Changes in male permanent contraception as partner access to long-acting reversible contraception (LARC) increases: an analysis of the National Survey for Family Growth, 2006-2010 versus 2017-2019.

OBJECTIVE: Male permanent contraception (PC), that is, vasectomy, is an effective way of preventing pregnancy. In the United States, male PC use has historically been concentrated among higher-educated/higher-income males of White race. In the last decade, use of long-acting reversible contraception (LARC) has increased dramatically. We sought to understand how sociodemographic patterns of male PC have changed in the context of rising LARC use. STUDY DESIGN: We examined the nationally representative male public use files of the National Survey for Family Growth (NSFG) across five survey waves. Our outcome was primary contraceptive use at last sexual encounter within 12 months. Using four-way multinomial logistic regressions (male PC, female PC, LARC, lower-efficacy methods), we compared sociodemographic factors predictive of male PC use versus reported partner LARC use between 2006-2010 (early) and 2017-2019 (recent) waves. RESULTS: We included 15 964 participants. From 2006 to 2019, there were absolute declines in male PC from 8.0% to 6.8%, while male-reported partner LARC use increased three-fold, from 3.4% to 11.0%. Among the highest economic strata, use of LARC converged with male PC. In adjusted analyses, high income significantly associated with male PC use in the early wave (OR 4.6 (1.4, 14.8)), but no longer in the recent wave (OR 0.9 (0.2, 4.2)). Marital status remained a significant but declining predictor of male PC across survey waves, and instead, by 2019, number of children newly emerged as the strongest predictor of male PC use. CONCLUSION: Sociodemographic variables associated with vasectomy use are evolving, especially among high-income earners.

Conducta sexual en adolescentes varones y anticoncepción / Sexual behavior in male adolescents and contraception

Se realiza un estudio prospectivo y longitudinal con el objetivo de determinar el grado de conocimiento, utilización y responsabilidad sexual ante la anticoncepción de adolescentes varones en nuestro medio. Se aplicó el método porcentual a las variables y para este fin se confeccionó una encuesta que fue aplicada de forma anónima y voluntaria a 400 varones de la enseñanza media, en el mes de mayo de 1999 en el municipio de Guane; las edades extremas de la muestra fueron los 13 y 18 años. Se encontró un elevado porcentaje de jóvenes con conocimientos sobre los métodos anticonceptivos, lo cual pone de manifiesto una disociación entre el conocimiento y la utilización de los métodos anticonceptivos del adolescente varón. La principal vía de conocimiento sobre los métodos está inculcada a la supuesta disminución de las sensaciones durante el coito que provoca el uso del condón; por último, se encuentra una tendencia machista respecto a la responsabilidad sexual del adolescente varón, lo que está dado por el no conocimiento de su responsabilidad ante la anticoncepción, así como el criterio de sentirse con el derecho de exigir a su pareja una relación segura(AU)

A prospective and longitudinal study was conducted in order to determine the degree of knowledge, use and sexual responsiblity of male adolescents in relation to contraception in our environment. The percentage method was applied to the variables and an anonymous and voluntary survey was done among 400 males aged 13-18 from the middle educational level, in the municipality of Guane, in May, 1999. It was found that a high proportion of teenagers knew about the contraceptive methods, which shows a dissociation between the knowledge and the utilization of contraceptive methods in the adolescent male. The main way of knowldege about these methods is associated with the supposed reduction of sensations produced by the use of condom during the sexual intercourse. It was also observed a trend toward machism concerning the sexual responsibility of the male adolescent due to the fact that they ignore their responsibilty as regards contraception and that they consider having the right to demand from their partners a safe sexual relation(AU)

Gossypol blood levels and inhibition of spermatogenesis in men taking gossypol as a contraceptive. A multicenter, international, dose-finding study.

The safety and efficacy of gossypol continues to be controversial. The aim of this study was to evaluate gossypol as a contraceptive pill for men at doses lower than those previously prescribed and in men from various ethnic origin. A total of 151 men from Brazil, Nigeria, Kenya, and China were divided into two groups. Both groups received 15 mg gossypol/day for 12 or 16 weeks to reach spermatogenesis suppression. Subjects were then randomized to either 7.5 or 10 mg/day for 40 weeks. In addition, 51 men were enrolled as a control group. In all, 81 subjects attained spermatogenesis suppression. Only one man discontinued treatment because of tiredness. Potassium levels fluctuated within the normal range. FSH increased consistently. Testicular volume decreased, but after discontinuation, values returned to levels not statistically different from admission. Of 19 subjects on the 7.5 mg/day dose group, 12 recovered sperm counts >20 million/mL within 12 months of discontinuing gossypol. In the 10 mg/day group, sperm counts recovered in only 10 of 24 subjects. Eight of the 43 patients remained azoospermic 1 year after stopping gossypol. All men diagnosed with varicocele failed to reverse spermatogenesis suppression. Gossypol blood levels indicated that sperm suppression occurs independently of concentration, whereas spermatogenesis recovery appears to be concentration-dependent. Gossypol may become a medical alternative to surgical vasectomy when the delay in onset of infertility is acceptable. When taken for 1 year, gossypol causes no reduction in sexual desire or frequency of intercourse. The possibility of reversal, occurring in 51% of the men on this regimen within 1 year after stopping gossypol, is an advantage of this compound as compared with surgical sterilization in many parts of the world.

