Hormonal birth control

 Hormonal contraception refers to birth control methods that act on the endocrine system. The original hormonal method—the combined oral contraceptive pill—was first marketed as a contraceptive in 1960.

Quotes

 * Over the last couple of decades a reduction of estrogen by at least 80% in combined oral contraceptives (OCs) and much research have resulted in effective and safe contraception. We still do not know longterm effects of OCs however. OCs may protect against endometrial and ovarian cancer. A link between current OC use and liver cancer exists in areas where liver cancer is rare. An association between OC use and cervical cancer disappears when researchers control for sexual activity and barrier method use. Some research shows OC use increases the risk of breast cancer, while other research does not. There does appear to be an increased risk of breast cancer developing in women younger than 46 years of age and who have used OCs for at least 10 years. Women who have a preexisting cardiovascular condition and/or smoke should not use OCs. OC progestogens may impair glucose metabolism in healthy women, but just for 6 months. Women with diabetes mellitus can use OCs, but may need to increase insulin intake. OCs can cause hypertension in 4-5% of healthy women and worsen hypertension in about 9-16% of hypertensive women. Progestogen-only OCs have fewer systemic side effects than combined OCs, but often cause menstrual changes. Their long term effects are not yet known. Injectables containing a progestogen cause few, if any, adverse effects. The subdermal implant, Norplant, tends to cause menstrual disturbances, but is safe and effective. Progestogen - only vaginal rings are as effective as progestogen-only OCs, but menstrual irregularities are common. Failure rates for combined vaginal rings match those of combined OCs. Long-term effects of vaginal rings are not known. Postcoital contraception does not cause serious side effects, but may cause vomiting and menstrual irregularities. A levonorgestrel-releasing IUD is effective and reduces menstrual blood loss, sometimes resulting in amenorrhea. Hormonal injections in men are unlikely in the near future.
 * D T Baird 1, A F Glasier, “Hormonal contraception”, N Engl J Med. 1993 May 27;328(21):1543-9.


 * In the early 20th century, Margaret Sanger became one of the most avid proponents of contraception in the United States. By 1950, she and Katharine McCormick had contracted with biologist Gregory Pincus to develop an effective birth control pill. A collaborative effort by Pincus and other researchers led to trials of the pill in Puerto Rico, Haiti, and Mexico between 1956 and 1957, which pro-vided the basis for an application to the Food and Drug Administration for approval of the first oral contraceptive.
 * E B Connell, “Contraception in the prepill era”, Contraception. 1999 Jan; 59(1 Suppl):7S-10S.


 * The large influx of poor immigrants and advocacy by women's rights groups provided the impetus for the birth control movement of the early 1900s. The subsequent development of the oral contraceptive pill gave women, for the first time, the ability to control their fertility.
 * E B Connell, “Contraception in the prepill era”, Contraception. 1999 Jan; 59(1 Suppl):7S-10S.


 * In 1961, when the pill was introduced to Britain, women pushed their, often reluctant, doctors to give them the drug. By the late 1960s, young women were talking about a revolution in women’s sexual attitudes, but since then the suggestion that the pill just meant women couldn’t say no has been widely repeated, alongside negative assessments of the ‘sexual revolution’. As early as the 1880s, there had been suggestions that fear of pregnancy gave wives an excuse for denying their husbands their conjugal right of sexual intercourse. By the early 1990s, over 80 per cent of British women of reproductive age since the early 1960s had taken the pill.
 * Cook, Hera, “The long sexual revolution: English women, sex and contraception 1800-1975”, Oxford University Press, 2004, p.1


 * [T]he pill did produce a situation in which these pre-existing social conditions led to a new twist on male sexual exploitation of young single women in the 1960s. Throughout the nineteenth and twentieth centuries, the family, the Church, and later schools had attempted to supervise and control unmarried women’s sexual behavior. In this social setting women might have had to struggle against persuasive male arguments and persistent groping but they had the entire weight of society, backed up by the ulti-mate sanction of pregnancy, supporting them if they did not wish to have intercourse. In the 1960s the arrival of the pill meant that for the first time women could have confidence that they would not get pregnant. There is a new sense of excitement and possibilities present in many accounts by heterosexual women who were young and single at this time. In choosing to reject the control of their sexual be-haviour they saw themselves as rejecting control over their lives as a whole However, abandoning the traditional moral position left many confused, with no substantial arguments against casual or dishonest male sexual exploitation. By the early 1970s, men assumed fashionable young women were on the pill and statistics show that well over half actually were.
 * Cook, Hera, “The long sexual revolution: English women, sex and contraception 1800-1975”, ‘Oxford University Press’’, 2004, p.3


 * Years of disappointment had taught Pincus that it wasn’t always the science that determined an experiment’s success; it was often the forces surrounding the science, including public sentiment. Now that Pincus had settled roughly on the hormone progesterone as the key to his pill, he needed to build the team to do the scientific work, forge alliances with manufacturers, conduct his trials, and, if all went well, spread the news of the coming invention so that it might have a chance at acceptance. He knew that his progestins (synthetic forms of progesterone) stopped ovulation in rabbits and rats. The next step was to test them on women. And to do that, he would have to add a player to his team—a doctor who could reassure patients they were safe and would convey to the drug companies supplying the drugs that no one would be harmed. There had never been a medicine made for healthy people before—and certainly not one that would be taken every day. The risks were enormous. Pincus settled on a physician named John Rock, a gynecologist respected by his peers and adored by his patients. Rock looked like a family physician from central casting in Hollywood: tall, slender, and silver-haired, with a gentle smile and a calm, deliberate manner. Even his name connoted strength, solidity, and reliability. Rock had one more thing going for him: He was Catholic.
 * Jonathan Eig, “The Team That Invented the Birth-Control Pill”, The Atlantic, (October 9, 2014)


 * The rapid increase in the world population makes it mandatory to develop new contraceptive methods. Disseminating reversible inexpensive and practical hormonal methods to developing countries is a target of many international agencies and funds.
 * Risto Erkkola, “Recent advances in hormonal contraception”, Curr Opin Obstet Gynecol. 2007 Dec;19(6):547-53.


 * In 1965, a brand called Oracon became the first to include placebo pills in its packaging. Oracon's most documented motivation behind the first placebo pills was to help women ensure that they were taking their pills correctly: Inactive pills meant that women now took a pill every single day, thus putting them on a more routine schedule and making it easier to notice if they'd missed one. Of course, the pill's engineers could have just as easily added an extra week of active pills so that women were still taking one a day. That, however, would have meant that women no longer bled once a month, and the 60s weren't quite ready for that. This formula—three weeks of hormonal pills, followed by one withdrawal week, complete with the requisite bleeding—remained unchanged for over 40 years. Then, in 2003, the drug company Barr released Seasonale. This was the first oral contraceptive to give women the option of foregoing monthly withdrawal bleeding; it contained 84 hormone pills and seven placebo pills. Women using this method would ex-perience withdrawal bleeding just four times a year—or once per season, as the drug name intimated. Four years later, the FDA approved Lybrel, the first oral contraceptive to offer continuous active pills with no breaks for withdrawal bleeding whatsoever.
 * Leila Ettachfini, “The Man Behind the Pill Decided Women 'Need' to Have Periods—But They Don't“, Vice, (Sep 21 2017)


 * Today, the science is more settled, though there hasn't been a long-term study on the continuous use of oral contraceptives yet. But based on data from the long-term use of non-extended cycle birth control pills, which are chemically the same as extended cycle contraceptives, gy-necologists have largely reached the conclusion that the practice is safe. "At this point, I can't think of any OB/GYNs that would have a problem with [extended cycle oral contraception]," says Dr. Lauren Naliboff, a fellow at the American Con-gress of Obstetricians and Gynecologists. A study by the Cochrane organization found that women on extended cycle pills "fared better in terms of headaches, genital irritation, tiredness, bloating, and menstrual pain" than those on pills with monthly bleeding. A peer-reviewed article by Acta Obstetricia et Gynecologica Scandinavica acknowledged that long-term studies are lacking, but ultimately concluded that continuous use oral contraceptives showed no unique side effects beyond increased spotting, and still resulted in less "bleeding days" than non-continuous birth control pills. Philosophical and scientific debates aside, perhaps the largest barrier between women and their right to decide whether or not they want to bleed is a lack of information. Many women are una-ware that consistently skipping withdrawal bleeding is an option, let alone that extended cycle pills ex-ist, or that menstrual suppression can also be accomplished with hormonal IUDs, NuvaRing, birth control injections, and contraceptive patches.
 * Leila Ettachfini, “The Man Behind the Pill Decided Women 'Need' to Have Periods—But They Don't“, Vice, (Sep 21 2017)


 * The invention of the pill was one of the most significant advancements in the fight for reproductive agency; it allowed us, as a society, to dramatically reconceptualize sexuality and gender relations. At the same time, our relationship to this groundbreaking medical technology has been shaped and con-strained by our own conceptions of what's "natural" and what defines a woman. Similar reproductive and sexually liberating advancements that target men—Viagra, for instance—have not led to similar debates on what it means to be a man, or to have an "unnatural" hard-on. And while Viagra is covered by insurance, Dr. Naliboff says that most insurance companies do not cover extended cycle birth control to this day, even in cases where patients are on the pill for medical issues like primary ovarian insufficiency or endometriosis. The discrepancy in education and affordable access is telling: The normalization of placebo pills and subsequent withdrawal bleeding means that even in 2017, many women do not know that extended cycle pills exist, let alone that menstrual suppression is a safe option. Combined with the fact that the percentage of schools teaching students about contraception has declined drastically since 2000, this means that many women are likely to stay in the dark about their options when it comes to choosing whether or not they want to bleed once a month.
 * Leila Ettachfini, “The Man Behind the Pill Decided Women 'Need' to Have Periods—But They Don't“, Vice, (Sep 21 2017)


 * What Pike discovered in Japan led him to think about the Pill, because a tablet that suppressed ovulation—and the monthly tides of estrogen and progestin that come with it—obviously had the potential to be a powerful anti-breast-cancer drug. But the breast was a little different from the reproductive organs. Progestin prevented ovarian cancer because it suppressed ovulation. It was good for preventing endometrial cancer because it countered the stimulating effects of estrogen. But in breast cells, Pike believed, progestin wasn’t the solution; it was one of the hormones that caused cell division. This is one explanation for why, after years of studying the Pill, researchers have concluded that it has no effect one way or the other on breast cancer: whatever beneficial effect results from what the Pill does is cancelled out by how it does it. John Rock touted the fact that the Pill used progestin, because progestin was the body’s own contraceptive. But Pike saw nothing “natural” about subjecting the breast to that heavy a dose of progestin. In his view, the amount of progestin and estrogen needed to make an effective contraceptive was much greater than the amount needed to keep the reproductive system healthy—and that excess was unnecessarily raising the risk of breast cancer. A truly natural Pill might be one that found a way to suppress ovulation without using progestin. Throughout the nineteen-eighties, Pike recalls, this was his obsession. “We were all trying to work out how the hell we could fix the Pill. We thought about it day and night.”
 * Malcolm Gladwell, “John Rock’s Error”, The New Yorker, (2000-03-10).


