Male contraception: expanding reproductive choice

The development of steroid-based oral contraceptives had revolutionized the availability of contraceptive choice for women. In order to expand the contraceptive options for couples by developing an acceptable, safe and effective male contraceptive, scientists have been experimenting with various steroidal/non-steroidal regimens to suppress testicular sperm production. The non-availability of a long-acting androgen was a limiting factor in the development of a male contraceptive regimen since all currently tested anti-spermatogenic agents also concurrently decrease circulating testosterone levels. A combination regimen of long-acting progestogen and androgen would have advantage over an androgen-alone modality since the dose of androgen required would be much smaller in the combination regimen, thereby decreasing the adverse effects of high steroid load. The progestogen in the combination regimen would act as the primary anti-spermatogenic agent. Currently, a number of combination regimens using progestogen or GnRH analogues combined with androgen are undergoing trials. The side effects of long-term use of androgens and progestogens have also undergone evaluation in primate models and the results of these studies need to be kept in view, while considering steroidal regimens for contraceptive use in men. Efforts are also being made to popularize non-scalpel vasectomy and to develop condoms of greater acceptability. The development of contraceptive vaccines for men, using sperm surface epitopes not expressed in female reproductive tract as source, still requires considerable research efforts.     

Epididymal approaches to male contraception

Today, a vast arsenal of contraceptive methods interfering at different levels of the female reproductive axis is available. This is not the case for men for whom, until now, there is no reliable male reversible method and for whom vasectomy, condom and withdrawal are the only options available. Despite this limited supply, more than one third of all contraceptive methods used worldwide rely on the cooperation of the male partner. Besides developing hormonal approaches to stop sperm production, there may be attractive approaches that will interfere with sperm functions rather than production. Sperm functions are primarily established during post-testicular maturation, with the epididymis accounting for the majority. The purpose of this review is to present some of the promising and/or already abandoned leads that emerge from research efforts targeting the epididymis and its activities as potential means to achieve male post-meiotic contraception.     

Men's social networks and contraception in Ghana

In this paper, longitudinal data from northern Ghana is used to assess the effects of encouragement to use family planning that men receive from their personal network partners on the adoption of modern contraception by their wives. The study tests a conceptual model that, in addition to the effect of men's network encouragement, incorporates the effect of encouragement to use family planning that women receive from their respective network partners and the effect of spousal communication on reproductive matters and approval of family planning. Results show that encouragement received by men from their social networks significantly increases the likelihood of subsequent contraceptive use by their wives but this effect operates primarily by galvanizing spousal communication on reproductive matters. The effect of encouragement received by women from their respective network partners is largely independent from the effect of male network encouragement but it influences contraceptive adoption both directly and through spousal communication.     

BET proteins: Investigating BRDT as a potential target for male contraception

While many contraception options are available for women, birth control methods for men are limited to condoms and vasectomy. Past research into male contraceptives has focused on hormonal options but the associated side effects have thus far precluded this method from reaching the market. Non-hormonal male contraceptives and vas occlusion have also been explored, but to date no method has progressed past clinical testing. Recent interest in epigenetic research has unveiled a new potential non-hormonal male contraceptive target: the testis-specific bromodomain BRDT. Potent inhibitors for bromodomain-containing proteins are described in the literature, but a BRDT-specific compound has yet to be designed, prepared and tested. The high similarity between bromodomain proteins of the BET family makes development of selective and specific inhibitors both difficult and necessary. Selective inhibition of BRDT by a small molecule is an exciting new target in the search for a new non-hormonal male contraceptive.     

