This newsletter is a monthly publication of two organizations working to speed development of new male contraceptives. We bring you all the latest news related to male contraceptive research from the andrology, infertility, urology, endocrinology and family planning service provision communities.
Who are we? The Male Contraceptive Coalition (MCC) increases networking among researchers and policymakers, along with providing information and advocacy tools for the public. It is best known for its top-ranked website MaleContraceptives.org.
The Male Contraception Information Project (MCIP) focuses on publicizing nonhormonal male contraceptive research. Its website provides the detailed review paper “Frontiers in Nonhormonal Male Contraception: The Next Step,” along with resources that help journalists write accurate coverage of your work.
This newsletter is intended as a service to the male contraceptive research community. Let us know if there is additional reporting that would be of use to you.
A summary of new publications related to andrology and male contraceptive research categorized by contraceptive approach. Don’t see your journal article listed here? Do let us know so we can tell your colleagues about your work.
Endocrine approaches
Novel androgen formulation tested in murine model
“Dimethandrolone Undecanoate, a New Potent Orally Active Androgen with Progestational Activity.”
Attardi BJ, Hild SA, Reel JR.
Endocrinology. 2006 Feb 23; [Epub ahead of print]
PMID: 16497801
Two new dual isozyme 5alpha-reductase inhibitors have contraceptive effect in murine model
“Actions of 5alpha-reductase inhibitors on the epididymis.”
Robaire B, Henderson NA.
Mol Cell Endocrinol. 2006 Feb 11; [Epub ahead of print]
PMID: 16476520
Men in a Phase II trial of TU im found monthly injections too frequent, but found the method acceptable overall
“The acceptability of an injectable, once-a-month male contraceptive in China .”
Zhang L, Shah IH, Liu Y, Vogelsong KM, Zhang L
Contraception. 2006 Jan 23; [Epub ahead of print]
No PMID
Efficacy of testosterone + LNG implant regimen in men of different ethnicities
“Levonorgestrel implants enhanced the suppression of spermatogenesis by testosterone implants: comparison between Chinese and non-Chinese men.”
Wang C, Wang XH, Nelson AL, Lee KK, Cui YG, Tong JS, Berman N, Lumbreras L,
Leung A, Hull L, Desai S, Swerdloff RS.
J Clin Endocrinol Metab . 2006 Feb;91(2):460-70. Epub 2005 Nov 8.
PMID: 16278260
Efficacy of various sc TD + ENG implant dose regimens
“A multicentre study investigating subcutaneous etonogestrel implants with injectable testosterone decanoate as a potential long-acting male contraceptive.”
Brady BM, Amory JK, Perheentupa A, Zitzmann M, Hay CJ, Apter D, Anderson
RA, Bremner WJ, Pollanen P, Nieschlag E, Wu FC, Kersemaekers WM.
Hum Reprod. 2006 Jan ;21(1):285-94. Epub 2005 Sep 19.
PMID: 16172147
Use of percutaneous aspiration to determine intratesticular T levels
“The androgen microenvironment of the human testis and hormonal control of spermatogenesis.”
Jarow JP, Zirkin BR.
Ann N Y Acad Sci. 2005 Dec;1061:208-20.
PMID: 16467270
Regulation of Sertoli cell tight junctions by claudin 3
“Androgens regulate the permeability of the blood-testis barrier.”
Meng J, Holdcraft RW, Shima JE, Griswold MD, Braun RE.
Proc Natl Acad Sci U S A. 2005 Nov 15;102(46):16696-700. Epub 2005 Nov 7.
PMID: 16275920
Immunological approaches
Anti-eppin antibodies bound to Eppin on sperm surface block semenogelin binding site
“Eppin: An effective target for male contraception.”
O'Rand MG, Widgren EE, Wang Z, Richardson RT.
Mol Cell Endocrinol. 2006 Jan 16; [Epub ahead of print]
PMID: 16423450
Vas approaches
In vitro AFM analysis of human sperm treated with RISUG
“Topological alterations in human spermatozoa associated with the polyelectrolytic effect of RISUG((R)).”
Kumar S, Chaudhury K, Sen P, Guha SK.
