Decline In Male Reproductive Health Research Articles

Unraveling the anti-androgenic mechanism of tris(2,3-dibromopropyl) isocyanurate (TBC) via the non-classical testosterone pathway and steroidogenesis: potential human reproductive health implications

The decline in male reproductive health, characterized by diminishing sperm count and testosterone levels, has raised concerns about environmental influences, particularly endocrine-disrupting chemicals (EDCs). Tris(2,3-dibromopropyl)isocyanurate (TBC), a novel brominated flame retardant widely used in electronics, textiles, and furniture, has emerged as a significant environmental contaminant with potential reproductive health implications. In this study, we investigated the molecular mechanisms underlying TBC-induced reproductive toxicity, particularly focusing on its impact on steroidogenesis and androgen signaling pathways using the GC-1 spg cell line as an in vitro model.Exposure of GC-1 spg cells to TBC, alone or in combination with testosterone or the anti-androgen flutamide resulted in decreased metabolic activity and increased lactate dehydrogenase release, indicating cytotoxic effects. Furthermore, TBC exposure led to a reduction in progesterone synthesis, while testosterone production remained unaffected. Interestingly, estradiol synthesis was diminished after TBC exposure, suggesting a disruption in steroid hormone balance critical for spermatogenesis. Mechanistic investigations revealed alterations in key proteins involved in the non-classical testosterone pathway and steroidogenesis. TBC exposure downregulated epidermal growth factor receptor (EGFR), protein kinase B (AKT), and phosphorylated cyclic AMP response element-binding protein (p-CREB), indicating suppression of non-classical androgen signaling. Additionally, decreased levels of steroidogenic acute regulatory protein (StAR) and 3-beta-hydroxysteroid dehydrogenase (HSD3β1) suggest impaired steroidogenesis. Here we uncover the intricate molecular mechanisms underlying TBC-induced reproductive toxicity, highlighting its potential to disrupt steroid hormone synthesis and androgen signaling pathways. Understanding the adverse effects of TBC on male reproductive health is crucial for developing strategies to mitigate its environmental impact and safeguard human fertility.

Dietary trends and the decline in male reproductive health.

Over the twentieth century, male reproductive health has suffered a substantial decline, as evidenced by decreases in sperm counts and testosterone levels and increases in reproductive pathologies. At the same time, the prevalence of chronic diseases such as obesity, diabetes, and metabolic syndrome has risen dramatically. Metabolic and reproductive health are highly interconnected, suggesting that their respective trends are intertwined and, given the timeframe of such trends, environmental and not genetic factors are most likely to be the primary causes. Industrialization, which began in Europe in the mid-eighteenth century, has resulted in profound changes to our diet, lifestyle, and environment, many of which are causal factors in the rise in chronic diseases. Industrialization results in a nutrition transition from an agricultural unprocessed to a modern processed diet, incorporating increases in sugar, vegetable oils, ultra-processed foods, linoleic acid, trans-fats, and total energy. This dietary shift has incurred numerous adverse effects on metabolic and reproductive health, characterized by chronic inflammation, oxidative stress, and insulin resistance. Moreover, these effects appear to multiply across subsequent generations via epigenetic inheritance. Men's fertility is markedly affected by obesity and diabetes, with an increase in total energy via processed food intake arguably being the key factor driving the diabesity pandemic. In contrast, wholefoods rich in micronutrients and phytonutrients support male fertility and a healthy body weight. Therefore, men wanting to maximize their fertility should consider making positive dietary changes, such as replacing processed foods with unprocessed foods that support metabolic and reproductive health.

A review of medicinal herbs in the management of male infertility

Male infertility can be caused by a variety of factors, including neurohormonal imbalances, reproductive tissue disturbances, and qualitative and quantitative degradation of semen. There is a global decline in male reproductive health, and modern therapeutic options to tackle male infertility are expensive, less accessible and have extended treatment durations and adverse effects. When it comes to male reproductive health, herbal therapies are in a much better position to provide more holistic approaches. As aphrodisiacs, a unique class of herbs defined in herbal pharmacology, nourish and stimulate the body's sexual tissues. A careful evaluation of the current information on drugs and their probable functions in treating male infertility is the purpose of this paper.

