Male Contraception.

Approximately 40 to 50% of pregnancies are unintended. Contraceptive use significantly reduces the risk of unintended pregnancy. Approximately 70% of couples' contraceptive use is female and 30% is male, attributable to the reliance on condoms and vasectomies. Unfortunately, many women cannot use currently available contraceptives due to medical contraindications or side effects. At the same time, men want additional safe and effective contraceptive methods. Because of this, work to develop novel, safe, and effective male contraceptives is underway. This review will briefly discuss the pros and cons of condoms and vasectomies, and then describe research into the development of novel methods of male contraception, by the mechanism of action of the contraceptive. First, we will discuss male contraceptives that block sperm transmission. Next, we will discuss male contraceptives that impair sperm production. Lastly, we will discuss male contraceptives that impair sperm function.

Continuing the search for a hormonal male contraceptive.

This chapter discusses the mechanisms of action of hormonal male contraception, which suppresses the hypothalamic-pituitary-testis axis. When the intratesticular concentration of testosterone is subsequently suppressed to adequately low concentrations, spermatogenesis is arrested. Androgens are a necessary hormonal male contraceptive component because they not only suppress the hypothalamic-pituitary-testis axis, but also provide the male hormone necessary to maintain peripheral androgen functions. Past studies using testosterone alone and testosterone combined with progestins demonstrated contraceptive efficacy in the female partner at rates similar to combined hormonal female methods. Newer hormonal male contraceptive formulations and the alternative routes of administration are discussed, along with potential barriers, challenges, and opportunities for hormonal male contraceptive development. Novel methods that are safe, effective, reversible, user-friendly, and coitus-independent are intrinsic to equitably meet the various needs and limitations of an increasingly diverse population.

Daily Oral Administration of the Novel Androgen 11ß-MNTDC Markedly Suppresses Serum Gonadotropins in Healthy Men.

BACKGROUND: 11ß-methyl-19-nortestosterone (11ß-MNT) is a modified testosterone (T) with androgenic and progestational activity. A single oral dose of the prodrug, 11ß-MNT dodecylcarbonate (11ß-MNTDC), was well tolerated in healthy men. METHODS: We conducted a randomized, double-blind study at 2 academic medical centers. 42 healthy men (18-50 years) were randomized to receive oral placebo or 11ß-MNTDC, 200 or 400 mg daily, for 28 consecutive days. Primary outcome (safety and tolerability) measures were assessed twice per week. Subjects underwent serial blood sampling over 24 hours on days 1 and 28 to assess secondary outcomes: pharmacokinetics (serum drug concentrations); pharmacodynamics of 11ß-MNTDC (serum sex steroids and gonadotropins); and mood and sexual function (via validated questionnaires). RESULTS: There were no serious adverse events. No participants discontinued because of an adverse event or laboratory test abnormality. 11ß-MNTDC resulted in a dose-related increase in serum 11ß-MNTDC and 11ß-MNT concentrations sustained over 24 hours. Administration of 11ß-MNTDC resulted in a marked suppression of serum gonadotropins, T, calculated free T, estradiol, and SHBG over the treatment period (P < 0.01). Adverse effects that may be related to 11ß-MNTDC included weight gain, acne, headaches, fatigue, and mild mood changes, with 5 men reporting decreased libido and 3 decreased erectile/ejaculatory function. Serum low-density lipoprotein cholesterol, weight (~2 kg), hematocrit, and hemoglobin increased and serum high-density lipoprotein cholesterol decreased in both 11ß-MNTDC groups. CONCLUSION: Daily oral 11ß-MNTDC for 28 days in healthy men markedly suppressed serum gonadotropin and T concentrations without serious adverse effects. These results warrant further evaluation of 11ß-MNTDC as a potential male oral contraceptive.

Safety & efficacy of an intravasal, one-time injectable & non-hormonal male contraceptive (RISUG): A clinical experience.

