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Despite significant interests in contraception by men, effective methods of male contraception are limited to vasectomy and condoms. Recently, there have been several promising advances in male contraceptive research. This review will update readers on recent research in both hormonal and nonhormonal approaches to male contraception. Hormonal approaches to male contraception have been stymied by adverse effects, formulations requiring injections or implants, a 5% to10% nonresponse rate, as well as poor understanding of user acceptability. In the last several years, research has focused on novel, orally bioavailable androgens such as dimethandrolone undecanoate and 11ß-methyl-19-nor-testosterone. Additionally, combinations of a topical testosterone gel combined with a gel containing segesterone acetate, a potent progestin, have shown promise in clinical trials recently. Simultaneously, significant preclinical progress has been made in several approaches to nonhormonal male contraceptives, including compounds that inhibit sperm motility such as eppin, compounds that inhibit retinoic acid binding or biosynthesis, and reversible approaches to obstruction of the vas deferens. It is imperative for these areas of research to continue making strides so that there is a gamut of contraceptive options for couples to choose from. Some of these approaches will hopefully reach clinical utility soon, greatly improving contraceptive choice for couples.

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World population continues to grow at an unprecedented rate, doubling in a mere 50years to surpass the 7-billion milestone in 2011. This steep population growth exerts enormous pressure on the global environment. Despite the availability of numerous contraceptive choices for women, approximately half of all pregnancies are unintended and at least half of those are unwanted. Such statistics suggest that there is still a gap in contraceptive options for couples, particularly effective reversible contraceptives for men, who have few contraceptive choices. Male hormonal contraception has been an active area of research for almost 50years. The fundamental concept involves the use of exogenous hormones to suppress endogenous production of gonadotropins, testosterone, and downstream spermatogenesis. Testosterone-alone regimens are effective in many men but high dosing requirements and sub-optimal gonadotropin suppression in 10-30% of men limit their use. A number of novel combinations of testosterone and progestins have been shown to be more efficacious but still require further refinement in delivery systems and a clearer understanding of the potential short- and long-term side effects. Recently, synthetic androgens with both androgenic and progestogenic activity have been developed. These agents have the potential to be single-agent male hormonal contraceptives. Early studies of these compounds are encouraging and there is reason for optimism that these may provide safe, reversible, and reliable contraception for men in the near future.

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Despite the variety of available female contraceptive methods, many pregnancies (~50%) are still undesired. Many men (>60%) want to participate equally with their partner in family planning; however, male contraceptive methods (MCMs) account for only 14% of those used worldwide and no pharmaceutical MCM is available so far. The only two MCMs currently available are condoms, which despite protecting against sexually transmitted diseases have high failure rates (~19%), and vasectomy, which though very efficient (99%) is poorly reversible (<50%). Among MCMs under investigation, male hormonal contraceptives (MHCs) are those that have come closest to commercialization. The action of MHCs relies on the disruption of spermatogenesis that exogenous androgen administration evokes by suppressing the hypophyseal-gonadal axis. Various regimens of androgens as monotherapy or in combination with progestins have been tested in clinical trials achieving a Pearl Index <1.0 (equal to that of the female oral contraceptive pill); however, concerns regarding the variable response rates observed (non-responders: 5-20%), the impracticality of parenteral administration and long-term prostate-associated or cardiovascular morbidity have deflected the interest of the pharmaceutical industry from further research. Non-hormonal contraception methods may be, at least theoretically, more specific by selectively disrupting spermatogenesis and sperm transport or fertilizing ability. Nevertheless, only a few have been tested in clinical trials (Reversible Inhibition of Sperm Under Guidance, RISUG, and Intra Vas Plugs); most of them are still in pre-clinical development or have been abandoned due to toxicity (gossypol). Consequently, until a reliable, safe and practical MCM is developed, women will continue to bear most of the contraception burden.

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The development of a "male pill" to control fertility is still a major challenge. Although women have several options to play an active role in the couple family planning, men are very limited in terms of contraceptive methods. Several approaches have been proposed to develop a male contraceptive and can be divided in two major groups: hormonal and non-hormonal methods. Within the testis, the somatic Sertoli cell (SC) is known as the "nurse cell" since it provides the physical and nutritional support for the developing germ cells. Moreover, adjacent SCs form the Sertoli/blood testis barrier (BTB), which divides the seminiferous epithelium into the basal and the apical compartments, controlling the passage of substances to the site where germ cells develop. Among the several functions of SC, its metabolism and the production of lactate, acetate and other metabolic factors are essential for the normal occurrence of spermatogenesis. In the last years, several works have highlighted that the metabolic cooperation established between SCs and developing germ cells is compromised in several diseases associated with male subfertility/infertility. Notably, several metabolismassociated proteins are specifically expressed in the testis. Thus, there are several evidences illustrating that the control of male fertility can be achieved by targeting testicular cells metabolism. Herein, we discuss the metabolic cooperation in testis as a potential pharmacological target to counteract subfertility/infertility promoted by several diseases, particularly metabolic diseases. We also discuss how it can contribute to the development of a male contraceptive.

