combined oral contraceptive pills ( COCP ), often referred to as birth control pills or colloquially as " pills " , is a type of birth control designed to be taken orally by women. These include a combination of estrogen (usually ethinylestradiol) and progestogen (especially progestin). When taken correctly, it changes the menstrual cycle to eliminate ovulation and prevent pregnancy.
They were first approved for contraceptive use in the United States in 1960, and were a very popular form of birth control. They are currently used by more than 100 million women worldwide and by nearly 12 million women in the United States. In 2012, 16% of US women aged 15-44 reported being on birth control pills, making it the most widely used method of contraception among women of that age range. Usage varies by country, age, education, and marital status. One-third of 16-49-year-old women in the UK currently use combination pills or progestogen-only pills, compared with only 1% of women in Japan.
Two forms of combined oral contraceptives are on the World Health Organization's Essential Drug List, the most important medication needed in the basic health system. The pill is the catalyst for the sexual revolution.
Video Combined oral contraceptive pill
Medical use
Contraception use
The combined oral contraceptive pill is a type of oral medication designed to be taken daily, at the same time, to prevent pregnancy. There are many different formulations or brands, but the average package is designed to be taken over a 28 day period, or cycle. During the first 21 days of the cycle, users take daily pills containing hormones (estrogen and progestogen). The last 7 days of the cycle are hormone-free days. Some packages contain only 21 pills and users are advised not to take pills during the following week. Another package contains 7 additional placebo pills, or pills that are not biologically active. Some new formulations have 24 days of active hormone pills, followed by 4 days of placebo (for example including Yaz 28 and Loestrin 24 Fe) or even 84 days of active hormone pills, followed by 7 days of placebo pills (Seasonale). A woman taking a pill will experience bleeding at any time during a placebo pill or not taking pills, and is still protected from pregnancy during this time. Then after 28 days, or 91 days depending on the type of person being used, the user starts a new package and a new cycle.
Effectiveness
If used exactly as instructed, the estimated risk of pregnancy is 0.3%, or about 3 out of 1,000 women on COCPs will become pregnant within one year. However, typical use is often inappropriate because of time errors, forgetful pills, or unwanted side effects. With typical use, the estimated risk of getting pregnant is about 9%, or about 9 out of 100 women in COCP will become pregnant within a year. The rate of complete failure of use is based on a review of pregnancy rates in clinical trials, a typical failure rate of use based on the weighted average forecasts from the 1995 and 2002 National Family Survey of the American Growth Family (NSFG), corrected for not reporting abortions.
Several factors explain the effectiveness of typical use lower than the effectiveness of perfect use:
- error on the part of those giving instructions on how to use the method
- errors in user section
- a conscious user does not follow instructions.
For example, a person using oral forms of hormonal birth control may be misinformed by health care providers such as frequency of intake, forgetting to take one day's pills, or simply not going to the pharmacy in time to update the recipe.
COCPs provide effective contraceptives from the first pill if started within five days of the start of the menstrual cycle (within five days of the first day of menstruation). When initiated at other times in the menstrual cycle, COCPs provide effective contraceptives only after 7 days of active pills, so that contraceptive reserve methods (such as condoms) should be used until active pills have been taken for 7 consecutive days. COCPs should be taken approximately at the same time each day.
The effectiveness of combined oral contraceptive pills seems to be the same whether active pills are taken continuously for long periods of time or if they are taken for 21 days active and 7 days as placebo.
Contraceptive efficacy may be impaired by: 1) loss of more than one active pill in the package; 2) delay in starting the next active pill package (ie, prolonging pill-free, inactive or placebo pills beyond 7 days); 3) intestinal malabsorption of active pills due to vomiting or diarrhea, 4) drug interactions with active pills that decrease estrogen or progestogen contraceptives. In this case, the backup method should be used until consistent use of active pills (for 7 consecutive days) has been continued, the interacting drug has been discontinued or the disease has been resolved.
According to the CDC guidelines, pills are only considered 'missed' if 24 hours or more have passed since the last pill was taken. If less than 24 hours have passed, the pill is considered "late."
Instructions for the missed pills:
- If one pill is delayed or missed (up to & lt; 48 hours late), take one pill as soon as possible. Continue to fetch the remainder of the package as instructed. No backup method is required as long as no other pills are missed in the cycle.
- If two or more pills are missed, take the missed pills as soon as possible. Continue to take the rest of the pack as instructed, even if it takes more than one pill in a day. Use the back up method for 7 days.
- If the pill disappears within the first 7 days of the cycle, and the user has unprotected sex within 5 days before starting menstruation, emergency contraception should be considered in addition to the back up method.
- If pills are lost within the last 7 days (15-21 days), continue to take hormonal pills until completion and immediately start a new package by taking a placebo pill. The backup method should still be used for 7 days.
- If menstruation occurs, wait one week then start a new pill set. If the pill does not use a monthly cycle, ask your doctor for information.
The role of placebo pills
The role of placebo pills is twofold: to allow the user to continue daily pill-taking routines and to simulate the average menstrual cycle. By continuing to take daily pills, users remain in the habit of daily even for a week without hormones. Failure to take pills during the placebo week did not affect the effectiveness of the pill, provided that daily consumption of active pills was continued at the end of the week.
