Combined oral contraceptive pill

Oral contraceptives are chemicals taken by mouth to inhibit normal fertility. All act on the hormonal system. Female oral contraceptives have been on the market since the early 1960s, and enjoy great popularity. They are used by millions of women around the world, though the acceptance varies by region: one quarter of reproductive age women in the United Kingdom use them, but they are less widely used in countries such as Japan. Male oral contraceptives remain a subject of research and development, and are not widely available to the public.

History

Invention

In the late 1940s, Russell Marker, a professor of botany at the Pennsylvania State University, became interested in hormones that were naturally found in plants. He searched the Southwest examining the cactus but the quantity of hormones in these plants was very low. He read an obscure article by a Japanese scientist who described a yam that could be found in Mexico that had a high content of hormones. He traveled to Mexico and obtained permission to harvest several of the plants. He claims one was stolen overnight but went forward with his work and produced a progestin.

He brought the new substance back to the U.S. where the scientific community was less than receptive to his findings. Major companies such as G.D. Searle and Merck were already using animal sources to make their hormones, which prevented them from being able to cheaply manufacture sufficient quantities. Returning to Mexico, Marker formed a company called Syntex (Synthetic + Mexico), which was incorporated in January 1944. This small company commenced to produce hormones from the Mexican yam and sold the product to other pharmaceutical companies.

At the end of the first year, Marker approached the president of the company and wanted his share of the profits. He was told that there were no profits because they were reinvested into Syntex. Very upset, Marker turned his back on the venture and returned to relative obscurity at Penn State, never to gain much credit for his initial work.

File:Miramontes notebook.jpg

Luis E. Miramontes signed laboratory notebook. October 15, 1951

When Marker left Mexico, his work had to be recreated to keep Syntex going. Hungarian scientist, George Rosencrantz, was found in Cuba, where he had recently escaped the growing threat of Hitler and was appointed director of the firm. He reproduced Marker's work using fewer chemical steps and Syntex was on its way again. Carl Djerassi, a young Bulgarian chemist was hired as scientific director and a number of Mexican scientists were also added coming from the newly-born Institute of Chemistry from the top Mexican university UNAM. Among them was Luis E. Miramontes, aged 26, who was Djerassi's student at the time. On October 15, 1951, Miramontes hand wrote on his laboratory notebook his own new procedure for the synthesis of the progestin norethindrone. Norethindrone formed the basis of some of the most powerful progestins.

At the Worcester Foundation for Experimental Biology in Shrewsbury, Massachusetts, Hudson Hoblin, Min Chueh Chang, Robert Kistner, and others, were doing work with hormones. They had in their possession two progestins, Northindrone (Syntex) and Northynodrel (G.D. Searle). Chang was working with rabbits and discovered that high doses of these progestins would shut down the ovaries and prevent ovulation. Margaret Sanger, a friend of Hudson Hoblin, along with Katherine Dexter McCormick visited the Worcester Foundation to discuss if there were any methods available for women to be able to plan their families. They apparently connected Dr. Chang's work and what they were discussing together. McCormick, whose fortune came from Cyrus McCormick's invention of the mechanical reaper, provided the research money for the Worcester Foundation to proceed.

After the animal studies were completed, the Worcester Foundation chose to use Searle's Northynodrel with an added estrogen to create the first pill. The first human use of oral contraceptives was in Puerto Rico, by patients of Edris Rice-Wray Carson. This formulation, Enovid, was introduced in the U.S. by G.D. Searle, who pioneered in marketing this concept. About a year later, Syntex licensed their version to Johnson & Johnson, which sold it as Ortho-Novuum. In 1964, Syntex started marketing Norinyl, which was the same product as Ortho-Novuum in a different dispenser.

Though the Food and Drug Administration approved it for clinical use on May 9, 1960, it took various high-profile court cases, such as Poe v. Ullman and Griswold v. Connecticut, to make it available to all women of reproductive age. Today much smaller amounts of the hormones are used and the formulations are offered in a variety of configurations.