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The spermatogenesis is a precisely-timed cellular proliferation that takes place in the seminiferous tubules of testes and is meticulously regulated by gonadotrophins, androgens and temperature. Hormonal, nonhormonal and thermal methods of male contraception have been researched with success; though a clinically viable method is yet to evolve. Testicular sperm lack motility and fertilizing ability, which they gain during their transit through the long epididymal conduit whose distal end serves as a store house of mature sperm in a quiescent state, ready for ejaculation during coitus. Epididymal maturation has been a target for male contraceptive research to avert interruptions of fundamental testicular functions like spermatogenesis and steroidogenesis. However, several experimental successes have not yet yielded a practicable method of fertility regulation. Coitus culminates in the propulsion of epididymal sperm within seconds through the vas deferens into the female vagina and marks the initiation of sperm motility, a vigorous physical activity that is crucial for fertilization. Highly motile spermatozoa have a brief stay in the vagina before starting their ascent in the female reproductive tract. Vaginal spermatozoa have been targeted for contraception since ages. Spermicides and sperm immobilizers inactivate sperm immediately on deposition in the vagina, while they are placed in a rather 'ex-vivo' condition outside the body. Their need based usage, minimal systemic involvement; easy application, self-controlled reversibility and potential capability to obliterate sexually transmitted infections add significant value to contraception. We have reviewed here our recent endeavors in this important area of chemical contraception by using designed chemical synthesis approach to inhibit spermatozoa and infection.

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The general interest in the availability of male contraceptives is on the increase across different cultures and ethnic backgrounds, due in part to the fact that men are now willing more than ever, to share the responsibility of family planning. Despite the expression of interest and tremendous advances in research however, a modern male hormonal contraceptive method has remained an elusive goal. Testosterone (T) alone, or in combination with a progestin currently provides the most promising lead to male hormonal contraception. The principle relies on enhanced negative feedback of exogenous T to suppress gonadotropins, thereby blocking the endocrine stimulus for the process of spermatogenesis. A serious drawback is the inconsistent suppression among men of different ethnic backgrounds. This has increased the quest for development to include other nonhormonal methods. In reality many obstacles still have to be overcome before an acceptable method is available. In this review, we highlight recent developments in male hormonal contraceptives methods. Based on our recent findings from animal experiment, we shed light on why the method is not achieving the intended results, and suggest possible ways forward.

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Population growth in the last century has raised important social and economic questions. Thus, current methods of fertility control have been under debate for a long period. Birth rates are essentially dependent on several environmental and social factors but women, who are great users of contraceptives, play a major role. Regulation of male fertility has been widely studied in recent years with the aim of developing a new male contraceptive for further inclusion of men's choice in family planning. Based on the ancient people techniques to control the birth rates, natural products appeared as a promising source for the development of a male contraceptive. Over the years, many plants and their main constituents have been studied in the search for their antifertility properties. Interestingly, some antispermatogenic effects have been reported. Herein, we will discuss the antispermatogenic properties of some natural products. We propose to discuss specific targets and sites of action of the selected natural products. Despite the advances in this field in the last years, the molecular mechanisms by which natural products can control fertility, need to be disclosed to develop an effective, reversible and safe male contraceptive and avoid undesired toxicity in other organs. To date, no natural-based male contraceptive is available in the commercial market, mostly due to the difficulty in reversing the effects of these products in male fertility.

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Current contraceptive options available to men include withdrawal, condoms, and vasectomy, each of which has its own drawbacks. In this chapter we will describe the pros and cons for each, as well as methodological and product updates. Statistics from the U.S. Centers for Disease Control on acceptance and satisfaction will be included. Advances in vasectomy and reversal will be presented. Methods to develop new contraceptive technologies fall into two categories: hormonal and non-hormonal. Many targets and strategies have been proposed for non-hormonal male contraception within the testis. Targets include structural components in the testis, as well as enzymes, ion channels and other proteins specific to spermatozoa. Here we provide an overview of the spermatogenic mechanisms and proteins that have received research interest to date. We also discuss potential novel targets, such as ubiquitin specific proteases, that warrant greater research emphasis.

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Petroleum ether, benzene and alcohol extracts of the seeds of Momordica charantia tested in rats at the dose level of 25 mg/100 g body weight for 35 days showed antispermatogenic activity as the number of spermatocytes, spermatids and spermatozoa was decreased. Increase in cholesterol level and Sudanophilic lipid accumulation indicates inhibition in the steroidogenesis. At the same time the weight of epididymis, prostate gland, seminal vesicle and levator ani was increased which showed its androgenic property. Out of the three extracts, the alcohol extract was more potent in its antispermatogenic, antisteroidogenic and androgenic activities.

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