The placebo, or free hormone, week in a 28-day pill package simulates the average menstrual cycle, although the hormonal events during the pill cycle are significantly different from the normal ovulatory menstrual cycle. As the pills suppress ovulation (to be discussed further in the Action Mechanism section), contraceptive users do not have the correct menstrual periods. Instead, it is the lack of hormones during the week that cause blood withdrawal. Bleeding withdrawal that occurs during the rest of the active pill has been considered reassuring, physical confirmation is not being pregnant. Bleeding withdrawal can also be predicted. Unexpected breakthrough bleeding can be a possible side effect of a long-term active regimen.
Because it is not uncommon for menstruating women to become anemic, some placebo pills may contain iron supplements. It replenishes iron stores that may become depleted during menstruation.
Without or less frequent placebo
If the formulation of monophasic pills, which means each hormonal pill contains a fixed-dose hormone, it is possible to bypass the bleeding and still be protected against conception by skipping the placebo pills at once and starting directly with the next packet. Trying this with a bi-or trifasic pill formulation brings an increased risk of breakthrough bleeding and may be undesirable. However, it will not increase the risk of getting pregnant.
Beginning in 2003, women can also use the three-month version of the pill. Similar to the effects of using constant dose formulations and skipping the placebo week for three months, Seasonale benefits from less frequent periods, on potential breakthrough bleeding weakness. Seasonique is another version where the placebo week every three months is replaced with one week of low-dose estrogen.
Versions of combined pills have also been packaged to completely eliminate the placebo pills and draw blood. Marketed as Anya or Lybrel, studies have shown that after seven months, 71% of users no longer experience breakthrough bleeding, the most common adverse event occurring in longer periods of time without a break from active pills.
While more research needs to be done to assess the long-term safety of using COCP continuously, studies have shown no difference in short-term adverse effects when comparing continuous use versus cyclic use of birth control pills.
Non-contraceptive use
Hormones in pills have also been used to treat other medical conditions, such as polycystic ovary syndrome (PCOS), endometriosis, adenomyosis, acne, hirsutism, amenorrhea, menstrual cramps, menstrual migraine, menorrhagia (excessive menstrual bleeding), associated menstruation or fibroid anemia and dysmenorrhea (painful menstruation). In addition to acne, no oral contraceptives have been approved by the US FDA for the aforementioned use despite extensive use for this condition.
PCOS
PCOS, or polycystic ovary syndrome, is a syndrome caused by hormonal imbalance. Women with PCOS often have higher levels of estrogen than normal all the time because of their irregular hormonal cycles. Over time, high levels of estrogen without barriers can cause endometrial hyperplasia, or overgrowth of tissue in the uterus. This overgrowth is more likely to be cancer than normal endometrial tissue. Thus, although the data varies, it is generally agreed by most gynecological societies that because of the high estrogen levels that women have with PCOS, they have a high risk for endometrial hyperplasia. To reduce this risk, it is often recommended that women with PCOS take hormonal contraceptives to regulate their hormones. Both COCP and progestin methods are recommended. COCP is preferred in women who also suffer from acne and uncontrolled hirsutism symptoms, or patterned male hair growth, because COCPs can help treat these symptoms.
Endometriosis
For pelvic pain associated with endometriosis, COCP is considered first-line medical treatment, along with NSAIDs, GnRH agonists, and aromatase inhibitors. COCP works to suppress the growth of uterine endometrium tissue. This serves to reduce the effects of inflammation. COCPs, along with other medical treatments listed above, do not eliminate the growth of extra-uterine tissue, they only reduce symptoms. Surgery is the only definitive treatment. Studies that looked at the recurrence rate of pelvic pain after surgery showed that continuous use of COCP was more effective in relieving pain relief than cyclic use.
Adenomyosis
Similar to endometriosis, adenomyosis is often treated with COCPs to suppress the growth of endometrial tissue that has grown into myometrium. However, unlike endometriosis, IUD-containing levonorgetrel is more effective in reducing pelvic pain in adenomyosis than COCPs.
Acne
Oral contraceptives are sometimes prescribed as a medication for mild or moderate acne, although none are approved by the US FDA for the sole purpose. Three different oral contraceptives have been FDA approved to treat moderate acne if the person is at least 14 or 15 years old, has started menstruating, and requires contraception. They include Ortho Tri-Cyclen, Estrostep, and YAZ.
Amenorea
Although these pills are sometimes prescribed to induce menstruation on a regular schedule for women disturbed by irregular menstrual cycles, it actually suppresses the normal menstrual cycle and then mimics the usual 28-day monthly cycle.
Women who experience menstrual dysfunction because triad athlete athletes are sometimes prescribed oral contraceptives as pills that can make menstrual bleeding cycles. However, the underlying cause of this condition is lack of energy and should be addressed by correcting the imbalance between calories eaten and calories burned with exercise. Oral contraceptives should not be used as an initial treatment for triads of female athletes.