 * Today, a growing movement of reproductive specialists has begun to campaign loudly against the standard twenty-eight-day pill regimen. The drug company Organon has come out with a new oral contraceptive, called Mircette, that cuts the seven-day placebo interval to two days. Patricia Sulak, a medical researcher at Texas A. & M. University, has shown that most women can probably stay on the Pill, straight through, for six to twelve weeks before they experience breakthrough bleeding or spot-ting. More recently, Sulak has documented precisely what the cost of the Pill’s monthly “off” week is. In a paper in the February issue of the journal ‘’Obstetrics and Gyne-cology’’, she and her colleagues documented something that will come as no surprise to most women on the Pill: during the placebo week, the number of users experiencing pelvic pain, bloating, and swelling more than triples, breast tenderness more than doubles, and headaches increase by almost fifty per cent. In other words, some women on the Pill continue to experience the kinds of side effects associated with normal menstruation. Sulak’s paper is a short, dry, academic work, of the sort intended for a narrow professional audience. But it is impossible to read it without being struck by the consequences of John Rock’s desire to please his church. In the past forty years, millions of women around the world have been given the Pill in such a way as to maximize their pain and suffering. And to what end? To pretend that the Pill was no more than a pharmaceutical version of the rhythm method?
 * Malcolm Gladwell, “John Rock’s Error”, The New Yorker, (2000-03-10).


 * In the 1960s, manufacturers of the new birth-control pill imagined their ideal user as feminine, maternal and forgetful. She wanted discretion. She was married. And she wanted visible proof that her monthly cycle was normal and that she wasn’t pregnant. In 2019, the user of the pill is perceived as an altogether different person. She’s unwed, probably would prefer to skip her period and is more forthright about when it’s that time of the month. As such, many birth-control brands now come in brightly colored rectangular packs that make no effort to be concealed. But one part of the equation remains: the week of placebo pills, in which hormones are abruptly withdrawn and a woman experiences what looks and feels a lot like her regular period — blood, cramps and all — but isn’t. Physicians have widely described this pseudoperiod as medically unnecessary. So why do millions still endure it? That’s largely the legacy of two men: John Rock and David Wagner.
 * Rachel E. Gross, “Why Women on the Pill Still ‘Need’ to Have Their Periods“, ‘’New York Times’’, (Dec. 11, 2019).


 * First there’s Rock, a Harvard fertility expert and a developer of the pill. There’s a longstanding myth that Rock, a Catholic, designed the pill in the 1950s with the church in mind and included a week of hormonal withdrawal — and therefore bleeding — to make his invention seem more natural. In fact, the thought never crossed his mind, the Rutgers University historian Margaret Marsh says. Instead, it was Gregory (Goody) Pincus, the other developer of the pill, who suggested that the pill be given as a 20-days-on, 5-days-off regimen. Pincus wanted to provide women in his trials with reassurance that they weren’t pregnant, and to know himself that the pill was working as a contraceptive. Rock agreed. After the F.D.A. approved the pill in 1960, however, those few days of light bleeding took on a new significance. Anticipating the church’s opposition, Rock became not just a researcher but also an advocate. In his 1963 book “The Time Has Come: A Catholic Doctor’s Proposals to End the Battle Over Birth Control,” he argued that the pill was merely a scientific extension of the church-sanctioned “rhythm method.” It “completely mimics” the body’s own hormones, he wrote, to extend the “safe period” in which a woman could have intercourse and not become pregnant. “It must be emphasized that the pills, when properly taken, are not at all likely to disturb menstruation,” he wrote. “It has been my consistent feeling that, when properly used for conception control, they merely serve as adjuncts to nature.” He was stretching the truth. Rock knew that the pill’s synthetic hormones caused the lining of a woman’s uterus to thin out, making it inhospitable for a fertilized egg. During the off week, when the hormones were withdrawn, her body got the signal that it was time to shed the lining. But because this event didn’t involve ovulation, it was better described as withdrawal bleeding than menstruation.
 * Rachel E. Gross, “Why Women on the Pill Still ‘Need’ to Have Their Periods“, ‘’New York Times’’, (Dec. 11, 2019).


 * In 1961, Wagner had concerns that his wife, Doris, wouldn’t reliably take her new birth-control pills, which came in a glass bottle with a complex set of instructions. She was to begin taking a five-milligram tablet on the fifth day of her period, continue taking one a day for 20 days, then take five days off, at which point her bleeding would start. “I was constantly asking her whether she had taken ‘the pill,’ and this led to some irritation and a marital row or two,” he later recalled. So Wagner, a product engineer for Illinois Tool Works, came up with a solution: a pill dispenser in the shape of a round plastic disc, which could be rotated to reveal the dose you were to take on any given day. It held 20 pills, plus a week’s worth of pill-size dimples that indicated the off week. His jerry-built design — he fashioned it out of a child’s toy, sheets of clear plastic and double-sided tape — was quickly picked up by Ortho Pharmaceuticals, and in 1963, the company began selling the pill in a Dialpak, a round foil blister pack with pills labeled with the days of the week. “The package that remembers for her,” the company advertised in 1964. “Easy for you to explain ... for her to use,” another ad promised.
 * Rachel E. Gross, “Why Women on the Pill Still ‘Need’ to Have Their Periods“, ‘’New York Times’’, (Dec. 11, 2019).


 * As more companies bought into the idea, the week of placebo pills was here to stay. Doctors liked that they made explaining the instructions to women easy. Women liked having one fewer thing to remember about their birth control. Few questioned why women on the pill should be having a “period” at all. Today there are a small handful of options that reduce or eliminate monthly bleeding: Seasonale, a form of the pill sold in packets of 84 active pills and seven placebos that make it so bleeding happens just four times a year, became available in 2003. In 2007, the F.D.A. approved Lybrel, the first oral contraceptive to provide continuous active pills, with no breaks for withdrawal bleeding. Doctors agree that a menstrual cycle can be a useful indicator of overall health, and yet it still isn’t necessary. When Dr. Lori Picco’s patients ask if they can skip the inactive pills, she says she tells them to go right ahead. “It’s completely fine — there’s no medical concerns,” says Dr. Picco, a gynecologist at Capital Women’s Care in Washington and a fellow of the  American College of Obstetrics and Gynecology. “Honestly, I would think people would want to do it all the time.”
 * Rachel E. Gross, “Why Women on the Pill Still ‘Need’ to Have Their Periods“, ‘’New York Times’’, (Dec. 11, 2019).


 * Ludwig Haberlandt is the 1st great name in hormonal contraception. As early as 1919 he was conducting studies which showed that transplants of tissues or extracts of these tissues (now known to contain progesterone) could produce infertility in rabbits and mice. In 1930 Reiprich of Breslau suggested that the antifertility action of estrogen might be the result of pituitary inhibition. In 1938 ethinyl estradiol was synthesized and 1 year later Dodds and his group reported the synthesis of a series of nonsteroidal estrogens (stilbestrol, hexestrol, and dienestrol). None of the clinical trials conducted in the 1940s could have demonstrated the superiority of 1 estrogen over another with respect to ovulation inhibition at equivalent estrogenic dosage. Studies of this aspect lagged until the 1960s. At that time it was clearly demonstrated that the ethinyl side-chain imparted an augmented pituitary inhibiting potency to estradiol as compared either to other natural estrogens or to other synthetics. It was a fortunate accident that the early clinical preparations of contraceptive progestins contained about 1% contamination with mestranol from the process of manufacture. While this quantity appeared trivial to the chemists, the presence of about 150 mcg of mestranol in the original 10 mg doses of the 19-norprogestins could have accounted totally for their contraceptive efficacy. It was not until several years later than estrogen-free norprogestins were prepared and their intrinsic antiovulatory action proven. When these purified progestins were used for contraceptive therapy, an increased incidence of menstrual irregularities appeared. One standardized quantity of ethinyl estrogen was reincorporated into contraceptive preparations for the control of menstrual regularity, but without any idea that a contribution was being made to contraceptive effectiveness. Clinical studies with continuous low-dose progestin only formulations have demonstrated that their effectiveness in inhibiting ovulation is substantially lower than that of sequential or combination type preparations. A progestational agent added to a baseline estrogen dose appears to produce a greater suppression of plasma gonadotropins than estrogen by itself. While cyclic estrogen administration is capable of inhibiting ovulation with a high degree of efficiency, such a therapeutic regimen is impractical from the point of view of menstrual regularity. The entire matter of cardiovascular hazards related to OC use has been called into question by studies of mortality statistics in the U.S., Great Britain, and Taiwan. In none of these studies is the predicted mortality from cardiovascular disease in OC users confirmed.
 * Goldzieher JW (1982). "Estrogens in oral contraceptives: historical perspective". Johns Hopkins Med J. 150 (5): 165–9.


 * Ludwig Haberlandt (1 February 1885 - 22 July 1932), pioneer in hormonal contraception, was born in Graz, where he graduated from the university in 1909 in medicine summa cum laude and began his career as a physiologist. The idea of temporary hormonal contraception in the female body entered his mind in February 1919, when he was already Professor of Physiology in Innsbruck. He pursued his project ambitiously and by 1921 demonstrated temporary hormonal contraception in a female animal by transplanting ovaries from a second, pregnant, animal. From 1923, after further successful scientific work in this field, he began highlighting the importance of clinical trials in presentations. From then, he was criticized by his colleagues, who accused him of hindering unborn life. His idea was contradictory to the moral, ethic, religious and political agendas of that time in Europe. In 1927 official reports escalated, his family was ostracized by the local population, and Ludwig Haberlandt refused any further interviews. Against all opposition, in 1930 he began clinical trials after successful production of a hormonal preparation, Infecundin, by the G. Richter Company in Budapest, Hungary. Although at the peak of his scientific career, he was unable to pursue other scientific agendas because of the disputed contraception project. After he committed suicide, on 22 July 1932, scientific discussion about hormonal contraception ceased until 1970 when scientists began referring to his earlier medical and scientific work.
 * Edda Haberlandt, “Ludwig Haberlandt--A pioneer in hormonal contraception”, Wien Klin Wochenschr . 2009;121(23-24):746-9.