PIP: The safety and efficacy of gossypol continues to be controversial. The aim of this study was to evaluate gossypol as a contraceptive pill for men at doses lower than those previously prescribed and in men from various ethnic origin. A total of 151 men from Brazil, Nigeria, Kenya, and China were divided into two groups. Both groups received 15 mg gossypol/day for 12 or 16 weeks to reach spermatogenesis suppression. Subjects were then randomized to either 7.5 or 10 mg/day for 40 weeks. In addition, 51 men were enrolled as a control group. In all, 81 subjects attained spermatogenesis suppression. Only 1 man discontinued treatment because of tiredness. Potassium levels fluctuated within the normal range. FSH increased consistently. Testicular volume decreased, but after discontinuation, values returned to levels not statistically different from admission. Of 19 subjects in the 7.5 mg/day dose group, 12 recovered sperm counts higher than 20 million/ml within 12 months of discontinuing gossypol. In the 10 mg/day group, sperm counts recovered in only 10 of 24 subjects. 8 of the 43 patients remained azoospermic 1 year after stopping gossypol. All men diagnosed with varicocele failed to reverse spermatogenesis suppression. Gossypol blood levels indicated that sperm suppression occurs independently of concentration, whereas spermatogenesis recovery appears to be concentration-dependent. Gossypol may become a medical alternative to surgical vasectomy when the delay in onset of infertility is acceptable. When taken for 1 year, gossypol causes no reduction in sexual desire or frequency of intercourse. The possibility of reversal, occurring in 51% of the men on this regimen within 1 year after stopping gossypol, is an advantage of this compound as compared with surgical sterilization in many parts of the world.

Ethnic differences in testicular structure and spermatogenic potential may predispose testes of Asian men to a heightened sensitivity to steroidal contraceptives.

Spermatogenesis in Asian men appears to be more susceptible to suppression by steroidal contraceptives administered in clinical trials than spermatogenesis in Caucasian men. The objective of this study was to determine whether ethnic differences exist in testicular structure and spermatogenic potential that might predispose Asians to a high sensitivity to steroidal contraceptives. Testes from 12 Chinese men were compared to those from 8 Hispanic men and 12 non-Hispanic Caucasian men of ages 29+/-3, 30+/-2, and 29+/-3 years, respectively. Testes were fixed by vascular perfusion with glutaraldehyde, further fixed in osmium, embedded in Epon, and evaluated by stereology using 0.5-microm sections stained with toluidine blue. Homogenates of fixed testes were evaluated for the number of Sertoli cells and the daily sperm production based on pachytene primary spermatocytes (PDSP) or spermatids with spherical nuclei (DSP). Paired parenchymal weight was less (P < 0.05) in Chinese men than in Hispanic or Caucasian men. The PDSP per gram of parenchyma was lower (P < 0.05) and the DSP per gram tended to be lower in Chinese men than in other groups. The histologic appearance, volume density, and length per man of seminiferous tubules were the same among the ethnic groups; however, the diameter of seminiferous tubules was less (P < 0.05) in Chinese than in Hispanic or Caucasian men. The PDSP per man and the DSP per man were lower (P < 0.05) in Chinese than in Hispanic or Caucasian men. The number of Sertoli cells per gram was higher (P < 0.05) in Chinese or Caucasian men than in Hispanic men, but the number of Sertoli cells per man was lower (P < 0.05) in Chinese men than in Hispanic or Caucasian men. Sertoli cell function, measured as the number of germ cells accommodated by a single Sertoli cell, was lower (P < 0.05) in Chinese men than in Caucasian men. The volume density of Leydig cell cytoplasm was greatest (P < 0.05) in Chinese men, but the number of Leydig cells was similar among the ethnic groups. Hence, smaller testes coupled with reduced Sertoli cell number and function and reduced daily sperm production could predispose Asian men to have a heightened negative response of testes to steroidal contraceptives, as compared to Caucasian men. Dampening (by exogenous androgens) of any physiological benefit to spermatogenesis that a high volume density of Leydig cell cytoplasm may bestow on the human testis (that Asian men may have evolved to require) would exacerbate ethnic differences in the spermatogenic response to hormonal contraceptives.