Maps Combined oral contraceptive pill
Contraindications
While combined oral contraceptives are generally regarded as relatively safe drugs, they are contraindicated for people with certain medical conditions. Estrogen in high doses may increase a person's risk for blood clots. Current COCP formulations do not contain high enough doses to increase the absolute risk of thrombotic events in healthy people, but people with pre-existing medical conditions that also increase their risk for blood clotting make COCP use more harmful. These conditions include but are not limited to high blood pressure, pre-existing cardiovascular disease, history of thromboembolism or pulmonary embolism, cerebrovascular accident, migraine with aura, family tendency to form blood clots (such as family factor V Leiden), and in smokers aged at over 35 years. COCPs are also contraindicated for people with advanced diabetes, liver tumors, hepatic adenomas or severe liver cirrhosis. COCP is metabolized in the liver and thus liver disease can lead to reduced drug elimination. Persons with known or suspected breast cancer or unexplained uterine bleeding may also not use COCP. Women who are known to be pregnant should not use COCP. Postpartum women who are breastfeeding are also advised not to start COCPs until 4 weeks after birth due to an increased risk of blood clots. Severe hypercholesterolemia and hypertriglyceridemia are also contraindicated at this time, but evidence suggests that the cause of COCP for poor outcomes in this population is weak. Obesity is not considered contraindicated to take COCPs.
Side effects
It is generally accepted that the health risks of oral contraceptives are lower than the risk of pregnancy and birth, and "the health benefits of contraceptive methods far outweigh any risks of the method". Some organizations argue that comparing contraceptive methods with no method (pregnancy) is irrelevant - on the contrary, security comparisons must lie between available contraceptive methods.
General
Different sources noted various adverse events. The most common side effect is breakthrough bleeding. A French review article in 1992 says that as many as 50% of new users first discontinue birth control pills before the end of the first year due to adverse events such as breakthrough bleeding and amenorrhea. One study found that women taking birth control pills blinked as much as 32% more often than those who did not use contraception.
On the other hand, pills can sometimes improve conditions such as pelvic inflammatory disease, dysmenorrhea, premenstrual syndrome, and acne, alleviate the symptoms of endometriosis and polycystic ovary syndrome, and decrease the risk of anemia. Oral contraceptive use also reduces the risk of ovarian cancer for life.
Nausea, vomiting, headache, bloating, breast tenderness, ankle/leg swelling (fluid retention), or weight changes may occur. Vaginal bleeding between periods (spotting) or missed/irregular periods may occur, especially during the first few months of use.
Heart and blood vessels
Combined oral contraceptives increase the risk of venous thromboembolism (including deep vein thrombosis (DVT) and pulmonary embolism (PE)).
COC pills with more than 50 Ã,Âμg estrogen increase the risk of ischemic stroke and myocardial infarction but lower doses appear to be safe. This risk is greatest in women with additional risk factors, such as smoking (which increases the risk substantially) and ongoing use of pills, especially in women over 35 years.
The overall absolute risk of venous thrombosis per 100,000 woman-years in current use of combined oral contraceptives was about 60, compared with 30 in non-users. The risk of thromboembolism varies with different types of birth control pills; compared with combined oral contraceptives containing levonorgestrel (LNG), and with the same estrogen dosage and duration of use, the ratio of internal venous thrombosis rates for combined oral contraceptive with norethisterone was 0.98, with norgestimate 1.19, with desogestrel (DSG) 1 , 82, with gestodene 1.86, with drospirenone (DRSP) 1.64, and with cyproterone acetate 1.88. For comparison, venous thromboembolism occurs in 100-200 per 100,000 pregnant women each year.
One study showed more than 600% increased risk of blood clots for women who consumed COCs with drospirenone compared with non-users, compared with 360% higher for women taking birth control pills containing levonorgestrel. The US Food and Drug Administration (FDA) started a study evaluating the health of over 800,000 women using COCPs and found that the risk of VTE was 93% higher for women who had been taking COCPs drospirenone for 3 months or less and 290% higher for women using COCPs drospirenone for 7-12 months, compared with women taking other types of oral contraceptives.
Based on this study, in 2012 the FDA updated the label for drospirenone COCPs to include warnings that contraceptives with drospirenone may have a higher risk of dangerous blood clots.
Cancer
The systematic review in 2010 did not support an overall increase in cancer risk in combined oral contraceptive pill users, but found little increased risk of breast cancer among current users, which disappeared 5-10 years after stopping use.
Protect effect
COC lowers the risk of ovarian cancer, endometrial cancer, and colorectal cancer. Two large cohort studies published in 2010 both found a significant reduction in the adjusted relative risk of ovarian and endometrial cancer deaths in users who had ever used oral contraceptives compared with never users.
The use of oral contraceptives (birth control pills) for five years or more reduces the risk of ovarian cancer in the future by 50%. Use of combined oral contraceptives reduced the risk of ovarian cancer by 40% and the risk of endometrial cancer by 50% compared with never users. Risk reduction increases with duration of use, with an 80% reduction in risk for ovarian and endometrial cancer with use for more than 10 years. Risk reduction for ovarian and endometrial cancer lasts for at least 20 years.