 * By 1960 the world's population had grown to around 3 billion people, having taken just 33 years to increase from 2 billion.1 Although many agreed that growth rates needed to fall, couples at the time had few reversible contraceptive choices: mainly barrier methods, spermicides, and a few plastic-only and metal-based intrauterine devices (IUDs). Many relied on ‘withdrawal’. This was soon to change dramatically because during the 1950s scientists had patented two synthetic progestogens, norethisterone and norethynodrel.2 Clinical studies showed that these hormones inhibited ovulation, although some accompanying oestrogen (initially mestranol, now ethinylestradiol) was needed for acceptable breakthrough bleeding and pregnancy rates. The first combined oral contraceptive was marketed in the US in 1960, and in the UK the following year. Many women enthusiastically embraced ‘the pill’; for some because it separated contraception from the act of intercourse and for others because it could be used without their partner's knowledge. Early on, howev-er, concerns were expressed about the method's carcinogenic potential, and about reports of associated venous thromboembolic and other cardiovascular events.2 Furthermore, the unfolding thalidomide tragedy of the early 1960s provided a powerful reminder of the epidemiological truth that when millions of people use a medicinal product small increases in risk still result in many people affected.
 * Philip Hannaford, Foresterhill, Toni Belfield, “The contraceptive revolution: some excellent progress but work still to be done”, Br J Gen Pract. 2009 Jan 1; 59(558): 4–6.


 * Oral contraception is now one of the most scrutinised medicinal products on the market. Two British investigations that celebrated their 40th anniversaries in 2008 have been major contributors to the evidence base for current clinical practice. Both illustrate the enormous research opportunity of NHS clinical records. The Oxford/Family Planning Association (Oxford/FPA) Study began in 1968, when 17 family planning clinics in England and Scotland started recruiting 17 000 white, married women using oral contraception, the IUD or the diaphragm.3 The Royal College of General Practitioners' (RCGP) Oral Contraception Study started at the same time, with 1400 GPs throughout the UK recruiting 47 000 mainly white, married (or living as married) women, half of whom were using oral contraception. Both studies have followed up their cohorts through a mixture of clinic or practice reports, personal contact, and the cancer and death notification services of the NHS Central Registries. Each study has provided, in different ways, key insights into the effects of different contraceptives; as well as novel information about other women's health issues. For example, the RCGP study was the first to show that the risk of cardiovascular disease is much higher in pill users who smoke,5 especially among older women, and that the risk of hypertension and arterial disease is related to the combined pill's progestogen content.6 The Oxford/FPA study assessed the effectiveness, safety, and return to fertility after stopping different methods. Long-term mortality and cancer results from both studies have been reassuring.
 * Philip Hannaford, Foresterhill, Toni Belfield, “The contraceptive revolution: some excellent progress but work still to be done”, Br J Gen Pract. 2009 Jan 1; 59(558): 4–6.


 * We now have a clearer picture of the cancer risks associated with combined oral contraception. Compared with non-users, current users have an increased risk of being diagnosed with breast,11 cervical,12 or hepatocellular cancer.13 Hepatocellular cancer is rare in developed countries. The breast and cervical cancer risks decline after stopping oral contraception, returning to that of non-users within about 10 years.11,12 Conversely, combined oral contraceptive users have a reduced risk of endometrial,13 ovarian,14 and colorectal cancer.13 The ovarian and endometrial benefits appear to persist for many years after stopping oral contraception, perhaps more than 15 years.13,14 Limited evidence suggests that today's lower oestrogen dose formulations provide similar protection against endometrial and ovarian cancer as older, higher-dose preparations.15,16 At least within the RCGP cohort, the long-term cancer benefits appear to counterbalance the short-term harmful ones; indeed there may even be a net public health gain.8 Collectively, the research shows that benefits of oral contraception use outweigh risks, when provided appropriately. Importantly, prolonged use of oral contraception does not appear to reduce future fertility.17
 * Philip Hannaford, Foresterhill, Toni Belfield, “The contraceptive revolution: some excellent progress but work still to be done”, Br J Gen Pract. 2009 Jan 1; 59(558): 4–6.


 * Ludwig Haberlandt, physiologist in Innsbruck, tried in the late twenties to develop hormonal contraceptives based on sex hygienic ideas of Sigmund Freud. Although the chemical-physiological knowledge of that time encouraged this plan, after Haberlandt's death in 1932 his tests were dropped and forgotten. It was after World War II, when research in this field was begun in the USA by Gregory Pincus, supported by "Planned Parenthood Federation" under leading of Margret Sanger. Although clinical tests proved to be successful, restrictive social-political conditions in the fifties delayed this project considerably. But in 1958 the first Anti-Baby-Pill reached the US-market.
 * Müller-Jahncke WD (Aug 1988). "Ludwig Haberlandt (1885–1932) and the development of hormonal contraception". Z Gesamte Inn Med (in German). GERMANY, EAST. 43 (15): 420–2. ISSN 0044-2542. PMID 3051743.


 * Women excrete estrogen naturally, and women on birth control pills also secrete the synthetic estrogen in those pills. And these estrogens, depending on the level of wastewater treatment, may not be completely broken down during sewage treatment, so they get discharged into rivers and streams. It doesn't take a lot of estrogen to feminize male fish and, based on the results of our experiment, to impact fish populations.
 * Karen Kidd as quoted in "Sex-Changing Chemicals Can Wipe Out Fish, Study Shows" by John Roach National Geographic News, May 21, 2007


 * When in 1953 Gregory Pincus approached Rock about collaborating on a study of the contraceptive effects of progesterone, Rock unhesitatingly signed on. The two scientists had known each other since the 1930s and closely followed each other’s work. Rock’s finding, in the course of his research on in-fertility treatments, that small amounts of female hormones inhibited ovulation, helped validate Pincus’s similar results in animal trials. Pincus needed someone with Rock’s clinical experience to ex-tend research trials to human subjects. And it helped in terms of fund-raising and public relations that Rock had an unimpeachable reputation as physician and medical researcher. Their cooperative work was made possible by an influx of funds from Katharine Dexter McCormick, whom Sanger had convinced to support Pincus’s promising research. Starting in the summer of 1953, McCormick began to immerse herself in the project and sent regular progress reports to Sanger mentioning Rock’s involvement. In November 1953 McCormick informed Sanger that Rock and Pincus had begun the first human trials in the study. But Sanger, who was preoccupied with setting up the International Planned Parenthood Federation (IPPF), did not appear to be aware of the extent of Rock’s participation. Nor did she feel completely comfortable with his involvement.
 * "John Rock's Catholic Faith: Sanger's Hard Pill to Swallow", “Margaret Sanger Papers Project”, Newsletter #55 (Fall 2010)


 * The use of contraceptives can be morally acceptable in other contexts as well, again, because such uses do not constitute acts of contraception. For example, when a woman has severe menstrual bleeding, or pain from ovarian cysts, the hormonal regimen contained in the Pill may sometimes provide a directly therapeutic medical treatment for the bleeding or the pain. This use of contraceptives is an act of medical therapy to address a pathological situation, not an act of contraception. The secondary effect from the treatment, namely, marital infertility, is only tolerated, and should not be willed, desired, or in-tended in any way by the couple. It is worth noting that it would not be acceptable to make use of contraceptives like the Pill for these medical cases if other pharmacological agents or treatments were available which would offer the same therapeutic benefits and effects without impeding fertility.
 * Pacholczyk, Tad (March 2016). "Catholics and Acceptable Uses of Contraceptives" (PDF). National Catholic Bioethic Center. (Retrieved November 18, 2018).


 * Although American scientists had been busy studying hormones in the 1930s and 1940s, Marga-ret Sanger's dream of a pill for birth control improbably came to fruition because of the discovery of a wild Mexican yam. The yam was key to the development of synthetic hormones, a scientific advance necessary for the creation of the Pill.
 * “The Development of Synthetic Hormones“, PBS.


 * Natural progesterone was hard to come by. Extracting it from animal sources was difficult, time consuming and prohibitively expensive. Natural progesterone drug therapy required huge doses to be effective, and at a cost of anywhere from $80 to $1,000 per gram, only the richest patients could afford the treatment. The only customers for the drug turned out to be world-class race horse breeders, who used it to improve the fertility of their mares. Aside from the high cost, the drug had to be given as an injection, and the shots were painful and not well metabolized. Unless researchers could find a way to produce a highly effective synthetic oral dosage of the hormone, the treatment would remain impractical. In 1943 a chemist by the name of Russell Marker came up with the answer. As a professor at Penn State, Marker had discovered a way to extract progestprogesterone from plant material. Soon after, he was able to create synthetic estrogen from vegetation as well. His path-breaking process, which became known as the "Marker Degradation," remains the basis of synthetic hormone production today. Marker still needed to find a plant that could yield enough progesterone to make mass production possible. He traveled across America in search of the right source, but came up empty-handed. Unwilling to abandon his quest, he headed south to Mexico in search of a plant called cabeza de negro that he had read about by chance in a dusty old regional Texas botany book. His hunch was correct, and the giant tubers proved to be an excellent source for the cheap mass production of progesterone.
 * “The Development of Synthetic Hormones“, PBS.


 * In the early 1950s, Frank Colton and Carl Djerassi, two chemists working independently at separate pharmaceutical companies, took Marker's work one step farther. The scientists each created a highly potent oral form of synthetic progesterone. Working for Syntex, a pharmaceutical company based in Mexico, Djerassi invented norethindrone. This synthetic progesterone was not only orally effective, it was also eight times more potent than natural progesterone. At Searle, Colton created another version of orally effective synthetic progesterone called norethynodrel. With the advent of these new drugs, the Pill came into existence. Although neither Djerassi or Colton developed the drug for contraceptive purposes, both Searle and Syntex had an oral contraceptive right under their noses. Although Djerassi synthesized his version of the drug first, Searle beat Syntex to market. Less than a decade after Colton and Djerassi's breakthrough, with Gregory Pincus making the connection to contraception, Searle's Pill would reach American consumers.
 * “The Development of Synthetic Hormones“, PBS.


 * On October 29, 1959, the pharmaceutical company G.D. Searle filed an application with the U.S. Food and Drug Administration (FDA) to license their drug Enovid for use as an oral contraceptive. Less than a decade after birth control activist Margaret Sanger first told scientist Gregory Pincus about her hopes for a "magic pill," it appeared that success was imminent. The trials presented in the application for FDA approval of Enovid as an oral contraceptive were the largest drug trials ever run. In the trials, 897 women had taken 10,427 cycles of the Pill with no side effects the doctors considered harmful. In 1959 the main hurdle to FDA approval for any new drug was that it be proven safe. Effica-cy was not yet a requirement. Since the FDA had already reviewed the issue of safety when it approved Enovid's use for menstrual disorders in 1957, Searle assumed the application would glide through the process. Searle and the Pill researchers were soon disappointed. The FDA sat on the application, and months went by without any word. Safety wasn't the issue clogging up the review process. It was the revolutionary nature of the Pill itself. Oral contraceptives would be the first drugs whose purpose was not to cure a medical ailment. Instead, the Pill would be given to healthy women for long-term use for a social purpose, and the FDA was uncomfortable with the concept.
 * “The FDA Approves the Pill”, PBS.


