Talk:Combined oral contraceptive pill

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[edit] Claim of Leonard's role in COCP

This claim recently been added and removed repeatedly. Debate needs now be had therefore to discuss this and clarify consensus. Clearly the citations provided confirm who he was (i.e. he existed) and that involved in establishing role of LH/FSH as controlling hormones on the ovary. Also that he worked on role of oestrogen in rats. However there is a jump to then stating he had suggested oestrogen as a contraceptive for humans (risk of WP:SYN). That his university would wish to suggest that his work formed a foundation for hormonal contraception (could equally claim Galen as an originator of medicine, also had a role), is not the same as being able to verify through direct citation that he had proposed the subsequent research path from his own work to that in humans - I'm not sure any of the given references confirm this (yet). David Ruben Talk 14:45, 2 December 2007 (UTC)

Here is excerpt from Leonard's obituary in the 11/23/07 NYTimes:
"Dr. Leonard was still a graduate student when he began his studies of sex hormones, produced at the base of the brain in the pituitary gland.
In the 1930s, in the infancy of endocrinology, it was known that the anterior pituitary had a general role in stimulating the ovaries and the testes. Dr. Leonard, then a doctoral student at the University of Wisconsin, working with F. L. Hisaw, his thesis adviser, and H. L. Fevold, determined that the pituitary actually produces two hormones with distinct effects on the sexual organs.
The researchers labeled the first hormone FSH, or follicle-stimulating hormone; the second they called LH, or luteinizing hormone, which is critical in the production of testosterone in men and can help trigger ovulation in women.
The findings went against a theory that held that there was only a single hormone involved. In 1931, when Dr. Leonard and his collaborators published their results in the American Journal of Physiology, they “created a storm that opened a series of investigations and fruitful research,” said Robert H. Foote, a professor emeritus of animal physiology at Cornell.
Dr. Foote said studies by other scientists reinforced the team’s findings. In the 1960s, FSH was employed in early experiments with female rabbits to increase the production of eggs; in the ’80s, it was used successfully in cattle. It was subsequently used to develop in vitro fertilization techniques for humans.
Also in the 1930s, Dr. Leonard looked at the function of estrogen in rats and rabbits and found that he could inhibit ovulation by manipulating estrogen levels, in a primitive form of contraception. In 1939, he conducted an elegant experiment with canaries after being asked why immature males were likely to sing, but females were not. He then treated female canaries with testosterone and induced them to sing as their male counterparts did.
The experiment was “an acute example of how sexual differentiation could be invoked by hormones alone,” Dr. Foote said."
And here is the excerpt from the Washington Post:
"Research that Dr. Leonard did more than 75 years ago has been described as a major step toward the modern sciences of fertility and birth control.
In one of his more striking experiments with hormones, he enabled female canaries to sing. (The male canary is generally the musically gifted one.)
As described by people who knew him, Dr. Leonard was a model of scientific, academic and personal accomplishment. By their accounts, he devoted the energies of an unusually long life to introducing undergraduates to zoology, mentoring graduate students, conducting research and setting examples of hard work and ethical behavior.
Three of his students became Cornell professors.
He was a "brilliant teacher and researcher and a very friendly guy," said one former student, Robert H. Foote, professor emeritus of physiology at Cornell.
A signal achievement credited to him was the finding that estrogen can prevent pregnancy.
The study was performed on rats, but it was hailed as an important step in the development of the birth control pill.
In addition, he was credited with discovering that the pituitary gland produces two hormones, each governing an important step in ovulation and reproduction. In the 1930s, Dr. Leonard drove cross-country for days to present his findings at a meeting of a national scientific society, at which he was told in no uncertain terms that he was in error.
But the discovery became widely accepted and used in enhancing and controlling fertility and the reproductive cycle.
Many of Dr. Leonard's research papers were published too early to be easily available on the Internet, where many scientists search for information."
Relevant journal citations:
  • Meyer,R.K., S.L.Leonard , F.L.Hisaw and S.J.Martin. 1930. Effect of oestrin(estrogen) on gonad stimulating power of the hypophysis(pituitary gland). Proc. Soc. Exp. Biol. Med. 27:702-704.
  • Leonard,S.L., R.K. Meyer, and F.L. HiSaw 1931. The effect of oestrin (estrogen) on development of the ovary in immature female rats. Endocrinology 15:17-24.
  • Leonard,S.L.1931.The nature of the substance causing ovulation in the rabbit. Am.J.Physiol.98:406-416.
  • Hisaw, F.L.,and S.L. Leonard.1930. Relationship of the follicular and corpus luteum hormones in the production of progestational proliferation of the rabbit's uterus. Am.J.Physiol.92:574-581.
—Preceding unsigned comment added by 71.123.17.215 (talk) 15:52, 2 December 2007
Cornell University Professor Emeritus Samuel L. Leonard died November 12, 2007 at age 101.
One week later the Cornell Chronicle Online announced Leonard's death in an obituary that recycled a 2005 Cornell Chronicle article's unsubstantiated assertions that Leonard played a key role in developing the birth control pill. These unsubstantiated assertions were subsequently incorporated into obituaries by the Associated Press and the Washington Post.
Since then, anonymous editors have repeatedly added this inaccurate and inconsequential digression as the opening paragraph of the History section:

American zoologist, Samuel Leeson Leonard, who died on November 12, 2007, at age 101, is known for his discovery that estrogen could be used as a female contraceptive in the late 1920s

citing the unsubstantiated 2005 Cornell Chronicle article and 2007 obituaries, and assorted articles from 1930 and 1931 by Leonard.
  1. In his introduction to a 1997 seminar video "As I Remember It. Reminiscing with Dr. Samuel L. Leonard," Robert H. Foote, the seminar host (a former student of Leonard who later also became a Cornell University professor) embellished the findings of a 1931 paper co-authored by Leonard saying it "had shown that estrogen could be used as a contraceptive agent," when the paper did not mention the use of estrogen as a contraceptive agent (Leonard does not mention contraception or the development of the birth control pill in 50+ minutes of reminiscing in his seminar video).

    Meyer RK, Leonard SL, Hisaw FL, Martin SJ (1930). Effect of oestrin on gonad stimulating power of the hypophysis. Proc Soc Exp Biol Med. 27:702-4.
    Leonard SL, Meyer RK, Hisaw FL (1930). The effect of oestrin on the growth of the ovary in immature female rats (abstract). Anat Rec. 45(3):268.
    Leonard SL, Meyer RK, Hisaw FL (1931). The effect of oestrin on development of the ovary in immature female rats. Endocrinology. 15:17-24.

    Leonard, Samuel L. (Nov. 19, 1997). As I Remember It. Reminiscing with Dr. Samuel L. Leonard. Seminar video (54:08)
    Foote, Robert H. (Nov. 19, 1997). Samuel Leonard. Introduction by seminar host. (first 3:45), at 1:39:

    By the age of 26, Dr. Leonard had published seven excellent papers and he became a major player in the developing field of endocrinology.
    By 1931, he had shown that estrogen could be used as a contraceptive agent and that the anterior pituitary gland produced two gonadotropins, FSH and LH.

  2. Eight years later, to commemorate Leonard's 100th birthday, Cornell Chronicle life sciences writer Krishna Ramanujan used Foote's embellishment of Leonard's 1931 paper as a starting point to concoct an article entitled "Cornell birth control pill pioneer Sam Leonard turns 100" that made unsubstantiated assertions that Leonard "was a pioneer of one of the most significant medical advances of the 20th century -- which liberated women's attitudes toward sex, galvanized the women's movement and launched the swinging '60s," "played a key role in developing the birth control pill," "is credited with the idea of using estrogen as a contraceptive," and "prevented pregnancy in rats with the female sex hormone in a 1931 study, three decades before human birth control pills hit the market."

    Ramanujan, Krishna (Dec. 13, 2005). Cornell birth control pill pioneer Sam Leonard turns 100, Cornell Chronicle Online.

  3. Two years later, the Cornell Chronicle announced Leonard's death with an obituary entitled "Birth control pill pioneer and Cornell zoologist Sam Leonard dies at age 101," that recycled Ramanujan's unsubstantiated assertions that Leonard "is known for discovering in the late-1920s that estrogen could be used as a contraceptive -- the finding that led to the creation of the birth control pill, which contributed to women's liberated attitudes toward sex and the sexual revolution of the 1960s."

    anonymous (Nov. 19, 2007). Birth control pill pioneer and Cornell zoologist Sam Leonard dies at age 101, Cornell Chronicle Online.

  4. In the late afternoon, an Associated Press obituary reported that Cornell had that day announced Leonard's death, and repeated the Cornell Chronicle's unsubstantiated assertions that Leonard's "pioneering work in reproductive endocrinology in the 1930s led to development of the birth control pill" and that Leonard "was credited with the idea of using estrogen as a contraceptive," and that "he prevented pregnancy in rats with the female sex hormone in a 1931 study, three decades before human birth control pills hit the market."

    anonymous (Nov. 19, 2007, 4:23 PM EST). Samuel Leonard, pioneer in reproductive science, dies at 101, Associated Press.