Background & objectives: For improved male contraception, a new polymeric drug molecule - Reversible Inhibition of Sperm under Guidance (RISUG) has been synthesized and has been found to be effective, safe and reversible in various animal species. Phase-I and phase-II clinical trials have confirmed its safety and contraceptive efficacy. The present study was undertaken as a multicentric-limited phase-III clinical trial to test the efficacy and safety of RISUG in human volunteers. Methods: One hundred and thirty nine young males each having at least two children and living with wife were given 120 µl of RISUG as bilateral vas intraluminal injection. After the single-dose administration, the individuals were followed in respect of general health and semen parameters. Their wives were also followed particularly to determine onset of pregnancy. Results: During the six month follow up, the health of male volunteers and their wives was normal with no significant adverse effects. Temporary scrotal enlargement and mild scrotal and inguinal region pain were manifested in most individuals and resolved within one month without any routine activity impairment. In six individuals, there was injection procedure failure and azoospermia was not achieved. The other 133 individuals had either severe oligozoospermia or azoospermia at the first semen examination one month following RISUG injection; 82.7 per cent individuals had continued azoospermia in the month following first semen examination onwards and the rest 17.3 per cent manifested azoospermia within three to six months. Interpretation & conclusions: RISUG intravasal injection appears to be a safe clinical procedure with no significant adverse effects and has high sustained contraceptive efficacy. The localized intervention and continued contraceptive action on single-dose administration were significant features of the RISUG technology.

Safety and Pharmacokinetics of Single-Dose Novel Oral Androgen 11ß-Methyl-19-Nortestosterone-17ß-Dodecylcarbonate in Men.

Context: 11ß-Methyl-19-nortestosterone-17ß-dodecylcarbonate (11ß-MNTDC) is an orally bioavailable prodrug of 11ß-methyl-19-nortestosterone (11ß-MNT) with androgenic and progestational activity. Objectives: (i) Quantify 11ß-MNT binding to androgen and progesterone receptors. (ii) Evaluate safety, tolerability, and serum gonadotropin and testosterone suppression by 11ß-MNTDC in men. Design and Setting: (i) In vitro receptor binding and transactivation studies and (ii) randomized, double-blind, placebo-controlled single-dose, dose-escalating phase I study at two academic medical centers. Participants and Intervention: Twelve healthy male volunteers were randomized (five active, one placebo) to escalating single oral doses (100, 200, 400, and 800 mg) of 11ß-MNTDC or placebo given with or without food. Main Outcome Measures: (i) In vitro 11ß-MNT/11ß-MNTDC human receptor binding and transactivation and (ii) safety and tolerability, pharmacokinetics, and quantification of serum gonadotropin and testosterone concentrations for 24 hours following dosing. Results: 11ß-MNT avidly binds and activates human androgen and progesterone receptors, but 11ß-MNTDC has minimal activity. Single oral doses of 11ß-MNTDC were well tolerated without serious adverse events. Administration of 11ß-MNTDC with food markedly increased average 11ß-MNTDC and 11ß-MNT serum concentrations (P < 0.001 for all doses) compared with fasting with a significant dose-related effect on average serum drug concentrations (P < 0.0001). The 200-, 400-, and 800-mg doses significantly suppressed average serum testosterone concentrations (P < 0.05). Conclusions: A single, oral dose of 11ß-MNTDC up to 800 mg administered with food is safe and well tolerated in healthy men. The active drug 11ß-MNT has androgenic and progestational activity, rapidly suppresses serum testosterone, and is a promising candidate for an effective once-daily oral male hormonal contraceptive.

Effects of 28 Days of Oral Dimethandrolone Undecanoate in Healthy Men: A Prototype Male Pill.

Context: Dimethandrolone (DMA) has androgenic and progestational activity. Single oral doses of DMA undecanoate (DMAU) were well tolerated and reversibly suppressed serum LH and testosterone (T) in men. Objective: Assess safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of oral DMAU. Design: Double-blind, randomized, placebo-controlled study. Setting: Two academic medical centers. Participants: Healthy men (18 to 50 years). Interventions: One hundred men received DMAU [0, 100, 200, or 400 mg, formulated in castor oil/benzyl benzoate (C) or powder (P)] for 28 days. Subjects underwent 24-hour PK sampling on days 1 and 28 and twice weekly ambulatory visits throughout treatment. Main Outcome Measures: Primary outcomes were safety and tolerability parameters (vitals, laboratory data, mood, and sexual function scores) and adverse events. Secondary outcomes were drug PK profiles and PD effects (serum LH, FSH, and sex hormones). Results: Eighty-two subjects completed the study and were included in the analysis. There were no serious adverse events. No clinically significant changes developed in safety laboratory parameters. A significant dose effect was seen for weight, hematocrit, high-density lipoprotein cholesterol, corrected QT interval, and sexual desire. Serum 24-hour average concentrations of DMAU and DMA showed dose-related increases (P < 0.001). All six subjects in the P400 group and 12 of 13 subjects in the C400 group achieved marked suppression of LH and FSH (<1.0 IU/L) and serum T (<50 ng/dL). Conclusions: Daily oral administration of DMAU for 28 days in healthy men is well tolerated. Doses of ≥200 mg markedly suppress serum T, LH, and FSH. These results support further testing of DMAU as a male contraceptive.