P–006 Simultaneous determination of bisphenol A and S in the samples of human seminal fluid

Abstract Study question Can we quantitatively determine concentrations of endocrine disruptors namely bisphenol A and S in seminal fluid? Summary answer We developed selective analytical method to simultaneously screen for the presence of bisphenol A (BPA) and S (BPS). What is known already The male reproductive system involves processes, which may be influenced by the disruption of the endocrine system by chemicals called endocrine disruptors (EDs). There is a growing evidence that EDs such as bisphenol A and S may be responsible for the decline in male reproductive health. To date, the claimed adverse effects on male fertility are largely based on the results from studies assessing the relationship between urinary BPA and BPS concentration and semen parameters. The best evidence of an adverse effect of BPA and BPS directly on spermatozoa could be provided by measuring bisphenols concentration directly in seminal fluid. Study design, size, duration To selectively and quantitatively analyzed bisphenols in any biological matrix advanced analytical tools and selective sample preparation protocols must be employed. In this study we developed targeted analytical method based on liquid chromatography tandem mass (LC-MS/MS) detection to measure bisphenol A and S in seminal fluid samples obtained from IVF clinic. A total of 140 samples were analysed. Participants/materials, setting, methods BPA and BPS was extracted from 140 seminal fluid samples using solvent extraction followed by preconcentration step. Samples were analyzed on Agilent 6495 Triple Quadrupole (Agilent Technologies, Santa Clara, CA) operating in the ESI-negative mode. Two MS/MS transitions were used for quantitative LC-MS/MS analyses. Chromatographic separation was achieved on Waters™ ACQUITY™ UPLC™BEH C18 (100 × 2.1 mm, 1.7 µm) column using gradient elution with a mixture of 0.1mM ammonium fluoride and methanol as mobile phases. Main results and the role of chance We developed selective sample preparation method for detection of BPA and BPS in seminal fluid followed by LC-MS/MS detection. The method validation was performed based on FDA guidelines. Validation criteria included limit of detection (LOD), limit of quantitation (LOQ), accuracy and precision. Due to the lack of the certified reference material the validation criteria of the method were assessed in pool of spiked seminal samples. The accuracy of the LC-MS/MS method was evaluated as a percent recovery of the amount of target analyte added into the sample. Recovery rates were above 80% for both analytes. LOD was 0.04 ng/mL for BPA and 0.01 ng/mL for BPS. LOQ was 0.14 ng/mL and 0.02 ng/mL for BPS. Measured BPA concentration ranged from 0.04 ng/mL to 1.62 ng/mL. For BPS, the concentration ranged from 0.01 ng/mL to 0.47 ng/mL. BPA and BPS were detected in 64% and 81% of samples, respectively. Interestingly, BPA showed lower detection frequency compared to BPS. These results are consistent with other studies performed on urine samples. Limitations, reasons for caution The limitation of the developed method is the time-consuming sample preparation and analysis cost. Wider implications of the findings: These results document for the first time the presence of BPS in seminal fluid. Knowing the concentration of BPA and BPS in seminal fluid is crucial for mitigating the associated health risks and initiating intervention and prevention strategies. Our future work will evaluate the influence of BPS concentration on spermatozoa. Trial registration number AZV NV18–01–00544; CZ.02.2.69/0.0/0.0/19_074/0012727

Morphological and transcriptomic alterations in neonatal lamb testes following developmental exposure to low-level environmental chemical mixture