Micron. 2006 Feb 9; [Epub ahead of print]
PMID: 16504524
Zona pellucida binding inhibitors
12 months of Zavesca has no side effects in murine model, reverses within 9 weeks
“Long-term non-hormonal male contraception in mice using N-butyldeoxynojirimycin.”
Walden CM, Butters TD, Dwek RA, Platt FM, van der Spoel AC.
Hum Reprod. 2006 Jan 5; [Epub ahead of print]
PMID: 16396932
Epididymal targets
Wyeth ’s search for drugable targets in the epididymal epithelium
“Epididymal genomics and the search for a male contraceptive.”
Turner TT, Johnston DS, Jelinsky SA.
Mol Cell Endocrinol. 2006 Feb 1; [Epub ahead of print]
PMID: 16458420
Schering’s search for drugable epididymal targets
“New approaches for male fertility control: HE6 as an example of a putative target.”
Gottwald U, Davies B, Fritsch M, Habenicht UF.
Mol Cell Endocrinol. 2006 Jan 23; [Epub ahead of print]
PMID: 16442214
Description of the structure of HE6, hypothesized to be involved in cell adhesion processes and as a g-protein coupled receptor found only in the efferent ducts and proximal epididymis
“Role of epididymal receptor HE6 in the regulation of sperm microenvironment.”
Kirchhoff C, Obermann H, Behnen M, Davies B.
Mol Cell Endocrinol. 2006 Jan 10; [Epub ahead of print]
PMID: 16413110
Ion channel mechanisms developed during epididymal maturation control the regulatory volume decrease (RVD) of sperm; RVD dysfunction leads to irregular angulation of the flagellum
“Physiological volume regulation by spermatozoa.”
Yeung CH, Barfield JP, Cooper TG.
Mol Cell Endocrinol. 2006 Jan 27; [Epub ahead of print]
PMID: 16446027
Coiled or rolled spermatozoa in various animals are the result of epididymal defects and suggest 3 possible mechanisms of post-testicular contraception
“Utility of infertile male models for contraception and conservation.”
Cooper TG, Barfield JP.
Mol Cell Endocrinol. 2006 Feb 20; [Epub ahead of print]
PMID: 16497433
Supporting research
Jackson Laboratory identifies 4 phenotypically infertile male mice with post-gonadal defects in sperm function
“Mutagenesis as an unbiased approach to identify novel contraceptive targets.”
Handel MA, Lessard C, Reinholdt L, Schimenti J, Eppig JJ.
Mol Cell Endocrinol. 2006 Jan 10; [Epub ahead of print]
PMID: 16412559
CDRI-84/35 and gossypol disrupt the supply of lactate to developing sperm by adversely affecting Sertoli cells
“Effect of antispermatogenic agents on cell marker enzymes of rat Sertoli cells in vitro.”
Ojha P, Dhar JD, Dwivedi AK, Singh RL, Gupta G.
Contraception. 2006 Jan ;73(1):102-6. Epub 2005 Nov 14.
PMID: 16371305
sNHE KO mice have nonmotile sperm; CatSper 1/2 KO mice sperm fail to hyperactivate
“Insights into sperm cell motility signaling through sNHE and the CatSpers.”
Quill TA, Wang D, Garbers DL.
Mol Cell Endocrinol. 2006 Jan 12; [Epub ahead of print]
PMID: 16413670
New formulation of papaya seed extract results in loss of sperm motility in murine model; mortality of 25% of the animals in 5× and 10× contraceptive dose groups is unexplained
“Toxicological investigations on the methanol sub-fraction of the seeds of Carica papaya as a male contraceptive in albino rats.”
Lohiya NK, Manivannan B, Garg S.
Reprod Toxicol. 2006 Mar 1; [Epub ahead of print]
PMID: 16515854
Reviews
Need for new male and female methods; brief overview of research on endocrine targets, GnRH-androgen regimens, cytokine inhibitors, lonidamine derivatives, and enzyme inhibitors.
“Contraception: an international perspective.”
Sitruk-Ware R.
Contraception. 2006 Mar;73(3):215-22. Epub 2005 Nov 14.
