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Potential long-acting contraceptive agents: esters and ethers of testosterone with alpha- and/or beta-chain branching.
STEROIDS. 1985 Dec; 46(6):947-53.A chemical synthesis program was established by the World Health Organization in 1975 with the primary goal of identifying long-acting male and female steroidal contraceptive agents. During the period 1977-80, 3 participating laboratories synthesized 12 related potential long-acting male contraceptive steroid esters, all derivatives of testosterone. 2 of the compounds were alpha-monosubstituted esters, 6 were alpha, alpha'-disubstituted esters, and 1 was a beta,beta'-disubstituted ester. Another 1 was a ditestosterone ester that was both alpha-monosubstituted and alpha, alpha'-disubstituted. 2 siloxy esters of testosterone were included for comparison given their similar alkyl substitution patterns. Testosterone 2-methyl propanate was prepared through use of the conventional method of reacting 2-methyl propanol chloride with testosterone in the presence of pyridine. For the esterification of the 17-OH group in testosterone with 3,3-dimethyl butanoic and 2-ethyl butanoic acids, the benzenesulfonyl chloride method was employed. This article sets forth the analytical, physical, and spectroscopic data for all the compounds synthesized and submitted for bioassay.
International Journal of Andrology. 1978 Oct; (1):93-101.In 1974, the year for which the most complete data are available, only 11% of the $60.6 million in international expenditures for reproductive research was allocated specifically to the male. 38% was designated for females; 39% was designated for both sexes. Funds for male-related research were allocated primarily (75%) for opportunity development (preclinical laboratory evaluation of possible new aproaches for fertility control). 12% each were spent on product development and on studies of effects of available methods. 1% was allocated for research professionals in the male research field. Money for male reproductive research was used in the United States (86%), with 12% going to other industrialized countries, and 1% to developing countries. 68% of U.S. funds came from the U.S.; 30% from industrialized countries; 1% from developing nations. The major supporter of each group was the government. 61% of U.S. funds were from government; the rest was equally divided between private foundations and pharmaceutical companies. In other industrialized nations, government spending was even greater. In 1975, the preponderance of male research money was spent for new opportunities by WHO (80%) and by U.S. government agencies (71%). Less was spent on product development by most agencies, except for the Population Council which allocated 55% for development research.
Asian and Pacific Population Programme News. 1977; 6(4):39.At a recent meeting of the IPPF Central Medical Committee (CMC) progress made in developing a male contraceptive was reviewed. The CMC had been given expert advice, and the latest publications on the subject had been put before it. In the light of that up-to-date knowledge, the following statement was issued about the present status of male contraception: "During the last few years several clinical trials have been carried out in order to evaluate the contraceptive effectiveness of some steroidal agents in men. Antiandrogens, androgens, progestins and oestrogens have been tried. Most compounds tested have been found to be able to depress spermatogenesis, but in some cases the occurrence of undesirable side effects has curtailed their potential use as contraceptives. The most promising trials were carried out with combination treatments of an androgen with a progestin. These treatments are effective and relatively well tolerated in short-term use, but acceptability and safety for long-term use have still not been proven. As most male contraceptives areabeing used only on an experimental basis, the CMC cannot recommend their use by family planning associations at present, but sees the development of a safe male contraceptive as highly desirable." The subject will be kept under review at further mettings of the CMC.(FULL-TEXT)