PIP: Multicenter studies conducted by the World Health Organization suggest that the efficacy of spermatogenesis suppression by hormonal contraception differs across racial and ethnic groups. For both androgens alone and androgens in combination with a progestin, the suppression of spermatogenesis to persistent azoospermia occurred in about 90% of Asian men compared to 60-70% of Caucasians. The present study investigated ethnic differences in testicular structure that may affect the sensitivity of the testis to gonadotropin suppression and the spermatogenic potential of the testis. Testes of 12 healthy Asian men from China who died of sudden traumatic injuries and of 8 Hispanic and 12 Caucasian men from the US who died of the same cause were obtained at autopsy and analyzed. Both paired testicular weight and paired testicular parenchymal weight were significantly lower in Chinese men than Hispanic or Caucasian men. Pachytene primary spermatocytes per gram of parenchyma and spermatids with spherical nuclei also were lower in Chinese men than in the other groups. The histologic appearance, volume density, and length per man of seminiferous tubules were the same across ethnic groups, but the volume of seminiferous tubules per man was significantly lower in Chinese men. The number of Sertoli cells per gram was significantly higher in Chinese and Caucasian men than in Hispanic men, but the number of Sertoli cells per man and Sertoli cell function were significantly lower in Chinese men than the other two groups. The volume density of Leydig cell cytoplasm was greater in Chinese men, but the number of Leydig cells was similar across groups. It is postulated that smaller testes, coupled with the reduced number and function of Sertoli cells and reduced daily sperm production, contribute to an inherently lower spermatogenic potential in Asian men, which predisposes them to a heightened negative spermatogenic response to steroidal contraceptives.

Gossypol: reasons for its failure to be accepted as a safe, reversible male antifertility drug.

Following clinical trials conducted in China in the 1970s, gossypol was proposed as a drug for male contraceptive use. This review summarizes the extensive investigations on formal animal toxicology and on the recovery of fertility in men after stopping gossypol treatment which led to the decision by the Special Programme of Research, Development and Research Training in Human Reproduction (HRP) at the World Health Organization (WHO), that gossypol would not be acceptable as an antifertility drug. It is concluded that the assessment of gossypol reinforces the mandatory requirement that future contraceptive drugs must be developed by the established routes of appropriate animal toxicology and phased clinical studies.

PIP: There have been reports that studies conducted in China confirm the efficacy of gossypol as a male antifertility drug. This paper presents the extensive investigations on formal animal toxicology and on the recovery of male fertility after cessation of gossypol use. Studies conducted by the International Organization for Chemical Sciences in Development showed that 40 of the 70 highly purified, novel structural forms of gossypol were no more active than gossypol. Experiments conducted on Sprague-Dawley rats and cynomolgous monkeys confirm that either (-) or (+) gossypol is too toxic to be developed for human contraception. Among the side effects associated with the use of gossypol, the most serious was hypokalemic paralysis, although differences in reported incidences could be attributed to the regional differences in dietary intake of potassium and genetic predisposition. On the other hand, studies that examine the risk of permanent sterility among healthy reproductive males were confirmed by two separate studies, which found an incidence of 25% irreversible sterility. The failure of recovery among those who stopped gossypol use could be attributed to longer treatment, greater total dose of gossypol, smaller testicular volume, and elevated follicle stimulating hormone concentrations. The cessation of clinical studies on gossypol because of increased risk in irreversible testicular damage and low therapeutic ratio is recommended.

Experimental male methods inhibit sperm.

PIP: Despite years of research, the development of new male methods of contraception is proceeding very slowly and no modern contraceptive drug exists for men. The most effective contraceptive options for men remain condom use or vasectomy and even the more promising experimental male methods are still at least one decade away from general use. A lack of commercial interest and funding has frustrated research. Progress has also been slow because of the difficulty involved in regulating the human male reproductive system. It is easier to interrupt a woman's ovulation than it is to interrupt sperm production. However, despite the challenge, research continues on a number of projects to identify new modern contraceptive methods for men. Current experimental prototypes typically either attempt to suppress sperm production by hormonal or nonhormonal means, or attempt to inhibit the fertilizing ability of sperm, usually by disrupting a key step in the conception process. Most research, however, is focused upon suppressing sperm production. Hormonal approaches, testosterone derivatives, nonhormonal suppression, and disrupting sperm function are discussed.^ieng

Phase II clinical trial of a vas deferens injectable contraceptive for the male.