Factors affecting ever-married men's contraceptive knowledge and use in Nigeria

African men play important roles in the decisions about family life, including fertility and family planning. However, fertility and family planning research and programmes have ignored their roles in the past, focusing only on women's behaviours. Since the 1994 International Conference on Population and Development (ICPD), interest in men's involvement in reproductive health has increased. Unfortunately, data on their knowledge and use of contraception are generally scanty. This paper examines knowledge and use of contraception among ever-married men in Nigeria. A total of 1451 ever-married men aged 18-55 were interviewed in Imo and Ondo States, Nigeria. The findings reveal that men's level of contraceptive knowledge is high in the study areas. About 90% knew at least one method of family planning. Furthermore, the level of contraceptive use among married men is such that men could participate in family planning activities if there were adequate programmes to involve them. Men in the sample areas were found not only to support their spouses' use of contraceptives, but were actually using condoms to delay or prevent pregnancy. Age, education, place of residence, number of living children and being counselled for family planning were identified as key factors determining contraceptive knowledge and use among married men in the study areas. To ensure increased participation of men in family planning, programmes must be designed to educate them on the need for family size limitation and involve them in service delivery, even if only to their male counterparts.     

Use of testosterone alone as hormonal male contraceptive

The world population continues to grow rapidly while resources for sustainable living dwindle and manmade ecological problems increase proportionally to the overpopulation. Family planning is required to reduce population growth in developing countries and to stabilize populations in developed countries. Contraception makes abortion superfluous and provides the key to family planning. Women increasingly demand that men share the burden and risks of contraception and ?? as opinion polls show ?? men would be willing to use contraceptives if they were available. Research has established the principle of hormonal male contraception based on suppression of gonadotropins and spermatogenesis. All hormonal male contraceptives use testosterone, but in East Asian men, testosterone alone can suppress spermatogenesis to a level compatible with contraceptive protection. In Caucasians additional agents are required of which progestins are favoured.     

Recent trends in contraceptive sterilization in Flanders

Elective sterilization started to spread rather late in Flanders. Despite the sharp increase of this contraceptive method since the end of the 1970s, its frequency is still lower than in many neighbouring countries and much lower than in the US and Canada, mainly due to the lag in male sterilization. Further increase in contraceptive sterilization and a greater participation of men is expected in the near future.     

Reproductive Potential of Patients Treated by Maintenance Haemodialysis

Three of the wives of 25 men undergoing maintenance haemodialysis for terminal renal failure became pregnant. This suggests that fertility is not necessarily impaired in these patients and that contraceptive methods should be used by women patients at risk.     

Reproductive mortality.

The transfer from traditional to modern methods of contraception in recent decades has been accompanied by a transfer of deaths from complications of pregnancy to deaths from complications of the modern contraceptive methods. In 1975, for example, it is estimated that there were more deaths at ages 25-44 years in England and Wales from adverse effects of oral contraceptive use than from all complications of pregnancy, delivery, and the puerperium combined. Thus maternal mortality is no longer an adequate indicator of the deaths associated with reproduction in the community. An alternative measure, the reproductive mortality rate should be used, which includes deaths from complications of contraceptive use as well as those from complications of pregnancy or abortion. The reproductive mortality rate in England and Wales seems to have declined continuously since 1950 for women aged 25-34. But after 1960 it increased for women aged 35-44, because of the higher mortality associated with oral contraceptive use in this age group.     

Current status of fertility control methods in India

Approximately 48.2% of couples of 15 to 49 years of age practice family planning methods in India. Female sterilization accounts for 34.2%, with male sterilization declining from 3·4% in 1992–93 to 1·9% in 1998–99. Use of the condom increased to 3·1% from 2·4%. There is an urgent need for research to develop new contraceptive modalities especially for men and also for women and to make existing methods more safe, affordable and acceptable. Current efforts in India to develop a male contraceptive are mainly directed towards (i) development of antispermatogenic agents to suppress sperm production, (ii) prevention of sperm maturation, (iii) prevention of sperm transport through vas deferens or rendering these sperm infertile and (iv) prevention of sperm deposition. Research work in the field of prevention of sperm transport through vas deferens has made significant advances. Styrene maleic anhydride (SMA) disturbed the electrical charge of spermatozoa leading to acrosome rupture and consequent loss in fertilizing ability of sperm. A multicentre phase-III clinical trial using SMA is continuing and it is hoped that the SMA approach would be available in the near future as an indigenously developed injectable intra-vasal male contraceptive. The safety and efficacy of available oral contraceptives were evaluated. An indigenously developed oral contraceptive ‘Centchorman’, which is a nonsteroidal, weakly estrogenic but potently antiestrogenic, was found to be safe and effective and is now being marketed in India since 1991 as a ‘once a week’ pill. Cyclofem and Mesigyna have been recommended as injectable contraceptives with proper counselling and service delivery by Indian studies. It has been recommended that these injectable contraceptives be added to the existing range of contraceptive methods available in the National Family Planning Programme. Based on the Indian studies CuT 200 was also recommended. Studies have indicated the advantage of intrauterine devices (IUD); they are long acting, relatively easily removed and fertility returns rapidly after their removal. Recent studies have recommended CuT 200 for use up to 5 years. The combination of some plant products i.e.Embelia ribes, Borax andPiper longum has been found to be safe and effective as a female contraceptive and the results of phase-I clinical trials are encouraging. Research work is going on in the country in various areas with special reference to hormonal contraceptive — a three monthly injectable contraceptive, immuno-contraceptives, antiprogestins, etc.     