 * When the Pill came on the market in 1960, it was enthusiastically embraced by the medical profession and the public. But by the end of the decade, after a crisis over the drug Thalidomide (which was prescribed for morning sickness and caused birth defects) and increasing reports of potential health risks from the Pill, confidence in the drug was ebbing. In 1969 concerns came to a head with the publication of The Doctor's Case Against the Pill.
 * “Senate Hearings on the Pill”, PBS.


 * In January 1970 experts assembled in the stately Senate chamber and began giving their testimony on the hazards of the Pill. Alice Wolfson, a member of the radical collective D.C. Women's Liberation, was sitting in the audience listening to the experts. Her group had come to the hearings because they had all taken the Pill at one time or another and had experienced side effects. The group was outraged that their doctors had never informed them of the risks when they prescribed the Pill. As they sat in the chamber and heard one male witness after another describe serious health risks, they were furious that there wasn't a single woman who had taken the Pill there to testify. After hearing one expert say, "Estrogen is to cancer what fertilizer is to wheat," the women spectators could no longer contain their anger. They stood up and started hurling questions at the men on the dais. The feminists set the room abuzz when they demanded, "Why are you using women as guinea pigs?" and "Why are you letting the drug companies murder us for their profit and convenience?" When told by Senator Nelson to sit down and remain quiet, they retorted, "We are not going to sit quietly! We don't think the hearings are more important than our lives!" Although Senator Nelson was the driving force behind the hearings, the young protesters were so angered by his failure to include women in the hearings -- and by what they viewed as his patronizing behavior --that they went on the attack. The group decided to protest the structure of the hearings and the men leading them, in addition to speaking out about the medical dangers of the Pill. The feminists' grievances gained national attention. National television networks covered the proceedings, and Wolfson's group appeared frequently on the nightly news during the hearings. An estimated eighty-seven percent of women between the ages of twenty-one and forty-five fol-lowed the hearings. Eighteen percent of them quit taking the oral contraceptive as a result of the hearings. In the hearings' aftermath, hormone levels in the Pill were lowered to a fraction of the original doses. A few years after the hearings, prescription rates rebounded, and the number of users in the United States peaked at approximately nineteen million. The real impact of the hearings was not on Pill usage, but on the nascent consumer health movement. D.C. Women's Liberation succeeded for the first time in making informed consent a national issue. In the aftermath of the hearings, the U.S. government would require the pharmaceutical industry to include a patient information sheet with complete information on side effects in every package of birth control pills sold. The growing women's movement was prompting women to assert control over their bodies, and in doing so it changed forever the way Americans take prescription medications.
 * “Senate Hearings on the Pill”, PBS.


 * With the arrival of the birth control pill in 1960, many believed the Church was about to change the position it had held for centuries. The Church was in the midst of reform, and in this climate of modernization it seemed possible that the Vatican might bend on birth control. Since 1957, Church law had allowed women with "irregular" cycles to take the Pill to regularize their cycle and enable them to better practice the rhythm method. Approval of the contraceptive pill, many believed, was soon to follow. Pro-Pill Catholics had a powerful ally on their side. John Rock, the eminent Catholic physician who had carried out Pill trials with Dr. Gregory Pincus, publicly argued that the Pill was merely an extension of the body's normal functioning. Since the Pill used the same hormones already present in the female reproductive system and did not tamper with sperm, Rock believed the Church should view the Pill as a "natural" form of contraception. The Vatican convened a commission to study the question of the Pill, but the Church would take eight years to determine its policy towards the Pill. In the interim, the Pill quickly became the most popular method of birth control among American women —regardless of religion.
 * “The Catholic Church and Birth Control”, PBS.


 * The introduction of oral contraception in 1960 was not the result of one person's fortuitous discovery as happened with X rays or penicillin. It was, rather, the product of small accretions of knowledge resulting from the effort, talent, and determination of many people over a period of years.
 * Perone N (1993). "The history of steroidal contraceptive development: the progestins". Perspect Biol Med. 36 (3): 347–62.


 * The chemical history of the pill begins with the isolation of progesterone in May 1933 by Corner and Allen. With the help of Dr. Hickman from the research laboratory of the Eastman Kodak Company, they used high-vacuum distillation of the oils extracted from corpora lutea to isolate the hormone in a crystalline form which they named progestin. Before the end of that year, Wintersteiner and Allen determined the structural formula of the hormone (C21 H30 O2). This admittedly was not difficult, since the structural formula of pregnanediol was known from previous work by Butenandt. As Allen later recalled, the correct structural formula of progesterone had originally been sketched on a napkin during a lunch with William Strain, long before the definitive structural proof was furnished! In the summer of 1934 the isolation of crystalline progesterone hormone was announced also by Butenandt and Westfall in Danzig, by Slotta et al. in Breslau, and in Switzerland by Hartman and Wettstein. A short time later Butenandt and Schmidt converted pregnandiol to progesterone, and Fernholz succeeded in synthesizing progesterone from stigmasterol.
 * Perone N (1993). "The history of steroidal contraceptive development: the progestins". Perspect Biol Med. 36 (3): 347–62.


 * The early production of progesterone was extremely complex and laborious and the resulting product prohibitively expensive. Butenandt required a ton of cholesterol, obtained from the brains and spinal cords of cattle and the grease from sheep's wool, to obtain 20 lbs of starting material from which commercial quantities of progesterone could be produced. Progesterone, when available, was quoted at $l,000/gm. What opened the door for the development of the pill were two advances in steroid chemistry: the introduction of a new technique that changed progesterone from an expensive rarity to the cheapest of all steroid hormones, and the subsequent modification of the progesterone molecule to make it effective orally.
 * Perone N (1993). "The history of steroidal contraceptive development: the progestins". Perspect Biol Med. 36 (3): 347–62.


 * I invented the pill at the request of a woman.
 * Gregory Pincus interview in Candide, 1966.


 * Historically, contraception was believed to affect the voice negatively. However, more recent studies using low-dose oral contraceptive pills (OCPs) show that they stabilize the voice. However, stabilization generally occurs only during sustained vowel production; connected speech appears unaffected. Therefore, singers may be the only population that experiences clinically increased vocal stability as a result of taking hormonal contraceptives.
 * Jennifer P Rodney, Robert Thayer Sataloff, “The Effects of Hormonal Contraception on the Voice: History of Its Evolution in the Literature“, J Voice. 2016 Nov;30(6):726-730.


 * [Margaret Sanger] said that when she started out in 1912, one of the first things she thought of was a new method for women to use. She after all was a nurse. She was an obstetrical nurse. She knew about birth control. She knew what methods were out there, and she knew they were lousy. She knew they worked sporadically. She knew it took the cooperation of the male and the female, the man and the woman, to make the method work. This was not always satisfactory, and she wanted to apply science and medicine to her feminist mission of giving women control of childbearing, so from the very early days in 1912, she dreamt of a pill. She knew the science wasn't there yet, which is why it took over four decades for this to happen.
 * Alex Sanger, “Roots of the Pill”, PBS.


 * The history of the development of oral contraceptives (OCs) has been a progressive reduction in dosage to what is now probably the lowest does that is compatible with the desired therapeutic effect -- to inhibit ovluation. Yet, controversy and argument continue.
 * R P Shearman, “Oral contraceptive agents”, J Aust. 1986 Feb 17;144(4):201-5.


 * There is not the slightest doubt that a woman who is over 35, who smokes, and who, in addition, may be obese and has hypertension should not use OCs. Progestogen (mini) OCs have a slightly higher failure rate and a greater incidence of irregular bleeding than have combined OCs. The mini OC has little place in women who need effective hormonal contraception and good cycle control. The mini OC may have a place in a patient who finds other contraception unacceptable and in whom estrogens are contraindicated specifically.
 * R P Shearman, “Oral contraceptive agents”, Med J Aust. 1986 Feb 17;144(4):201-5.


 * The possibility of hormonal contraception was postulated as early as 1919 by the physiologist Ludwig Haberlandt in Innsbruck. The same year, he began to test his hypothesis in animal experiments. In 1924 he succeeded in his efforts to render mice infertil by orally administering ovarian and placental extracts. He failed to have his method tried in women.
 * H H Simmer, “On the beginnings of hormonal contraception (author's transl)”, Geburtshilfe Frauenheilkd. 1975 Sep;35(9):688-96.


 * One of the early female graduates of the Massachusetts Institute of Technology, Katharine McCormick believed in science and in the advancement of women. Margaret Sanger witnessed unwanted pregnancies -- and desperate abortion attempts -- when she worked as a nurse among New York's poorest women. Though they came from different worlds, the two women set out to improve women's lives through "birth control," a phrase Sanger coined. When Sanger and McCormick first met in 1917, women had been working for decades to achieve the vote. Thirty-nine years had gone by since a constitutional amendment for women's suffrage was first proposed, and three more years would pass before the states ratified it. At a time when women struggled for voting rights, job opportunities, or access to education, both McCor-mick, a suffragist, and Sanger, a birth control proponent, were outspoken advocates for giving women more control over their own lives. Thirty years later, McCormick's sizable inheritance combined with Sanger's tireless advocacy would bring about the birth control pill and spark a revolution. "An estimated eighty percent of all American women born since 1945 have taken the Pill," says historian An-drea Tone, giving them the ability to plan their reproductive lives.
 * Andrea Tone, “Roots of the Pill”, PBS.


 * McCormick's involvement with the Pill is extraordinary. I think she's one of the most underappreciated figures in not just Pill history, but the entire history of scientific and technological innovation. First of all, it was very uncommon for a woman in the 1950s to have the kind of fortune that McCormick had. She had a fortune that was so vast that, as John Rock said at one point, she couldn't even spend the interest on the money that she had. So she was unique from the get-go in simply having this access to capital... At the time, the pharmaceutical companies which had historically been involved in some kinds of birth control production, like condom production and diaphragm production, saw the Pill project also as too controversial. Many large companies had passed on the opportunity to develop the Pill, including Pfizer and Merck, because they just didn't want to touch it. And so, were it not for McCormick, it's unclear how the Pill would have been developed. She really deserves credit for single-handedly financing one of the most important developments of the 20th century.
 * Andrea Tone, “Roots of the Pill”, PBS.


 * Introduction of the birth control pill in the United States in 1960 marked the end of a relatively short period of time (< 10 years) to intentionally produce an oral contraceptive, and the beginning of a relatively long period of controversy surrounding the use of the pill. Availability of the pill had an impact on various aspects of social life, including women's health, fertility trends, laws and policies, religion, interpersonal relationships and family roles, feminist issues, and gender relations, as well as sexual practices among both adults and adolescents. The pill proved to be highly effective from the outset. Although safety issues developed with the earlier formulations, continued evolution of pill hormones and doses has resulted in a greatly improved and safe oral contraceptive. A broad range of noncontraceptive health benefits also is associated with the pill. These health effects are significant, as they in-clude protection against potentially fatal diseases, including ovarian and endometrial cancers, as well as against other conditions that are associated with substantial morbidity and potential hospitalization and associated costs. The popularity of the pill has remained high, with rates of use in the past 30 years in the United States ranging from one-quarter to almost one-third of women using contraception. Almost 40 years after its introduction, the pill's contraceptive efficacy is proven, its improved safety has been established, and the focus has shifted from supposed health risks to documented and real health bene-fits.
 * L Tyrer, “Introduction of the pill and its impact”, Contraception. 1999 Jan; 59(1 Suppl):11S-16S.


