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Fertility and Sterility. 2003 Jul; 80(1):1-15.Objective: To give an historical record of the research of the World Health Organization (WHO) Task Force to develop methods of male contraception; to examine the social, political, medical, pharmaceutical, funding, and other factors that influenced progress; and to suggest reasons why such methods are only now becoming available. Design: Review of basic and clinical research over 30 years. Setting: Task force of a multinational agency and collaborating agencies. Conclusion(s): Through the involvement of many international scientists, the WHO Task Force has uniquely contributed to the exploratory phases of the research in male contraception and by its multicenter contraceptive efficacy studies has accelerated progress towards the ideal hormonal method. Despite an adverse climate involving social and political attitudes, funding constraints, and pharmaceutical industry hesitations, WHO formed coalitions with governments and international agencies to sustain research with results that apply to men in culturally diverse populations and thereby to influence activities across the whole range of global reproductive health and family planning. (author's)
Geneva, World Health Organization, 1964. (Technical Report Series No. 280.) 30 p.A WHO Scientific Group on the Biology of Human Reproduction was convened in Geneva from April 2-8, 1963, for the purpose of advising the Director-General on developments and major research needs in that field. The biology of human reproduction is an extremely broad scientific topic, which impinges to some degree on virtually all the basic medical disciplines. Major topics included in the report are: 1) comparative aspects of reproduction; 2) neuroendocrine aspects of reproduction; 3) biology of the gonads and gametes; 4) gestation; 5) biochemistry of the sex steroids; 6) immunological aspects of reproduction; and 7) pharmacological aspects of reproduction. The Group recommends: 1) that WHO assist in the development of fundamental knowledge of the biology of human reproduction and of other fields on which that knowledge is based and 2) that WHO convene meetings of appropriate specialist groups to consider practical methods of implementing certain proposals concerning organization of surveys, provision of services, and promotion of relevant research.
PROGRESS IN HUMAN REPRODUCTION RESEARCH. 1995; (33):2.Research results by the UNDP/UNFPA/WHO/World Bank Special Program in Human Reproduction published in 1990 showed that hormones can be used to reduce men's sperm levels to virtual infertility. Weekly injections of testosterone enanthate (TE) produced azoospermia in most men. A multicenter study was also completed in 1994 involving a total 399 men in nine countries who were given regular injections of TE. High contraceptive effectiveness resulted among those men whose sperm concentrations were reduced to 3 million or less per ml (oligozoospermia). The failure rate was 1.4 pregnancies per 100 person-years, similar to that of oral contraceptives. It took an average of 68 days to reach oligozoospermic and 100 days to reach azoospermic sperm counts after the 1st injection. To return to normal levels after the last injection took 112 days and 203 days, respectively, in oligozoospermic and azoospermic men. Testing of testosterone buciclate (TB) was also carried out in Germany to assess the effect of longer-acting androgen esters suppressing gonadotrophin secretion. Azoospermia was achieved in some men by giving a single dose of 1200 mg of TB, but at half that dose oligozoospermia was not reached. Research is also continuing into the male contraceptive effect of progestogen-androgen combinations. Progestogen prevents the production of sperm at much lower doses than androgen. Androgen is given to replace testosterone that is inhibited as a result of the suppression of gonadotrophin, but it is needed less frequently. The combination seems to suppress sperm production more quickly than the androgen alone. In China, India, and Indonesia, plans are prepared for efficacy studies with such combinations. The drawback for large-scale use is that the components have to be injected at different intervals. This may be overcome by combining TB with a progestogen with the same duration of action and giving both at the same time.
BRITISH MEDICAL BULLETIN. 1993 Jan; 49(1):210-21.The search for new, safe, effective, and reversible contraceptive methods for men as pursued by several agencies and probable future developments until the year 2000 is reviewed. A WHO consultation between vasectomy and the risk of cancer of the prostate or testis is unlikely and changes in family planning policies are unwarranted. Research in China has led to the ligation of the vas by percutaneous injection of sclerosing agents through a puncture opening. The suppression of secretion of either both luteinizing hormone and follicle-stimulating hormone (FSH) or of FSH alone; the recovery of circulating androgen to physiological levels; and the assessment of the functional capacity of residual sperm. Hormonal methods comprise the contraceptive efficacy of testosterone enanthate-induced azoospermia and oligozoospermia; and gonadotropin-releasing hormone analogue-androgen combinations. A large number of non-hormonal chemical agents lead to total spermatogenic arrest and to irreversible sterility. Gossypol was studied as an antifertility agent in clinical studies on more than 8000 Chinese men, but its use for contraception was halted owing to the high incidence of irreversibility and serious side effects such as hypokalemia. Among drugs and plant products for inhibition of sperm maturation, Chinese investigation showed that a multiglycoside extract of the plant Tripterygium wilfordii caused reductions in sperm motility and concentration in patients. A program established between Chinese, Thai, and UK centers aims to isolate pure compounds extracted from the plant for antifertility actions. In regard to contraceptive vaccines, passive or active immunization against FSH has resulted in significant decreases in sperm counts in macaque monkeys with inconsistent effects on fertility.
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.
In: Sciarra, J.J., Markland, C. and Speidel, J.J., eds. Control of male fertility. (Proceedings of a Workshop on the Control of Male Fertility, San Francisco, June 19-21, 1974). Hagerstown, Maryland, Harper and Row, 1975. p. 274-307Literature on research approaches to permanent and relatively reversible methods of male fertility control is reviewed. Sources and expenditures for research into male fertility control are noted. Permanent methods discussed include electrocautery of the vas, transcutaneous interruption of the vas, vasectomy clips, chemical occlusion of the vas, and passive immunization. Reversible methods reviewed include vasovasotomy, intravasal plugs, and vas valves. Current research into animal models, reversibility after vas occlusion, nonocclusive surgical techniques, pharmacological alteration of male reproductive function, including adrenergic blocking agents, steroidal compounds, inhibitors of gonadotropin secretion, clomiphene citrate, organosiloxanes, prostaglandins, alpha-chlorohydrin, heterocyclic agents, and alkylating agents, and delivery systems for antifertility agents is discussed. Research into semen storage and improved condoms is also reviewed. As a relatively low proportion of funds are committed to research in male fertility control, a greater investment in applied and clinical research is warranted.