Zero-Order Release of Gossypol Improves Its Antifertility Effect and Reduces Its Side Effects Simultaneously.

Gossypol was considered a promising male contraceptive but finally failed due to two side effects: hypokalemia and the irreversibility of its contraceptive effect. Here we demonstrate that sustained zero-order release could be a solution for these problems. The in vitro release of gossypol from gossypol/PEG layer-by-layer films follows a perfect zero-order kinetics. In vivo tests indicate that the films can maintain the plasma drug concentration constant in male SD rats for ∼20 days for a 30-bilayer film. The plasma drug concentration is 2 orders of magnitude lower than the peak plasma drug concentration when administered orally and the daily dose is >50-fold lower than the commonly used contraceptive oral dose. However, significant antifertility effects were still observed. Furthermore, hypokalemia was not observed, and the antifertility effects can be reversed after a recovery period. The results suggest that zero-order release can significantly improve the desired antifertility effect of gossypol and, meanwhile, significantly reduce its side effects. We envision the drug could be developed to be an effective, safe, and reversible male contraceptive by zero-order release.

Impact of various progestins with or without transdermal testosterone on gonadotropin levels for non-invasive hormonal male contraception: a randomized clinical trial.

Although several progestins have been tested for hormonal male contraception, the effects of dosage and nature of various progestins on gonadotropin suppression combined with and without additional testosterone has not been performed in a comparative trial. The aim of this study was to evaluate the differential impact of four oral or transdermal progestins on the suppression of gonadotropins in healthy men: oral: cyproterone acetate (CPA), levonorgestrel (LNG), norethisterone acetate (NETA), and transdermal: Nestorone® (NES), all in combination with transdermal testosterone (T). Randomized clinical trial testing was performed with four progestins at two doses each. After a 2-week progestin-only treatment, transdermal T was added for further 4 weeks and was followed by a 3-week recovery period. Progestin-dose per day: CPA 10 mg/20 mg, NES 2 mg/3 mg/dose e.g. 200/300 µg/day absorbed, NETA 5 mg/10 mg, LNG 120 µg/240 µg. From an andrology outpatient clinic, 56 healthy men aged 18-50 years, with body mass index ≤33 kg × m-2 were included in the study. Serum concentrations of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were studied. Secondary outcome measure included were serum testosterone concentrations, sperm concentrations, and safety parameters. Intergroup comparisons demonstrated that CPA and LNG had the strongest effect on LH/FSH suppression. Nevertheless, every substance showed significant inhibitory effects on gonadotropin secretion, especially in combination with transdermal T. A decrease in hematocrit and insulin sensitivity as well as cholesterol subfractions and triglycerides was uniformly seen for every group. The combination of oral or transdermal progestins with a transdermal testosterone preparation is able to suppress gonadotropins. Further dose titration studies with sperm suppression as an end-point should be conducted to determine the lowest effective dose for hormonal male contraception.

Comparison of the single dose pharmacokinetics, pharmacodynamics, and safety of two novel oral formulations of dimethandrolone undecanoate (DMAU): a potential oral, male contraceptive.

