Happy holidays and best wishes for 2008 to all!
— Kirsten Thompson and Elaine Lissner
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MALE CONTRACEPTION UPDATE |
December 2007 |
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Happy holidays and best wishes for 2008 to all!— Kirsten Thompson and Elaine Lissner 
Summaries of new peer-reviewed publications Endocrinological approaches Endocrinological approach supporting research “This study aimed to test metered spray delivery of a precise dosage of Nestorone® (NES) progestogen as a possible transdermal progestogen-only contraceptive [in women]… All subjects achieved satisfactory serum levels, although substantial intersubject variation was noted. The apparent elimination half-life of NES after the last dose on Day 5 was 26.8 hours.” “19-nor-4-androstenediol-3β,17β-diol (3β,19-NA) increases muscle and bone mass without significant stimulation of prostate growth, suggesting it may have some properties of a steroidal SARM.” “Biological variation generally accounted for more of total intraindividual variation than did assay variation. Day-to-day biological variation accounted for more of the total than did long-term biological variation. Short-term variability was greater in hormones with pulsatile secretion (e.g. LH) than those that exhibit less ultradian variation. Depending on the hormone, the intraindividual standard deviations imply that a clinician can expect to see a difference exceeding 18-28% about half the time when two measurements are made on a subject. The difference will exceed 27-54% about a quarter of the time.” “This increase in apoptosis was attributable to an increase in spermatogonial apoptosis via the intrinsic, rather than extrinsic pathway, as shown by increased activated caspase 9 positive spermatogonia. The concomitant suppression of FSH and LH/T showed that T alone or together with FSH was more important in spermatocyte and spermatid survival by regulating both apoptotic pathways.” “The results suggest that adrenomedullin (ADM), via its control in the secretion of inhibin B, may play a role in regulating spermatogenesis as well as the hypothalamus-pituitary-gonad feedback system. In addition, like in the Leydig cell, ADM and endothelin 1 (EDN1) were found to regulate the production of each other in opposite directions in the Sertoli cells, suggesting the presence of yet another local regulatory mechanism in the rat testis which may be important in modulating testicular functions regulated by gonadotropins.” “The purpose of this article is to introduce the current problems of androgen measurement by immunoassays, to describe the novel in vitro bioassay techniques and to review the current information on their application in clinical research.” Cell adhesion target supporting research “[Recent] findings have shown that ectoplasmic specialization (ES) also confers cell orientation and polarity in the seminiferous epithelium, illustrating that some of the functions initially ascribed to tight junctions (TJ), such as conferring cell polarity, are also part of the inherent properties of the AJ (e.g., apical ES) in the testis.” “Inactivated nectin-2 and nectin-3 [which are expressed at the ectoplasmic specializations between Sertoli cells and maturing spermatids] disrupted the nectin-afadin-actin system, and finally the actin filaments disappeared. As a result, the specialization lost the function and detachment of spermatids was observed. One of the functions of the specialization seems to be to hold maturing spermatids until spermiation.” Motility targets Motility target supporting research A broad review of the role of calcium cations in cell signaling. “Sperm swim without extracellular Ca 2+, although Ca 2+ clearly regulates flagellar shape.” “Flagellar CrPKD2 increased fourfold during gametogenesis, and several Chlamydomonas reinhardtii ciliary polycystic kidney disease 2 (CrPKD2) RNA interference strains showed defects in flagella-dependent mating. These results suggest that the CrPKD2 cation channel is involved in coupling flagellar adhesion at the beginning of mating to the increase in flagellar calcium required for subsequent steps in mating.” Vasa deferentia targets Epididymal target supporting research Proteomic / genomic supporting research “Ten protein spots were identified as expressing differentially between the normal testes and pathological testes with sloughing and disorganization of germ cells; these included the phospholipid hydroperoxide glutathione peroxidase, peroxiredoxin 4 (Prx4), heat shock protein beta-1 (HSP27), and cathepsin D (CTSD)… These 10 proteins may help in elucidating the pathways involved in human spermatogenesis.” “In the absence of [the stress-inducible polyubiquitin gene] Ubb, spermatocytes and oocytes arrest during meiotic prophase, before metaphase of the first meiotic division. Although cellular ubiquitin levels are believed to be maintained by a combination of functional redundancy among the four ubiquitin genes, stress-inducibility of the two polyubiquitin genes and ubiquitin recycling by proteasome-associated isopeptidases, our results indicate that ubiquitin is required for and consumed during meiotic progression.” “Our data suggested that integral membrane protein 2b (Itm2b) expression is upregulated by testosterone and might play a role in rat male reproduction.” Review
In memory of Dr. Matt HardyNews of Dr. Matt Hardy ’s death has come as a shock to us all. We share two tributes:  “Matt Hardy, senior scientist at the Population Council’s Center for Biomedical Research, died Sunday, November 4, at home, after running his 12th New York City marathon. “Council president Peter J. Donaldson said, ‘The Population Council has lost a productive scientist, a supportive colleague, and a dear friend. My deepest condolences go to his wife Dianne, also a scientist at the Center for Biomedical Research, and to his family and friends…’ “Matt joined the Council in 1991. His research focused on the endocrinology of the male reproductive system. Matt was an expert on Leydig cell function, the cells in the testis that make testosterone. He studied the effects of stress on testosterone secretion, the impact of environmental toxicants on male fertility, and potential new targets for male contraception.” Council Mourns the Loss of a Scientific Leader “With great warmth and profound sadness we remember Dr. Matthew P. Hardy who died unexpectedly on Sunday, November 4, after completing the New York Marathon. In Matt's quiet, unassuming way, he had become one of the preeminent reproductive biologists in the country, one who deservedly enjoyed a national and international reputation. He was also longtime and loyal member of the American Society of Andrology where he contributed mightily of his time and talent.” In Memoriam: Matthew P. Hardy, Ph.D., 1957-2007. We would like to echo the sentiment that Matt will be greatly missed.
