Scientist Solutions - Toxicity Study of Male Contraceptive

Hello Chintan:

Here are some links you might find helpful...

The Male Contraception Information Project

The Male Contraception Information Project is entirely nonprofit and works in three areas:
- raising public awareness of promising nonhormonal male
contraceptives
- advocating increased and expedited government research
- serving as a resource for journalists who wish to write about
the subject

MCIP Reference Page

Male contraceptives.org

We believe that men can, and should, have access to contraceptive options beyond condoms and vasectomies.

Researchers around the world are working toward male contraceptives that are potentially safer, more effective and more convenient than any contraceptives on the market today. New leads are being discovered all the time Adjudin and the 'dry orgasm' pill are two recent finds.

Times have changed: despite persistent myths, sociological surveys show that men are ready for new contraceptive options. Reliable, reversible male contraception would allow both men and women to participate fully in family planning.

Some policymakers and pharmaceutical companies are skeptical about the public's interest in new male contraceptive products, and much of the research is underfunded. You can help change this by participating in our survey. The aggregated results of the survey are used to show policymakers that there is demand for new male contraceptives.

Looking for a male contraceptive? Right now the only way to get access to them is to participate in a clinical trial.

MaleContraceptives.org is a project of the Male Contraception Coalition, whose mission is to help speed the development of new contraceptives for men.

Guidelines for the Clinical Testing of Male

"These are guidelines for the investigation of drugs administered systemically for the temporary inhibition of male fertility. This excludes drugs or agents which are not indicated for contraception, although they may affect male fertility and suppress spermatogenesis, such as immunosupressants or anticancer drugs. It also excludes definitive and possibly irreversible methods of male contraception, such as vasectomy.
Drugs affecting male fertility may be divided into two general classes:
1. Hormonal, eg, steroids and peptides;
2. Nonhormonal, eg, cytotoxic agents, diamines.

It must be emphasized that drugs which affect spermatogenesis because of a general toxic effect have only a theoretical importance, and their clinical applicability remains to be demonstrated. A more practical classification of male contraceptive drugs may be:
1. Drugs producing oligo- or azoospermia, ie, affecting the
concentration of spermatozoa; and
2. Drugs decreasing sperm motility or in some manner
affecting fertilizing capacity, ie, affecting the function of
spermatozoa. This category might include drugs affecting
the composition of the seminal fluid."

G. Waites. Development of methods of male contraception: impact of the World Health Organization Task Force. Fertility and Sterility, Volume 80, Issue 1, Pages 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 hesitation, 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.

N.R. Moudgal, M. Jeyakumar, H.N. Krishnamurthy, Surekha Sridhar, H. Krishnamurthy and Flora Martin. Development of male contraceptive vaccine - a perspective. Human Reproduction Update 1997, Vol. 3, No. 4 pp. 335346.

This paper reviews the recent advances that have occurred in the area of development of a male contraceptive vaccine. The vaccine candidates considered for review are hormone/hormone receptorbased proteins including luteinizing hormone-releasing
hormone (LHRH)/LH, follicle stimulating hormone (FSH), as well as LH and FSH receptor proteins. The review also highlights the advances in our basic understanding of gonadotrophin action which have led to development of these vaccines. Focus is mainly on studies in the non-human primate which may be directly relevant to projected studies in the human. The data
indicate that the vaccines are well tolerated by the primate (including the human based on limited data) and do not give rise to any known toxic symptoms or immediate health hazards. The response to the immunogen has been uniform and it may be possible to increase antibody titres as well as prolong the immune response by adding acceptable immune stimulators to
the adjuvant cocktail and developing better immunization
schedules or immunogen delivery systems. Contraceptive vaccines for the male are a feasible proposition and attention should now be focussed on evaluating carefully the bioefficacy of antibodies raised to recombinant ovine FSHb or FSH receptor protein fragments in both human and non-human primates. The
advantage of the FSH/FSH receptor over the LHRH/LH-based vaccine lies in the fact that the former does not require an exogenous testosterone supplement to maintain accessory gland function, libido etc. The LHRH/LH-based vaccine results in azoospermia, while the FSH vaccine causes the production of low numbers of poor quality spermatozoa which are incapable of
impregnating cycling females.

A. Shafik. ADVANCES IN MALE CONTRACEPTION. Archives of Andrology, Volume 45, Issue 3 November 2000 , pages 155 - 167.

The methods devised for male contraception are meager. The authors review the various nonhormonal methods applied for contraception including vas deferens interference and heat. The former comprises the no-scalpel vasectomy, percutaneous vasal injection, the "Shug" method, and the argon laser vasal photocoagulation. Heat methods used wet heat, and artificial cryptorchidism was created by testicular suspension. The testicle was suspended in the superficial inguinal pouch close to the scrotal neck using 2 methods: stitch and ball. Two recently developed methods for male contraception-polyester-induced azoospermia and prolactin injection - are described. The azoospermic effect of the polyester sling seems to be due to (1) creation of an electrostatic field across the intrascrotal structures, and (2) disordered thermoregulation. Prolactin administration as a contraceptive method is efficient and safe and has the potential to be developed as a male contraceptive. The methods, especially testicular suspension and polyester suspensors, are simple and easily applicable and were well accepted by the subjects.

Methods for the regulation of male fertility
P.D. Griffin

The Task Force on Methods for the Regulation of
Male Fertility was established in 1972 to develop new,
safe, effective, reversible and acceptable methods of fertility
regulation for men and to monitor the safety and
efficacy of existing methods.

Ali BH. Dimethyl sulfoxide: recent pharmacological and toxicological research.. Vet Hum Toxicol. 2001 Aug;43(4):228-31.

A survey of the literature published in the past 2 decades on the basic pharmacology, therapeutic uses and toxicity of dimethyl sulfoxide (DMSO) is presented. A salient pharmacological action of DMSO is its ability to scavenge oxygen-free radicals implicated in xenobiotic-induced tissue damages when given before, during or several hours after the tissue insult. More trials with DMSO in diseases and conditions caused by oxygen-free radicals are warranted.

Glycosphingolipid Inhibition and Spermatogenesis in Man: A Pilot Study (MIG 2)

The purpose of this research study is to help in the development of safe, effective and reversible male contraception. We are examining the impact of the drug Miglustat on sperm production in normal men.

We want to see if Miglustat will inhibit sperm production in men and act as a reversible male contraceptive, as a study in mice administered Miglustat showed a reversible inhibition of sperm production. We believe Miglustat may have some potential as a safe, reversible male contraceptive.