Dimethandrolone (DMA, 7α,11ß-dimethyl-19-nortestosterone) has both androgenic and progestational activities, ideal properties for a male hormonal contraceptive. In vivo, dimethandrolone undecanoate (DMAU) is hydrolyzed to DMA. We showed previously that single oral doses of DMAU powder in capsule taken with food are well tolerated and effective at suppressing both LH and testosterone (T), but absorption was low. We compared the pharmacokinetics and pharmacodynamics of two new formulations of DMAU, in castor oil and in self-emulsifying drug delivery systems (SEDDS), with the previously tested powder formulation. DMAU was dosed orally in healthy adult male volunteers at two academic medical centers. For each formulation tested in this double-blind, placebo-controlled study, 10 men received single, escalating, oral doses of DMAU (100, 200, and 400 mg) and two subjects received placebo. All doses were evaluated for both fasting and with a high fat meal. All three formulations were well tolerated without clinically significant changes in vital signs, blood counts, or serum chemistries. For all formulations, DMA and DMAU showed higher maximum (p < 0.007) and average concentrations (p < 0.002) at the 400 mg dose, compared with the 200 mg dose. The powder formulation resulted in a lower conversion of DMAU to DMA (p = 0.027) compared with both castor oil and SEDDS formulations. DMAU in SEDDS given fasting resulted in higher serum DMA and DMAU concentrations compared to the other two formulations. Serum LH and sex hormone concentrations were suppressed by all formulations of 200 and 400 mg DMAU when administered with food, but only the SEDDS formulation was effectively suppressed serum T when given fasting. We conclude that while all three formulations of oral DMAU are effective and well tolerated when administered with food, DMAU in oil and SEDDS increased conversion to DMA, and SEDDS may have some effectiveness when given fasting. These properties might be advantageous for the application of DMAU as a male contraceptive.

Male contraception.

Although female contraceptives are very effective at preventing unintended pregnancy, some women can not use them because of health conditions or side-effects, leaving some couples without effective contraceptive options. In addition, many men wish to take active responsibility for family planning. Thus, there is a great need for male contraceptives to prevent unintended pregnancies, of which 80-90 million occur annually. At present, effective male contraceptive options are condoms and vasectomy, which are not ideal for all men. Therefore, efforts are under way to develop novel male contraceptives. This paper briefly reviews the advantages and disadvantages of condoms and vasectomies and then discusses the research directed toward development of novel methods of male contraception.

Pipeline for contraceptive development.

The high rates of unplanned pregnancy reflect an unmet need for effective contraceptive methods for women, especially for individuals with health risks such as obesity, diabetes, hypertension, and other conditions that may contraindicate use of an estrogen-containing product. Improvements in safety, user convenience, acceptability, and availability of products remain important goals of the contraceptive development program. Another important goal is to minimize the impact of the products on the environment. Development of new methods for male contraception has the potential to address many of these issues of safety for women who have contraindications to effective contraceptive methods but want to protect against pregnancy. It would also address a huge unmet need for men who want to control their fertility. Products under development for men would not introduce ecotoxic hormones into the water system.

Hot issues in female and male hormonal contraception.

In recent years a number of significant developments in the field of female hormonal contraception have been made which have produced new formulations and delivery systems providing high efficacy, safety and important non-contraceptive benefits. In particular long-acting reversible contraception (LARC) formulations have been demonstrated to ensure extremely high efficacy in typical use, minimal contraindications, optimal safety in all women thereby representing the best option for most women of all ages. Their effectiveness is not reliant upon user adherence and their ability to reduce unintended pregnancies and abortions has been proven. Unfortunately the same considerations cannot be made for male hormonal contraception. Although a large number of men are interested and would welcome the opportunity to use male contraceptive methods, no safe, effective and reversible methods are available on the market. Current methods available for men are limited to condoms and vasectomy. Highly effective prototype regimens have been developed but the pharmaceutical industry is unwilling to pursue further development and market these products. Of all new approaches to male contraception, hormonal methods are the closest to clinical application. These are based on the reversible suppression of luteinizing hormone and follicle stimulating hormone with subsequent reversible inhibition of spermatogenesis and consequent replacement to maintain androgen dependent physiological functions. Most approaches tested combination regimens such as testosterone and a progestin or testosterone and a GnRH analog.

Biology of male fertility control: an overview of various male contraceptive approaches.

The population of our planet continues to grow at an alarming rate. If the growth continues at the present rate, the estimated current world population of about seven billion is expected to double in the next forty years. Accumulated data from surveys by the United Nations Population Control Division suggest that a majority of today's young men in many countries are willing to have fewer children than their parents did. However, the contraceptive options available to them have not changed in several decades. In spite of the general agreement that men, like women, must take full responsibility of their fertility, the availability of safe, reversible and affordable contraceptives for men have lagged behind because of the complexity of the science of the male reproductive system. Thus, the contraceptive needs of millions of men/couples go unmet every single day and results in millions of unwanted pregnancies. In this article, we intend to discuss new hormonal and non-hormonal contraceptive approaches that are at various stages of research and development and may someday provide new contraceptives for men. In addition, we intend to discuss many details of three safe, effective, affordable and reversible vas-based approaches that are inching closer to being approved for use by millions of men in multiple countries. Finally, our intention is to discuss the male contraceptive pill that will soon be available to men only in Indonesia. The availability of these male contraceptives will allow both men and women to take full control of their fertility and participate in slowing down the growth of world population.

