanism of Action


The injectable contraceptives act by inhibiting ovulation in most women. They also work by making cervical mucus thick and scanty, thus creating a barrier to sperm penetration, and making the endometrium less suitable for implantation.


Noncontraceptive Benefits

  1. It cures menstrual troubles like menorrhagia and dysmenorrhea
  2. Medical management of endometriosis (pseudo pregnancy regimen)
  3. Prevention and treatment of endometrial hyperplasia.
  4. DMPA prevents sickling and the development of abnormal-shaped red blood cells, and lessens episodic bone pain in women suffering from sickle cell diseases; it is thought to be the best contraceptive for patients of sickle cell anemia.
  5. DMPA reduces the risk of pelvic inflammatory disease and ectopic pregnancy.
  6. DMPA use protects against the risk of endometrial and ovarian cancer.
  7. Injectables are suitable in cases with myoma and endometriosis, as contraception is provided without estrogen effect.

Side Effects

  1. Irregular menstrual bleeding and spotting, as well as temporary amenorrhea, are the most common side effects in DMPA and NET EN users.
  2. Weight gain: The average weight gain is 1-3 kg in most cases.
  3. There is a delay of few months in becoming pregnant following discontinuation of the injection.
  4. Bone density changes: There is a risk of bone loss among long-term DMPA users leading to osteoporosis; however, this bone loss is reversible on cessation of the contraception.

Combined (estrogen + progesterone) monthly injectable contraceptives:

  1. DMPA 25 mg plus estradiol cypionate 5 mg marketed as l<3clofem"
  2. NET EN 50 mg plus estradiol valerate 5 mg marketed as "Mesigna"

Contraceptive Implants

The Norplant system consists of six silastic capsules each containing 36 mg of LNG. These are inserted under the skin in the inside of the upper arm or forearm in most cases, in a fan-shaped manner under local anesthesia. It is effective for 5 year.


Norplant II or Jadelle has two rods, and remains effective for 5 years.


Norplant prevents pregnancy in three ways: (1) it makes cervical mucus thicker and scantier, preventing sperm penetration; (2) LNG suppresses ovulation and (3) it depresses the endometrial growth, necessary for implantation of the ovum.

Both Norplant and LNG rod (Norplant II or Jadelle) have a failure rate of 0.4-0.8%.


Implanon is a new contraceptive implant. It is a single-rod device containing 67 mg of the progestogen 3-keto-degigestrel, also called etonogestrel (ENG).


It is placed subcutaneously on the inner side of the upper arm under local anesthesia. Implanon acts primarily by inhibiting ovulition, supplemented by the usual mucus and endometrial effects (similar to Norplant).


NO PREGNANCIES have been reported so far with the use of Implanon.

Contraceptive Rings

  1. Nuva Ring:
    1. It is a soft vaginal ring that releases 15 μg EE and 120 μg ENG, the active metabolite of desogestrel, per day as a controlled delivery system.
    2. Women keep the NuvaRing in the vagina for 3 weeks and then remove it for 1 week, during which they have withdrawal bleeding.
    3. A new vaginal ring is needed for each 4-week cycle.
    4. Increased patient compliance is the advantage over OC pills.
    5. It has been launched in India in November 2009.
    6. The efficacy rate of NuvaRing is like that of COCs-the failure rate after perfect use is 0.3%.
  2. A vaginal progesterone-only ring called "Progering" has been developed and has been undergoing clinical trials.
    It contains natural hormone progesterone. These rings are slightly less effective than combined vaginal rings; however, they are very effective in lactating women because breast feeding itself provides some protection against pregnancy. They do not contain estrogen, which can reduce milk production. Each ring releases 10 mg of progesterone daily and lasts for 3 months.
  3. LNG ring: It contains 5 mg LNG, 20 μg/ day, is released; left inside vagina for 3 months continuously.

Transdermal Contraceptive Patch

The combined patch delivers 150 μg of the proestrogen (norelgestromin) and 20 μg of EE per day. A woman wears a patch for 1 week and then replaces it by another one placed at a different site for a total of 3 weeks, followed by 1 week with no patch.


The patches work by preventing ovulation, thickening the cervical mucus, and suppressing endometrial growth.


It provides effectiveness and cycle control like those of OCs when used. The failure rate with typical use within the first year is 2 per 100 women and with perfect use 0.3 per 100 women.

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