Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Could a birth control pill for men be on the horizon?

06.06.2011
Retinoic acid receptor antagonist interferes with sperm production

Researchers at Columbia University Medical Center are honing in on the development of what may be the first non-steroidal, oral contraceptive for men. Tests of low doses of a compound that interferes with retinoic acid receptors (RARs), whose ligands are metabolites of dietary vitamin A, showed that it caused sterility in male mice.

Earlier results of the experiments using this RAR antagonist were published in the June 1st issue of Endocrinology, and an abstract extending the studies to longer drug delivery periods is scheduled for the Late Breaking Oral Session of ENDO 2011: The 93rd Annual Meeting & Expo in Boston, Massachusetts.

(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.

Karin Eskenazi | EurekAlert!
Further information:
http://www.columbia.edu

More articles from Life Sciences:

nachricht First line of defence against influenza further decoded
21.02.2018 | Helmholtz-Zentrum für Infektionsforschung

nachricht Helping in spite of risk: Ants perform risk-averse sanitary care of infectious nest mates
21.02.2018 | Institute of Science and Technology Austria

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: In best circles: First integrated circuit from self-assembled polymer

For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.

In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...

Im Focus: Demonstration of a single molecule piezoelectric effect

Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale

Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...

Im Focus: Hybrid optics bring color imaging using ultrathin metalenses into focus

For photographers and scientists, lenses are lifesavers. They reflect and refract light, making possible the imaging systems that drive discovery through the microscope and preserve history through cameras.

But today's glass-based lenses are bulky and resist miniaturization. Next-generation technologies, such as ultrathin cameras or tiny microscopes, require...

Im Focus: Stem cell divisions in the adult brain seen for the first time

Scientists from the University of Zurich have succeeded for the first time in tracking individual stem cells and their neuronal progeny over months within the intact adult brain. This study sheds light on how new neurons are produced throughout life.

The generation of new nerve cells was once thought to taper off at the end of embryonic development. However, recent research has shown that the adult brain...

Im Focus: Interference as a new method for cooling quantum devices

Theoretical physicists propose to use negative interference to control heat flow in quantum devices. Study published in Physical Review Letters

Quantum computer parts are sensitive and need to be cooled to very low temperatures. Their tiny size makes them particularly susceptible to a temperature...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on High Temperature Shape Memory Alloys (HTSMAs)

15.02.2018 | Event News

Aachen DC Grid Summit 2018

13.02.2018 | Event News

How Global Climate Policy Can Learn from the Energy Transition

12.02.2018 | Event News

 
Latest News

Helping in spite of risk: Ants perform risk-averse sanitary care of infectious nest mates

21.02.2018 | Life Sciences

Fraunhofer ISE Supports Market Development of Solar Thermal Power Plants in the MENA Region

21.02.2018 | Power and Electrical Engineering

A variety of designs for OLED lighting in one easy kit

21.02.2018 | Trade Fair News

VideoLinks
Science & Research
Overview of more VideoLinks >>>