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[Problems of male contraception. 2. Male hormonal contraception, post-testicular points of attack, immunization and enzyme inhibition].

In principle control of male fertility is possible by mechanical, surgical and pharmacological methods. However, up to now only the following mechanical and surgical procedures are practicable: coitus interruptus, coitus condomatus and vasectomy. Since the safety of the latter is comparable to the pill, vasectomy is a major alternative to the contraceptive methods used by the female partner. Practical aspects of vasectomy and possible complications are reviewed. Finally, pharmacological approaches and problems involved in the control of male fertility are discussed with special reference to antispermatogenic substances, steroid hormones, immunization and enzyme inhibitors. The concept of antienzymatic contraception is based on the inhibition of penetration of enzymes (acrosin) localized within the acrosomal cap. Unfortunately, penetration of most of the acrosin inhibitors into the acrosome to inactivate acrosin is prevented by the high selectivity of the acrosomal membranes. Thus, pharmacological control of male fertility is still far from being practicable.

Acrosin

Ultrasound as a new method of male contraception.

Twenty male cats were treated once or twice with 1 watt/sq cm of ultrasound for 10 minutes. Each of 24 male dogs received one to three treatments with 1 watt/sq cm for 10 minutes. Another six dogs were treated with 2 watts/sq cm for 15 minutes. Four Cebus apella monkeys were treated with the same dosage as that used for the cats and dogs. A dosage of 1 watt/sq cm for 10 minutes was also applied to four human patients without the use of anesthetics, and no pain or side effects were noted. In all treated animals as well as in human patients the results indicate that ultrasound significantly suppresses spermatogenesis according to the dosage and frequency of treatment, without any effect on Leydig cells or blood testosterone levels.

Animals

Passive immunization against prostatic 'inhibin' peptide as a male contraceptive.

Passive immunization of adult male hamsters for 12 weeks against peptide (As-PIP), a sperm coating antigen, resulted in selective elevation of the blood levels of FSH, impairment of spermatogenesis, and complete infertility when males were mated with normal cycling females. Passive immunization of male marmosets with As-PIP for 8 weeks was also effective and was reversible, without causing any obvious change in mating behaviour. These preliminary studies in hamsters and marmosets indicate that antibodies to a prostatic 'inhibin' peptide represent a promising new approach to male contraception.

Animals

Depot gonadotropin-releasing hormone agonist blunts the androgen-induced suppression of spermatogenesis in a clinical trial of male contraception.

Thus far, when tested as male contraceptives, GnRH agonists in combination with androgens were not very effective in producing azoospermia. Since in previous studies androgens were always given simultaneously with the GnRH agonist or later, we tested whether GnRH agonist administration after an initial androgen suppression phase might yield better results. After a control period, 3 groups of young healthy men (n = 8/group) received an initial loading dose of 400 mg 19-nortestosterone hexyloxyphenylpropionate (19NT-HPP), followed by 200 mg of the ester every 3 weeks for 24 weeks. One week after the first 19NT-HPP injection, 2 groups were given a single sc implant injection of 3.3 or 6.6 mg of the GnRH agonist buserelin, respectively, whereas a placebo implant was given to the third group. In the group receiving only 19NT-HPP, serum LH and FSH were markedly suppressed and remained low during the treatment phase. In the 16 volunteers receiving the buserelin implant LH and FSH were also suppressed on day 7, followed by a marked increase in the gonadotropins up to 2 weeks after buserelin implant injection. While LH was consistently suppressed for the remaining treatment phase, FSH returned to almost normal values in weeks 9-15. In contrast to the group treated with 19NT-HPP alone, in which sperm concentrations were reduced to oligozoospermia after only 3 weeks of treatment, the first suppressive effect in the 19NT-HPP/buserelin-treated groups was not seen before week 9. After 30 weeks, when the maximal suppression of spermatogenesis was seen, 4 of 8 volunteers in the group treated with 19NT-HPP alone were azoospermic, and the remaining 4 volunteers were oligozoospermic. In the groups treated with 19NT-HPP/buserelin, no more than 4 of 16 volunteers were azoospermic, and no more than 8 of 16 volunteers were oligozoospermic at any time point. It is concluded that GnRH agonist depot preparations have a blunting effect on the suppression of pituitary and testicular function caused by androgens in men participating in contraceptive trials.

Adult

Pregnancies associated with sperm concentrations below 10 million/ml in clinical studies of a potential male contraceptive method, monthly depot medroxyprogesterone acetate and testosterone esters.