 * By the end of their reproductive years, more than 80% of US women will have used oral contraceptives (OCs), for an average of about 5 years. The pill has had a dramatic impact on social life in the US, affecting women's health, fertility trends, laws and policies, religion, interpersonal relations, family roles, women's careers, gender relations, and premarital sexual practices. The emergence of the women's rights movement of the 1960s and 1970s was significantly related to the availability of the pill and the control over fertility it enabled. This capability allowed women to make choices about other life arenas, especially work. Over the past 40 years, both the content and dose of the steroid components of OCs have changed significantly, with consequent reduced health effects. This improved safety profile has been further bolstered by the identification of women with risk factors such as smoking, high blood pressure, history of cardiovascular disease, and diabetes with vascular disease. In recent years, the emphasis has shifted from the health risks of OC use to the noncontraceptive health benefits.
 * L Tyrer, “Introduction of the pill and its impact”, Contraception. 1999 Jan; 59(1 Suppl):11S-16S.


 * Progestin-only contraceptives are known to alter the cervical mucus, exert a progestinal effect on the endometrium, interfering with implantation, and, in some patients, suppress ovulation.
 * United States Food and Drug Administration, Federal Register, 41:236, December 7, 1976, page 53,634.


 * Oral contraceptives (OC) convey a protection against ovarian, endometrial and perhaps colorectal cancer. However, OC use is associated with excess risk of breast (current or recent use only), cervical and liver cancer. Benefits and risks of OC use on cancer were reviewed in 2005 by a Working Group at the International Agency for Research on Cancer, which concluded that combined OCs are carcinogenic to humans, based on an increased risk for hepatocellular carcinoma, cervical and (for current use only) breast cancers. The Working Group also concluded that there is conclusive evidence that OCs have a protective effect against cancers of the ovary and endometrium.
 * C La Vecchia, “[Oral contraceptives and cancer“], Minerva Ginecol. 2006 Jun;58(3):209-14


 * "It is the prerogative of the human intellect to dominate the energies offered by irrational nature and to orient them towards an end conformable to the good of man." In regard to your question as to why the pill is so bad if it is permitted by the Church to be used sometimes and at other times it is forbidden. The answer is that the pill is not intrinsically evil, of itself. It is made up of varying levels of the hormones called progestogens and estrogens. There is nothing evil about these hormones; God Himself created them! Yet He created them with a biological purpose of giving the female body the potential for fertility . ..
 * Fr. Emmanuel Vita; in Fr. Augustine Mary “Contraception, What's Allowed?“, EWTN, (1996)


 * When one approaches the cycle of a woman's body from the standpoint that God made it and has made it for a purpose, one can then understand the relation of the pill to this cycle. To be blunt, a woman's cycle is ordered toward fertility, toward life. The pill, when used as an oral contraceptive, is ordered toward infertility, toward death. The pill (made up of estrogen and progestogen) is ordered toward infertility because it inhibits the release of the follicle stimulating hormone and stops the luteinizing hormone from triggering ovulation. The pill is ordered toward death because both estrogen and progestogen "change the endometrium in such a manner that even if ovulation did take place, implantation of the fertilized egg would be unsuccessful." In some cases, a child is conceived, and the pill acts as an abortifacient. This is the murder of an innocent!
 * Fr. Emmanuel Vita; in Fr. Augustine Mary “Contraception, What's Allowed?“, EWTN, (1996)

== Marc Dhont, “History of oral contraception”, The European Journal of Contraception & Reproductive Health Care, Volume 15, 2010 - Issue sup2 ==
 * On the 50th birthday of the pill, it is appropriate to recall the milestones which have led to its development and evolution during the last five decades. The main contraceptive effect of the pill being inhibition of ovulation, it may be called a small miracle that this drug was developed long before the complex regulation of ovulation and the menstrual cycle was elucidated. Another stumbling block on its way was the hostile climate with regard to contraception that prevailed at the time.
 * Almost every decade we have witnessed a breakthrough in oral contraception. Social and moral objections to birth control have gradually disappeared and, notwithstanding some pill scares, oral contraceptives are now one of the most used methods of contraception.
 * It had already been known for several decades that sex hormones were able to suppress ovulation in animals. Ludwig Haberlandt, an Austrian physiologist is sometimes called the grandfather of the pill. Indeed, in 1921 he found that rabbits and guinea pigs became temporarily sterile after transplantation of ovaries from pregnant animals. These experiments paved the way for pharmacological studies on the effect of progesterone on ovulation. The anti-ovulatory effect of progesterone was demonstrated by A. W. Makepeace and co-workers in 1937 who injected progesterone in mated female rabbits. Large-scale experiments with progesterone, which hitherto had been extracted from animal ovaries became possible after Russell E. Marker, a professor of organic chemistry, found that progesterone could be manufactured from a substance named diosgenin, extracted from the root of a plant (Dioscorea mexicana) which grows in Mexican jungles.
 * Pincus made his name in the field of experimental biology when, in 1934, he produced rabbits in vitro by parthenogenesis. In 1944, he established the Worcester Foundation for Experimental Biology where he surrounded himself with a group of brilliant young investigators. One of them was a Chinese immigrant, Min-Chueh Chang, who repeated and refined the experiments of Makepeace and established the experimental model to study the anti-ovulatory effect of sex steroids. The impetus for converting findings of animal experiments into human hormonal contraception was given by Margaret Sanger, founder of the Planned Parenthood Federation of America (PPFA). She approached Pincus in 1951 and provided a small grant to begin hormonal contraceptive research. In the same period, John Rock, an expert in the treatment of infertility, was experimenting with the oral administration of high doses of oestrogen (diethylstilboestrol) and progesterone to induce pseudo-pregnancy in infertile women. He reasoned that high doses of sex steroids promoted the growth of the uterus and the Fallopian tubes and so restored fertility; but he also found that this treatment suppressed ovulation. The biologist Pincus and the gynaecologist Rock shared their experience and their intention to develop a hormonal oral contraceptive.
 * There is a vast difference between the original pill and the current forms of hormonal contraception. This evolution was characterised by the reduction of hormonal dosages, introduction of new progestins, elaboration of various oestrogen-progestin administration schemes and the development of alternative routes of administration. It was driven by the search for oral contraceptives causing less side effects, but also by competition between pharmaceutical companies, and was facilitated by advances in the knowledge of hormonal mechanisms and the monitoring of the endocrine and metabolic effects OCs elicit.
 * Epidemiological studies by the Medical Research Council, in the UK, revealed that pill users were more susceptible than nonusers to thromboembolism9. On second thoughts, this complication could be anticipated because of the established link between high oestrogen levels and thromboembolism during pregnancy. Later, it was shown that oestrogens and ethinylestradiol in particular stimulate the synthesis of several clotting factors and hepatic proteins among which the renin substrate angiotensinogen, re-sponsible for pill-induced hypertension in susceptible women. This first pill scare led to the gradual reduction in the dosage of ethinylestradiol from 50 to 30, 20 and even 15 μg. This dose reduction was associated with less side effects such as breast tenderness, nausea and bloating. But, even at these low doses, oral contraceptives still exert a prothrombotic effect.

== Junod SW, Marks L (2002). "Women's trials: the approval of the first oral contraceptive pill in the United States and Great Britain" (PDF). J Hist Med Allied Sci. 57 (2): 117–60. ==
 * ON June the United States celebrated the fortieth anniversary of the approval of Enovid, the first oral contraceptive. From the time of the first clinical trials to the present, nearly million women have swallowed various formulations of the contraceptive pill, making it one of the most widely consumed class of drugs in the world. By the end of the twentieth century oral contraceptives had become a feature of everyday life, with more than 70 million women reaching for their pill packet on a daily basis around the globe. Widely regarded as a revolutionary drug in its early years, the pill might retrospectively be considered the first “designer” or “lifestyle” drug of the twentieth century.
 * p.117


 * Developed in the1950s, the pill was once optimistically hailed as a scientific cure for the world’s rising population and its consequent social and political ills. Historians, however, have begun to show that the oral contraceptive did not prove to be the social panacea envisioned by its inventors, and that its history is more complex. Much of its history cannot be disentangled from the wider political, economic, and social issues of the day .Watkins, for instance, has shown that the availability of the pill in the United States had a major impact on the relationship between doctors and female patients in the1960s. Similarly, Critchlow has illustrated how the contraceptive controversy in American politics started with the appearance of the pill and continued with the debates surrounding RU-486, the abortion pill. More recently, Marks has challenged previous histories, which have championed the pill as a North American product that fuelled the sexual revolution, suggesting that its roots and subsequent adoption were much more diverse in origin and can only be understood within a wider international framework.
 * p.118


 * Adding to the growing knowledge about the pill and its wide spread influence on twentieth-century history, we offer a detailed cross-cultural (or at least transatlantic) history of the actual processes by which the first pill formulation, Enovid (U.S.) and Enavid (U.K.) came onto the market. Such a detailed account of the marketing of the pill emphasizes that the birth control pill was introduced in various stages, rather than simply approved at a single point in time. The drug was first marketed in 1957 for treating gynecological disorders. Only in 1960 was it allowed to carry a contraceptive claim, and only after 1961 did reports begin to appear that the drug could cause serious, albeit rare, thrombotic complications (blood clots). Between the time that Enovid was approved as a menstrual regulator and then as a contraceptive, attitudes regarding the perception of safety changed greatly, as did the evaluations carried out to assess risk and efficacy.
 * p.118


 * For most women, thalidomide came to epitomize the potential and unknown dangers posed by any drug used in pregnancy, while the horror that this drug inspired led directly to stronger laws governing the marketing of new drugs in Britain, the United States, and most of Europe between 1962 and 1964. As a drug intended to prevent pregnancy, the pill played a special role in the debate about the safety and efficacy of drugs.
 * p.120


 * By 1967, British scientists had conclusively linked the pill with thrombosis, but they did so relying largely on epidemiological data. This increasing reliance on statistical evidence supported and advanced a more analytical and less communally determined drug approval process. This change in the risk-benefit equation calculations of a new drug, of course, may have been inevitable and had been initiated with an earlier drug, chloramphenicol, but it was the stature and novelty of Enovid that propelled it forward so dramatically. In the United States, concerns about the safety of the pill before 1967 led to the creation of the Food and Drug Administrations ”first permanent advisory committee, further changing the nature of the drug approval process and initiating what Jasanoff would later call the “fifth branch” of government in the United States.
 * pp.121-122