Following up on an earlier clinical trial demonstrating the safety of an intra-vas deferens injection of a contraceptive drug named Risug, comprised of styrene maleic anhydride (SMA) in a solvent vehicle of dimethylsulphoxide (DMSO), a study to assess the contraceptive effectiveness of a specific dose (60 mg) of SMA bilaterally was planned and implemented. Male subjects and their wives with normal reproductive profiles were the volunteer subjects. The wives were not using any contraceptives. The results reconfirm the safety and show that for a period of at least 1 year, the treatment leads to azoospermia in the male and gives pregnancy protection.

PIP: A Phase I clinical trial documented the safety of an intra-vas deferens injection of a contraceptive agent (Risug) containing up to 140 mg of styrene maleic anhydride (SMA) in a solvent vehicle of dimethylsulfoxide. This Phase II study sought to determine whether a single injection of a fixed dose of SMA into the lumen of the vas deferens controls fertility for a period of at least 12 months. 12 male subjects whose wives were not using a contraceptive method were administered 60 mg of SMA bilaterally. This regimen produced sustained azoospermia in all 12 subjects, with no changes in other parameters over the course of the 12-month study period. Spermatozoa all along the length of the vas deferens appeared to be inactivated immediately following injection. No pregnancies were reported. The findings confirm the safety of this method and indicate that the treatment leads to azoospermia for at least 1 year.

Gossypol-induced hypokalemia and role of exogenous potassium salt supplementation when used as an antispermatogenic agent in male langur monkey.

In our earlier study, we have observed that hypokalemia in langur monkeys, following gossypol acetic acid (GAA) treatment (5 mg dose level) when used as an antispermatogenic agent, and potassium salt supplementation partially maintained body potassium level of the animals. The aims of the present investigation was to confirm further occurrence of hypokalemia in the monkey (comparatively at two higher dose levels) and the role of potassium salt in preventing occurrence of gossypol-induced hypokalemia. Highly purified gossypol acetic acid alone at two dose levels (7.5 and 10 mg/animal/day; oral) and in combination with potassium chloride (0.50 and 0.75 mg/animal/ day; oral) was given for 180 days. Treatment with gossypol alone as well as with the supplementation of potassium salt resulted in severe oligospermia and azoospermia. Animals receiving gossypol alone showed significant potassium deficiency with signs of fatigue at both dose levels. Enhanced potassium loss through urine was found in potassium-deficient animals, whereas animals receiving gossypol acetic acid plus potassium salt showed normal serum potassium with a less significant increase in urine potassium level during treatment phases. Other parameters of the body remained within normal range except gradual and significant elevation in serum transaminases activity. The animals gradually returned to normalcy following 150 and 180 days of termination of the treatment.

PIP: An earlier study conducted by the authors indicated that body potassium levels were partially maintained in male langur monkeys treated with gossypol acetic acid (5 mg) and potassium salt supplementation. The present study sought to confirm the persistence of hypokalemia at two higher dosage levels (7.5 and 10 mg/animal/day) and assess the role of exogenous potassium salt (0.50 and 0.75 mg/animal/day) in preventing gossypol-induced hypokalemia. The two dosages of highly purified gossypol acetic acid were administered alone and in combination with potassium chloride for 180 days. All regimens produced severe oligospermia and azoospermia. However, monkeys who received gossypol alone showed significant potassium deficiency with signs of fatigue at both doses. On the other hand, animals receiving gossypol acetic acid and potassium salt supplementation showed normal serum potassium with a less significant increase in urine potassium level during treatment. Also noted was a gradual but significant elevation in the activity of serum transaminases. All parameters returned to normal 150-180 days after treatment termination. The hypokalemic effect documented in this study with gossypol alone may be due to renal leakage and gastrointestinal disturbances.

Use of norethisterone and estradiol in mini doses as a contraceptive in the male. Efficacy studies in the adult male bonnet monkey (Macaca radiata).