Increased risk
A report by the working group of the International Agency for Research on Cancer 2005 (IARC) says that COCs increase the risk of breast cancer (between current and recent users), cervix and liver (among low-risk populations of hepatitis B virus infection). A meta-analysis of 2013 concluded that any use of birth control pills was associated with a slightly increased risk of breast cancer (relative risk 1.08) and decreased risk of colorectal cancer (relative risk 0.86) and endometrial cancer (relative risk 0.57). The risk of cervical cancer in those infected with human papilloma virus increases. A similar small increase in breast cancer risk was seen in other meta-analyzes.
Weight
A systematic review of Cochrane 2011 found that a combination study of hormonal contraceptives showed no major differences in body weight when compared with placebo or no intervention group. The evidence is not strong enough to ensure that contraceptive methods do not cause weight changes, but no major effects are found. The review also found "that women do not stop using pills or patches due to weight changes."
Sexuality
COCP can increase natural vaginal lubrication. Other women experience decreased libido during pill taking, or decreased lubrication. Some researchers question the causal relationship between COCP use and decreased libido; a 2007 study of 1,700 women found that COCP users did not experience a change in sexual satisfaction. A 2005 laboratory study of genital arousal tested fourteen women before and after they started using COCPs. The study found that women experience a much wider stimulus response after starting the pill; decrease and increase in the size of arousal are common.
A 2006 study of 124 pre-menopausal women measured sex hormone-binding globulin (SHBG), including before and after discontinuation of oral contraceptive pills. Women who continue using oral contraceptives have a SHBG rate four times higher than those who have never used it, and rates remain high even in groups that have discontinued their use. Theoretically, an increase in SHBG may be a physiological response to elevated levels of the hormone, but it can lower other free hormone levels, such as androgens, since there is no effect on sex hormones.
A study in 2007 found that the pill could have a negative effect on sexual attraction: scientists found that estradiated lapdancers received more tip than those who did not, while those on oral contraceptive pills did not have such peak income.
Depression
Low levels of serotonin, a neurotransmitter in the brain, have been linked to depression. High levels of estrogen, as in first-generation COCP, and progestin, as in some progestin contraceptives alone, have been shown to decrease brain serotonin levels by increasing the concentration of brain enzymes that reduce serotonin. More and more research evidence suggests that hormonal contraception can adversely affect the psychological health of women. By 2016, a large Danish study of one million women (followed up from January 2000 to December 2013) suggests that the use of COCPs, especially among adolescents, is associated with a statistically significant increase in the risk of depression, although the effect size is small (eg, 2 , 1% of women who took the form of oral birth control were prescribed anti-depressants for the first time, compared with 1.7% of women in the control group). Similarly, by 2018, findings from a large Swedish national cohort study that investigated the effects of hormonal contraceptives on mental health among women (n = 815,662, age 12-30) were published, highlighting the relationship between hormonal contraception and subsequent use of psychotropic drugs. for women of reproductive age. This relationship is very large for young adolescents (ages 12-19). The authors ask for further research on the effect of various types of hormonal contraceptives on the psychological health of young women.
Progestin contraception alone is known to worsen the condition of depressed women. However, current medical reference books on contraception and major organizations such as the American ACOG, WHO, and RCOG UK agree that current evidence suggests low-dose combined oral contraceptives are unlikely to increase the risk of depression, and it is unlikely to worsen the condition in women who are currently depressed.
Hypertension
Bradikinin lowers blood pressure by causing dilation of blood vessels. Certain enzymes are able to break down bradykinin (Angiotensin Converting Enzyme, Aminopeptidase P). Progesterone may increase levels of P-Aminopeptidase (AP-P), thereby increasing the breakdown of bradykinin, which increases the risk of developing hypertension.
Other effects
Other side effects associated with low-dose COCPs are leukorrhea (increased vaginal secretion), decreased menstrual flow, mastalgia (breast pain), and decreased acne. Side effects associated with older higher doses of COCP include nausea, vomiting, elevated blood pressure, and melasma (discoloration of facial skin); this effect is not strongly associated with low-dose formulations.
Excessive estrogen, such as from birth control pills, seems to increase cholesterol levels in bile and reduce gallbladder movement, which can lead to gallstones. The progestin found in certain oral contraceptive pill formulations may limit the effectiveness of weight training to increase muscle mass. This effect is due to the ability of some progestin to inhibit androgen receptors. One study claims that the pill can affect the body odor of a man favored by a woman, which in turn affects her partner's choice. The use of combined oral contraceptives was associated with a reduced risk of endometriosis, giving a relative risk of endometriosis of 0.63 during active use, but with limited evidence quality in accordance with systematic reviews.
Combined oral contraceptives lower total testosterone levels by about 0.5 nmol/l, free testosterone by about 60%, and increase the amount of sex hormone binding globulin (SHBG) by about 100 nmol/l. Contraceptives containing second generation progestin and/or estrogen doses of about 20 -25 mg EE were found to have a smaller impact on SHBG concentrations. Combined oral contraceptives can also reduce bone density.
Drug interactions
Some medications reduce the effect of the pill and may cause breakthrough bleeding, or increase the likelihood of pregnancy. These include drugs such as rifampicin, barbiturates, phenytoin, and carbamazepine. In addition, attention is given to broad-spectrum antibiotics, such as ampicillin and doxycycline, which can cause problems "by damaging the bacterial flora responsible for recycling ethinylestradiol from the large intestine" (BNF 2003).