France

The Pill was declared to be legal in 1967 after the introduction of the Neuwirth Law.

Japan

In Japan, lobbying from the Japan Medical Association led to the Pill being not approved for nearly 40 years. Two main objections raised by the association were safety concerns over long-term use of the Pill, and concerns that Pill use would lead to diminished use of condoms and thereby potentially increase sexually-transmitted infection rates. Some voiced suspicions that potential loss of income due to lower abortion rates that could result from Pill use might have been a factor in the organization's objection. The association responded to its critics by pointing out that doctors would have received higher monetary compensation from prescribing pills, given Japan's national health insurance system. Partially due to the widespread regular use of condoms, Japan did avoid the spread of AIDS early in the epidemic. The low rate of HIV infection in Japan is cited by the association as a vindication of their policy.

The Pill was finally approved for use in 1999, however the Pill prescription guidelines the government endorsed are quite stringent. They require Pill users to visit a doctor every three months for pelvic examinations and undergo tests for sexually transmitted diseases and uterine cancer. In the United States and Europe, in contrast, an annual examination is standard for Pill users. Still only very few women take it up. For a detailed discussion of abortion and pill politics in Japan see Tiana Norgren (2001) Abortion before Birth Control.

Principles

Female oral contraceptives, colloquially known as the Pill, are the most common form of pharmaceutical contraception. They are used to prevent pregnancy. The pill is also used for certain medical conditions, in particular: to control symptoms of polycystic ovary syndrome (PCOS), irregular or painful menstrual cycles (dysmenorrhea), anemia related to menstruation, and certain disorders where there is dysfunctional uterine bleeding, as well as situations of endometriosis.

Female oral contraceptives consist of a pill that women take daily and that contains doses of synthetic hormones (always a progestin and most often also an estrogen). In some types of pill the doses of hormones are adjusted to be in synchrony with the menstrual cycle (two- or three-phase pills), while others keep a constant level of the hormones.

Use

The Pill must be ingested daily, within 12 hours of the same time each day (for progesterone/estrogen pills - as opposed to within 3 hours for Progesterone only pills). Most brands are packaged with 21 days of active (hormone-containing) pills followed by either 7 days of placebo pills, or instructions to not take pills for seven days. A woman on the pill will have a withdrawal bleed, or period, sometime during the placebo week.

If a woman just starting the pill begins taking them on the first day of her menstrual cycle (first day of red bleeding), she will have pregnancy protection from the very first pill. If a woman begins taking the pill at another time in her menstrual cycle, she must use a different form of contraception for seven days.

Mechanism of action

Oral contraceptive

Several different types of 'the Pill' exist. Generally, they all have different synthetic estrogens and progestins, chemical analogues of the natural hormones, estradiol (an estrogen) and progesterone (a progestagen). Most common brands use 20 to 40 micrograms of ethinyl estradiol as the estrogen component and either a fixed or varying (the bi- and triphasic pills) amount of either levonorgestrel or norethindrone as the progestagen component. An exception is the Progesterone only pill, which lacks estrogen and thus generally has fewer side effects than the combined pill.

The combined Pill prevents pregnancy primarily by preventing ovulation. It also has the side-effect of thickening the mucous over the cervix, which can prevent or slow sperm entry into the uterus. The Pill also thins the endometrium (the lining of the uterus).

Contraception vs Abortion debate

There are physicians who point to this thinning of the endometrium as evidence that the Pill is an abortifacient. This claim is based on experiences with in vitro fertilisation which demonstrated that thinner uterine linings correlated with increased difficulty in getting the test-tube-fertilized eggs to implant. However, other physicians (including some pro-life physicians) are unconvinced that this truly does decrease the likelihood that a fertilized egg will implant itself in the uterine lining.