Perspectives of contraceptive choices for men

Apart from condoms and vasectomy, which have several limitations of their own, no other methods of contraception are available to men. Various chemical, hormonal, vas based and herbal contraceptives have been examined and few of them have reached the stage of clinical testing. Promising leads have been obtained from testosterone buciclate/undecanoate, alone or in combination with levonorgestrel butanoate or cyproterone acetate, RISUG, an injectable intravasal contraceptive and a few herbal products, particularly the seed products of Carica papaya. It is feasible that an ideal male contraceptive, that meets out all the essential criteria will be made available to the community in the near future.     

Male contraception: Another holy grail

The idea that men should participate in family planning by playing an active role in contraception has become more acceptable in recent years. Up to the present the condom and vasectomy have been the main methods of male contraception. There have been and continue to be efforts to develop an acceptable hormonal contraceptive involving testosterone (T) suppression. However the off target affects, delivery of the analogs and the need for T replacement have proven difficult obstacles to this technology. Research into the development of non-hormonal contraception for men is progressing in several laboratories and this will be the subject of the present review. A number of promising targets for the male pill are being investigated. These involve disruption of spermatogenesis by compromising the integrity of the germinal epithelium, interfering with sperm production at the level of meiosis, attacking specific sperm proteins to disrupt fertilizing ability, or interfering with the assembly of seminal fluid components required by ejaculated sperm for acquisition of motility. Blocking contractility of the vas deferens smooth muscle vasculature to prevent ejaculation is a unique approach that prevents sperm from reaching the egg. We shall note the lack of interest by big pharma with most of the support for male contraception provided by the NIH.     

Barriers to the use of modern contraceptives and implications for woman-controlled prevention of sexually transmitted infections in Madagascar

Globally, unplanned pregnancies and sexually transmitted infections (STIs) persist as significant threats to women's reproductive health. Barriers to the use of modern contraceptives by women might inhibit uptake of novel woman-controlled methods for preventing STIs/HIV. Use of modern contraceptives and perceptions and attitudes towards contraceptive use were investigated among women in Antananarivo, Madagascar, using qualitative research. The hypothetical acceptability of the diaphragm--a woman-controlled barrier contraceptive device that also holds promise of protecting against STIs/HIV--was assessed. Women consecutively seeking care for vaginal discharge at a public health clinic were recruited for participation in a semi-structured interview (SSI) or focus group discussion (FGD). Audiotaped SSIs and FGDs were transcribed, translated and coded for predetermined and emerging themes. Of 46 participating women, 70% reported occasional use of male condoms, mostly for preventing pregnancy during their fertile days. Although women could name effective contraceptive methods, only 14% reported using hormonal contraception. Three barriers to use of modern contraceptives emerged: gaps in knowledge about the range of available contraceptive methods; misinformation and negative perceptions about some methods; and concern about social opposition to contraceptive use, mainly from male partners. These results demonstrate the need for programmes in both family planning and STI prevention to improve women's knowledge of modern contraceptives and methods to prevent STI and to dispel misinformation and negative perceptions of methods. In addition, involvement of men will probably be a critical component of increased uptake of woman-controlled pregnancy and STI/HIV prevention methods and improved health.     

