男人的避孕药可以在地平线上吗？

（纽约，纽约）哥伦比亚大学医学中心的研究人员正在磨砺可能是第一个可能是男性的第一个非甾体口腔避孕药的开发。低剂量低剂量的化合物，其干扰视黄酸受体（Rars），其配体是膳食维生素A的代谢物，表明它在雄性小鼠中引起无菌性。使用此Rar拮抗剂的实验结果在6月1日发表的内分泌学中公布，并举办了将研究扩展到更长的药物交付期的摘要被安排为2011年的Endo迟到的口头会议：波士顿的第93届年会和世博会，马萨诸塞州。(The abstract, titled Meeting Men’s Contraceptive Needs—Long-Term Oral-Administered Retinoic Acid Receptor Antagonist Inhibits Spermatogenesis in Mice with a Reversible and Rapid Recovery, will be presented at the session by first author Sanny S. W. Chung, Ph.D., on Saturday, June 4, 11:15 a.m., Room 157ABC, Boston Convention & Exhibition Center). The researchers found that low doses of the drug stopped sperm production with no apparent side effects. And crucial for a contraceptive, normal fertility was restored soon after drug administration was terminated. Earlier research had led the investigators to the discovery that manipulating the retinoid receptor pathway could interfere with the process of spermatogenesis, which is necessary for sperm production. Scientists have known for almost 100 years that depriving an animal of dietary vitamin A causes male sterility. While investigating targeted loss of function of the gene encoding one of the RARs, RARalpha, which results in male infertility, senior author Debra J. Wolgemuth, Ph.D., ran across a paper by Bristol-Myers Squibb on a compound that was being tested for the treatment of skin and inflammatory diseases. The compound seemed to cause changes in the testis similar to the mutation that she and Dr. Chung were studying in Dr. Wolgemuth’s lab. (Dr. Wolgemuth is professor of genetics and development and of obstetrics and gynecology; and Dr. Chung is an associate research scientist, both at Columbia University Medical Center). Bristol-Myers dropped its interest when it found that the compound also was – in the company’s words – “a testicular toxin.” The paper did not elaborate on how the drug caused infertility, so Dr. Wolgemuth and her team tested the drug in mice to find out; they noted that the changes it caused were similar to what one sees with vitamin A-deficiency and loss of function of RARalpha. “We were intrigued,” said Dr. Wolgemuth. “One company’s toxin may be another person’s contraceptive.” To investigate whether the compound prevented conception at even lower levels than those cited in the company’s study, Dr. Wolgemuth and her team placed the treated male mice with females and found that reversible male sterility occurred with doses as low as 1.0mg/kg of body weight for a 4-week dosing period. One advantage of using a non-steroidal approach, the researchers say, is avoiding the side effects commonly associated with steroidal hormone-based methods. Male steroid-based options have been plagued with adverse effects, including ethnic variability in efficacy, as well as an increased risk of cardiovascular disease and benign prostatic hyperplasia. Another side effect of hormonal options for men has been diminished libido. That drawback will also likely be avoided if a method involving manipulation of the retinoid receptor pathway proves successful. “We have seen no side effects, so far, and our mice have been mating quite happily,” said Dr. Wolgemuth. The researchers say the drug will not affect vision. Although dietary vitamin A is responsible for the production of light-sensitive receptors in the eye, it does not use the RARs in this process. “An additional benefit of our compound is that it can be taken orally as a pill, avoiding the injection process. It also appears to have a very rapid effect on sperm production and an even more rapid recovery when fertility is desired,” said Dr. Chung. But to make the pill a reality, researchers need to show that the compound is safe, effective – and reversible – when used for years. Drs. Wolgemuth and Chung are now planning longer-term studies to determine how long fertility can be disrupted and still recover after administration of the drug stops. “We hope that in the not so distant future, we may finally have more choices for people,” said Dr. Chung. Authors of the Endocrinology study are Sanny S. W. Chung, Xiangyuan Wang, Shelby S. Roberts, Stephen M. Griffey, Peter R. Reczek, and Debra J. Wolgemuth. This study was supported in part by grants initially from CONRAD and subsequently from the NIH, NICHD. The authors declare no financial or other conflicts of interest. Columbia University Medical Center provides international leadership in basic, pre-clinical and clinical research, in medical and health sciences education, and in patient care. The medical center trains future leaders and includes the dedicated work of many physicians, scientists, public health professionals, dentists, and nurses at the College of Physicians and Surgeons, the Mailman School of Public Health, the College of Dental Medicine, the School of Nursing, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. Established in 1767, Columbia's College of Physicians and Surgeons was the first institution in the country to grant the M.D. degree and is among the most selective medical schools in the country. Columbia University Medical Center is home to the largest medical research enterprise in New York City and State and one of the largest in the United States.

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