Effective Male Contraceptives Research Articles

Emerging approaches to male contraception.

Currently, approximately half of all pregnancies worldwide are unintended. Contraceptive use significantly reduces the risk of unintended pregnancy; however, options for men are particularly limited. Consequently, efforts are underway to develop novel, safe, and effective male contraceptives. This review discusses research into emerging male contraceptive methods that either inhibit sperm production or impair sperm function. It focuses on those in the preclinical or early clinical stages of development.

Factors affect the vasectomy uptake of married couples in Bangka Belitung Islands, Indonesia

Vasectomy is a highly effective male contraception. However, the 2007 to 2017 Indonesia Demographic and Health Surveys reported no vasectomy cases in Bangka Belitung Islands. This study aimed to identify the number and its barriers to low vasectomy use in the Bangka Belitung Islands. The combination of qualitative and quantitative methods used in this study. This study utilized health clinics’ reports between 2015 and 2018 to identify whether or not vasectomy was executed in Bangka Belitung Islands. In-depth interviews were also carried out for medical practitioners, husbands, and wives to point out other crucial purposes of low vasectomy cases in the area. Vasectomy is regarded as a sexual displeasure contraceptive method. Those husbands had perceptions that vasectomy was similar to castration. They consider it as a sickening procedure. The wives perceived that vasectomy could make their husbands promiscuous. The misconceptions and stigma had been found as barriers for the low practice of vasectomy in the Islands. Reproductive health counseling for both husbands and wives need to be intensified to clarify those misconceptions about vasectomy. Vasectomy-specified campaign messages through various media channels should be conducted for couples in the area.

Role of zonadhesin during sperm–egg interaction: a species-specific acrosomal molecule with multiple functions

Sperm-zona adhesion is an essential event in mammalian fertilization, failure of which causes sterility. However, the molecular mechanisms involved in this process are still poorly understood. It has been suggested by few laboratories studying gamete interaction that acrosomal molecules are implicated in sperm-zona pellucida adhesion prior to the acrosome reaction (AR). Zonadhesin, a sperm-specific protein located in the acrosome is critically involved in zona binding. Here we describe the cellular and molecular interaction of zonadhesin during fertilization and also discuss its role in species-specific gamete interaction--an intriguing question in biology. We propose a model in which sperm could transiently expose acrosomal molecules that adhere to the zona independently of the AR in a 'kiss and run' mechanism. This could be a valuable framework for further investigations and a detailed understanding of the molecular events during gamete adhesion is likely to provide new approaches for the design of more effective male contraceptives and better diagnostic methods for sperm dysfunction.

Differential Proteomics of Sperm: Insights, Challenges and Future Prospects

Male factors account for 40% of infertility cases and most are caused by low sperm count, poor sperm quality or both. Defects in sperm are directly linked to reproductive malfunctions, and these defects may be caused by genetic mutations, environmental factors and exposure to free radicals, for example. Almost half of the male infertility cases have no known cause, indicating the lack of sensitive tests for the diagnosis of infertility. Proteomics has evolved as a major research field in biology and medicine, to identify and validate potent targets, at the molecular level, for development of more sensitive diagnostic tools. The recent advances in this field focus on the identification of differentially expressed proteins and analyzing their functional aspects for better understanding of the biological pathways. It not only provides a platform to discover biomarkers of infertility, but may also help in the design of effective male contraceptives. This article discusses various insights of proteomics for exploring biomarkers of male infertility in sperm. It also discusses the enhanced understanding of reproductive physiology offered by data produced by proteomic studies of spermatozoa.

Body Fat Content and Testosterone Pharmacokinetics Determine Gonadotropin Suppression After Intramuscular Injections of Testosterone Preparations in Normal Men

Interindividual differences in gonadotropin suppression achieved by short- and long-acting intramuscular testosterone (T) preparations were studied to detect factors hindering complete suppression of gonadotropins as the prerequisites for effective male contraception. Forty healthy men received a single injection of T propionate; 4 weeks later they received 2 injections of 1000 mg of T undecanoate (TU) given 6 weeks apart. Following TU, declines of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels were consistent in 17.5% and almost absent in 25% of men. Men showing the most rapid and consistent declines in LH and FSH levels received a slightly higher dose per body weight of TU (13.1 +/- 0.6 vs 11.3 +/- 0.6 mg/kg; P = NS) and reached higher maximal concentrations of total T (40 +/- 4.8 vs 18.4 +/- 2.4 nmol/L; P < .001) and free T as well as estradiol. Men with high fat mass (mean +/- SEM, 10.3 +/- 1.5 vs 23.2 +/- 6.4 kg) had a delayed increase in T levels and an impaired relative decline in LH (12 +/- 2% vs 53 +/- 10%) and FSH (17 +/- 6%. vs 70 +/- 25%) levels within the first 2 weeks after the first TU injection. We conclude that overweight reduces the chance of rapid and profound gonadotropin suppression during treatment with TU. Body weight needs to be considered to avoid failure of hormonal male contraception.