Family Planning Knowledge,Attitude and Practice among Married Couples in Jimma Zone,Ethiopia

Background

Understanding why people do not use family planning is critical to address unmet needs and to increase contraceptive use. According to the Ethiopian Demographic and Health Survey 2011, most women and men had knowledge on some family planning methods but only about 29% of married women were using contraceptives. 20% women had an unmet need for family planning. We examined knowledge, attitudes and contraceptive practice as well as factors related to contraceptive use in Jimma zone, Ethiopia.

Methods

Data were collected from March to May 2010 among 854 married couples using a multi-stage sampling design. Quantitative data based on semi-structured questionnaires was triangulated with qualitative data collected during focus group discussions. We compared proportions and performed logistic regression analysis.

Result

The concept of family planning was well known in the studied population. Sex-stratified analysis showed pills and injectables were commonly known by both sexes, while long-term contraceptive methods were better known by women, and traditional methods as well as emergency contraception by men. Formal education was the most important factor associated with better knowledge about contraceptive methods (aOR = 2.07, p<0.001), in particular among women (aOR_women = 2.77 vs. aOR_men = 1.49; p<0.001). In general only 4 out of 811 men ever used contraception, while 64% and 43% females ever used and were currently using contraception respectively.

Conclusion

The high knowledge on contraceptives did not match with the high contraceptive practice in the study area. The study demonstrates that mere physical access (proximity to clinics for family planning) and awareness of contraceptives are not sufficient to ensure that contraceptive needs are met. Thus, projects aiming at increasing contraceptive use should contemplate and establish better counseling about contraceptive side effects and method switch. Furthermore in all family planning activities both wives'' and husbands'' participation should be considered.     

Voluntary sterilization in Flanders

From 1966 to 1990 there was a marked rise in the use of voluntary sterilization in Flanders, followed by a fall in women under the age of 40. In the last three decades a remarkable change has occurred in the choice between male and female sterilization. Compared with many other European countries, sterilization of men and women is widely practised in Flanders. In 1996 40% of 40- to 44-year-old women underwent voluntarily sterilization or had voluntarily sterilized partners. Additionally, another 9% of these women were sterilized for medical reasons. Voluntarily sterilized couples are on average older than non-sterilized couples, and, obviously, consider their families to be complete. For couples with a complete family, parity is the most important predictor in the choice between sterilization and non-sterilization. Regularly practising Catholics undergo sterilization least. Also, highly educated couples are less likely to have a sterilization. Couples who ever experienced a contraceptive failure choose sterilization more. Voluntary sterilization has no substantial effect on the fertility of the population since the effect on the prevented numbers of both wanted and unwanted births appears to be small. However, if voluntary sterilization did not occur, differences in fertility within the population would probably increase. It is presumed that the popularity of voluntary sterilization in Flanders has passed its peak and that its use will decline in the near future.     

Effects of partner conception risk phase on male perception of dominance in faces

Several studies have suggested that women may prefer to engage in extra-pair copulations with males who appear dominant and to do so near ovulation. While there is some evidence that males are more jealous of dominant rivals and more proprietary when their partners are near ovulation, there is none that suggests the existence of counterstrategic perceptual shifts that mirror those seen in women. We provide such evidence here. Composites of male faces that were either high or low in rated dominance were presented to male participants who provided ratings of dominance. A three-way interaction between stimulus-face dominance, partner conception risk phase, and partner oral contraceptive use was found; men whose partners did not use an oral contraceptive and were in the high conception risk phase of their cycle displayed increased dominance ratings of high-dominance male faces. We conclude that males have evolved counterstrategies to deal with female infidelity that include an overattribution of dominance to those rivals most likely to present a threat at times when that threat is greatest. This overattribution is likely to lead to increases in jealousy and mate-retention behaviors.     

Fluctuations of unbound whole blood polyamine levels during the menstrual cycle.

