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Desde sempre que a responsabilidade na contracepção e planeamento familiar tem recaído no elemento feminino do casal. No entanto, a partilha de responsabilidades no seio do casal é cada vez mais equitativa, e o homem desempenha nos dias de hoje um papel activo no controlo da natalidade. É deste modo de fundamental importância encontrar alternativas para os métodos contraceptivos masculinos existentes. Um estudo de 2005 revelou que cerca de 60 % dos homens na Alemanha, Espanha, Brasil e México desejam usar um novo método contraceptivo masculino e, um outro realizado na Inglaterra demonstrou que 80% dos homens colocam uma hipotética pílula masculina no topo das suas preferências no que concerne à contracepção. Nos últimos dez anos, têm surgido numerosos estudos de investigação na tentativa de compreender a fisiologia da espermatogénese, bem como alguns trabalhos epidemiológicos, cujo objectivo é encontrar métodos eficazes que permitam anular a formação do espermatozóide, e atingir a contracepção desejada de forma eficaz, reversível e segura. Com recurso a livros de texto de referência na área da biologia celular e da biologia e fisiologia da reprodução, assim como em artigos de revistas científicas da especialidade, a presente monografia sintetiza a informação existente sobre os últimos avanços no campo da contracepção masculina. Fornece uma base para a compreensão de todo o processo que leva a formação do espermatozóide e enfatiza as investigações mais promissoras ao nível dos locais de possível intervenção no processo. Nas espermatogónias a presença do factor neutrofílico derivado de uma linha da célula da glia é crucial na proliferação mitótica, e a sua descoberta ao nível do testículo humano vem trazer perspectivas interessantes para o desenvolvimento de um método que permita bloquear numa etapa muito precoce o processo de espermatogénese. No que toca às células de Sertoli as junções de oclusão são de particular interesse pois em conjunto formam a barreira hematotesticular, a zona que protege as células germinativas de qualquer agressão externa e interna. Os análogos da Lonidamina e o péptido de ocludina permitem quebrar essa barreira. Ao nível de actuação no epidímio a proteína eppin parece ser a mais promissora, dada a sua extrema importância na manutenção da fertilidade. No espermatozóide as possibilidades existentes vão de encontro às alterações estruturais do mesmo. A Planta Ruta Graveolens liofilizada e o Reversible Inhibition of Sperm Under Guidance permitem, respectivamente, alterar a mobilidade e desintegrar o espermatozóide. Na ejaculação, pode-se intervir ao nível da contractilidade do músculo liso das estruturas envolvidas no transporte e emissão do espermatozóide. A tansolusina afecta esse sistema levando a disfunções ejaculatórias. A nível hormonal existem estudos promissores com a combinação Dianogest com Decanoato de Testosterona, e a molécula (S)-N-(4-ciaano-3-trifluorometil-phenil)-3-(3-fluoro,4-clorofeenoxi)-2-hidroxi-2-metilpropanamida (que revelam eficácia, reversibilidade e poucos efeitos adversos) nos mamíferos. Comenta de igual forma os trabalhos epidemiológicos mais recentes na área da contracepção masculina. São apresentados os trabalhos existentes que demonstram a aplicabilidade prática das combinações de etonogestrel com Undecanoato de Testosterona e testosterona com acetato de medroxiprogesterona, e a utilização isolada de 7α-Methyl-19-Nortestosterona. Apesar de todos eles terem aspectos positivos e negativos, o estudo feito com a combinação de testosterona com acetato de medroxiprogesterona é o mais promissor pois revela reprodutibilidade (foi testada a capacidade de fertilização por parte do homem), eficácia (índice de falha entre 0-8%) e reversibilidade (contagens de espermatozóides acima dos 20 milhões/ml). No fim concluímos que apesar do avanço no conhecimento da espermatogénese e identificação de possíveis alvos de actuação para alcançar a contracepção masculina, muito mais há a fazer para atingir um método contraceptivo reversível, eficaz e seguro.