Germ Cell Research: A Personal Perspective

My interest in germ cells began when I first witnessed sea urchin fertilization and embryo development during a laboratory class at Hokkaido University, Sapporo, Japan, almost 60 yr ago. Weismann's concept of germ cells that I learned during my undergraduate years became the driving force of my entire research career. During the early years, my associates and I used mainly the golden hamster and the guinea pig as model animals because their spermatozoa had large acrosomes and we could readily follow changes in the acrosomes without killing or staining spermatozoa. We later used the mouse as our model organism because we wanted to produce live offspring with known genetic backgrounds. A summary of the findings we made during those years includes the following: (1) first in vitro sperm capacitation; (2) discovery of sperm hyperactivation; (3) demonstration of the importance of Ca(2+) in sperm acrosome reaction, hyperactivation, sperm-egg fusion, and egg activation; (4) development of the sperm's fusion competence during the acrosome reaction; (5) characterization of sperm-oviduct relationships before and during fertilization; (6) use of zona-free hamster eggs to examine fertilizing ability and chromosomes of human spermatozoa; (7) development and use of intracytoplasmic sperm injection; (8) use of prespermatozoal cells for the production of offspring; (9) sperm preservation by freeze-drying and freezing whole-animal bodies; and (10) mouse cloning by somatic cell nuclear transfer. My current interests and my visions for the future include the following: (1) mass production of mature eggs and spermatozoa in vitro, (2) permanent sperm preservation at ambient temperature, (3) development of safer and more efficient assisted fertilization (reproduction) technologies, (4) development of safe and efficient methods of cloning, (5) production of artificial organs such as an artificial uterus, (6) development of safe and effective male contraceptives, and (7) prevention of cancer through germ cell research.

The low gonadotropin-independent constitutive production of testicular testosterone is sufficient to maintain spermatogenesis.

Spermatogenesis is thought to critically depend on the high intratesticular testosterone (T) levels induced by gonadotropic hormones. Strategies for hormonal male contraception are based on disruption of this regulatory mechanism through blockage of gonadotropin secretion. Although exogenous T or T plus progestin treatments efficiently block gonadotropin secretion and suppress testicular T production, only approximately 60% of treated Caucasian men reach contraceptive azoospermia. We now report that in luteinizing hormone receptor knockout mice, qualitatively full spermatogenesis, up to elongated spermatids of late stages 13-16, is achieved at the age of 12 months, despite absent luteinizing hormone action and very low intratesticular T (2% of control level). However, postmeiotic spermiogenesis was blocked by the antiandrogen flutamide, indicating a crucial role of the residual low testicular T level in this process. The persistent follicle-stimulating hormone action in luteinizing hormone receptor knockout mice apparently stimulates spermatogenesis up to postmeiotic round spermatids, as observed in gonadotropin-deficient rodent models on follicle-stimulating hormone supplementation. The finding that spermatogenesis is possible without a luteinizing hormone-stimulated high level of intratesticular T contradicts the current dogma. Extrapolated to humans, it may indicate that only total abolition of testicular androgen action will result in consistent azoospermia, which is necessary for effective male contraception.

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Male contraception--a review.

This review of male contraception provides a basis for understanding the main methods of contraception as well as which methods are more effective than others. An effective male contraceptive must be safe reversible rapid in action acceptable to the user and without adverse consequences on sexual potency or libido. There are many points along the axis of the reproductive system at which intervention could either reduce or abolish fertility; there are 2 main points at which intervention can be applied--during spermatogenesis and when spermatozoa mature. Inhibition of the normal negative feedback system may be achieved intentionally by means of administration of pharmacological amounts of these compounds; spermatogenesis would consequently be suppressed. Estrogens and progestogens are effective male contraceptives but they tend to depress the circulating testosterone which in turn produces an unacceptable reduction in libido. Other drugs that act at the hypothalamic level are: androgens anabolic steroids estrogens or progestogens with androgens medroxyprogesterone acetate/percutaneous testosterone d-Norgestrel and testosterone enanthate and levo-norgestrel and testosterone enanthate. Some drugs have been found experimentally to reduce spermatogenesis via a mechanism which bypasses the hypothalamus and anterior pituitary gland. However these compounds acting at testicular levels are often toxic to body cells in general and some may even produce genetic defects. Exmaples include: tetramine (TEM) triethylene-phosphoramide (TEPA) and gossypol. Gossypol has been claimed to be 99% effective in producing infertility within 2 to 3 months of commencing therapy; however gastrointestinal symptoms skin rashes and fatigue are undesirable side effects that have been reported. Drugs impairing sperm maturation such as chlorohydrin chlorinated sugars and antiandrogens affect the already formed and stored spermatozoa and should be able to produce infertility within as little as a few days. Drugs which are analogues of gonadotrophin releasing hormones immunological control of fertility vasectomy spermicidal agents and the sheath are 5 other types of male contraceptives discussed. Because of the side effects often associated with all types of male contraceptives whatever the future reveals it is generally agreed that it will be many years before a satisfactory male contraceptive can be available.