  5. Three days later, an obituary by Washington Post staff writer Martin Weil recycled the unsubstantiated Cornell Chronicle assertions that: "Dr. Leonard's finding that estrogen can prevent pregnancy paved the way for the birth control pill," "research that Dr. Leonard did more than 75 years ago has been described as a major step toward the modern sciences of fertility and birth control," "a signal achievement credited to him was the finding that estrogen can prevent pregnancy," and "the study was performed on rats, but it was hailed as an important step in the development of the birth control pill."

    Weil, Martin (Nov. 22, 2007). Zoologist Samuel L. Leonard, 101, The Washington Post, p. B07.

  6. The following day, an obituary by New York Times science obituary writer Jeremy Pearce was more detailed, acknowledged some of Leonard's coauthors, and did not recycle the unsubstantiated Cornell Chronicle assertion that Leonard played a key role in developing the birth control pill, only making the dubious assertion: "Also in the 1930s, Dr. Leonard looked at the function of estrogen in rats and rabbits and found that he could inhibit ovulation by manipulating estrogen levels, in a primitive form of contraception." (Leonard found that injection of estrogen prevented the ovaries of immature rats from reaching full growth and development when injections were continued beyond the age (60 days) of normal sexual maturity and attributed this to partial inhibition of follicular development and ovulation by the influence of estrogen on the pituitary; he did not investigate or discuss this as "a primitive form of contraception.")

    Pearce, Jeremy (Nov. 23, 2007). Samuel L. Leonard, Cornell Zoologist, Dies at 101, The New York Times, p. B.8.

As noted in Talk: Archive 1: Percy Julian, the History section of this article is based on books about the history of the Pill, supplemented by journal articles (some by the developers of the Pill) to fill in details:
  • many of the books and journal articles on the history of the development of the Pill mention scores of scientists and physicians who played a role in the development of the Pill or the research that preceded it, only a few of whom are mentioned in the history section of this encyclopedia article because it is a section of an encyclopedia article and not a book or an extended journal article
  • Leonard is not mentioned in any book or journal article on the history of the development of the Pill
  • Leonard's publications are not cited in any publication by the developers of the Pill
Also, as the books and journal articles on the history of the development of the Pill make clear, the Pill was:
  • initially developed as a progestogen-only pill
  • found at the onset of large clinical contraceptive trials to be contaminated with a small percentage of the ethynyl estrogen mestranol
  • breakthrough bleeding occurred when the estrogen was completely removed
  • so a small amount of ethynyl estrogen was intentionally reinstated to prevent breakthrough bleeding
Obituaries are poor sources for this article when so many books and journal articles on the history of the development of the Pill have been written by historians and by participants in the development of the Pill.
Lynn4 17:03, 2 December 2007 (UTC)

The point of Lynnn4 that the "Pill" was, "initially developed as a progestogen(progesterone)-only pill", is well taken...

"But though it took Julian almost 4 years before he could return to his stigmasterol, the dogged persistence prevailed. Soybean oil contains only 0.2 of 1% sterols, of which only 18% is stigmasterol--it would take 1000 pounds of soybean oil to yield 2 pounds of stigmasterol. Obviously, so much precious oil could not be destroyed just for this purpose.

One day a worker in the plant called Julian, as chief "trouble shooter," to counsel on what was to be done with a 100,000 gallon tank of "purified" soybean oil into which water had leaked. "The tank," phoned the worker, "contains a mass of white solid." Remembering his DePauw experience, Julian was there in a matter of minutes, had the whole tank centrifuged, and came out with an oily mass containing about 15% of mixed soya sterols. A modification of this accidental procedure introduced into the oil refining soon found Julian producing 100 pounds of mixed soya sterols daily. This was in 1940, and the value of this daily by-product production, in terms of the sex hormones that might be obtained from it, was then about $10,000 daily, but who could devise a facile industrial process for producing the sterols, for synthesizing the hormones, and who could possibly use so much hormone--as much as 5 to 6 pounds daily?

Julian, however, was soon ozonizing 100 pounds daily of mixed sterol dibromides, the first time that so large an ozonizer had been industrially employed for a potentially dangerously explosive reaction. The result: the female hormone, Progesterone, was put on the American market in bulk for the first time, and other sex hormones soon followed."