Traditional herbal remedies of St. John's Wort have also been involved due to the improvement of the P450 system in the liver.
Action mechanism
Oral contraceptive pills were developed to prevent ovulation by suppressing gonadotropin release. Combined hormonal contraceptives, including COCPs, inhibit follicle development and prevent ovulation as the main mechanism of action.
Progestogen negative feedback decreases the frequency of the release of the gonadotropin-releasing hormone (GnRH) by the hypothalamus, which decreases the follicle follicle (FSH) secretion and greatly decreases the secretion of luteinizing hormone (LH) by the anterior pituitary. A decrease in FSH levels inhibits follicle development, preventing elevated levels of estradiol. Progestogen negative feedback and lack of estrogen positive feedback on LH secretion prevent middle-cycle LH spikes. Inhibition of follicular development and absence of LH surges prevent ovulation.
Estrogen was initially included in oral contraceptives for better cycle control (to stabilize the endometrium and thereby reduce the incidence of breakthrough bleeding), but also found to inhibit follicle development and help prevent ovulation. Negative feedback of estrogen in the anterior pituitary greatly decreases FSH secretion, which inhibits follicle development and helps prevent ovulation.
Another major mechanism of action of all progestogen-containing contraceptives is inhibition of sperm penetration through the cervix to the upper genital tract (uterus and fallopian tubes) by lowering the water content and increasing the viscosity of cervical mucus.
Estrogens and progestogens in COCPs have other effects on the reproductive system, but these have not been shown to contribute to their contraceptive effectiveness:
- Decreased tubal motility and egg transport, which can interfere with fertilization.
- Endometrial atrophy and changes in metalloproteinase content, which may inhibit sperm motility and viability, or theoretically inhibit implantation.
- Endometrial edema, which can affect implantation.
The evidence is not sufficient on whether endometrial changes can actually prevent implantation. The main mechanism of action is so effective that the chances of conception during COCP use are very small. Since pregnancy occurs despite endometrial changes when the main mechanism of action fails, endometrial changes are unlikely to play an important, if any, role in the observed effectiveness of COCPs.
Formulation
Oral contraceptives come in a variety of formulations, some contain estrogen and progestin, and some contain only progestin. The dose of component hormone also varies between products, and some monophasic pills (giving the same dose of hormone daily) while others are multifasa (doses vary daily).
COCPs seem inconsistently grouped into "generations" in the medical literature based on when they were introduced.
- First generation COCP is sometimes defined as containing noretynodrel progestin, norethisterone, norethisterone acetate, or etynodiol acetate; and is sometimes defined as all COCPs containing> = 50Ã,Âμg ethinylestradiol.
- Second generation COCP is sometimes defined as containing the norgestrel or levonorgestrel progestin; and sometimes defined as those containing norethisterone progestin, norethisterone acetate, etynodiol acetate, norgestrel, levonorgestrel, or norgestimate and & lt; 50 Ã,Âμg ethinylestradiol.
- The third generation COCP is sometimes defined as containing the progestin of desogestrel or gestodene; and is sometimes defined as containing desogestrel, gestodene, or norgestimate.
- 4th generation COCP is sometimes defined as those containing drospirenone progestin; and is sometimes defined as containing drospirenone, dienogest, or nomegestrol acetate.
History
In the 1930s, Andriy Stynhach had isolated and determined the structure of steroid hormones and found that high-dose androgen, estrogen or progesterone inhibited ovulation, but obtained these hormones, produced from animal extracts, from European pharmaceutical companies was extremely expensive.
In 1939, Russell Marker, a professor of organic chemistry at Pennsylvania State University, developed a method of synthesizing progesterone from plant steroid sapogenins, initially using sarsapogenin from sarsaparilla, which proved too expensive. After three years of extensive botanical research, he found a much better starting material, a saponin from an uneaten mexican (Dioscorea mexicana) and Dioscorea composita ) found in the Veracruz rainforest near Orizaba. Saponin can be converted in laboratory to diosgenin part aglikonnya. Unable to attract the interest of his research sponsor, Parke-Davis, in the commercial potential of synthesizing progesterone from Mexican yam, Marker left Penn State and in 1944 founded Syntex with two partners in Mexico City. When he left Syntex a year later barbasco sweet potato trade had begun and the heyday of Mexico's steroid industry had begun. Syntex broke the monopoly of European pharmaceutical companies on steroid hormones, reducing progesterone prices nearly 200-fold over the next eight years.
Mid-20th century, the stage set for the development of hormonal contraceptives, but pharmaceutical companies, universities and government showed no interest in pursuing research.
Progesterone to prevent ovulation
In early 1951, reproductive physiologist Gregory Pincus, a leader in hormonal research and founder of the Worcester Foundation for Experimental Biology (WFEB) in Shrewsbury, Massachusetts, first met the founder of the American-born movement Margaret Sanger at a Manhattan dinner hosted by Abraham Stone. , medical director and vice president of Planned Parenthood (PPFA), who helped Pincus get a small grant from PPFA to begin a hormonal contraceptive study. The study began on 25 April 1951 with reproductive physiologist Min Chueh Chang repeating and extending the 1937 experiment from Makepeace et al. showing progesterone injections suppressing ovulation in rabbits. In October 1951, G. D. Searle & amp; The company rejected Pincus's request to finance the study of hormonal contraceptives, but held them as consultants and continued to provide chemical compounds for evaluation.