A potential male contraceptive approach was evaluated in clinical trials involving monthly injections of depot medroxyprogesterone acetate and either subdermal implants of testosterone propionate or monthly injections of testosterone enanthate. Pregnancies occurred in partners of 9 men with recent sperm counts of 10 million/ml or below. In 5 of the 9 instances, the sperm counts were less than 1 million/ml. It appears that male contraceptive methods involving spermatogenic suppression may require attainment and maintenance of azoospermia. The pregnancy rate cannot be calculated, because the extent of other contraceptive use is uncertain. There were no spontaneous abortions. 6 pregnancies were carried to term, and all progeny were normal, based on physical examination at birth or 3 months after birth.

Contraceptive Agents, Male

Male contraception.

Although the modern era of contraception has focused attention on the female, research into male contraception is continuing on several fronts. Despite the widespread use of premature withdrawal, the condom and vasectomy, there is no acceptable drug for controlling fertility in the male. New advances have been made in influencing the maturation and fertility capacity of sperm. Techniques are being developed for reversibly blocking sperm transport. The functions of seminal fluid are under intensive investigation.

Antispermatogenic Agents

An evaluation of male contraceptive acceptance in rural Ghana.

To evaluate the effect of male contraceptive acceptance on fertility, the Danfa Family Planning Project in rural Ghana studied a sample of its male family planning acceptors. The findings show that half of the survey respondents accepted foam for use by their partners and half accepted the condom. The continuation rate (69 percent at 12 months) and use-effectiveness rate (80 percent at 12 months) reported by men were higher than those reported by women program acceptors. It is felt that men can play a significant role in affecting fertility through their influence on a couple's choosing to use contraception and as a result of their motivation to obtain contraception and see that it is used. It is urged that increasing emphasis be placed on providing family planning services for men in African programs.

Adolescent

Surgical male contraception.

After giving a short account on the possible ways of male contraception, the authors outline the administration of surgical sterilization and its professional follow-up based on their own experience. Their suggestions concerning legal regulations aim, on the one hand, at the extension of the topic, on the other hand at supporting the specialists interested in surgical contraception.

Adult

Immunoneutralization of gonadotropin-releasing hormone and subsequent treatment with testosterone Silastic implants in rats: an approach toward developing a male contraceptive.

STUDY OBJECTIVE: To determine the extent to which increasing doses of exogenous testosterone (T) administered via Silastic implants can restore spermatogenesis and fertility to rats made azoospermic by active immunization against gonadotropin-releasing hormone (GnRH). DESIGN: Male rats were made azoospermic by active immunization against GnRH. Increasing doses of exogenously administered T (via Silastic implants) were administered for 8 weeks, and testicular sperm concentration and ability to impregnate female rats were evaluated. SETTING: Reproductive Endocrinology Laboratory, Department of Obstetrics and Gynecology, University of Colorado Health Sciences Center, Denver, Colorado. ANIMALS: Sexually mature male Sprague Dawley rats (SASCO, Omaha, NE). RESULTS: Suppression of gonadotropins and azoospermia was achieved by actively immunizing rats against GnRH. Testosterone was capable of restoring quantitatively complete spermatogenesis and fertility in GnRH-immunized azoospermic rats. This relationship was dose-dependent, as evidenced by the partial restoration of spermatogenesis and fertility observed in animals replaced with smaller T Silastic implants. CONCLUSION: Gonadotropin-releasing hormone immunization and T-filled Silastic implants may provide a model to study isolated gonadotropin deficiency and for the development of a reversible male contraceptive.

Animals

Residual sperm function in oligozoospermia induced by testosterone enanthate administered as a potential steroid male contraceptive.

To investigate the fertility of men who remain oligozoospermic despite sex steroid suppression, the in-vitro fertilizing capacity of residual spermatozoa was assessed in 30 men receiving intramuscular testosterone enanthate (TE). Spermatozoa were prepared by either Percoll or repetitive centrifugation/washing. Although the mean (+/- SEM) pretreatment zona-free hamster oocyte penetration (HOP) rates were similar (59.4 +/- 10.1 and 63.8 +/- 10.8%), following the induction of oligozoospermia the Percoll-prepared spermatozoa exhibited a penetration rate (26.9 +/- 10.2%) which was markedly greater than that obtained for sperm prepared by repetitive washing (0 +/- 0%). In addition, the partners of two men exhibiting a HOP test with Percoll-prepared spermatozoa, conceived despite a sperm concentration of 3 x 10(6) ml-1 and a negative HOP test with spermatozoa prepared by repetitive washing. These results suggest that Percoll preparation optimizes the assessment of in-vitro sperm function and that the fertility of men with TE-induced severe oligozoospermia is suppressed but not abolished.

Adult