From Bernhard Witkop...Biographical Memoirs. National Academy of Sciences, 52(1980).223-266. http://www.nap.edu/html/biomems/pjulian.html —Preceding unsigned comment added by 71.123.17.215 (talk) 18:48, 2 December 2007 (UTC)

The unsubstantiated assertion that Leonard discovered "that estrogen could be used as a female contraceptive in the late 1920s"
is also inconsequential because:
  • the Pill was developed to prevent ovulation using a progestogen not an estrogen
and a digression because:
  • the History section already begins with the observation that:

    By the 1930s, scientists had isolated and determined the structure of the steroid hormones and found that high doses of androgens, estrogens or progesterone inhibited ovulation


As discussed in Talk: Archive 1: Percy Julian:
Julian is not mentioned in the History section of this encyclopedia article because:
  • Julian is not mentioned in any of the books or journal articles on the history of the development of the Pill
Julian is not mentioned in any of the books or journal articles on the history of the development of the Pill because:
  • Julian did not play a role in the history of the development of the Pill
Lynn4 22:52, 2 December 2007 (UTC)

If it looks like a duck; walks like a duck; quacks like a duck; and defecates like a duck: It is a duck!! —Preceding unsigned comment added by 71.123.17.215 (talk) 14:09, 3 December 2007 (UTC)

Now lets see, given the failure to provide a reference to a specific paper by Leonard to substantiate claim that he moved from understanding the role of hormones in normal ovulation & sexual differentiation to that of suggesting external hormone to specifically provide human contraception, we are left to ponder the exuberance of the in-house Cornell Chronicle's writer. Now were that same Cornell Chronicle to have discussed a football team's mascot of a duck... well it would look like a duck, possibly try to walk like a duck and certainly after the end of the game the relevant actor would waddle like a duck off the pitch to go to the toilet - but I would still not accept Cornell Chronicle's statement of the Team X being supported by a "Duck" as being accurate or that it belongs to anatidae.
Somewhat more seriously, Cornell Chronicle is not an independant 3rd party reporter of the work of Cornell university, and if other published works merely duplicate those claims, then proof remains to be provided.
As things currently stand, without evidence to support the obituary writer's and the university' flamboyant claims, the only way to include the information under NPOV would be to diminish his otherwise important constributions by something along lines of "Although Cornell univerity's inhouse magazine claims that Dr Leonard's had been the first to propose the role of these hormones for human contraception,[1] no paper by him ever made such claims." - no reference need be given for the final clause, as if any paper can be cited then clearly his historical role would be confirmed and we would not be having this discussion. Note well, WP:Cite from WP:Reliable sources to WP:Verify without making original WP:Synthesis are guidelines & policies of Wikipedia. Likwewise it is the responsibility of editors adding material to provide the appropriate references, else "Any edit lacking a reliable source may be removed" (see WP:PROVEIT). To continue to add claim of COCP being directly suggested by Leonard, would IMHO be against policy and above consensus of above discussion (again, provide the single paper of Leonard that made the claim, not some university press department's retrospectively embelishing history).David Ruben Talk 04:27, 5 December 2007 (UTC)

Since, neither the Cornell Press Office nor Professor Robert H. Foote has responded the connection between Dr. Leonard and COCP is a moot question. However, the very important question regarding Dr.Percy Lavon Julian's relationship to COCP must be decided: in 1940, under his direction, the Glidden Co. of Chicago was ozonizing 100 lbs daily of stigmasterol and sitosterol(mixed sterols), both of which could be converted into synthetic progesterone which was put on the American market in bulk. Julian was issued an American patent for a foam method to recover soy sterols from soybean oil:P.L.Julian,E.W.Mayer, N.C.Krause(to the Glidden Co) U.S.Patent 2,218,971(October 22,1940).. By 1940, Russel Earl Marker had made his best attempt at producing synthetic progesterone from plant steroid saponins with the result that he had managed to synthesize 35 grams. It wasn't until 1943-44 that Marker came upon the wild yam and its enormous quantity of saponins in its huge tuber. Moreover, after founding Syntex to extract the saponin he resigned after only one year. On this basis Julian had as much or even more influence on the future direction of progesterone applications for birth control than did Marker. It is only fair that Julian be included in this article on COCP.

From Wikipedia article on Russel Earl Marker: "In 1936 Parke-Davis sent him a steroid extract from the urine of pregnant mares. From this, he isolated pregnanediol, which he converted by already published chemistry to 35 grams of progesterone in 1937. The batch of steroid he synthesized was the largest produced till that time. Parke-Davis provided annual funding that eventually reached $10,000. Ultimately, more than 160 papers in the steroid area were published.