In women who do not take The Pill, the uterine lining is usually unreceptive to implantation prior to ovulation. The purpose of the hormones released by the corpus luteum is to cause the endomitrium to thicken and become receptive to implantation (which occurs between six and twelve days after ovulation if the ovum is fertilized). Thus, simple observations that the uterine lining is too thin to support implantation during a cycle where no ovulation has occurred is insufficient to support the claim that there is a reduced likelihood of implantation in ovulatory Pill cycles. Currently, no research has been conducted on the behavior of the endometrium in ovulatory Pill cycles.

The theory that the pill has postfertilization effects is also based on some studies that found the ratio of extrauterine to intrauterine ratio of pregnancies increases by 70-1390% in women using the pill although not all research reaches the same conclusions. The asserted increased proportion of extrauterine pregnancies is most likely explained by interference of the pill with the normal process of implantation.

The medical consensus is that pregnancy starts with implantation, not fertilization. This definition of pregnancy did not start until the advent of in vitro fertilization - having eggs fertilized in a laboratory is not generally accepted to make a woman pregnant. Many sources do still define pregnancy as beginning with fertilization. Therefore, the determination of whether oral contraceptives are abortificants depends largely on a person's individual definition of pregnancy.

Effectiveness

The Pearl Index is often used to compare the effectiveness of various methods of contraception. It is expressed as the "number of pregnancies in 100 normally fertile women over the period of one year". Each method of birth control has two Pearl index numbers:

• method effectiveness: is the Pearl index number for use under perfect conditions. The method effectiveness Pearl index for the Pill has been measured as low as 0.3 and as high as 1.25, which means that under ideal conditions, anywhere from 0.3 to 1.25 out of 100 users will become pregnant during one year of perfect use (Pearl index = 0.3 to 1.25).

• user effectiveness or typical effectiveness: is the Pearl index number for use that is not consistent or always correct. The user effectiveness measured by the Pearl index for the Pill has been measured as low as 2.15 and as high as 8.0, which means that anywhere from 2.15 to 8.0 out of 100 women will become pregnant during the first year of typical use (Pearl index = 2.15 to 8.0).

Many women occasionally forget to take the Pill daily, impairing its effectiveness. Correct use of the pill usually implies taking it every day at the same hour for 21 days, followed by a pause of seven days.

Use of other medications can prevent the Pill from working, due to interactions with the metabolism of the hormonal constituents. Diarrhea will also stop the Pill from working, because the hormones are not properly absorbed by the bowels.

While the Pill is usually effective, its wide availability has not prevented all unplanned pregnancies.

Packaging

Half-used blister pack of Levlen®ED

The Pill usually comes in two different packet sizes, where each usually has days marked off for a cycle lasting of 28 days. For the 21-pill packet, a pill is consumed daily for three weeks, followed by one week of waiting period before starting the next packet. For the 28-pill packet, pills are consumed daily as well. However, instead of taking pills for 21 days only, the user also takes seven placebo or sugar pills included. Once they are finished, the next packet can be started right away.

The purpose of the placebo pills is that the user, out of habit, can take a pill on every day of her menstrual cycle, instead of calculating the date she should start the next dose. If the pill formulation is monophasic, it is possible to skip menstruation and still remain protected against conception by skipping the placebo pills and starting directly with the next packet. Attempting this with bi- or tri-phasic pill formulations carries an increased risk of breakthrough bleeding and may be undesirable. It will not, however, increase the risk of getting pregnant. The presence of placebo pills is thought to be comforting, as menstruation is a physical confirmation of not being pregnant. Breakthrough bleeding also becomes a more common side effect as a woman attempts to go longer periods of time between menstrual periods. The pills may contain an iron supplement, as iron requirements increase during menstruation.

Drug interactions

Some drugs reduce the effect of the Pill and can cause breakthrough bleeding, or pregnancy (together with unprotected sex, of course). These include antibiotics, barbiturates, phenytoin and carbamazepine. The traditional medicinal herb St John's Wort has also been implicated.