 * Much of the criticism of the pill, however, as Watkins has shown, arose from the fact that the pill altered the relationship between women and their physicians. In retrospect, it is clear that women’s rejection of medical paternalism underlay much of the social criticism leveled at the pill. We believe that the unique decision-making processes that introduced oral contraceptives and allowed them to remain on the market even after potentially dangerous side effects were discovered are an important and instructive example of the intermingling of science, policy, and practicability in the approval process for a revolutionary twentieth-century drug.
 * p.122


 * The process by which the pill came to be marketed in Britain and the United States differed, according to the distinct drug regulatory mechanisms of each country. The United States had some premarketing control over the introduction of new drugs onto the marketplace, which had been established in 1938, but Britain had no premarketing controls aside from a requirement that all pharmaceutical manufacturers be licensed. In the end, however, both countries had similar versions of the pill on the market within months of each other.
 * p.124


 * In Britain, government control over the manufacture and supply of pharmaceutical drugs had been tightened in 1947 and 1957. Such restrictions, however, primarily concerned dangerous drugs and self-medication drugs, as well as biological products (e.g., antibiotics, vaccines, and insulin, all of which had to best and ardized by biological techniques). Products had to be scrutinized to insure that their manufacturing methods and potency testing met the stipulated requirements. Drugs subject to these restrictions were only a small minority in the pharmacopoeia. All other drugs could be released onto the British market without submitting to any formal procedure. In general, the British government took a laissez-faire approach toward pharmaceutical companies in the1950s. The only restriction imposed on drugs in this period was that they could not be advertised as curing cancer, venereal disease, or Bright’s disease. Britain and the United States thus had very limited testing requirements when the first pill was initially approved, and Enovid underwent governmental premarket review only in the United States. The 1938 Food, Drug and Cosmetic Act specified that a drug is not defined by its ability or lack of ability to treat a disease, but rather as any product “affecting the structure or function of the body.” This language had been incorporated into the 1938 law for the explicit purpose of giving the FDA jurisdiction over products such as obesity drugs (obesity was not considered a disease), nose straighteners, and especially contraceptive devices such as pessaries and condoms, which, like oral contraceptives, had both therapeutic and contraceptive applications. Therefore, by definition, Enovid was a product that clearly fell under the jurisdiction of the FDA.
 * pp.125-126


 * G.D. Searle and Company made the first American application for the approval of Enovid to the FDA in 1957.The company sought approval for the use of Enovid in cases of menstrual irregularities, including amenorrhea, dysmenorrhea, and menorrhagia, as well as endometriosis (a painful proliferation of uterine tissue outside the uterus) and infertility. Incases of infertility, it had been shown that women who were given the drug for several months-to “rest” their ovaries-often went on to conceive, a phenomenon often referred to as the “Rock Rebound” effect. Although the original submission addressed only gynecological disorders, it was well known among many scientists that this particular formulation could prevent ovulation and therefore could be used as a contraceptive. Publications worldwide had reported Pincus’s work and has speculated on the pills clinical prospects.
 * p.126-127


 * Once marketed in the United States and Britain, Enovid/Enavid was freely available to women whose doctors would prescribe it, either as a treatment for infertility or for menstrual disorders. Medical doctors in both countries could then, as they can now, prescribe drugs for purposes other than those approved because neither country has ever sought to regulate the practice of medicine. The fact that so many women may (or may not) have had access to Enocid/Enavid years before it was formally approved by FDA as a contraceptive makes any discussion about the approval of the pill which centers upon numbers very difficult. The most commonly cited figure is that by 1959 more than 500,000 women were taking the drug for menstrual disorders in the United States.
 * p.128-129


 * When Searle notified the FDA in 1959 that it wished to submit a supplemental application for Enovid to expand the drug’s labeling indications to include use as an oral contraceptive, it rapidly became clear that the American federal government wanted little to do with the process and saw it as no more than routine bureaucratic process of new drug review and approval at the FDA. As Critchlow and Watkins have discussed in great detail, there mere mention of contraception as a credible component of overseas aid had drawn the opposition of American Catholic bishops. Moreover, with the 1960 presidential election looming, neither President Eisenhower nor the Catholic presidential candidate, John Kennedy, wanted to make an issue out of contraception and the pending approval of the contraceptive pill. In Britain, the central government also vigorously refused to initiate debate over the pill. The British Ministry of Health had stated as early as 1955 that it did not want any involvement with contraceptive testing and approval. Again, in 1956, when news emerged of the possible availability of a contraceptive pill in the United States, the Medical Research Council, the main British government body responsible for clinical trials since 1919, refused to sponsor any monitoring of the new drug on the grounds that it was too politically and morally sensitive an issue for them to handle.
 * p.129


 * Searle had originally asked the FDA to consider simultaneously an application for three dosages of Enovid: 10, 5, and 2.5 milligrams. Searle was particularly interested in promoting the lower dosage forms of Enovid because one of the chief criticisms of the pill up to this point had not been a medical one, but rather an economic one. Partly developed in response to concerns about world hunger, it was feared that Enovid would prove far too expensive for woen in poorer countries. The cost of the hormone was directly proportionate to the cost of the drug and the dose. Lowering the dose significantly lowered the cost of Enovid. Searle, therefore, had great incentive to prove the safety and efficacy of its lower dosage pills. As far as Searle officials were concerned, the lower dose of Enovid should not have required a separate NDA because they considered it merely an alternative dose of the same drug. As one Searle representative wrote when seeking approval of the lower dosage: “[I find it] very difficult to understand how less of a drug can be more dangerous than a larger dose...a basic fact of any drug use is adjustment of the dosage to a particular individual’s requirement. That’s all we are trying to do with the lower dosage forms of Enovid....I find it impossible to understand how one increases danger by reducing the dose.” The FDA, however, viewed the dosage question as an issue of efficacy and possibly safety in 1959. The lower doses produced an increased incidence of breakthrough bleeding. It was not immediately clear whether this was an indication that ovulation had not been effectively suppressed. If so, it would have undermined Enovid’s effectiveness as a contraceptive, rendering it unapprovable. The FDA was therefore very cautious in considering any alteration in the original dose formulation of the pill.
 * p.143-144


 * By the end of the fourth quarter of 1964, more than 4 million women had used Searle’s pill. Such unexpected and unprecedented popularity not only surprised the pharmaceutical industry, but amazed physicians, family planners, social reformers and politicians as well. The early enthusiasm for oral contraceptives, however, was soon dampened as the high hormonal doses of the first pill produced nausea, headaches, and dizziness so severe that some women abandoned the pill as quickly as they had embraced it.
 * p.153


 * In Britain, publicity over the pill’s potential risks reached a crescendo in late 1969, when a number of British medical journals and popular newspapers published articles accusing the medical profession of being too complacent on the links between the pill and thrombosis. The debate intensified in December 1969 when Professor Victor Wynn, an endocrinologist and an expert on metabolic effects of anabolic steroids, appeared on a David Frost television program and detailed before millions of British viewers a panoply of risks associated with the pill. Appearing in a total of three Frost programs that month, one of which was broadcast to an audience in the United States, Wynn’s testimony caused public and parliamentary uproar. These broadcasts, together with the publication of the British epidemiological studies linking the pill with thrombotic complications, resulted in the British government warning doctors to no longer prescribe the higher dose (10-milligram) pills. In the United States, an impassioned public debate on the safety of the pill had also been inaugurated with the publications of journalists Morton Mintz and Barbara Seaman. Both journalists challenged what they characterized as the “diplomatic immunity” which had dominated news about the oral contraceptives up to that time by questioning not only the overall safety of the pill but the way in which the U.S. regulatory authorities had approved it. Mintz, in particular, widely publicized as fact that the pill had been tested on only 132 women prior to its approval for contraception and that its safety had not been proven before it went on the market. By the end of 1969 Senator Gaylord Nelson called for congressional hearings (known as the Nelson hearings) on the safety of the pill. The primary focus of the Nelson hearings was on safety and informed consent: Had women been adequately informed about the risks and significant side effects of the pill? Should the pill be removed from the market, or should new studies be instituted?
 * pp.157-158


 * As Watkins has discussed, the Nelson hearings infuriated many women. During the 1960s many feminists had begun to protest against the paternalistic attitudes of the state and male-dominated medicine. After the hearings, women were critical of the process, which excluded testimony from female patients, and angry about the analogies to women as guinea pigs. Many responded by parading in front of the hearings carrying placards demanding “Feed the Pill to your guinea pigs at the FDA not live women.” After the hearings, women’s groups, particularly the Washington D.C.-based Women’s Liberation group, called for new separate hearings centered around women’s concerns, angrily arguing that, “In spite of the fact that it is women who are taking the pill and taking the risks, it was the legislators, the doctors, and the drug company’s representatives, all men of course, who were testifying and dissecting women as if they were no more important than the laboratory animals they work with every day.” In this charged atmosphere, there is no doubt that what feminists took away from the writings of journalists and the Nelson hearing proceedings was that women had indeed served as guinea pigs as drug companies prospered, and that, even ten years later, physicians were still not sure if the pill was safe.
 * pp.158-159


 * By the 1970s, however, there had been a sea tide of change in the evaluation of the safety of oral contraceptives since 1960. In 1962, before the British researchers established the statistical link with thrombosis, many physicians felt that the whole question of the pill’s side effects had been magnified, not by the actual danger, but by the concerns over thalidomide. No one disputed, however, that there was a need for more research to substantiate the concerns. By the time of the Nelson hearings, several large-scale studies of the pill and of thrombotic phenomena had been designed, and others were underway. The American Cancer Society, to cite a single example, initiated a seven-year study comparing 5000 pill users with 5000 nonusers. Experience with such large studies and interpretation of their results, as well as the new drug evaluation methods mandated by laws and regulations enacted in the wake of the thalidomide disaster, strengthened the entire new drug approval system worldwide.
 * p.159-160


 * The pill, of course, is still on the market, and although it is still controversial in some corners, the social and medical concerns it originally engendered have now been supplanted by concerns over the abortion drug RU-486, approved in the United States in 1999. The pill, like other drugs before and after it, added experience and knowledge that strengthened the regulatory process. Moreover, early and continuing public criticism of the pill and its approval was crucial in opening up the larger debate over the safety, labeling, and information provided to consumers of prescription drugs in both countries. Seaman’s tireless, and at times heroic, efforts to mandate a “patient package insert” for the oral contraceptives cannot be overlooked as a major contribution to the history of the women’s health movement. Because of the knowledge gained from Enovid/Conovid, pharmaceutical researchers have gone on to create a new generation of oral contraceptives which are, in the words of journalist Robin Herman,“99.9% effective,” but are generally safer and have far fewer side effects than any of the original pill formulations. Only in 1995 was it established that a mutant gene (called factor V Leiden) puts some women at increased risk of venous thrombosis. With the recent commercial availability of genetic screening for this gene, women now have the option of being screened before they take the pill.
 * p.160

