Oral Contraceptive Drugs

Oral contraceptives are among the most widely used agents throughout the world of drugs requiring a prescription.They have influenced the lives of untold millions of individuals and have had a revolutionary impact on global society, since they became available in 1960. For the first time in history a convenient, affordable and completely reliable means of contraception was available for family planning and the avoidance of unplanned pregnancies.

A large number of oral contraceptives containing estrogens or progestins (or both) are now available for clinical use. These preparations vary chemically and, as might be expected, have many properties in common, but they exhibit definite differences.

Important Use of Oral Contraceptives

1. Hormonal contraceptives are among the most effective drugs available.
2. A variety of agents with substantially different components, doses, and side effects are available and provide real therapeutic options.
3. In contrast to drugs that are used to treat disease, these agents generally are used in a relatively young and healthy population; the consideration of possible side effects thus is especially important.
4. In addition to contraceptive actions these agents have substantial health benefits.
5. Because of differences in doses and specific compounds used, it is not appropriate to extrapolate directly untoward effects of hormonal contraceptives to hormone replacement therapy, or vice versa.

Three types of preparations are used for oral contraception: (1) Combination Oral Contraceptives (combinations of estrogens and progestins); (2) Sequential Preparations; and (3) Progestin-Only Contrceptives (continuous progestin therapy without concomitant administration of estrogens. The preparations for oral use are all well absorbed, and in combination preparations, the pharmacokinetics of neither drug is significantly altered by the other.

Mechanism Of Action

Combination Oral Contraceptives

Combination oral contraceptives act by preventing ovulation. Direct measurements of plasma hormone levels indicate that Luteinizing Hormone (LH) and Follicle-Stimulating Hormone (FSH) levels are suppressed, a midcycle surge of LH is absent, endogenous steroids levels are diminished, and ovulation does not occur. While either component alone can be shown to exert these effects in certain situations, the combination synergistically decreases plasma gonadotropin levels and suppresses ovulation more consistently than either alone.

Progestin-Only Constraceptives

Progestin-only contraceptives prevent ovulation in 70% to 80% of cycles, largely by slowing the frequency of the gonadotropin-Releasing Hormone GnRH pulse generator and blunting the LH surge. There is, however, a great deal of variability in LH and FSH patterns in women receiving these drugs. These effects are thought to be largely at the hypothalamic level since the pituitary can respond to exogenous GnRH is women receiving these agents. However, the effectiveness of these agents generally is considered to be approximately 96% to 98%, suggesting that other mechanisms are involved in their actions. A thickening of the cervical mucus to decrease sperm penetration and endometrial alteration that impair implantation are thus thought to contribute significantly to their efficacy.

List of OralContraceptive Drugs (Click Here)

Other Pharmacological Effects

Effects on the Ovary:

Chronic use combination agents depresses ovarian function. Follicular development is minimal, and corpora lutea larger follicles, stromal edema, and other morphological features normally seen in ovulating women are absent. The ovaries usually become smaller even when enlarged before therapy.

Effects on the Uterus:

After prolonged use, the cervix may show some hypertrophy and polyp formation. There are also important effects on the cervical mucus, making it more like postovulation mucus, ie, thick and less copious.

Effects on the Breast:

Stimulation of the breasts occurs in most patients receiving estrogen containing agents. Some enlargement is generally noted. The administration of estrogens and combinations o estrogens and progestins tends to suppress lactation. When the doses are small, the effects on breast feeding are not appreciable. Preliminary studies of the transport of the oral contraceptives into the breast milk suggest that only small amounts of these compounds are found, and they have not been considered to be of importance.

Effects on the central nervous system:

Estrogen tend to increase excitability in the brain, whereas progesterone tends to decrease it. The thermogenic action of progesterone and some of the synthetic progestins is also thought to be in the central nervous system.

Effects on endocrine function:

The inhibition of pituitary gonadotropin secretion has been mentioned. Estrogens are known to alter adrenal structure and function. Estrogens incerase the plasma concentration of the alpha2-globulin that binds hydrocortisone (corticosteroid-binding globulin). This does not appear to lead to any chronic alteration in the rate of secretion of cortisol, but plasma concentrations may be more than double the levels found in untreated individuals. It has also been observed that ACTH response to the administration of metyrapone is attenuated by estrogens and the oral contraceptives.