In March 1952, Sanger wrote a brief note mentioning Pincus's research to his longtime friend and supporter, suffragist and philanthropist Katharine Dexter McCormick, who visited WFEB and co-founder and old friend Hudson Hoagland in June 1952 to learn about contraceptive research in there.. Frustrated when the research stalled from a lack of interest in PPFA and a small amount of funding, McCormick arranged a meeting at WFEB on June 6, 1953 with Sanger and Hoagland, where he first met Pincus who was committed to dramatically expanding and speeding up research with McCormick providing fifty times the PPFA previous funding.
Pincus and McCormick enrolled Harvard professor of gynecology John Rock, head of gynecology at the Free Hospital for Women and an expert in infertility treatment, to lead clinical research with women. At a scientific conference in 1952, Pincus and Rock, who had known each other for years, found that they used a similar approach to achieve opposing goals. In 1952, Rock induced anovulation of three months of "pseudo-pregnancy" states in eighty infertility patients by continuously increasing the oral dose of estrogen (diethylstilbestrol 5-30 mg/day) and progesterone (50-300 mg/day) and within the next four months 15% become pregnant.
In 1953, at the suggestion of Pincus, Rock induced a three-month "pseudo-pregnancy" anovulatory state in his twenty-seven infertility patients with an oral progesterone regimen of only 300mg/day for 20 days from days 5-24 cycles followed. by pipe free days to produce a withdrawal bleeding. This results in the same 15% pregnancy rate over the next four months without amenorrhea from previous continuous estrogen and progesterone regimens. But 20% of women experience breakthrough bleeding and in the first cycle ovulation is suppressed only in 85% of women, suggesting that higher and more expensive oral progesterone doses will be needed to initially consistently suppress ovulation.
Progestin to prevent ovulation
Pincus asked his contacts at pharmaceutical companies to send him chemical compounds with progestogenic activity. Chang filtered out nearly 200 chemical compounds in animals and found the three most promising compounds are Syntex's norethisterone and Searle's noretynodrel and norethandrolone.
Chemists Carl Djerassi, Luis Miramontes, and George Rosenkranz at Syntex in Mexico City have synthesized the first orally active orally active progestin in 1951. Frank B. Colton at Searle in Skokie, Illinois has synthesized a highly orally active orgynecell progestin an isomer of norethisterone) in 1952 and norethandrolone in 1953.
In December 1954, Rock began the first study of 5-50 mg dose-suppressive potential of three oral progestin for three months (for 21 days per cycle - days 5-25 followed by pills-free days to generate bleeding) in fifty her infertility patient in Brookline, Massachusetts. Norethisterone or noretynodrel 5 mg dose and all ovulation doses suppressed norethandrolone but cause breakthrough bleeding, but 10 mg and higher dose norethisterone or noretynodrel suppress ovulation without breakthrough bleeding and cause a 14% pregnancy rate in the next five months. Pincus and Rock chose noretynodrel Searle for the first female contraceptive trial, citing the lack of androgenisity versus very small syntex nortisintesis in animal tests.
Oral contraceptive combination
Noretynodrel (and norethisterone) were later found to be contaminated with a small percentage of estrogen mestranol (intermediate in their synthesis), with noretynodrel in 1954-5 Rock's study containing 4-7% mestranol. When further purifying noretynodrel containing less than 1% mestranol causes breakthrough bleeding, it was decided to deliberately combine 2.2% mestranol, a percentage unrelated to breakthrough bleeding, in the first female contraceptive trial in 1956. noretynodrel and combination mestranol were given name of Enovid ownership.
The first Enovid contraceptive experiments led by Celso-RamÃÆ'³n GarcÃÆ'a and Edris Rice-Wray began in April 1956 in RÃÆ'o Piedras, Puerto Rico. The second contraceptive experiment of Enovid (and norethisterone) led by Edward T. Tyler began in June 1956 in Los Angeles. On January 23, 1957, Searle held a symposium reviewing gynecology and contraceptive research on Enovid until 1956 and concluded Enovid estrogen content could be reduced by 33% to decrease the incidence of estrogenic gastrointestinal side effects without significantly increasing the incidence of breakthrough bleeding.
Public availability
United States
On June 10, 1957, the Food and Drug Administration (FDA) approved Enovid 10 mg (9.85 mg noretynodrel and 150Ã,Âμg mestranol) for menstrual disorders, based on data from its use by more than 600 women. Many additional contraceptive trials show Enovid at 10, 5, and 2.5 mg doses to be very effective. On July 23, 1959, Searle submitted additional applications to add contraceptives as an approved indication for Enovid's 10, 5, and 2.5 mg doses. The FDA refuses to consider the application until Searle agrees to withdraw the lower dosage form from the application. On May 9, 1960, the FDA announced it would approve Enovid 10 mg for contraceptive use, and did so on June 23, 1960. By that time, Enovid 10 mg had been used in general for three years and, with conservative estimates, at least half a million women had use it.