== Drew C. Pendergrass and Michelle Y. Raji, “The Bitter Pill: Harvard and the Dark History of Birth Control“, The Crimson, (September 28, 2017) ==
 * The trials began with small-scale tests on rats and rabbits. Each day, for a period of five days, re-searchers pumped immature female rabbits full of the reproductive hormones estrogen and progesterone. On the fifth day, the scientists allowed the rabbits to copulate, then removed their fallopian tubes and examined them for signs of egg fertilization. For years, Massachusetts scientists worked diligently on hundreds of caged rabbits in a basement lab on a shoestring budget, searching for the perfect compound. On June 23, 1960, a decade after the tests began, the hormonal birth control pill hit the market. The idea was simple: Take a little white pill once a day, avoid accidental pregnancy. The implications were revolutionary.
 * On June 23, 1960, a decade after the tests began, the hormonal birth control pill hit the market. The idea was simple: Take a little white pill once a day, avoid accidental pregnancy. The implications were revolutionary. Women could work without fear of becoming pregnant. Sex before marriage be-came less risky. Sex after marriage became less fraught. Feminist historians herald this day as the be-ginning of the sexual revolution—but the story of the birth control pill is also one of conflicting ideologies and medical exploitation. The Harvard-educated scientists who formulated the pill relied on invasive tests and shaky medical consent.
 * After her husband died on January 19, 1947, Katharine D. McCormick came into $35 million. A life-long feminist and birth control advocate, she spent the money on what Margaret Sanger, famous feminist and Planned Parenthood founder, explained to her as “the greatest need of the whole [Planned Parenthood] movement”—“a simple, cheap, contraceptive.” Feminists had dreamed of a birth control pill a woman could take without a man’s knowledge, and Rock and Pincus were their best chance yet.
 * Ten years after its first release, the birth control pill made headlines again during the Nelson Pill Hearings, a Capitol Hill investigation into the pill’s safety. When feminist activists noticed that no women were being invited to testify, they interrupted the proceedings and testified from their seats. “Why isn’t there a pill for men?” activist Alice Wolfson shouted. “Why are 10 million women being used as guinea pigs?”
 * [M]edical history is often swept clean, praising progress without remembering those who suffered to create it. For the most part, the popular narrative of the pill is one of celebration. When a 2009 Harvard Gazette story discussed Harvard’s role in creating the birth control pill, they did so without referencing the Puerto Rican trials or the asylum testing. Pincus and Rock are largely remembered for their contributions to women’s reproductive empowerment, without reference to their troubling methods.

“A History of Birth Control Methods “, Planned Parenthood

 * By the beginning of the 20th-century, the idea of oral contraception in conventional medicine had died. It was not to be revived until the century was half over. The woman who made it happen was Margaret Sanger (Riddle, 1992).
 * p.9


 * The efforts of Sanger and McCormick would have been for naught, however, if it hadn’t been for the medical folk traditions of the descendants of the Aztecs. The basic research for the pill became possible when Russell Marker discovered that generations of Mexican women had been eating a certain wild yam ⎯the Barbasco root, also called cabeza de negro⎯for contraception (Chesler, 1992). It was from these yams that Marker was able to extract the progestin that  Gregory Pincus combined with estrogen to formulate the first birth control pill (Grimes, 2000). The first pill was far from perfect ⎯but its effectiveness, simplicity, and ease of use extended to millions of women an unheard-of control over reproduction, for the first time allowing them to truly separate vaginal intercourse from procreation (Bullough & Bullough, 1990). Margaret Sanger’s pill made the sexual liberation movement of the ‘60s a lot less risky than the one that occurred after World War I. More than 20years ago, the FDA proclaimed that “...more studies have been done on the pill to look for serious side effects than have been done on any other medicine in history” (Asbell, 1995). That scientific scrutiny has continued to this day. The pill of today, as well as other more recent combined hormone methods —the patch and the ring—offer safety and effectiveness with greatly decreased doses of hormone (Knowles &Ringel, 1998).
 * p.9


 * During the 1950s, in the early days of hormonal contraceptive research, pellets of progesterone were inserted under the skin of rabbits to prevent them from conceiving (Asbell, 1995). Forty years later, a variation on those experiments became an approved form of birth control in the U.S. ⎯Norplant. But just as with DMPA, American women had to wait longer than their sisters around the world to have access to this very effective method (Asbell, 1995). Developed by the Population Council and distributed in the U.S. by Wyeth-Ayerst Laboratories, Norplant was approved by the WHO in 1984, after nearly 20 years of research and clinical trials. WHO heralded Norplant as an “effective and reversible long-term method of fertility regulation ⎯particularly advantageous to women who wish an extended period of contraceptive protection” (Population Council, 1990).Six years later, the FDA approved Norplant for use in the U.S. By then it had been used by a half-million women in 17 countries where it had received regulatory approval (Grimes, 2000). By July 1994, nearly a million women in the United States had chosen to use Norplant implants (Lewin, 1994).
 * p.10

== "Pro-Life Activist's Encyclopedia", American Life League, “The Birth Control Pill: Enabler of the Sexual Revolution“, ETWN ==
 * The Searle Company developed the first oral contraceptive (OC), Enovid, in the late 1950s. In keeping with defensive anti-litigation strategy, the company extensively tested the Pill on Puerto Rican women before concluding that it was safe for American women to use in 1961.
 * The original class of birth control pills contained a high dosage of both estrogen and progestin, which led to a variety of side effects, including blurred vision, nausea, cramping, irregular menstrual bleeding, headaches, and possibly breast cancer. Beginning in about 1975, the manufacturers of the Pill, in reaction to adverse publicity generated about the severe side effects caused by the high-dosage pills, steadily decreased the content of estrogen and progestin in their products.
 * Users of the "old" high-dosage birth control pills experienced relatively severe side effects. However, many of these pills were generally considered non-abortifacient in their two-fold ("biphasic") modes of action. The pills would thicken cervical mucus and inhibit ovulation, but they would generally not inhibit implantation of the blastocyst (the five-day old, 256-cell developing human being) in the uterine lining. However, the new low-dosage pills are "triphasic." They have three modes of action; they thicken cervical mucus, inhibit ovulation, and block implantation. Therefore, the "new" Pills are all abortifacient in nature. The Department of Health and Human Services (HHS), in its 1984 pamphlet entitled "Facts About Oral Contraceptives," said that "Though rare, it is possible for women using combined pills (synthetic estrogen and progestogen) to ovulate. Then other mechanisms work to prevent pregnancy. Both kinds of pills make the cervical mucus thick and 'inhospitable' to sperm, discouraging any entry to the uterus. In addition, they make it difficult for a fertilized egg to implant, by causing changes in Fallopian tube contractions and in the uterine lining. These actions explain why the minipill works, as it generally does not suppress ovulation."
 * It is known that pills which contain only progestin alter the cervical mucus. They also interfere with implantation by affecting the endometrium and suppressing ovulation in some patients by reducing the presence of follicle-stimulating hormone (FSH). This mechanism is confirmed by the United States Food and Drug Administration (FDA), which stated that "Progestin-only contraceptives are known to alter the cervical mucus, exert a progestinal effect on the endometrium, interfering with implantation, and, in some patients, suppress ovulation." The manufacturers of the minipills also acknowledge this mode of action. For example, Syntex Laboratory spokesman Russ Wilks announced that its progestin-only Pill "... did not interfere with ovulation ... It seems to affect the endometrium so that a fertilized egg cannot be implanted."
 * According to United States Federal courts, the birth control pill has been classified as "unavoidably unsafe." This means that, implicit in a woman's consent to use the pill, even if she is not entirely informed of its dangers, is an acknowledgement of physical risk.
 * The most dangerous and well-documented side effects commonly associated with the Pill are heart attacks and strokes. The eight-year Nurse's Health Study at Harvard Medical School found that Pill users are 250 percent as likely to have heart attacks and strokes than those who don't use the Pill, probably because the Pill excessively increases blood clotting ability.
 * [I]t is obvious that the Pill has contributed greatly to our country's exploding divorce rate, which was about 18 percent in 1965 and now stands at about 50 percent.
 * After the Pill was introduced in the mid-1960s, fornication and 'shacking up' both almost doubled in a period of only five years. This behavior also increased steeply when abortion was legalized in 1973. People of all ages (but especially teenagers) are fornicating more than ever before. Wife-swapping clubs, sex addiction treatment organizations, hard-core pornography, and 'fantasy [sex] tours' to Far East nations have increased tremendously. Even the original developers of the birth control pill now acknowledge that their invention has led to widespread promiscuity. Dr. Robert Kirstner of  Harvard Medical School said that "For years I thought the pill would not lead to promiscuity, but I've changed my mind. I think it probably has." And Dr. Min-Chueh Chang, one of the co-developers of the birth control pill, has acknowledged that "[Young people] indulge in too much sexual activity ... I personally feel the pill has rather spoiled young people. It's made them more permissive."

Reed, James, “The Birth Control Movement and American Society: From Private Vice to Public Virtue”, Princeton University Press, (1984)

 * Since preventing ovulation prevents pregnancy, one could employ the same principles in birth control as in preventing dysmenorrhea [painful menstruation] Thus, for example, if an individual took 1 mg. of diethylstilbestrol [a synthetic estrogen] by mouth daily from the first day of her period for the next six weeks, she would not ovulate during this interval. A hormone regiment would have to be worked out that allowed periodic menstruation, but the medication could be administered to make the menstrual period come on the least undesirable day. Such manipulation of one’s menstrual rhythm is probably not to be advocated indiscriminately, but there is no evidence at the present time to suggest that the individual will not return to her pre therapeutic rhythm on cessation of therapy. By the 1950s both endocrinology and steroid chemistry had advanced far enough so that a hormonal contraceptive was possible. The initiative for a major effort to develop a physiological contraceptive did not come from scientists or physicians, however, but from laywomen. And the scientist that they chose to realize their hopes for better birth control was a refugee from academic biology.
 * p.316


 * G.D. Searle and Company was only able to patent the specific steroids developed in its laboratories, not the term “The Pill” or the concept of using steroids as contraceptives. And Searle never would have supplied Pincus with the experimental drugs he needed if in doing so they had risked their right to exclusive control over compounds they developed. Nevertheless, Pincus only encouraged McCormick to make all of her contributions directly to the foundation after G.D. Searle had begun supporting the pill project with both experimental drugs and specific research grant.
 * p.343