In 1944, Marker cofounded Syntex. In May of 1945, Marker inquired as to the profits of the company and was told there were none. He severed all ties with Syntex, and the company was unable to make more progesterone because Marker not only had done the synthesis himself but had coded the reagent bottles and took his lab notebooks."

—Preceding unsigned comment added by 71.123.17.215 (talk) 15:16, 5 December 2007 (UTC)

Please see:
Russell Marker
  • Marker invented the chemistry (the Marker degradation) in 1938 to synthesize progesterone and other steroids from sapogenins, including diosgenin from Dioscorea
  • Marker discovered in 1942 that the inedible Mexican wild yams cabeza de negro (Dioscorea mexicana) and the more remote barbasco (Dioscorea composita) were exceptionally rich sources of diosgenin and excellent raw materials from which to synthesize progesterone and other steroids
  • Marker synthesized 3 kg of progesterone from cabeza de negro in 1943, founded Syntex in 1944, founded Botanica-Mex (which became Hormonosynth then Diosynth) in 1945, and thereby founded the Mexican steroid industry
  • Syntex, using the Marker degradation and the raw material (Mexican barbasco) discovered by Marker, reduced the bulk price of progesterone almost 200-fold over 8 years -- from $80/g in 1943 to $0.48/g in 1951
  • Syntex supplied the progesterone used by Pincus and Chang when they began their contraceptive research in 1951 by repeating the 1937 experiments in rabbits of Makepeace et al.
  • Syntex supplied the progesterone used by Pincus and Rock in their clinical trials of progesterone in 1953
  • Djerassi et al. at Syntex in 1951 synthesized (from steroids using the Marker degradation and the raw material (Mexican barbasco) discovered by Marker) the first (norethisterone) of the three progestins used in Pincus and Rock's clinical trials of progestins beginning in 1954
  • Almost all of the oral contraceptives manufactured in the 1960s were produced from Mexican steroids using the Marker degradation and the raw material (Mexican barbasco) discovered by Marker
Percy Julian
  • Julian did not play a role in the history of the development of the Pill
  • The Glidden Company did not play a role in the history of the development of the Pill
  • Julian Laboratories, Inc. did not play a role in the history of the development of the Pill
  • Smith Kline and French did not play a role in the history of the development of the Pill (and never developed any contraceptives)
Lynn4 (talk) 23:31, 5 December 2007 (UTC)

[edit] Postfertilization mechanisms

In the United States, at least, there is a good deal of controversy over postfertilization mechanisms of hormonal contraceptives. For example, many pharmacists are now refusing to dispense prescriptions for COCPs because they believe the pills cause abortions [2]. The current version of the article states, "insufficient evidence exists on whether [these] changes... prevent implantation", which is my understanding of the situation. However, the current version goes on to state, "endometrial changes are unlikely to play an important role, if any, in the observed effectiveness of COCPs" (bolding mine). I believe this last sentence violates NPOV because it argues one point of view (postfertilization mechanisms do not exist).

The current paragraph does not explain that some groups have labeled COCPs as abortifatients because of the possible postfertilization mechanisms. I believe the paragraph is also misleading because it implies endometrial changes are the only possible postfertilization mechanism, when in fact several such mechanisms have been proposed.

The current paragraph is 61 words long. I had modified it to address my concerns (mention controversy over postfertilization mechanisms, that more than one such mechanism has been proposed, remove POV). The resulting paragraph was 103 words. I do not believe this length presents problems with undue weight of postfertilization effects in comparison to the primary mechanism of action (which has three paragraphs devoted to it) or the uncontroversial effect of COCPs on cervical mucus (which has one paragraph).

My modification was reverted with the comment that the sources I used were poor. The editor also linked to the most recent archive. No section was linked, but I suspect the editor was thinking of postfertilization effects, where (s)he had criticized the peer-reviewed paper I used as a source: it was written by family physicians, not by "experts on hormonal contraception". This editor also linked to the other paper I used as a source, as evidence that that first paper did not represent a majority view. Since my point in using the sources was to imply there was no majority view, I don't understand how this July 2007 statement (which was added on to a conversation I had in December 2006) explains this reversion of my edits.

I would appreciate a more specific explanation, and also any input other editors have on my edit. LyrlTalk C 00:41, 28 February 2008 (UTC)