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At least 19 recordsLinked to original sources
PubMed1988

Is high dosage testosterone an effective male contraceptive agent?

In male contraceptive trials, approximately half of normal men become azoospermic on high dosages of testosterone enanthate (TE), whereas the other half of men become severely oligozoospermic. To determine whether sperm function is reduced in men with severe oligozoospermia induced by TE, we studied sperm function in six normal men whose sperm counts were reduced to less than or equal to 5 X 10(6)/ml but not to azoospermia by high-dosage TE administration for 5 to 6 months and five normal men who received placebo (sesame oil) injections for the same period of time. Seminal fluid analysis and sperm function (as assessed by zona pellucida-free hamster ova penetration test, HOPT) were performed during a pretreatment period and after at least 3 months of TE or placebo treatment. HOPT was severely reduced in all six men, whose sperm counts were suppressed to severe oligozoospermia during TE (0.8 +/- 0.8% compared to 37 +/- 14% during the pretreatment period, P less than 0.05). Five men failed to penetrate any hamster ova, while the remaining man penetrated only 5% of ova during TE treatment. There were no significant changes in other seminal fluid measurements during high-dosage TE. The five men who received placebo injections did not demonstrate any significant changes in HOPT or seminal fluid analysis during the treatment period. In summary, we found that the fertilizing capacity of sperm is markedly diminished when sperm production is severely reduced by high-dosage TE administration. These findings suggest that male contraception may be achievable by reduction of spermatogenesis to severe oligozoospermia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Effects of the male contraceptive agent gossypol on meiotic chromosomes of the male rat.

Synaptonemal complexes (SCs) of rat spermatocytes were analyzed in silver-stained meiotic preparations 10-24 days after treatment with gossypol acetic acid, 30 mg/kg/day, for 70 days. Gossypol did not affect SC formation or function, as judged by the absence of pairing anomalies, SC fragmentation, or presynaptic arrest. The unpaired lateral axes could be seen at zygotene, and at pachytene normal SCs could be observed. The behavior of the XY axes also appeared to be normal.

Animals↗
PubMed1983

The effect of the male contraceptive agent Gossypol on human lymphocytes in vitro: traditional chromosome breakage, micronuclei, sister chromatid exchange, and cell kinetics.

The male antifertility agent Gossypol did not affect the level of traditional chromosome breakage or number of micronuclei in 66-hour lymphocyte cultures at concentrations up to 40 micrograms/ml. It did increase the frequency of SCE slightly, although the inter-individual variation was greater than the increase resulting from Gossypol, and, even at the highest concentration (40 micrograms/ml), the SCE rate was still within the normal range. It also affected cell kinetics, reducing the mitotic index and the proportion of second and third metaphases after BUdR incorporation.

Adult↗
PubMed1993

The effect of the male contraceptive agent gossypol acetic acid on mouse bone marrow cells in vivo: micronuclei and mitotic index.

In this work the genotoxic effect of gossypol acetic acid (gossypol) was evaluated by determining the frequency of micronuclei and mitotic index in male mouse bone marrow cells in vivo. Bone marrow cells were collected at 24th hour after the single intraperitoneal (20, 40, and 80 micrograms/g) administration of gossypol. Polychromatic erythrocytes (PCEs) in the bone marrow were then evaluated with respect to micronuclei frequency. The dose-dependent increase in the micronuclei frequency was observed. However, when compared with the control group, the increase was not found to be significant (P > 0.05). Also the mitotic index values were not found to be different from those control values (P > 0.05). The results suggest that gossypol is not a clastogenic and mutagenic agent in mouse bone marrow cells in vivo.

Animals↗
PubMed1986

[Male contraception].

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Contraceptive Agents, Male↗
PubMed2004

Update on the male hormonal contraceptive agents.

