Journal für Reproduktionsmedizin und Endokrinologie – Journal of Reproductive Medicine and Endocrinology – Andrologie • Embryologie & Biologie • Endokrinologie • Ethik & Recht • Genetik Gynäkologie • Kontrazeption • Psychosomatik • Reproduktionsmedizin • Urologie The Pill at 50 (in Germany): Thriving or Surviving? Djerassi C J. Reproduktionsmed. Endokrinol 2011; 8 (Sonderheft 1), 14-31 www.kup.at/repromedizin Online-Datenbank mit Autoren- und Stichwortsuche Offizielles Organ: AGRBM, BRZ, DVR, DGA, DGGEF, DGRM, D·I·R, EFA, OEGRM, SRBM/DGE Indexed in EMBASE/Excerpta Medica/Scopus Krause & Pachernegg GmbH, Verlag für Medizin und Wirtschaft, A-3003 Gablitz FERRING-Symposium digitaler DVR 2021 Mission possible – personalisierte Medizin in der Reproduktionsmedizin Was kann die personalisierte Kinderwunschbehandlung in der Praxis leisten? Freuen Sie sich auf eine spannende Diskussion auf Basis aktueller Studiendaten. SAVE THE DATE 02.10.2021 Programm 12.30 – 13.20Uhr Chair: Prof. Dr. med. univ. Georg Griesinger, M.Sc. 12:30 Begrüßung Prof. Dr. med. univ. Georg Griesinger, M.Sc. & Dr. Thomas Leiers 12:35 Sind Sie bereit für die nächste Generation rFSH? Im Gespräch Prof. Dr. med. univ. Georg Griesinger, Dr. med. David S. Sauer, Dr. med. Annette Bachmann 13:05 Die smarte Erfolgsformel: Value Based Healthcare Bianca Koens 13:15 Verleihung Frederik Paulsen Preis 2021 Wir freuen uns auf Sie! The Pill at 50 The Pill at 50 (in Germany): Thriving or Surviving? * C. Djerassi This article describes in detail the history behind the chemical development of oral contraceptives, notably the synthesis of norethindrone, which repre- sents the chemical template from which virtually all subsequent oral contraceptives are derived. Attention is also paid to the introduction of the most recent oral contraceptives in Germany and reasons are provided for the dim overall prognosis about the future of contraception, namely that nothing fundamentally new is on the horizon. J Reproduktionsmed Endokrinol 2011; 8 (Special Issue 1): 14–31. Key words: norethindrone, norethynodrel, levonorgestrel, chemistry of oral contraceptives, Ludwig Haberlandt Which 50th Birthday? 2010, I was bombarded by requests from Pill] is entirely the invention of men. And many American print, radio, and TV re- why did they do it? … Because they are How many people – other than those try- porters to comment on the “50th birth- extraordinarily unwilling to experiment ing to hide their age – celebrate the same day” of the Pill, because the media were with their own bodies … and they’re birthday in successive years? And why dating the Pill’s debut to the formal ap- extremely willing to experiment with should that happen to a drug? Yet in proval by the Food and Drug Adminis- women’s bodies … it would be much 2001, several people (starting with Carl tration (FDA). While such dates may be safer to monkey with men than monkey Djerassi [1]) celebrated the 50th birthday occasions for celebrations, “birthdays” with women.” While Mead’s irritation of the Pill, while 9 years later a media they are not. The Viennese event was may well be understandable, it neverthe- frenzy exploded all over the world with equivalent to celebrating a baby’s arrival less represents a gross oversimplifica- another 50th anniversary celebration of in a town far away from its original birth- tion that ignores that nature had pro- the Pill. And now, in 2011, we are doing place and the 50th “birthday”, especially vided scientists with a crucial hint on it again by commemorating the date, 50 hyped by the American media, could which to build – women do not get preg- years ago, when the Pill was introduced be equated to the date on which the nant during pregnancy because of the in Germany. In terms of this article’s baptismal certificate was issued in continuous secretion of progesterone – title, this would clearly mean that the Pill Washington. As far as I am concerned whereas no such clue exists in male re- is thriving. And in a way it is, especially (and I was concerned), the real birth date productive biology. Dr. Shipley’s contri- in light of two overwhelming facts of the of the Pill was October 15, 1951, the day bution is significant for an additional last half century – the global population we completed at Syntex in Mexico City reason that may explain some of Mead’s explosion and the rise of women’s rights the first synthesis of a steroid eventually indignation: fifty years ago women were – without which oral contraceptives destined to be used for oral contracep- still largely excluded from many areas of would just have been another medical tion. A few days later, the first few pre- scientific research. In a field that was un- advance and not an invention with enor- cious milligrams of “norethindrone” deniably a male province, Dr. Shipley mous societal consequences. Yet in this – the generic designation of the formally had to do her work in a commercial labo- article, I