The concern with contraception and family planning has been over the years a responsibility of the feminine element of the couple. However, the sharing of responsibilities within a couple is actually more equitable, and men play nowadays an active role in birth control. Therefore, it is of fundamental importance to find out alternatives for the existing male contraceptive methods. A 2005 study found that approximately 60% of men in Germany, Spain, Brazil and Mexico want to use a new male contraceptive method. Another report conducted in England showed that 80% of men pose a hypothetical male pill on top of their preferences with regard to contraception. Over the past decade, there have been numerous research studies in an attempt to understand the physiology of spermatogenesis, as well as some epidemiological studies, whose aim to find effective methods that allow nullify the formation of sperm, and achieve the desired contraception effectively and reversibly. Using reference textbooks of biology and cellular biology and physiology of reproduction, as well as articles in scientific journals specialized in the area, this monograph summarizes the available information on the latest advances in male contraception. It provides the basis for the understanding of the process that leads to the formation of sperm, and emphasizes the most promising investigations envisaging the sites of possible intervention in order to achieve contraception. The glial cell line-derived neurotrophic factor is a crucial molecule in the mitotic proliferation of spermatogonia and its discovery in human testis has brought interesting perspectives for the development of a method allowing disruption of spermatogenesis at earlier steps. With regard to Sertoli cell, tight junctions are of particular interest because together they form the testis barrier, the structure that protects the germ cells of any external aggression and internal. Analogues of lonidamine and occludin peptide help to break this barrier. At the level of epididymis the eppin protein is the most promising, as it was shown its extreme importance maintaining fertility. The possibilities in the sperm will meet essential actions on structural changes. The lyophilized Ruta Graveolens and Reversible Inhibition of Sperm Under Guidance allows to change sperm mobility and cell structural integrity,respectively. Concerning ejaculation, interventions can be considered on smooth muscle contractility of structures involved in sperm transport and emission. . The tansolusin affect this system leading to ejaculatory dysfunction. Studies manipulating hormonal levels are promising and the combination of Dianogest with Testosterone Decanoate, and the molecule (S)-N-(4-cyano-3-trifluoromethyl-phenyl)-3-(3-fluoro, 4- chlorophenoxy)-2-hydroxy-2-methyl-propanamide shows effectiveness, reversibility, and few adverse effects in mammals. Recent epidemiological studies in the field of male contraception also are commented. These studies demonstrate the practical applicability of the combinations of etonogestrel and testosterone with Testosterone Undecanoate, with medroxyprogesterone acetate, and the isolated use of 7α-Methyl-19-Nortestosterone. Although they all have positive and negative aspects, the use of the testosterone and medroxyprogesterone acetate combination is the most promising one since it shows reproducibility (we tested the ability of fertilization by the male), efficacy (failure rate between 0 -8%) and reversibility (sperm counts above 20 million / ml). In conclusion, despite the advances deepening our knowledge of spermatogenic process, and the identification of new possible intervention targets , much more has be done in order to achieve a reversible, safe and effective contraceptive method.
The concern with contraception and family planning has been over the years a responsibility of the feminine element of the couple. However, the sharing of responsibilities within a couple is actually more equitable, and men play nowadays an active role in birth control. Therefore, it is of fundamental importance to find out alternatives for the existing male contraceptive methods. A 2005 study found that approximately 60% of men in Germany, Spain, Brazil and Mexico want to use a new male contraceptive method. Another report conducted in England showed that 80% of men pose a hypothetical male pill on top of their preferences with regard to contraception. Over the past decade, there have been numerous research studies in an attempt to understand the physiology of spermatogenesis, as well as some epidemiological studies, whose aim to find effective methods that allow nullify the formation of sperm, and achieve the desired contraception effectively and reversibly. Using reference textbooks of biology and cellular biology and physiology of reproduction, as well as articles in scientific journals specialized in the area, this monograph summarizes the available information on the latest advances in male contraception. It provides the basis for the understanding of the process that leads to the formation of sperm, and emphasizes the most promising investigations envisaging the sites of possible intervention in order to achieve contraception. The glial cell line-derived neurotrophic factor is a crucial molecule in the mitotic proliferation of spermatogonia and its discovery in human testis has brought interesting perspectives for the development of a method allowing disruption of spermatogenesis at earlier steps. With regard to Sertoli cell, tight junctions are of particular interest because together they form the testis barrier, the structure that protects the germ cells of any external aggression and internal. Analogues of lonidamine and occludin peptide help to break this barrier. At the level of epididymis the eppin protein is the most promising, as it was shown its extreme importance maintaining fertility. The possibilities in the sperm will meet essential actions on structural changes. The lyophilized Ruta Graveolens and Reversible Inhibition of Sperm Under Guidance allows to change sperm mobility and cell structural integrity,respectively. Concerning ejaculation, interventions can be considered on smooth muscle contractility of structures involved in sperm transport and emission. . The tansolusin affect this system leading to ejaculatory dysfunction. Studies manipulating hormonal levels are promising and the combination of Dianogest with Testosterone Decanoate, and the molecule (S)-N-(4-cyano-3-trifluoromethyl-phenyl)-3-(3-fluoro, 4- chlorophenoxy)-2-hydroxy-2-methyl-propanamide shows effectiveness, reversibility, and few adverse effects in mammals. Recent epidemiological studies in the field of male contraception also are commented. These studies demonstrate the practical applicability of the combinations of etonogestrel and testosterone with Testosterone Undecanoate, with medroxyprogesterone acetate, and the isolated use of 7α-Methyl-19-Nortestosterone. Although they all have positive and negative aspects, the use of the testosterone and medroxyprogesterone acetate combination is the most promising one since it shows reproducibility (we tested the ability of fertilization by the male), efficacy (failure rate between 0 -8%) and reversibility (sperm counts above 20 million / ml). In conclusion, despite the advances deepening our knowledge of spermatogenic process, and the identification of new possible intervention targets , much more has be done in order to achieve a reversible, safe and effective contraceptive method.
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Keywords
Contracepção masculina Contracepção masculina - Espermatogénese Contracepção masculina - Espermiogénese Contracepção masculina - Espermatozóide Contracepção masculina - Células de Sertoli Contracepção masculina - Hormonas Contracepção masculina - Testículo
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Universidade da Beira Interior