Administration of norethisterone (NET) or NET + estradiol benzoate using an Alzet minipump or as once-a-month intramuscular injection of their depot forms, NET-enanthate (NET-EN) and estradiol valerate (E-val), resulted in azoospermia in all monkeys (n = 13) within 60 to 150 days of treatment. Although addition of depot form of testosterone (T, 20 mg/month) to the regimen restored the behavioral response typical of a normal male, it did not reverse the azoospermic state. Serum T (heightened nocturnal) levels were significantly reduced (> 85%, p < 0.001) in all the treated groups. Evidence for blockade in spermatogenesis following treatment was obtained by DNA flow cytometry. Following withdrawal of treatment, the T level was restored to normalcy within 15 days but 120 days more were required for the animals to exhibit normal sperm counts. In conclusion, the efficacy of once-a-month injection of relatively low doses of NET-EN + E-Val to bring about azoospermia in monkeys, in a relatively short time, has been demonstrated. As the results are uniform and reproducible, it appears desirable that this steroid regimen be tested in man for its contraceptive efficacy.

PIP: Monthly intramuscular injection with an Alzet minipump of depot norethisterone enanthate and estradiol valerate (E-val) produced azoospermia in 13 adult male bonnet monkeys within 60-150 days. Although azoospermia was achieved earlier when E-val was added to the injection, this agent can be eliminated once azoospermia occurs. Addition of the depot form of testosterone (20 mg/month) restored the sexual behavioral response but did not reverse azoospermia. Serum testosterone levels were significantly reduced in all treatment groups. DNA flow cytometry revealed evidence for blockade in spermatogenesis after treatment. There were no changes in the serum lipid profile. The testosterone level returned to normal within 15 days after the end of treatment, but normal sperm counts were not observed for another 120 days. Since the steroid formulation investigated in this study has been used effectively in women for over a decade, tests of its contraceptive efficacy in men now seem warranted.

Comparison between testosterone oenanthate-induced azoospermia and oligozoospermia in a male contraceptive study. IV. Suppression of endogenous testicular and adrenal androgens.

Administration of supraphysiological doses of testosterone to normal men causes inhibition of spermatogenesis, but while most become azoospermic, 30-55% maintain a low rate of spermatogenesis. We have investigated whether there are differences in endogenous androgen production, of testicular and adrenal origin, which may be related to the degree of suppression of spermatogenesis. Thirty-three healthy Caucasian men were given weekly i.m. injections of 200 mg testosterone oenanthate (TE), 18 became azoospermic, while 15 remained oligozoospermic. Urinary excretion of epitestosterone, a specific testicular product, was reduced to <10% of pretreatment values, with no differences between the groups. Similar results were obtained for other markers of testicular steroidogenesis. Urinary and plasma adrenal androgens were also reduced during TE treatment: a statistically significant decrease in both (P < 0.001 and P < 0.05 respectively) was seen in the azoospermic but not oligozoospermic responders. These results suggest that testicular steroidogenesis is decreased to <10% by the administration of supraphysiological doses of exogenous testosterone. Differences in the degree of ongoing steroidogenesis in the testis do not appear to account for incomplete suppression of spermatogenesis, thus differences in androgen metabolism may underlie this heterogeneous response. A small but significant reduction in secretion of adrenal androgens was also detectable, the relevance of which is unclear.

Research closing in on birth control pill for men. Contraception (health).

PIP: This news brief informs about the breakthrough in the development of a suitable male contraceptive pill. Joseph Hall, a biochemist at North Carolina State University in Raleigh, developed a synthetic compound that interferes with sperm maturation. This male contraceptive was developed over a 10-year period with the support of the National Science Foundation's division of integrative biology and neuroscience. The compound is a sugary substance that inhibits 98% of enzyme activity needed for sperm maturation and fertility in male rats. The substance did not alter the hormone balance and had few effects on the sex drive. There was no effect on fertility after the dosage was stopped. The substance inhibited the activity of the 'B' form of the N-acetyl-beta-D-hexosaminidase enzyme, which is secreted and inserted into sperm cells after leaving the testes. The sperm cells traverse the tube-like epididymis and after ejaculation are unable to recognize, bind with, and penetrate the egg membranes, which prevents fertilization. The enzyme's 'A' and 'B' forms both perform the same physiological functions, but the 'B' enzyme was only found in sperm cells. The analog inhibited 98% of enzyme activity required for union with the egg in "in vitro" experiments. Oral administration of the analog blocked fertilization about 90% of the time. Further experimentation will be conducted in order to understand how the analog is metabolized. The compound is being tested on bull and human sperm. The research was conducted in part due to a challenge from the researcher's wife to develop a safe, effective male birth control pill.^ieng

Progestin-androgen combination regimens for male contraception.