Gossypol promotes degeneration of ovarian follicles in rats.

The present study aimed to determine if gossypol interferes with ovarian follicles in rats. Twenty-four female Wistar rats were assigned to two equal groups: one control group and the other dosed with gossypol (25 mg/kg/day, subcutaneously) for 15 days. Ovarian follicles were histologically classified according to the stage of development and as normal or atretic. Gossypol treatment reduced the length of estrous with an increase in the duration of the diestrus phase. This compound was responsible for reduced serum levels of T4 and progesterone. Treatment with gossypol was responsible for a significant reduction in the number of normal ovarian follicles and a significant increase in the number of atretic follicles, both in all stages of development. Thus, treatment of rats with gossypol was responsible for reduction in the number of viable follicles and changes in hormone levels that resulted in interference of the estrous cycle.

Injection of a chemical castration agent, zinc gluconate, into the testes of cats results in the impairment of spermatogenesis: a potentially irreversible contraceptive approach for this species?

Male sterilization by chemical agents is a nonsurgical contraceptive approach designed to induce azoospermia and, therefore, infertility. Intratesticular injection of zinc gluconate for sterilization of dogs has been described, but its use in cats remains limited. The objective of the present study was to evaluate, by light and transmission electron microscopy, the efficacy of a single intratesticular injection of a zinc gluconate solution (Testoblock) as a sterilant for male cats. Twelve sexually mature mixed breed cats were allocated at random into two groups (control = 6; treated = 6) and given a single injection into each testis of either isotonic saline or zinc gluconate, respectively. Histopathologic and ultrastructural evaluation was assessed at 120 days postinjection. Histopathologic changes were not detected in the testes from the control group. However, histologic evaluation of the treated group revealed atrophic and dilated seminiferous tubules, a decrease in the number of germ cells, and incomplete spermatogenesis. Sertoli cells had various degrees of cytoplasmic vacuolization. Intertubular tissue revealed active fibroblasts, collagen deposition, and inflammatory cells. The diameter of seminiferous tubules, epithelial height and tubular area were reduced (P < 0.05) in the treated group compared with controls. Azoospermia occurred in 8 of the 11 treated cats (73%). Ultrastructural evaluation of Leydig cells revealed loss of nuclear chromatin, increased smooth endoplasmatic reticulum, and mitochondria degeneration. Intratesticular injection of zinc gluconate solution impaired spermatogenesis in cats and has great potential as a permanent sterilant in this species.

Inhibition of sperm capacitation and fertilizing capacity by adjudin is mediated by chloride and its channels in humans.