Side-effects

When starting to take the Pill some women report slight weight gain, although most studies show that the incidences of this is about 50% and as many women experience slight weight loss. Some women also notice changes in the intensity of sexual desire, vaginal discharge and menstrual flow.

Other possible side effects are: breakthrough bleeding, nausea, headaches, depression, vaginitis, urinary tract infection, changes in the breasts, changes in blood pressure, skin problems, skin improvements, and gum inflammation. The insert included with each pill packet usually has a more extensive list of recognized side effects.

Formulations

See oral contraceptive formulations

Effects on sexuality

The effect of the Pill on a woman’s sexuality are difficult to judge; depending on the individual and the particular formula, the Pill may enhance or disrupt a woman’s (or couple’s) sex life. Neither the woman who uses the Pill nor her partner need take any special action before or during intercourse, which makes birth control "invisible" and sex spontaneous and more natural. When combined with the Pill’s high degree of effectiveness, this may enable the couple, and especially the woman, to relax more easily during sex. Masters and Johnson, among others, reported more than one woman who experienced her first orgasm during intercourse shortly after going on the Pill.

On the other hand, the Pill’s various side effects may prove disruptive on a physiological or even a psychological level. The hormonal disruption caused by the Pill may result in mood swings, lower libido, excessive or insufficient vaginal lubrication during intercourse, and possibly an injured self-image due to weight gain. Some women who use the Pill despite the teachings of their religious traditions may feel conscious or unconscious guilt; others may not fully trust an "invisible" method of birth control. This wide range of variables makes prediction of the Pill's effect on sexuality difficult, but the fact that the Pill can and does have an impact in this area, for good or for ill, is well-documented.

Cautions and contraindications

Oral contraceptives may influence coagulation, subtly increasing the risk of deep venous thrombosis (DVT) and pulmonary embolism, stroke and myocardial infarction (heart attack). However, estrogen contraceptives are usually only contraindicated in women with pre-existing cardiovascular disease, in women who have a familial tendency to form blood clots (such as familial factor V Leiden), women with severe obesity and/or hypercholesterolaemia (high cholesterol level) and most notably in smokers.

Estrogen based pills have also been linked to an increased risk of breast cancer, although newer Pill types may not influence breast cancer risk. In rare cases, high estrogen Pills may trigger benign intracranial hypertension.

The chance of developing most of the above problems increases with age - especially when certain other health problems are present. The risks are even greater for women who are age thirty five or older, smoke more than fifteen cigarettes a day, or have conditions associated with heart attack, such as diabetes, high blood pressure, or high levels of cholesterol, and certain inherited conditions that increase the risk of blood clotting. Women using the Pill who undergo major surgery seem to have a greater chance of having blood clots.

In Our Sexuality, Crooks and Baur state a commonly held medical opinion about risks associated with Pill use: "In general, the health risks of oral contraceptives are far lower than those from pregnancy and birth."

Non-Contraceptive Uses

The hormones in "the Pill" are used to treat medical conditions. Because of the effect on the uterine lining, oral contraceptives are a gentler way to administer certain hormonal therapies. For example, in some disorders, the uterine lining doesn't shed completely; this increases the risk of uterine cancer.

Ortho Tricyclen, in the well-known Ortho Dialpak dispenser. Introduced in the 1990s, Tricyclen was the first oral contraceptive found by the U.S. Food and Drug Administration to be an effective treatment for acne. This announcement, highly touted by its manufacturer, helped to make Tricyclen one of the most widely-used contraceptives in history, especially among younger women.

Aside from being a contraceptive, and controlling the symptoms of some hormonal disorders, many women use the Pill so their periods will be predictable (although the Pill does not treat many underlying causes of irregular cycles). There may also be incidental benefits to the Pill. There is some evidence that use of the pill might reduce the incidence of ovarian cancer and endometrial cancer. It may also be beneficial in the treatment of acne. As there is also evidence that use of the pill may increase the risk of developing breast cancer or deep-vein thrombosis, particularly in women who smoke and women over age 35, individuals must do their own cost-benefit analyses.