Although FDA approved for contraceptive use, Searle never marketed Enovid 10 mg as a contraceptive. Eight months later, on February 15, 1961, the FDA approved Enovid 5 mg for contraceptive use. In July 1961, Searle finally began marketing Enovid 5 mg (5 mg noretynodrel and 75Ã,Âμg mestranol) to the doctor as a contraceptive.
Although the FDA approved the first oral contraceptive in 1960, contraception was not available for married women in all states until Griswold v. Connecticut in 1965 and not available to unmarried women in all states to Eisenstadt. v. Baird in 1972.
The first published case report of a blood clot and pulmonary embolism on a woman using Enavid (Enovid 10 mg in the US) at a dose of 20 mg/day did not appear until November 1961, four years after her approval, at that time has been used by more than one million woman. It takes nearly a decade of epidemiological studies to convincingly establish an increased risk of venous thrombosis in oral contraceptive users and an increased risk of stroke and myocardial infarction in oral contraceptives who smoke or have high blood pressure or other cardiovascular or cerebrovascular risk factors. The risk of oral contraceptives is dramatized in the 1969 book The Doctors' Case Against the Pill by feminist journalist Barbara Seaman who helped organize the Nelson Pill 1970 welcome by Senator Gaylord Nelson. The hearing was conducted by all male senators and witnesses in the first round of hearings were all men, leading Alice Wolfson and other feminists to protest the hearing and generate media attention. Their work led to the mandate of inserting patient packages with oral contraceptives to explain the possible side effects and their risks to help facilitate informed consent. Oral contraceptives The standard dose of today contains a third lower dose of estrogen than first marketed oral contraceptives and contains lesser doses of stronger and more potent progestins in various formulations.
Australia
The first oral contraceptive introduced outside the United States was Schering's Anovlar (norethisterone acetate 4 mg ethinylestradiol 50 Âμg) on ​​January 1, 1961 in Australia.
German
The first oral contraceptive introduced in Europe was Schering's Anovlar on June 1, 1961 in West Germany. Lower hormonal doses, still used, were studied by Belgian gynecologist Ferdinand Peeters.
English
Before the mid-1960s, the British Empire did not require the approval of pre-marketing drugs. The UK Family Planning Association (FPA) through its clinic then became the premier provider of family planning services in the UK and provided only the contraceptives contained in the Approved List of Contraceptives (established in 1934). In 1957, Searle began marketing Enavid (Enovid 10 mg in the US) for menstrual disorders. Also in 1957, the FPA established a FIFality Control Procedure Council (CIFC) to test and monitor oral contraceptives initiating oral contraceptive testing and in 1960 and 1961 started three major clinical trials in Birmingham, Slough and London.
In March 1960, the Birmingham FPA started a pilot test of noretynodrel 2.5Ã, mg mestranol 50Ã,Âμg, but a high pregnancy rate initially occurred when a pill that inadvertently contained only 36Ã,Âμg mestranol - the experiment was continued with noretynodrel 5Ã, mg mestranol 75Ã, Âμg (Conovid in UK, Enovid 5 mg in US). In August 1960, Slough FPA initiated a test of noretynodrel 2.5Ã, mg mestranol 100Ã,Âμg (Conovid-E in England, Enovid-E in the US). In May 1961, the London FPA started Schering's Anovlar trial.
In October 1961, upon the recommendation of its CIFC Medical Advisory Board, the FPA added Searle's Conovid to the Approved List of Contraceptives. On December 4, 1961, Enoch Powell, then Minister of Health, announced that the oral contraceptive pill Conovid can be determined via the NHS at a subsidized price of 2 per month. In 1962, Schering's Anovlar and Searle's Conovid-E were added to the FPA-Approved List of Contrast.
French
On December 28, 1967, Neuwirth's Law legalized contraception in France, including pills. Pills are the most popular form of contraception in France, especially among young women. It accounts for 60% of the birth control used in France. The rate of abortion has remained stable since the introduction of the pill.
Japanese
In Japan, lobbying from the Japan Medical Association prevented the pill from being approved for general use for nearly 40 years. High doses of "second-generation" pills are approved for use in cases of gynecological problems, but not for birth control. The two main objections raised by the association are concerns about the safety of long-term use of the pill, and concerns that pill use will lead to a decrease in condom use and thus potentially increase the rate of sexually transmitted infections (STIs).
However, when the Ministry of Health and Welfare approved the use of Viagra in Japan after just six months of filing applications, while still claiming that the pills needed more data before approval, female groups cried foul. The pill was then approved for use in June 1999. However, the pill has not become popular in Japan. According to estimates, only 1.3 percent of the 28 million Japanese women of childbearing age use pills, compared with 15.6 percent in the United States. Prescription pill guidelines that have been approved by the government require pills users to visit the doctor every three months for pelvic examination and undergo tests for sexually transmitted diseases and cervical cancer. In the United States and Europe, on the contrary, annual or bi-annual clinical visits are standard for pill users. However, starting from 2007, many Japanese OBGYN only require annual visits for pill users, with some annual checks recommended only for those who are older or at an increased risk of side effects. In 2004, condoms accounted for 80% of the use of birth control in Japan, and this could explain the relatively low level of Japanese AIDS.
