Editing Gossypol (section)

===Contraception===
A 1929 investigation in [[Jiangxi]] showed correlation between low [[fertility]] in males and use of crude [[cottonseed oil]] for cooking. The compound causing the contraceptive effect was determined to be gossypol.<ref name=andrology>{{cite journal | last1=YU | first1=ZONG-HAN | last2=CHAN | first2=HSIAO CHANG | title=Gossypol as a male antifertility agent - why studies should have been continued | journal=International Journal of Andrology | volume=21 | issue=1 | year=1998 | issn=0105-6263 | doi=10.1046/j.1365-2605.1998.00091.x|doi-access=free| pages=2–7| pmid=9639145 }}</ref>
In the 1970s, the [[Government of the People's Republic of China|Chinese government]] began researching the use of gossypol as a [[contraceptive]]. Their studies involved over 10,000 subjects, and continued for over a decade. They concluded that gossypol provided reliable contraception, could be taken orally as a tablet, and did not upset men's balance of hormones.

However, gossypol also had serious flaws. The studies also discovered an abnormally high rate (0.75%) of [[hypokalemia]] (low blood [[potassium]] levels) among subjects.<ref name=andrology/><ref name="Gossypol">{{cite web|url=http://malecontraceptives.org/methods/gossypol.php|title=Gossypol|website=Malecontraceptives.org|date=2011-07-27|archive-date=2013-05-18|archive-url=https://web.archive.org/web/20130518114513/http://malecontraceptives.org/methods/gossypol.php|url-status=dead}}</ref> Hypokalemia causes symptoms of [[fatigue (medical)|fatigue]], muscle weakness, and at its most extreme, [[paralysis]]. In addition, about 7% of subjects reported effects on their [[digestive system]]s,<ref name=andrology/> about 12% had increased fatigue, some subjects experienced impotence or reduced libido, and 9.9% became irreversibly infertile, apparently associated with longer treatment and greater total dose of gossypol.<ref name=andrology/> Most subjects recovered after stopping treatment and taking potassium supplements. The same study showed taking potassium supplements during gossypol treatment did not prevent hypokalemia in [[primate]]s.<ref name="Gossypol"/> The potassium deficiency may also be a result of the Chinese diet or genetic predisposition.<ref name="Gossypol"/>

In the mid-1990s, the Brazilian pharmaceutical company Hebron announced plans to market a low-dose gossypol pill called Nofertil, but the pill never came to market. Its release was indefinitely postponed due to unacceptably high rates of permanent infertility.{{citation needed|date=November 2012}} 5% to 25% of the men remained [[azoospermic]] up to a year after stopping treatment.<ref name="Gossypol"/> 

Researchers have suggested gossypol might make a good noninvasive alternative to surgical [[vasectomy]].<ref>{{cite journal|journal=Contraception| last=Coutinho |first=F. M.| title = Gossypol: a contraceptive for men| year = 2002| volume = 65| issue = 4| pages = 259–263| pmid= 12020773| doi = 10.1016/S0010-7824(02)00294-9}}</ref>

In 1986, in conjunction with the Chinese Ministry of Public Health and the [[Rockefeller Foundation]], the [[World Health Organization]] formalized a decision to discontinue research into gossypol as a male contraceptive drug.<ref name="IJA199804">{{cite journal |journal=International Journal of Andrology |issn=0105-6263 |title=Gossypol: Reasons for its failure to be accepted as a safe, reversible male antifertility drug |publication-date=April 1998 |pages=8–12 |given1=G. M. H. |surname1=Waites |given2=C. |surname2=Wang |given3=P. D. |surname3=Griffin |year=1998 |department=Point of View Review |volume=21 |number=1 |doi=10.1046/j.1365-2605.1998.00092.x|pmid=9639146 |doi-access=free }}</ref> In addition to the other side effects, the WHO researchers were concerned about gossypol's toxicity: the {{LD50}} in primates is less than 10 times the contraceptive dose,<ref name="Gossypol"/> creating a small [[therapeutic window]]. This report effectively ended further studies of gossypol as a temporary contraceptive, but research into using it as an alternative to vasectomy continues in Austria, Brazil, Chile, China, the Dominican Republic, and Nigeria.