PIP: Testosterone enanthate (TE) administration is associated with a failure rate (3.4/100 person-years) considerably lower than that of other currently available reversible male contraceptive methods. However, acceptability of this regimen is limited by the need for weekly injections, the lack of complete azoospermia, and the decrease in high-density lipoprotein (HDL)-cholesterol. Under investigation is the concurrent administration of a progestin that can act synergistically with TE in the suppression of gonadotropins. Because of the additive effects, the dose of each steroid can be decreased, minimizing androgen-related side effects. Third-generation progestins and hybrid progestins seem to offer the most potential for such an approach. In particular, the combination of cyproterone acetate (CPA) and TE has been found to result in a rapid, profound suppression of spermatogenesis, without side effects, through its ability to block both the follicle-stimulating hormone and androgen effects at the testis level. The anti-androgenic action of CPA is based on its ability to competitively inhibit the binding of testosterone and dehydrotestosterone to androgen receptors. The block of intratesticular testosterone effect by CPA is presumed to cause a decrease in cell-adhesion molecule concentrations and contribute to the premature sloughing of permatids from the seminiferous epithelium, thereby resulting in the early disappearance of spermatozoa from the ejaculate. This regimen did not cause any changes in plasma HDL or other lipoproteins or affect liver function test results.^ieng

Physiological relationships between inhibin B, follicle stimulating hormone secretion and spermatogenesis in normal men and response to gonadotrophin suppression by exogenous testosterone.

Inhibin has been postulated to be secreted by Sertoli cells in response to follicle stimulating hormone (FSH) and in turn to exert an inhibitory effect on FSH production. We have investigated this relationship using an assay specific for dimeric inhibin B. A total of 56 normal men received 200 mg testosterone enanthate (TE) i.m. weekly, for 65 +/- 1 weeks in a trial of hormonal male contraception. Before treatment a significant negative correlation between inhibin B and FSH concentration (r = 0.49, P < 0.001) was observed. During TE treatment, luteinizing hormone (LH) and FSH were rapidly suppressed. This was followed by a parallel decline in inhibin B and sperm concentration. During the early recovery phase, inhibin B concentrations remained suppressed in men who showed a delay in resumption of spermatogenesis, despite higher FSH concentrations. Inhibin B returned to pretreatment concentrations after 24 weeks recovery, when the inverse relationship with FSH was restored. Our results showed the expected inverse physiological relationship between inhibin B and FSH in normal men, with a decline during TE treatment and alpha subsequent resumption of the inverse relationship during recovery. These data clearly support the hypothesis that inhibin B plays a physiological role in the feedback control of FSH secretion, and reflects FSH-stimulated Sertoli cell function.

Contraceptive technologies: how much choice do we really have?

PIP: Despite the wide array of contraceptive methods available, the continuing need for more effective, easier, safer, and more appealing methods is highlighted by the fact that nearly 60% of pregnancies in the US are mistimed or unwanted, nearly half of all pregnancies end in abortion, adolescent pregnancy is one of the most pressing social problems in the US, and nearly 75,000 women die each year in developing countries from unsafe abortion. All heterosexually active women of reproductive age risk an unintended pregnancy, and this risk would be reduced if contraceptive technologies were improved. Improved methods would also help reduce the rate of population growth and reduce the transmission of sexually transmitted diseases and HIV/AIDS. Roadblocks to the development and marketing of improved contraceptive methods are political and economic rather than scientific. Some currently-available technologies, such as the IUD, emergency postcoital contraception, and the vaginal sponge, are underutilized. Contraceptive research has been or continues to be conducted into development of immunocontraception (pregnancy vaccines), male methods that prevent sperm formation or impair sperm movement in the epididymis, menses-inducer once-a-month pills, vaginal rings, injectables, implants, medical abortion using RU-486, new progesterone-releasing IUDs, barrier methods (such as Lea's Shield, the Femcap, a silicone diaphragm used without a spermicide, a new contraceptive sponge, and improved male and female condoms) and microbicides. Obstacles to funding of these research efforts include unpredictable market demand, regulatory issues, concerns over manufacturer liability, and pressure from anti-abortion groups. Thus, the social, economic, political, and legal climate in the US must change in order to foster the research in contraception that will result in improved contraceptive technologies and increased options.^ieng

Male contraception: ideas for the future.

PIP: Numerous global surveys have confirmed that men are willing to assume a more central role in family planning, especially if a wider range of contraceptive methods were available. At present, hormonal approaches to systemic male contraception represent the only hope for a marketable new technology within the next decade. Steroid regimens are reversible, inexpensive, free from major side effects, and can be delivered in convenient sustained-release formulations lasting several months. Gonadotropin-releasing hormone analogues are also promising. This article highlights recent advances in this important new area of research. All hormonal strategies require supplementation with androgens, whose long-term impact on lipid and prostate physiology needs further clarification. Unfortunately, research in the field of male contraception has been virtually abandoned by the pharmaceutical industry, which seems to underestimate men's interest in playing a more equitable role in family planning.^ieng

Progress towards a male pill.