Exposure to anthropogenic environmental chemical mixtures could be contributing to the decline in male reproductive health. This study used the biosolid treated pasture (BTP) sheep model to assess the effects of exposure to low-dose chemical mixtures. Maternal BTP exposure was associated with lower plasma testosterone concentrations, a greater proportion of Sertoli cell-only seminiferous tubules, and fewer gonocytes in the testes of neonatal offspring. Transcriptome analysis highlighted changes in testicular mTOR signalling, including lower expression of two mTOR complex components. Transcriptomic hierarchical analysis relative to the phenotypic severity demonstrated distinct differential responses to maternal BTP exposure during pregnancy. Transcriptome analysis between phenotypically normal and abnormal BTP lambs demonstrated separate responses within the cAMP and PI3K signalling pathways towards CREB. Together, the results provide a potential mechanistic explanation for adverse effects. Exposure could lower gonocyte numbers through mTOR mediated autophagy, but CREB mediated survival factors may act to increase germ cell survival.

'Man Up': the importance and strategy for placing male reproductive health centre stage in the political and research agenda.

Approximately 1 in 20 young men today have sperm counts low enough to impair fertility, whereas this may not have been the case historically. The cause(s) of such a decline in male reproductive health is unknown, despite it being a global health issue. Concomitantly, little progress has been made in answering fundamental questions in andrology or in developing new diagnostic tools or alternative management strategies to ICSI in infertile men. We advocate formulation of a detailed roadmap for male reproductive health to facilitate development of a research agenda that highlights the present unmet needs and key unanswered questions, and seeks to deliver effective funding and investment to address them. This vision we term ‘a Male Reproductive Health Ecosystem’.

Sirtuins: Novel Players in Male Reproductive Health.

The current lifestyle of "western societies" is based on excessive consumption of high-energy diets and physical inactivity. Such behavior has pressured biological systems towards the development of metabolic diseases. This increased incidence of metabolic disorders is also accompanied by a decline in male reproductive health, particularly among young males. Male fertility is sensitive to metabolic dysfunctions, such as diabetes mellitus, which disrupt the link between energy metabolism and reproduction. Evidences showed that compromised sperm parameters induced by diabetes are associated with impaired testicular metabolism, suggesting that deficient testicular bioenergetics contributes to a decline in spermatogenesis. Energy metabolism is a well-coordinated process that involves a network of carbohydrate, lipid and protein metabolic pathways. This intricate process is an act of balance between mitochondria and nucleus, governed by metabolic sensors, such as sirtuins. The emerging role of sirtuins in the control of metabolism has been highlighted, specially in cancer metabolism. Little attention has been given to their role in non-cancerous cells that exhibit a "Warburg-like metabolism", such as Sertoli cells. Spermatogenesis is highly dependent on glycolytic metabolism, since the lactate produced by Sertoli cells is the major substrate of germ cells. The regulation of sirtuins in the glycolytic metabolism not only increases their physiological relevance to the testicular environment, but also suggests that these proteins may control male fertility. This review will discuss the recent findings in the role of sirtuins in testicular metabolism and will address the concept that sirtuins can be a potential target to counteract subfertility/infertility promoted by diabetes mellitus.

Population Based Nationwide Study of Hypospadias in Sweden, 1973 to 2009: Incidence and Risk Factors

We studied the incidence of hypospadias in Sweden during a 40-year period to determine if changes were associated with known risk factors. We analyzed prospective data from nationwide health care and demographic registers collected for all males (1,948,591 total) born in Sweden between 1973 and 2009. The incidence of hypospadias per 1,000 live-born boys was calculated as number of cases divided by total number of births yearly. The association between hypospadias and risk factors was estimated using logistic regression, expressed as odds ratios. The nationwide incidence of boys diagnosed with hypospadias was approximately 4.5 per 1,000 live-born boys until 1990, increasing to 8 per 1,000 boys during the following decade. Mild and severe phenotypes comprised the increase. Boys born small for gestational age (OR 4.34), as a twin (OR 1.8), as a result of in vitro fertilization (OR 1.15), or with parents from Asia (OR 1.45) or continental Europe (OR 1.41) were at increased risk for hypospadias. Multivariate analyses revealed that changes in risk factors did not explain the increased incidence. However, a systematic change in the classification of the diagnosis in registers could not be ruled out. This nationwide study demonstrates an increased incidence of hypospadias diagnoses in Sweden from 1990 to 1999 that is not attributable to previously known risk factors. The increase includes mild and severe phenotypes, suggesting that shifts in the diagnostic criteria are not the underlying cause.