Society and culture
The pill was approved by the FDA in the early 1960s; its use spread rapidly by the end of the decade, resulting in enormous social impact. Time placed the pills on the cover in April 1967. First, it was more effective than most of the previously restored birth control methods, giving women unprecedented control over their fertility. Their use is separate from sexual intercourse, requiring no special preparation during sexual activity that may interfere with spontaneity or sensation, and the option to take the pill is a private pill. This combination of factors makes the pill very popular within a few years since its introduction. Claudia Goldin, among others, argues that this new contraceptive technology is a key player in shaping the modern economic role of women, where it extends the age at which the first married women allow them to invest in education and other forms of human capital and generally become more oriented career. Immediately after the birth control pill was passed, there was a sharp increase in attendance at college and graduation rates for women. From an economic point of view, birth control pills reduce the cost of staying in school. The ability to control fertility without sacrificing sexual intercourse allows women to make long-term educational and career plans.
Because the pill is highly effective, and soon spread, it also raises the debate about the moral and health consequences of premarital sex and promiscuity. Never had sexual activity so divorced from reproduction. For couples who use pills, sexual intercourse becomes purely a love expression, or a means of physical pleasure, or both; but it is no longer a reproduction tool. While this is true of previous contraceptives, their relatively high failure rates and less extensive use fail to emphasize these differences as clearly as pills. The spread of oral contraceptive use has led many religious and institutional figures to debate the exact role of sexuality and its relationship to procreation. The Roman Catholic Church in particular, after studying the phenomenon of oral contraceptives, re-emphasized the declared teaching of birth control in the papal encyclic of 1968 Humanae vitae . The encyclical repeats the existing Catholic teaching that artificial contraception distorts the nature and purpose of sex. On the other hand Anglicans and other Protestant churches, such as the Evangelical Church in Germany (EKD) receive combined oral contraceptive pills.
The United States Senate started a hearing on pills in 1970 and there are different points of view heard from medical professionals. Dr. Michael Newton, President of the College of Obstetricians and Gynecologists says:
"The evidence is not clear that this is still really causing cancer or related to it.The FDA's Advisory Committee made comments on this, that if there is not enough evidence to show whether the pill is linked to cancer progression, and I think it's still thin you should be careful about them, but I do not think there is any clear evidence, one way or another, that they do or do not cause cancer. "
Another doctor, Dr. Roy Hertz of the Population Council, says that whoever takes this should know "our knowledge and ignorance in this" and that all women should be made aware of this so he can decide to take the pills or not.
The Secretary of Health, Education and Welfare at the time, Robert Finch, announced the federal government had received a compromise warning statement that would accompany all sales of birth control pills.
Results of popular culture
The introduction of birth control pills in 1960 allowed more women to find employment opportunities and continue their education. As more women gain employment and education, their husbands must begin to take over household chores like cooking. Wanting to stop the changes that occur in terms of gender norms in American households, many movies, television shows, and other popular cultural items illustrate how an ideal American family should be. Below are some examples:
Poetry
- Pill Versus the Springhill Mine Disaster is the title of a poem from the 1968 collection by Richard Brautigan.
Music
Singer Loretta Lynn commented on how women no longer had to choose between the relationship and career of her 1974 album with the song "The Pill", which tells the story of drug use by married women. free himself from his traditional role as wife and mother.
Environmental impact
A woman who uses COCPs removes from urine and estrogen naturally, estrone (E1) and estradiol (E2), and estrogen esterogenic etinilestradiol (EE2). These hormones can pass water treatment plants and into rivers. Other forms of contraception, such as the contraceptive patch, use the same synthetic estrogen (EE2) found in COCPs, and can increase hormonal concentration in water when flushing to the toilet. This excretion has been shown to play a role in causing endocrine disorders, which affect sexual and reproductive development, in wild fish populations in the river segment contaminated by waste treated wastes. A study conducted in the English rivers supports the hypothesis that the incidence and severity of intersex wild fish populations was significantly correlated with E1, E2, and EE2 concentrations in rivers.
An overview of the performance of active sludge plants found that estrogen removal rates varied greatly but averaged 78% for estrone, 91% for estradiol, and 76% for ethinylestradiol (estriol fluid concentrations were between estrone and estradiol, but estriol was a much less potent endocrine fish intruders).
Numerous studies have shown that increased access to contraception, including birth control pills, can be an effective strategy for climate change mitigation and adaptation. According to Thomas Wire, contraception is the 'greenest technology' because of its cost-effectiveness in combating global warming - every $ 7 spent on family planning will reduce global carbon emissions by 1 ton over four decades, while achieving the same result with low carbon technologies requiring $ 32. If all current unmet needs for contraception are met, it will reduce global carbon dioxide emissions by 34 gigatons between 2010 and 2050.
See also
- an oral contraceptive containing Estradiol
- Hormone replacement therapy (HRT)
- List of estrogens available in the United States
- List of progestogen available in the United States
- Progestogen alone injection contraceptives
References
External links
Media related to the contraceptive pill in Wikimedia Commons
- Birth Control Pill - CBC Digital Archive
- Birth birth control pill - slide show by Life magazine
Source of the article : Wikipedia
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