PIP: In order to determine the demand for hormonal male contraceptive agents, a survey was undertaken of the attitudes of 450 men in four centers of a Contraceptive Development Network: Edinburgh, Scotland; Cape Town, South Africa; Hong Kong; and Shanghai, China. In Edinburgh and Cape Town, 66-68% of the men indicated that they would definitely or probably use a male daily pill, but this percentage dropped to 48-50% in Hong Kong and Shanghai. Except in Cape Town, there was little support for a monthly injection, and the idea of implants was universally unpopular. To determine the attitudes of women about a male contraceptive pill, a survey was made of over 400 women attending family planning clinics in Edinburgh and Shanghai. In each case, most of the women were positive about the possibility and indicated that they would adopt such a method. There was also almost universal agreement that women bear too much of the responsibility for contraception. Currently, one of the greatest challenges facing development of an acceptable male hormonal contraceptive is discovering a satisfactory formulation to replace testosterone at physiological doses while inhibiting sperm production. Two World Health Organization trials have revealed that incomplete suppression of spermatogenesis remains a problem, and research is focusing on development of a long-lasting testosterone injection with administration of an oral gestagen. Development of a safe and reliable male oral contraceptive may require another 5-10 years.^ieng

Contraceptive efficacy and adverse effects of testosterone enanthate in Thai men.

In conclusion, the present study demonstrated that induced severe oligozoospermia or azoospermia by weekly testosterone enanthate injection was sufficient for male contraception. The low rates of discontinuation due to side-effects of the hormone and incidental medical conditions in this study confirms the safety and acceptability of such androgen administration found in studies with up to 18 months exposure. The long-term hazards remain uncertain and require investigation for risk. The possible long-term benefits from androgen use for bone, muscle and blood metabolism will also need to be assessed before the net risk-benefit effects of an androgen-containing regimen can be fully evaluated. In summary, the contraceptive efficacy for male contraception in this study demonstrated that weekly injections of testosterone enanthate can provide safe and effective contraceptive protection. The practicability of this approach may be improved by the use of longer-acting testosterone preparations which are under development.

PIP: To assess the safety and efficacy of testosterone enanthate as a fertility control method, 17 healthy Thai men 21-45 years of age were administered weekly intramuscular injections of 200 mg of the androgen. All men were in stable relationships in which fertility had been established by a prior pregnancy. The study consisted of suppression, efficacy, and recovery phases. The median time required for the first semen sample to show azoospermia was 85 days. The three men who entered the efficacy phase still oligozoospermic (sperm concentrations under 3 million/ml) all achieved azoospermia early in the 12-month evaluation. There were no pregnancies during 6 months of exposure involving men with severe oligozoospermia and 152 months of exposure in azoospermic men. The regimen was associated with significant increases in body weight, hemoglobin, hematocrit, and testosterone and decreases in testicular volume, plasma urea, luteinizing hormone (LH), and follicle-stimulating hormone (FSH). Plasma LH and FSH levels recovered to pretreatment levels after cessation of treatment. Two men discontinued during the efficacy phase: one because of weight gain and hypertension, and another due to abnormal liver function tests. Testosterone has the advantages of providing simultaneous gonadotropin suppression and androgen replacement, making it an ideal single-agent hormonal male contraceptive. Compliance would be improved by the use of long-acting depot preparations. Although this study confirms testosterone's well-sustained suppression of spermatogenesis and lack of short-term adverse effects, long-term effects on cardiovascular and prostatic disease require investigation.

Suppression of spermatogenesis by testosterone enanthate in Thai men.

To investigate the effect of testosterone enanthate on suppression of spermatogenesis in Thai men, 17 normal Thai men were given 200 mg testosterone enanthate weekly by intramuscular injection. During treatment, semen was collected regularly to monitor spermatogenesis. Median times for the first semen sample reaching sperm concentration threshold of 5, 3, 1 and 0 million/ml were 58, 70, 84, and 85, respectively. Subsequently, all men became azoospermic. Among 17 men entering the efficacy phase, 14 (82.3%) achieved consistent azoospermic from the beginning of efficacy phase, the remaining 3 (17.7%) were initially severe oligozoospermic but later became azoospermic. Only one case achieved consistent oligozoospermia but did not achieve azoospermia within 6 months. After stopping injection, sperm first reappeared in the ejaculate of formerly azoospermia men at 73 days. Recovery of sperm output to normal sperm concentration (> 20 million/ml) was achieved by all men at a median time of 3.9 months and recovery to their own baseline in one year after the last injection was established in 13/17 (76.5%) at a median time of 4.9 months, respectively. In conclusion, testosterone enanthate alone is effective in suppression of spermatogenesis for male hormonal contraception due to the high rate of azoospermia induced, which is known to ensure reliable and effective, reversible contraception.