A Unique Combination of Male Germ Cell miRNAs Coordinates Gonocyte Differentiation

The last 100 years have seen a concerning decline in male reproductive health associated with decreased sperm production, sperm function and male fertility. Concomitantly, the incidence of defects in reproductive development, such as undescended testes, hypospadias and testicular cancer has increased. Indeed testicular cancer is now recognised as the most common malignancy in young men. Such cancers develop from the pre-invasive lesion Carcinoma in Situ (CIS), a dysfunctional precursor germ cell or gonocyte which has failed to successfully differentiate into a spermatogonium. It is therefore essential to understand the cellular transition from gonocytes to spermatogonia, in order to gain a better understanding of the aetiology of testicular germ cell tumours. MicroRNA (miRNA) are important regulators of gene expression in differentiation and development and thus highly likely to play a role in the differentiation of gonocytes. In this study we have examined the miRNA profiles of highly enriched populations of gonocytes and spermatogonia, using microarray technology. We identified seven differentially expressed miRNAs between gonocytes and spermatogonia (down-regulated: miR-293, 291a-5p, 290-5p and 294*, up-regulated: miR-136, 743a and 463*). Target prediction software identified many potential targets of several differentially expressed miRNA implicated in germ cell development, including members of the PTEN, and Wnt signalling pathways. These targets converge on the key downstream cell cycle regulator Cyclin D1, indicating that a unique combination of male germ cell miRNAs coordinate the differentiation and maintenance of pluripotency in germ cells.

Widely Used Pesticides with Previously Unknown Endocrine Activity Revealed as in Vitro Antiandrogens

BackgroundEvidence suggests that there is widespread decline in male reproductive health and that antiandrogenic pollutants may play a significant role. There is also a clear disparity between pesticide exposure and data on endocrine disruption, with most of the published literature focused on pesticides that are no longer registered for use in developed countries.ObjectiveWe used estimated human exposure data to select pesticides to test for antiandrogenic activity, focusing on highest use pesticides.MethodsWe used European databases to select 134 candidate pesticides based on highest exposure, followed by a filtering step according to known or predicted receptor-mediated antiandrogenic potency, based on a previously published quantitative structure–activity relationship (QSAR) model. In total, 37 pesticides were tested for in vitro androgen receptor (AR) antagonism. Of these, 14 were previously reported to be AR antagonists (“active”), 4 were predicted AR antagonists using the QSAR, 6 were predicted to not be AR antagonists (“inactive”), and 13 had unknown activity, which were “out of domain” and therefore could not be classified with the QSAR (“unknown”).ResultsAll 14 pesticides with previous evidence of AR antagonism were confirmed as antiandrogenic in our assay, and 9 previously untested pesticides were identified as antiandrogenic (dimethomorph, fenhexamid, quinoxyfen, cyprodinil, λ-cyhalothrin, pyrimethanil, fludioxonil, azinphos-methyl, pirimiphos-methyl). In addition, we classified 7 compounds as androgenic.ConclusionsDue to estimated antiandrogenic potency, current use, estimated exposure, and lack of previous data, we strongly recommend that dimethomorph, fludioxonil, fenhexamid, imazalil, ortho-phenylphenol, and pirimiphos-methyl be tested for antiandrogenic effects in vivo. The lack of human biomonitoring data for environmentally relevant pesticides presents a barrier to current risk assessment of pesticides on humans.