STUDY QUESTION: Does adjudin disrupt chloride ion (Cl⁻) ion transport function in human sperm and impede sperm capacitation and fertilizing ability in vitro? SUMMARY ANSWER: In this study the results indicate that adjudin is a potent blocker of Cl⁻ channels: disrupting Cl⁻ ion transport function results in a decline in sperm capacitation and fertilizing ability in humans in vitro. WHAT IS KNOWN ALREADY: Although our previous studies have demonstrated that adjudin exerts its effect by disrupting sertoli-germ cell adhesion junctions, most notably apical ectoplasmic specialization by targeting testin and actin filament bundles that disrupts the actin-based cytoskeleton in sertoli cells, it remains unclear whether adjudin impedes Cl⁻ ion transport function in the human sperm. STUDY DESIGN, SIZE AND DURATION: Semen samples were obtained from 45 fertile men (aged 25-32). Spermatozoa were isolated from the semen in the human tube fluid (HTF) medium by centrifugation through a discontinuous Percoll gradient, and incubated with adjudin at 10 nM-10 µM and/or other reagents under capacitating conditions for 0-5 h. PARTICIPANTS/MATERIALS, SETTING, METHODS: We evaluated the effect of adjudin and different reagents on sperm functions with which they were incubated at 37 °C. Sperm motility and hyperactivation were analyzed by a computer-assisted sperm analysis (CASA) system. Sperm capacitation and the acrosome reaction were assessed by chlortetracycline fluorescence staining. Sperm fertilizing ability was evaluated by sperm penetration of zona-free hamster egg assay, and cellular cAMP levels in spermatozoa were quantified by the EIA kit. The proteins tyrosine, serine and threonine phosphorylation in the presence or absence of adjudin were analyzed by means of a immunodetection of spermatozoa, especially, compared the effect of adjudin on sperm hyperactivation and capacitation in the complete HTF medium with the Cl⁻-deficient HTF medium as well as the various Cl⁻ channel blockers. MAIN RESULTS AND THE ROLE OF CHANCE: Adjudin significantly inhibited sperm hyperactivation but not sperm motility. Adjudin-induced inhibition of sperm capacitation was reversible, and it was found to block the rhuZP3ß- and progesterone-induced acrosome reaction in a dose-dependent manner. Adjudin also blocked sperm penetration of zona-free hamster eggs, and significantly inhibited both forskolin-activated transmembrane adenylyl cyclase and soluble adenylyl cyclase activities leading to a significant decline in the cellular cAMP levels in human spermatozoa. Adjudin failed to reduce sperm protein tyrosine phosphorylation but it did prevent sperm serine and threonine protein phosphorylation. Interestingly, adjudin was found to exert its inhibitory effects on sperm capacitation and capacitation-associated events only in the complete Cl⁻-HTF medium but not Cl⁻-deficient medium, illustrating the likely involvement of Cl⁻. Adjudin inhibits the fertility capacity of human sperm is mediated by disrupting chloride ion and its transport function. LIMITATIONS, REASONS FOR CAUTION: This study has examined the effect of adjudin only on human sperm capacitation and fertilizing ability in vitro and thus has some limitations. Further investigations in vivo are needed to confirm adjudin is a potent male contraceptive. WIDER IMPLICATIONS OF THE FINDINGS: Our studies demonstrated that adjudin inhibition of capacitation is reversible and its toxicity is low, opening the door for the examination of adjudin as a mediator of male fertility control. Adjudin may be a safe, efficient and reversible male antifertility agent and applicable to initial clinical trials of adjudin as a male antifertility agent in humans. STUDING FUNDING/COMPETING INTEREST(S): This work was supported by the National Basic Research Program of China (2006CB504002), the Nature Science Foundation of China (Nos. 81000244 and 81170554), Zhejiang Project of Science and Technology (2011C23046), the Nature Science Fund of Zhejiang province (Nos.Y2100058 and Y2090236), the key Science and Technology Innovation Team of Zhejiang Province (No.2012R10048-07) and the National Institutes of Health (NICHD U54 HD029990 project 5), USA. The authors declare no conflict of interest.

Evaluation of genotoxicity in leukocytes and testis following intra-vasal contraception with RISUG and its reversal by DMSO and NaHCO3 in Wistar albino rats.

Evaluation of genotoxicity of RISUG® - a vas based contraceptive, was carried out in the present study. Animals were allotted into groups of sham operated control, vas occlusion with RISUG (5-7 µl) for 360 days and reversal by DMSO (250-500 µl) and 5% NaHCO3 (500 µl). Blood samples and testis were collected at 360 days of vas occlusion and 90 days of vas occlusion reversal for comet analysis. Hydrogen peroxide induced samples were used as positive control. Olive moment, tail length and percentage DNA in tail were recorded with minimum variation in all groups for both leukocytes and testis. When compared with positive control the variation was highly significant for both 20 µM and 50 µM H2O2 (p<0.001). It is concluded that vas occlusion with RISUG at the contraceptive dose regimen is not associated with genotoxicity in leukocytes or the testis of pre- and post-reversal rats.

Demand for male contraception.

The biological basis for male contraception was established decades ago, but despite promising breakthroughs and the financial burden men increasingly bear due to better enforcement of child support policies, no viable alternative to the condom has been brought to market. Men who wish to control their fertility must rely on female compliance with contraceptives, barrier methods, vasectomy or abstinence. Over the last 10 years, the pharmaceutical industry has abandoned most of its investment in the field, leaving only nonprofit organisations and public entities pursuing male contraception. Leading explanations are uncertain forecasts of market demand pitted against the need for critical investments to demonstrate the safety of existing candidate products. This paper explores the developments and challenges in male contraception research. We produce preliminary estimates of potential market size for a safe and effective male contraceptive based on available data to estimate the potential market for a novel male method.