PMID: 16472559
Overview of research to date on endocrine targets (T formulations, progestins, GnRH antagonists) and brief summaries of Eppin, CCBs, lonidamine analogues, triptolide and N-BDNJ
“Reversible, non-barrier male contraception: status and prospects.”
Hoesl CE, Saad F, Poppel M, Altwein JE.
Eur Urol. 2005 Nov;48(5):712-22; discussion 722-3. Epub 2005 Apr 1. Review.
PMID: 16230226
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The work of the male contraceptive research community is of increasing interest to the press. Below are some examples of popular press coverage during the last month. Articles like these are putting male contraception on the radar of policymakers and federal funding agencies. Keep their interest piqued by publicizing your work. If your organization does not have a press office, the Male Contraception Information Project will help you get your work in the news via the American Association for the Advancement of Science’s EurkeAlert news press release service. For further information, contact Elaine Lissner.
New male contraceptive clears hurdle (30 March, EurekAlert!)
Researchers in India receive approval to begin enrolling additional study volunteers in a Phase III clinical trial of RISUG, “a reversible, nonhormonal contraceptive that provides 10 or more years of protection after a 10-15 minute procedure.” Additional toxicology studies were performed during the four year delay.
Societal shift in the role of fathers (21 March, Fox News)
Brief mention of new male contraceptive options -- with links to MaleContraceptives.org and MCIP.info -- within the context of the larger fathers’ rights movement. “Birth control advances have focused upon women even though effective male birth control is feasible.” Coverage contains some inaccuracies.
Male birth control in development (17 March, Oregon Daily Emerald)
University of Oregon student and faculty perspectives on the hurdles to the development of a hormonal male contraceptive.
Equal efforts in birth control (1 March, Minnesota Daily)
Opinion editorial: “Many men would welcome this burden in exchange for more reliable birth control and getting rid of that pesky latex…”
Birth control for men ‘possible’, unlikely (27 Feb, Agence France-Presse)
Carl Djerassi asserts that “no pharmaceutical company is interested in developing a male pill”, despite the involvement of Schering, Organon, Wyeth and half a dozen other smaller pharmaceutical companies.
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Announcements of funding opportunities from the National Institutes of Health’s NICHD, CONRAD, AMPPA-II and the National Science Foundation:
NICHD Request for applications – Contraceptive Research Centers
On 2 March, the National Institutes of Child Health and Human Development released a request for applications for the Contraceptive Development Research Centers Program (U-54, RFA-HD-06-014). “The aim of the program is to conduct a wide range of research, both basic and applied, with the ultimate goal of developing clinically useful contraceptive products. The NICHD intends to commit approximately $5.9 million in total costs [Direct plus Facilities and Administrative costs] in FY 2007. Up to three new and/or competing continuation awards will be made.” A letter of intent must be received by 14 July; a full application must be received by 14 August. For further information, contact Dr. Diana Blithe.
NICHD Program annoucement – Joint Indian and U.S. Contraceptive Research
On 1 March, the NICHD announced the Indo-U.S. Program on Contraception and Reproductive Health Research (R-03, PAR-06-197). The goal of this program is to “build upon previous research cooperation by drawing on the expertise of Indian and U.S. scientists and institutions to promote and support collaborative research that will result in expanded contraceptive options and improved reproductive health… New methods of male contraception including post-testicular methods and non-surgical methods of sterilization” are identified as high priority product development areas. Grant applicants can receive up to $50,000 each year for 2 years. The deadline for application is 5 May. For further information contact Dr. Dan Raiten.
NICHD Student loan debt repayment
The NICHD also sponsors the Contraception and Infertility Research Loan Repayment Program (CIR-LRP). The program “provides for the repayment of the educational loan debt of qualified health professionals (including graduate students) who agree to commit to a period of obligated service of not less than two years conducting research with respect to contraception and/or infertility at an NICHD intramural laboratory or in a qualified domestic non-profit institution. The CIR-LRP will pay up to $35,000 of the principal and interest of such individual's educational loans for each year of obligated service.” For more information, contact Dr. Susan Streufert.
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