PIP: To assess the effect of testosterone enanthate on the suppression of spermatogenesis, 17 healthy Thai men received weekly intramuscular injections (200 mg) of the hormone, and spermatogenesis was monitored during the suppression, efficacy, and recovery phases. All subjects reached the oligozoospermic threshold during the suppression phase. Median times for the first semen sample to reach sperm concentrations of 5, 3, 1, and 0 million/ml were 58, 70, 84, and 85 days, respectively, and both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were suppressed below the detection limit. 14 men (82.3%) were consistently azoospermic from the onset of the efficacy phase, while the 3 initially oligozoospermic subjects achieved azoospermia. Variations in rates of azoospermia were unrelated to age, body size, initial testicular volume, or baseline sperm concentrations. There were 2 discontinuations during this phase (due to abnormal liver function tests in 1 case and weight gain and hypertension in another). After injections were stopped, sperm first reappeared in the ejaculate after a median interval of 73 days and normal sperm concentrations were recorded at 3.9 months. Plasma FSH and LH levels rebounded after a median time of 3 months. These findings confirm the potential of testosterone injection as a safe, reversible, effective method of male hormonal contraception.

Male involvement and contraceptive methods for men: present and future.

PIP: The four standard male methods of fertility control--coitus interruptus, periodic abstinence, vasectomy, and condoms--account for only 30% of worldwide contraceptive use. The failure of family planning programs to acknowledge the crucial role played by men in the contraceptive decision-making process may be responsible, in part, for stagnant contraceptive prevalence rates in some parts of the world. The development of new, reversible male methods of fertility control with adequate acceptability levels represents a major challenge in the field of reproductive health. Most promising are hormonal methods such as combined androgens and progestogens given as injections or implants. These hormones suppress spermatogenesis by inhibiting luteinizing hormone and follicle-stimulating hormone. Volunteers for early clinical trials of male hormonal methods have been motivated by a desire to share responsibility for family planning and concerns about side effects associated with many female methods. Genetic and immunologic approaches have long-term potential, but remain at the basic science level. Despite a trend toward increasing public support for male involvement in family planning, a strong financial commitment to research on the part of the pharmaceutical industry is lacking and impedes progress in this area.^ieng

A combined regimen of cyproterone acetate and testosterone enanthate as a potentially highly effective male contraceptive.

In this study we tested the effectiveness of the combined administration of cyproterone acetate (CPA) and testosterone enanthate (TE) in suppressing spermatogenesis. After a control phase of 3 months, 15 normal men were randomized to receive TE (100 mg/week) plus CPA at a dose of 100 mg/day (CPA-100; n = 5) or 50 mg/day (CPA-50; n = 5) or TE (100 mg/week) alone (n = 5) for 16 weeks. Semen analysis was performed every 2 weeks. Every 4 weeks, fasting blood samples were drawn for the measurement of LH, FSH, testosterone, estradiol, and biochemical and hematological parameters; subjects underwent a physical examination; and they and their partners filled in a sexual and behavioral questionnaire. Regardless of the dose, each of the 10 subjects receiving CPA plus TE became azoospermic, whereas only 3 of 5 subjects treated with TE alone achieved azoospermia. Times to azoospermia were 6.8 +/- 0.5, 8.4 +/- 1.0, and 14.0 +/- 1.2 weeks in groups CPA-100, CPA-50, and TE alone, respectively (P = NS). Throughout treatment, both gonadotropins tended to be higher in the TE alone group than in the other groups. This difference was mostly due to the higher gonadotropin levels present in the 2 men treated with TE alone that remained oligospermic. No difference in testosterone or estradiol levels was found among the groups. No significant change in lipoprotein levels or liver function tests could be detected. In the CPA-100 and CPA-50 groups, hemoglobin, hematocrit, and red blood cells were lower at the end of the treatment phase, whereas no change was detected in TE alone group. A tendency for a decrease in body weight was detected in subjects treated with CPA, whereas there was no change in subjects receiving TE alone. At the end of the treatment phase, a decrease in testis size was present in all groups. There was no significant change in sexual function, aggressive behavior, mood states, or satisfaction with relationship in any group. These results suggest that the combined administration of CPA and TE is very effective in suppressing spermatogenesis and may represent a promising regimen for reversible contraception in males.