Society of Andrology, India 2007 highlightsOn December 15-16, India’s top andrology researchers met to present findings and updates. With plane flights getting more and more expensive, many researchers from Europe and North America missed out – just as most scientists from India and China were unable to make it to the NICHD/CONRAD Future of Male Contraception conference in Seattle this past September. We bring you the highlights relevant to male contraception:
The full program and abstracts are available in the IMCC’s archive:
From the mailbag: "Medical tourism" to get RISUG?The Male Contraception Information Project get letters all the time from men who are willing to go to great lengths to get new contraceptive options. For example, Tim from Canada writes: Q: A: Hopefully there will be opportunity for collaboration on studies here in North America soon! Although a Canadian doctor participating in a World Health Organization site visit in 2002 learned to do the RISUG procedure, collaboration between RISUG’s developers and other international researchers has been difficult until recently. The government of India, which has supported the development of RISUG, may be willing to share expertise once enrollment in its own clinical trial is completed and energies are freed up for new projects. An obvious first step would be collaboration on manufacturing, and a US research group has expressed interest in collaborating on a rabbit study once that is done. Beyond technical expertise, bringing RISUG to North America will require the solid support of our own policymakers. Reproductive health budgets are tight these days, but attitudes are changing, thanks in part to input like yours. I am sorry not to be able to give you a different answer. In the meantime, please do ask your friends to fill out the survey at MaleContraceptives.org and write about their interest in the letter; it really makes a difference when policymakers see this kind of demand. And let them know about the newsletter mailing list so they can stay up to date on news and find out when there are calls for advocacy! This process is painfully slow, but we think it is moving in the right direction. With the largest-ever set of young men and women now entering reproductive age around the world, there's plenty of incentive to start putting together the brains and resources from both sides of the ocean, and soon!
Male contraceptives in the newsMCIP’s director was interviewed on Florida’s “105.5 The Beat” radio. Here are some other features: A snarky piece from the Times Online (UK) about why men can’t be trusted to use birth control. “Men cannot be trusted to change their underwear regularly, never mind take a tablet.” Completely ignores the potential of long-acting methods, not to mention that men already contribute about a third of contraception between condoms and vasectomy. Readers spare nothing in their comments: “This sort of man-slagging is distinctly un-feminist” (a woman) and “I would think that the author's attitude is all the contraception that she will ever need” (a man). Coverage of the C-31 SARM development work in rats by Dr. Duane Miller at the University of Tennessee in conjunction with the Memphis-based company GTx – in the context of the first rise in the U.S. teen birth rate since 1991. Details on the C-31 progress: “[An] experimental drug called C-31 had rendered 100 percent of male rats sterile… [The] effect was fully reversible, raising hopes of progress for a long sought pharmaceutical: a male birth-control pill... But the company and the researchers involved are cautious. GTx spokesman McDavid Stilwell described the research as early stage, and Jim Dalton, who recently left UT's pharmacy department to work full time with GTx, said the firm is placing a much higher priority on Ostarine, a related drug meant to fight bone and muscle wasting in patients with cancer and other conditions.” A significant portion of the men we hear from worry about women “running out of time” to have a baby and telling them they are using contraception when they aren’t. Are there really women out there like that, or is it an urban myth? This article profiles two women, one of whom, though the process may not involve deception, admits to taking advantage of some men’s willingness to have unprotected sex in the heat of the moment. “Should I hang my head in shame admitting I had sex with men because I wanted to get pregnant, even though they were not actively complicit in my desire?” Coverage of Bioqual's succesful monkey study on the nonhormonal compound CDB-4022, reported at last September's NICHD conference. Dr. Sheri Hild is interviewed: "It was a beautiful study. Sperm counts went down to a level considered infertile and came back up on their own. And it didn't have any effects on hormones such as testosterone, so we are very excited about it." .
Calendar of eventsPlanning to attend a male contraception or andrology-related event that's not listed here? Let us know so we can post it and alert your colleagues to interesting upcoming events.
EditorsKirsten Thompson, Director of the Male Contraception Coalition (MCC) Elaine Lissner, Director of the Male Contraception Information Project (MCIP)
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