shall also make the contradic- named “17α-ethynyl-19-nortestostero- ratory she had founded next door to the tory argument that the Pill is only surviv- ne” – was already in the mail from University of Wisconsin where her hus- ing, because nothing else is on the hori- Mexico City to Dr. Elva G. Shipley band, Roland K. Meyer, was Professor zon in terms of fundamentally new at Endocrine Laboratories Inc., a com- of Zoology at a time when nepotism methods of birth control. mercial establishment in Madison, rules were still inviolate. Wisconsin, with the request that the sub- During those years, I have been inter- stance be tested for oral progestational A pervasive sense of the ironies of this viewed, filmed, and encouraged to pon- activity. historic male bias has caused various tificate on the occasion of various birth- writers and journalists to search far and days of the Pill, perhaps because one of Mothers of the Pill? wide for female heroes in the record of the ironies of the Pill’s career is that its the Pill. Margaret Sanger is the favorite, own conception has been so hard to pin I mention Dr. Shipley here primarily be- probably for reasons stated in the final down. It all depends (as any obstetrician cause her early participation in the Pill’s paragraph of David Kennedy’s definitive will tell you) on who is counting. In history impinges on a claim often heard biography [3]: “Yet the praise Margaret 1997, I spoke at a medical congress in – that the scientists involved in the de- Sanger received often seemed out of Vienna commemorating the 35th anni- velopment of oral contraceptives were proportion to her achievement. Part of versary of the Pill in Austria – not an in- uniformly males. This belief has grated the hyperbole, undoubtedly, derived appropriate geographic choice as I will on women for decades. As Margaret from her personal magnetism, which demonstrate shortly – while in May Mead [2] put it in the late 1960s: “[The rarely failed to bring those who met her * Portions of this article come from [1]. Received and accepted: February 24, 2011 Correspondence: Carl Djerassi, Department of Chemistry, Stanford University, Stanford, CA 94305-5080; e-mail: [email protected] 14 J Reproduktionsmed Endokrinol 2011; 8 (Special Issue 1) For personal use only. Not to be reproduced without permission of Krause & Pachernegg GmbH. The Pill at 50 into her orbit. But a larger part reflected lished the high progestational activity of Mrs. Sanger’s symbolic satisfaction of a orally-administered norethindrone. If pervasive psychological need. American her results had been negative, we would society in this century has not realized its have dropped the project and would frequently stated ideal of equal status for never have sent the material to other bi- women. Perhaps, therefore, the apo- ologists, including Gregory Pincus, theosization of a feminist heroine like who, as I will demonstrate below, can Margaret Sanger reflects society’s rec- rightfully be called a “father of the Pill”. ognition of the continuing victimization of women, and the desire, in some way, Since the Pill is so intimately connected to find a redemptress. For that role Mar- with human reproduction, albeit in terms garet Sanger, at her best and at her worst, of preventing it, let me pursue the Pill’s was well suited.” genealogy through the metaphor of re- production. Call the Pill the baby and Figure 1. Title page of Haberlandt's book. Still, Sanger’s historic, though certainly follow its birth through (1) the first (un- not scientific role in fostering the birth successful) attempts at conception, (2) control movement in the USA would the ovulation of a fertile egg, (3) the validate her choice as one of the grand- ejaculation of various sperm, (4) the suc- mothers of the Pill. A more romanticized cessful fertilization, (5) the implantation candidate is Katherine McCormick, a of the embryo, (6) the fetal development, wealthy philanthropist, who was per- and finally (7) the birth of the baby. Geo- suaded by Sanger in the early 1950s to graphically, the first step occurred in subsidize some of the biological work at Austria, the second in Mexico, the next Figure 2. Newspaper headlines (1927) about Pill for the Worcester Foundation for Experi- 3 in the continental United States, and Women. mental Biology that under the leadership the last in Puerto Rico – not untypical for of Gregory Pincus contributed heavily to a baby in the present highly mobile soci- years, Haberlandt – invariably using the the development of the Pill. However ety. first person singular, so strikingly differ- commendable such philanthropy is, ent from today’s insistence by scientists anointing Katherine McCormick as one The Overlooked Role of on the royal “we” – emphasized the ob- of “the indisputable mothers of the Pill” vious applicability of his animal experi- (as was done by one journalistic author, Ludwig Haberlandt ments to human contraception.