 * McCormick apparently never understood that Searle had paid a large portion of Pincus’ salary for years. Rather, as McCormick explained to Abraham Stone, Pincus was “acquainted with some one [sic] in the Searl [sic] Company.” Exactly how he was able to convince them to provide free experimental drugs for the project on a large scale was never explained. In fact, Searle’s steroid chemists played an important role in the pill’s development. Although similar feats were being duplicated in a number of competing industrial laboratories, the large number of synthetic hormones that a they were producing gave Pincus an essential variety of compounds with a  wide range of effects that he could try on animals, selecting for clinical trial only a few of the most promising out of the dozens that had some contraceptive effect. But McCormick has shielded from the commercial aspects of the project she was subsidizing. Nevertheless, her contribution was vital. She provided the funds that turned  a desultory PPFA project into a crash program to develop an oral contraceptive. Pincus asked Searle for substantial help on the project only after he had suppressed ovulation in women with a progesterone regimen. By then he knew that he could develop an oral contraceptive. Searle’s cooperation simply hastened the process. When the first successful use of synthetic steroids as an oral contraceptive in women was announced in ‘’Science’’ in 1956, Sanger wrote McCormick: You must, indeed, feel a certain pride in your judgment. Gregory Pincus had been working for at least ten years on the progesterone of the reproductive process in animals. He had practically no money for this work and Dr. Stone and I did our best to get a few dollars for him and I think that the amount we collected went to pay the expenses of Chang [senior scientist, WFEB]. Then you came along with your fine interest and enthusiasm and with your faith and . . .things began to happen and at last the reports . . . are now out in the outstanding scientific magazine and the conspiracy of silence has been broken. Although “conspiracy of silence” may have been an exaggeration, throughout the late 1950s few scientists believed an oral contraceptive was at hand.
 * ”The Pill”, p.344


 * IN 1967 the National Science Foundation commissioned a study of the relationship between basic research and technological innovation. What role did “nonmission” research, research motivated solely by a desire for knowledge,, play in the development of new products of great economic and social significance, such as the electron microscope, the videotape recorder, and the oral contraceptive pill? Since the National Science Foundation existed to promote research, it was not surprising when the study revealed that 70 percent of the key events leading to technological innovation resulted from so-called nonmission research. Seventy-six percent of this basic work was done in university laboratories; 14 percent in research institutes and government laboratories. Industrial laboratories made only 10 percent of the original discoveries that advanced knowledge. Large diagrams were provided on which the red dots representing basic research stretched far into the past, while the blue symbols for “mission-oriented research” and the green symbols for “development and application” were clustered near the present. In the diagram explaining the origins of the pill, Arnold Berthold’s 1984 demonstration that castrated roosters do not behave like roosters was given equal billing with key events in the development of twentieth century endocrinology. The overall impression was one of a long chain of basic researches leading inevitably to an oral contraceptive.
 * Chapter 27: "The Product Champion", p.346

Paul Weckenbrock, Couple to Couple League, “The Pill: How Does it Work? Is it Safe?“, ETWN, (1993)

 * Controversy has surrounded "the Pill" ever since it was first marketed in the United States in 1960. It has been studied medically, sociologically and morally, and yet much confusion still exists concerning these potent artificial steroids. The billions of dollars at stake in the marketing of the Pill and the power of the birth control industry to lobby both lawmakers and the media can easily divert the average person from the truth. Research has been published, books have been written, and common sense should make one cautious.
 * The Pill manufacturers and many in organized medicine are mainly concerned about the Pill's medical side effects and its effectiveness in preventing pregnancies and are less concerned about how the drug achieves its effectiveness. Unfortunately, many "otherwise" pro-life physicians and pharmacists find it hard to admit that these abortifacient properties exist because they would have to discontinue prescribing and dispensing the Pill if they were to remain consistent in their respect for life at all its stages of development. Pro-abortion organizations and their lawyers readily admit the early abortion potential of the Pill. In February 1992, writing in opposition to a Louisiana law banning abortion, Ruth Colker, a Tulane Law School professor, wrote, "Because nearly all birth control devices, except the diaphragm and condom, operate between the time of conception...and implantation.., the statute would appear to ban most contraceptives." In 1989, attorney Frank Sussman argued before the U. S. Supreme Court that ". . . IUDs (and) low dose birth control pills. . . act as abortifacients."
 * The health risks of the Pill outweigh by far the risks of pregnancy and childbirth to a woman's health, and any claim to the contrary is based on erroneous comparisons between healthy women on the Pill and women who do not receive normal care during pregnancy. A precondition for obtaining the Pill is routine medical care and checkups. For example: if such a woman on the Pill is diagnosed as "precancerous," or if some other side effect is exhibited, she has the advantage of early detection. However, many pregnant women do not receive routine medical care. A clearer picture of the safety of the Pill compared to the safety of pregnancy would be made if healthy women receiving routine medical care during pregnancy and delivery were compared with women receiving routine medical care while taking the Pill.
 * Fifty percent of woman taking the Pill discontinue it within the first year because of side effects, the development of benign breast disease, or some abnormality of the sexual organs. Studies of Pill usage do not include these women, and the result is an unbalanced picture of only the healthiest of women who tolerate the Pill. This is compared with the general population of women who are pregnant. The fact is that there are 13.8 million women in the U.S. and 60 million women worldwide who use the Pill (conservative numbers). And there are 7.9 Pill-related deaths per 100,000 women ages 15-44. Therefore, one can calculate that there are over 1090 deaths each year in the U.S. alone simply due to the Pill.

== Lisa L. M. Welling, “Psychobehavioral Effects of Hormonal Contraceptive Use”, Evolutionary Psychology www.epjournal.net – 2013. 11(3) ==
 * Although female use of hormonal contraceptives (HCs) has been associated with a variety of physical side effects, the psychological and behavioral side effects have received comparatively little attention until recently. Indeed, the long-term impact of HC use on human psychology has been vastly under-researched and has only recently become a focus for mainstream scholars. Women who use HCs report higher rates of depression, reduced sexual functioning, and higher interest in short-term sexual relationships compared to their naturally-cycling counterparts. Also, HC use may alter women’s ability to attract a mate, as well as the mate retention behaviors in both users and their romantic partners. Some evidence even suggests that HC use alters mate choice and may negatively affect sexual satisfaction in varous women, with potential effects on future offspring.
 * p.719


 * From 2006-2008, the number of US women who had ever used the oral contraceptive pill stood at 82%, with 22% of women having used an injectable or shot (Mosher and Jones, 2010). Indeed, the popularity of HCs crosses both political and religious boundaries. High proportions of HC users can be found in developed nations as well as in emerging and developing economies (United Nations, 2009).
 * p.720


 * Recently, researchers have documented negative effects on mood and psychological well-being as a consequence of HC use in women (Bancroft, Sanders, Warner, and Loudon, 1987; Herzberg and Coppen, 1970; Kahn and Halbreich, 2001; Kurshan and Epperson, 2006; Oinonen and Mazmanian, 2002). DeSoto, Geary, Hoard, Sheldon, and Cooper (2003) found that women using HCs exhibited more symptoms of borderline personality disorder (BPD), a disorder characterized by a pervasive pattern of instability in affect regulation, impulse control, interpersonal relationships, and self-image (Lieb, Zanarini, Schmahl, Linehan, and Bohus, 2004), and that women with high pre-existing levels of BPD symptoms became significantly worse after starting HC use (DeSoto et al., 2003). Sanders, Graham, Bass, and Bancroft (2001) found that negative changes in emotional and sexual well-being were important predictors of discontinuation of oral contraceptives (see also Graham, Ramos, Bancroft, Maglaya, and Farley, 1995; Rosenberg and Waugh, 1998; Rosenberg, Waugh, and Meehan, 1995), although HC users report experiencing less variability in affect across the menstrual cycle and less negative affect during menstruation (Oinonen and Mazmanian, 2002). While women low in social anxiety are more likely to use oral contraceptives (Leary and Dobbins, 1983), HC users describe higher rates of depression (e.g., Kulkarni, 2007) than normally cycling women. On the other hand, pair-bonded (but not single) women report lower levels of intrasexual competition when using HCs as compared to when they are regularly cycling (Cobey, Klipping, and Buunk, 2013). Oral contraceptive-using women also showed significantly attenuated cortisol responses to stressors compared to controls (Roche, King, Cohoon, and Lovallo, 2013), with peak cortisol levels only slightly elevated above baseline levels (Kirschbaum, Pirke, and Hellhammer, 1995). Therefore, HC use appears to interfere with the adrenocortical response to psychological stress by influencing the amount of bioavailable unbound cortiso l (see also Kirschbaum, Kudielka, Gaab, Schommer, and Hellhammer, 1999), although reports of affective responses to identical stressor tasks do not differ as a function of HC use (Marinari, Leshner, and Doyle, 1976). Furthermore, Egarter, Topcuoglu, Imhof, and Huber (1999) found that a low-dose oral contraceptive actually improved patients’ perceptions of their own quality of life (see also Caruso et al., 2011; Ernst, Baumgartner, Bauer, and Janssen, 2002), highlighting the need for further research.
 * p.722


 * HCs appear to influence sexual behavior, with reported or apparent reduced sexual functioning and interest in humans (Bancroft et al., 1987; Caruso et al., 2004; Graham et al., 1995; Sanders et al., 2001; Wallwiener et al., 2010; but see Caruso et al., 2005) and in other primates (Guy et al., 2008; Michael, Saayman, and Zumpe, 1968; Nadler, Dahl, Gould, and Collins, 1993; Shimizu, Takenoshita, Mitsunaga, and Nozaki, 1996; Steklis et al., 1982). However, human female HC use is also associated with a greater number of reported sexual partners (Little, Jones, Penton-Voak, Burt, and Perrett, 2002) and significantly greater interest in engaging in short-term sexual relationships across all phases of the menstrual cycle (Guillermo, Manlove, Gray, Zava, and Marrs, 2010), indicating that women who choose to use HCs may differ from others in their degree of sociosexuality.
 * p.722


 * Currently, it is unclear whether HCs influence actual mate choice and whether this has real-life consequences for potential offspring. Although HC use may negatively affect intra-couple behavior (Cobey et al., 2011, 2012; Havlíček and Roberts, 2009; Roberts et al., 2012; Vollrath and Milinski, 1995; Welling et al., 2012) and may alter preferences for MHC heterozygosity (Havlíček and Roberts, 2009; Roberts et al., 2008; Wedekind et al., 1995; Wedekind and Füri, 1997), which could hypothetically have negative consequences for future offspring (e.g., Reznikoff-Etievant et al., 1991), direct empirical evidence for these theoretical longitudinal consequences of HC use is lacking.
 * p.729


 * In closing, it should be noted that although a full and complete understanding of the potential effects of hormonal contraceptive use on physiology, psychology, and behavior is incredibly important, any effects should be weighed against the multiple benefits that the revolutionary invention of HCs has brought. Effective contraceptive methods have given women control over their fertility that is unprecedented and has aided in many personal and economic achievements for women (Go ldin and Katz, 2002). Regardless, future independent and comparative research on the psychological and behavioral effects of HC use in humans and nonhuman primates is crucial. The additional knowledge gained from this research could help in the development of new contraceptive methods and will allow women to make more informed decisions regarding the type and timing of their HC use.
 * pp.729-730