Perchloric acid-extractable whole blood spermidine and spermine concentrations were determined over a 4-week period in three men, four women, and one ovariectomized woman. Individual male spermidine/spermine ratios showed little fluctuation and similar values were obtained for each of the three males studied. Male spermidine and spermine concentrations, although stable for each male, varied from one subject to the next. Individual female spermidine/spermine ratios, as well as individual concentrations, fluctuated substantially when compared to those valued obtained for males; female ratios appear to rise and fall as a function of the menstrual cycle. The spermidine/spermine ratios obtained from a normal female receiving oral contraceptive, as well as those from an ovariectomized female, were characteristic of values obtained form men. It is suggested that a sex-related hormone(s) influences sperimidine and spermine concentrations in females.     

The menstrual cycle and susceptibility to virtual simulation sickness

Virtual simulation sickness (VSS) is a form of visually induced motion sickness that can result from immersion in a virtual environment (VE). As in their susceptibility to the sickness induced by real motion, women have been reported to be more susceptible than men to VSS, yet the reason for this difference is not known. The aim of the current study was to investigate the influence of the menstrual cycle on susceptibility to VSS in 16 naturally cycling women and to compare the responses of this group with control groups consisting of 1) 16 premenopausal women taking a combined monophasic oral contraceptive and 2) 16 men. All female participants were immersed in a nauseogenic VE on days 5, 12, 19, and 26 of their menstrual/pill cycle. These days were chosen because they fall in line with peaks and troughs of ovarian hormone levels. Menstrual cycle phase was confirmed by salivary estradiol and progesterone levels. A 4-week "pseudo-cycle" was assigned to the male participants. Hormone analysis revealed that 9 participants in the experimental group had been tested at the desired phases of their cycle. These participants exhibited a significant increase in susceptibility to VSS on day 12 of their cycle. The hormone analysis also showed that the cycles of the 7 remaining members of the experimental group had not precisely followed the expected pattern, and so these people had been tested on days that did not coincide with peaks and troughs of ovarian hormone levels. No consistent variation in susceptibility was observed over the cycle in these volunteers. In addition, no change in susceptibility was observed over the pill cycle of the oral contraceptive group nor over the pseudo-cycle applied to the male control group. The authors conclude that susceptibility to VSS varies over the menstrual cycle as a consequence of hormonal variation.     

Azoospermia in rabbits following an intravas injection of Vasalgel ™

Background

Vasectomy is currently the only long-acting contraceptive option available for men, despite increasing demand and potentially significant positive impacts on human health of additional male contraceptive options. Vasalgel ? is a high molecular weight hydrogel polymer being developed as a non-hormonal long-acting reversible male contraceptive. Vasalgel consists of styrene-alt-maleic acid dissolved in dimethyl sulfoxide, which is distinct from styrene-alt-maleic anhydride materials previously studied.

Methods

The goal of the study was to determine the contraceptive efficacy of two test articles with different levels of styrene maleic acid (100 %, and 80 % acid/20 % anhydride). The test articles were injected bilaterally in the vasa deferentia of mature male rabbits. Post-implantation analyses of semen parameters were completed over a 12 month period and compared to baseline measures of sperm concentration, motility and forward progression.

Results

Both test articles were effective in blocking the passage of spermatozoa through the vasa deferentia in the 12 subjects completing the study. A significant decrease in sperm concentration occurred following implantation of the test material, with no measurable sperm concentration except for a few samples in one animal that were markedly oligospermic. Vasalgel produced a rapid onset of azoospermia, with no sperm in semen samples collected as early as 29–36 days post-implantation, and was durable over a 12 month period.

Conclusion

This study indicated that Vasalgel is an effective non-hormonal long-acting male contraceptive in a rabbit model.

     

Attitudes towards the male contraceptive pill: psychosocial and cultural explanations for delaying a marketable product

Even though years of research on the male contraceptive pill have been conducted, a marketable product is still absent from the arsenal of male and female products of contraception. In this paper, the following psychosocial and cultural factors have been elicited from the literature in order to reveal explanations for this delay: acceptability, trust, fear of side-effects, perceptions of contraceptive responsibility and fear of losing connotations of masculinity. Regardless of cultural variation, overall there seems to be a positive attitude towards the acceptability of male contraceptive for both males and females, especially males in stable relationships. Some indication shows that the media have played an important role in distorting the results of research regarding male and female trust. Ongoing and future researches into several projects on psychosocial and cultural factors are described.