There remains a need for new acceptable and effective male contraceptives to increase the choice for couples throughout the world. There have been no recent advances in available male contraceptive methods although a number of promising approaches have been identified, of which the hormonal approach is currently undergoing clinical investigation. In recent years the pace of research in this area has quickened significantly with increasing interest and now investment by the pharmaceutical industry. This is vital if the work undertaken so far by the public sector is to be transformed into a commercial reality. The hormonal approach is based on suppression of pituitary gonadotropin secretion resulting in a reversible reduction in spermatogenesis with azoospermia in all men being the ultimate aim. Without stimulation by luteinising hormone from the pituitary, testicular testosterone production also ceases. Therefore, androgen administration to restore physiological levels is an essential component of all male hormonal contraceptive regimes. Male hormonal contraceptives can consist of testosterone alone, or either a progestogen or gonadotropin-releasing hormone antagonist with 'add-back' testosterone. This article reviews the current state of progress in this field.

Androgens↗
PubMed1981

Effect of testosterone enanthate on testis size.

We treated chronically 39 normal men with a depot androgen, testosterone enanthate (200 mg. intramuscularly), to assess its potential as a male contraceptive agent. Careful examination and quantification of testicular volume were done before, during and after several dose regimens of androgen therapy. After 4 months of weekly or bimonthly treatment with testosterone enanthate testicular volume decreased by 19.0 plus or minus 2.1 and 16.5 plus or minus 3.4 per cent, respectively. Decrease in testicular volume was related directly to decrease in sperm count. A total of 17 subjects on either weekly or bimonthly injections failed to suppress sperm counts to less than 5 million per cc after 16 weeks; testicular volume was not significantly less than control at this time. Four to 12 weeks of additional weekly injections decreased sperm counts to less than 5 million per cc in 13 of the 17 patients and decreased testicular volume by 23.0 plus or minus 4.8 per cent. The 16 additional weeks of less frequent injections (every 3 or 4 weeks) resulted in an increase in testicular volume with a return to normal size after treatment was discontinued.

Adult↗
PubMed1988

Large-scale resolution of gossypol enantiomers for biological evaluation.

Gossypol has been resolved into its pure optical isomers by conversion into the Schiff's base derivative of (+)-phenylalanine methyl ester, normal or reverse phase chromatography and hydrolysis. Forty grams of pure (-)-gossypol has been prepared in a micronised form for assessment of its antifertility and toxicological effects.

Administration, Oral↗
PubMed1995

Structure-activity studies of 2,3,4,4a,5,9b-hexahydroindeno[1,2-c]pyridines as antispermatogenic agents for male contraception.

Analogs of (4aRS,5SR,9bRS)-2-ethyl-2,3,4,4a,5,9b-hexahydro-7-meth yl-5-p- tolyl-1H-indeno[1,2-c]pyridine (Sandoz 20-438, 10a; R1 = ethyl, R2 = R3 = methyl, R4 = H) have been synthesized and tested in mice for their ability to reduce testes weight and disrupt spermatogenesis. The activity was strongly dependent on stereoisomerism and chirality, consistent with a mechanism of action involving interaction with a specific macromolecule. It was affected by changes in the nitrogen substituent and most strikingly by changes in the p-substituent of the 5-aryl ring. A hydrogen, fluorine, hydroxy, or methoxy substituent led to loss of activity, whereas methyl (Sandoz 20-438, 10a), carboxylate (RTI-4587-054, 10k; R1 = ethyl, R2 = methyl, R3 = COOH, R4 = H), ester (RTI-4587-056, 12b; R1 = ethyl, R2 = methyl, R3 = COOMe, R4 = H), formyl (RTI-4587-030, 12i; R1 = ethyl, R2 = methyl, R3 = CHO, R4 = H), or hydroxymethyl (RTI-4587-055, 12g; R1 = ethyl, R2 = methyl, R3 = CH2OH, R4 = H) groups resulted in antispermatogenic compounds. Methyl ester 12b was an effective antifertility agent, without apparent effects on mating, when given orally to male mice at 7-15 mg/kg daily for 35 days. Further evaluation of these compounds as male contraceptive agents and probes for study of spermatogenesis appears warranted.

Administration, Oral↗