Although the FDA does not officially condone the use of the Pill as a minor breast enhancer, many women have gone on the pill in order to increase their breast size. This results from the low doses of estrogen present along with the progesterone. Results vary widely.

Social and cultural impact

Introduced at the beginning of the tumultuous decade of the 1960s, the Pill was nothing short of revolutionary. In the first place, it was far more effective than any previous method of birth control, giving women unprecedented control over their fertility. Its use was separate from intercourse, requiring no special preparations at the time of sexual activity that might interfere with spontaneity or sensation. When a woman of childbearing age began using the Pill, for the first time in history she and her partner could enjoy, at any time in her menstrual cycle, a completely natural-seeming act of intercourse, up to and including her partner’s ejaculation within her vagina, with a virtual guarantee that pregnancy would not result. This combination of factors served to make the Pill immensely popular within a few years of its introduction.

Also unlike other contraceptives, the Pill had potential uses other than contraception, such as the control of heavy menstrual bleeding or cramps (dysmenorrhea). Since dysmenorrhea is a common disorder, this allowed some women to obtain contraceptives without having to acknowledge that they were engaging in socially unsanctioned sexual activity.

The fact that the Pill was a female method of contraception came to play a complex gender-relationship role. During the 1960s, its effectiveness, for the first time in history, allowed women the same degree of sexual freedom that had before belonged only to men. This contributed to the rise of the sexual revolution as the decade wore on.

Because the Pill was so effective, and soon so widespread, it also heightened the debate about the moral and health consequences of pre-marital sex and promiscuity. Never before had sexual activity been so divorced from reproduction. For a couple using the Pill, intercourse became purely an expression of love, or a means of physical pleasure, or both; but it was no longer a means of reproduction. While this was true of previous contraceptives, their relatively high failure rates and their less widespread use failed to emphasize this distinction as clearly as did the Pill. The spread of oral contraceptive use thus led many religious figures and institutions to debate the proper role of sexuality and its relationship to procreation. The Catholic Church in particular, after studying the phenomenon of oral contraceptives, re-emphasized traditional Catholic teaching on birth control in the 1968 papal encyclical Humanae Vitae. The encyclical, which reiterated the traditional Catholic teaching that artificial contraception distorted the nature and purpose of sex, was greeted with open dissent by many Catholics, which contributed to the rise of a culture of dissent in following years on other Catholic teachings.

A backlash against oral contraceptives occurred in the early and mid-1970s, when reports and speculations appeared that linked the use of the Pill to breast cancer. Until then, many women in the feminist movement had hailed the Pill as an "equalizer" that had given them the same sexual freedom as men had traditionally enjoyed. This new development, however, caused many of them to denounce oral contraceptives as a male invention designed to facilitate male sexual freedom with women at the cost of health risk to women. At the same time, society was beginning to take note of the impact of the Pill on traditional gender roles. Women now did not have to choose between a relationship and a career; singer Loretta Lynn commented on this in 1975 with a song entitled "The Pill," which told the story of a married woman's use of the drug to liberate herself from her traditional role as wife and mother.

Further, married women had control over their family size, even if their belief was that the woman was obligated to submit to her husband's sexual desires -- regardless of her interest -- which had been a prevailing view in many cultures. For women with abusive husbands or women who had had high risk pregnancies, this control was potentially lifesaving; however, it did lead to the conflict of obtaining medication without fully informing the husband.

In time, however, as society adjusted to these new facts, the Pill largely regained its reputation, due to its indisputable effectiveness and convenience. According to some sources, 80 percent of American women use the Pill at some point in their lives,

External Links

• CBC Digital Archives - The Birth Control Pill
• Roe Depot ~ a forum on reproductive rights & alternative birth control

See also

• Morning-after pill
• Progesterone only pill