Effects on blood:

The oral contraceptives do not consistently alter bleeding or clotting times. The changes that have been observed are similar to those reported in pregnancy. There is an increase in factors VII, VIII, IX and X. Increased amounts of coumarin derivatives may be required to prolong prothrombin time in patients taking oral contraceptives.

Effects on the liver:

These hormones also have profound effects on the function of the liver. Important alterations in hepatic drug excretion and metabolism occur. The effects on serum proteins result from the effects of the estrogens on the synthesis of the various alpha2-globulins and fibrinogen. Serum haptoglobins that also arise from the liver are depressed rather than increased by estrogen.

Effects on lipid metabolism:

Estrogens increase serum triglycerides and free and esterified cholesterol. Phospholipids are also increased, as are high-density lipoproteins. Preparations containing small amounts of estrogen and progestin may slightly decrease triglycerides and high-density lipoproteins.

Effects on carbohydrate metabolism:

The administration of oral contraceptives produces alterations in carbohydrate metabolism similar to those observed in pregnancy. These is a reduction in the rate of absorption of carbohydrates from the gastrointestinal tract. Progesterone increases the basal insulin level and the rise in insulin induced by carbohydrate ingestion. Preparations with more potent progestins such as norgestrel may cause progressive decreases in carbohydrate tolerance over the years. However, the changes in glucose tolerance are reversible on discontinuing medication.

Effects on the cardiovascular system:

These agents cause small increases in cardiac output associated with higher systolic and diastolic blood pressure and heart rate.

Effects on the skin:

The oral contraceptives have been noted to increase pigmentation of the skin (chloasma). This effect seems to be enhanced in women who have dark complexions and by exposure to ultraviolet light. Some of the androgen-like progestins may increase the production of sebum, causing acne in some patients. However,, since ovarian androgen is suppressed, many patients noted decreased acne and terminal hair growth. The sequential oral contraceptive preparations as well as estrogens often decrease sebum production. This may be due to suppression of the ovarian production of androgens.

Untowards Effects

Mild Adverse Effects:

1. Nausea, mastalgia, breakthrough bleeding, and edema are related to the amount of estrogen in the preparation.
2. Changes in serum proteins and other effects on endocrine function.
3. Headache is mild and often transient.
4. Withdrawal bleeding sometimes fails to occur

Moderate Adverse Effects:

1.Breakthrough bleeding is the most common problem in using progestational agents alone for contraception.

2. Weight gain is more common with the combination agents containing androgen-like progestins.
3. Increased skin pigmentation may occur, especially in dark-skinned women.
4. Acne may be exacerbated by agents containing androgen-like progestins, whereas agents containing large amounts of estrogen usually cause marked improvement in acne.
5. Hirsutism may also be aggravated by the 19-nortosterone derivatives, and combination containing nonandrogenic derivatives, and combinations containing nonandrogenic progestins are preferred.
6. Ureteral dilation similar to that observed in pregnancy has been reported, and bacteriuria is more frequent.
7. Vaginal infections are more common and more difficult to treat in patients who are receiving oral contraceptives.
8. Amenorrhea – following cessation of administration of oral contraceptives, 95% of patients with normal menstrual histories resume normal periods and all but a few resume normal cycles during the next few months.

Severe Adverse Effects:

1. Venous thromboembolic disease.
2. Myocardial infarction
3. Cerebrovascular disease
4. Gastrointestinal disorders
5. Depression
6. Carcer

Beneficial Effects of Oral Contraceptives

It has become apparent during the last decade that reduction in the dose of the constituents of oral contraceptives has markedly reduce mild and sever adverse effects, providing a relatively safe and convenient method of contraception for many young women. Treatment with oral contraceptives has now been shown to be associated with many benefits unrelated to contraception. These include a reduced risk of ovarian cysts, ovarian and endometrial cancer, and benign breast disease. There is a lower incidence of pelvic inflammatory disease and ectopic pregnancy. Iron deficiency, duodenal ulcer, and rheumatoid arthritis are less common, and premenstrual symptoms, dysmenorrhea, and endometriosis are ameliorated with their use.