Effect of honey on testicular functions in rats exposed to cigarette smoke

Summary Honey is traditionally consumed by the local Malaysian population as a nutrient, as well as for the enhancement of fertility. The decline in male reproductive health and fertility in the last 30 years has been linked to environmental toxicants including cigarette smoke (CS). In human and experimental studies, CS exposure has been associated with decreased plasma testosterone level, lower sperm count and increased percentage of abnormal sperm. The aim of this study, therefore, was to determine the possible protective role of honey against the toxic effects of CS on testicular functions in rats. Thirty-two adult Sprague-Dawley rats were randomly divided into 4 groups (8 rats per group) i.e. control group, honey-treated group (H), cigarette smoke-exposed group (CS) and honey-treated plus CS-exposed group (H+CS). Rats in control and CS groups received oral administration of distilled water daily while rats in H and H+CS groups received honey (1.2 g/kg body weight) orally by gavage daily. Rats in CS and H+CS groups were also exposed to CS for 8 min (3 times/day). After 13 weeks of treatment, each rat was sacrificed for reproductive parameters analysis. Rats in CS group had significantly lower sperm count, daily sperm production, percentage of motile sperm and testosterone level as well as a higher percentage of abnormal sperm compared to control and H groups. However, supplementation of honey significantly improved all these parameters in H+CS group. Administration of honey significantly attenuated the toxic effects of CS on spermatogenesis and testosterone level in rats. This study suggests that honey might have a protective effect against CS-induced impaired testicular functions in rats.

Review: Environmental endocrine disruptors of testicular function

In the last 50 years the incidence of infertility, testicular and prostate cancers and associated maladies has increased significantly. Infertility now affects 15-20% of couples as opposed to 7-8% fifty years ago. Average sperm counts among adult men have decreased by 50% since 1938, with a decline of 2% every year from 1973. This decline in male reproductive health has been linked to an increased presence in the environment of chemical contaminants in the form of pesticides and plastics. Rapid and unplanned industrialization caused large amounts of these synthetic compounds and their by-products to be released in the environment (air, soil, water and food). studies have shown that occupational exposure to pesticides caused neonatal deaths, congenital defects, testicular dysfunction and male infertility. Many of these chemicals found in our environment and households have oestrogenic properties (“xenoestrogens”) and are toxic because they affect the endocrine system (“endocrine disruptors”). Evidence of the health hazards of endocrine disrupting chemicals continues to mount. In terms of male fertility, it now seems that these ubiquitous chemicals are a significant threat at various stages, from testicular development to sperm production to the functionality of healthy sperm. This class of chemicals appears to be threatening male fertility on several fronts. That endocrine disruptors abound in our environment is not in doubt. Clinicians and other health practitioners confronted with the challenges of managing male infertility should attempt to identify the aetiology of a possible exposure to endocrine disruptors, and initiate a plan to control and prevent exposure to others. In addition, concerted efforts should be made by both government and non-governmental agencies to institute local studies that will assess local endocrine disruptors, degree of contamination, level of exposure and proffer control and preventive measures. Emphasis should be placed on establishment of chemical screening and testing program, research into dose and vulnerable periods, institution of surveillance of disease incidence, improvement of exposure monitoring, and educating community leaders and the public in general. Keywords: Endocrine disrupt ors, testis, testosterone, environment, infertility, peticides.

Declining Sperm Counts and Increases in Testicular Cancer: A Legacy of the Cold War?

To the Editor: In stark contrast to impressive gains in health and longevity in industrialized countries, male reproductive health appears to be in decline (Sharpe and Skakkebæk, 2003; Skakkebæk et al, 2006). This is believed to be because of early, primarily prenatal exposure to environmental endocrine disruptors. In particular, estrogenic compounds are a likely underlying cause of these declines in sperm count and increased incidence of testicular cancer (Sharpe and Skakkebæk, 2003). I would like to propose that exposure to radioactive fallout generated by testing nuclear weapons represents another potential mechanism of the decline in male reproductive health. The arms race after World War II involved atmospheric testing of nuclear weapons in desert regions of the United States, the Soviet Union, and Africa that introduced massive amounts of radioactive compounds into the upper layer of the atmosphere. This material was gradually distributed over the entire Northern Hemisphere, with gravity sedimentation and rains leading to its removal and deposition on the soil and vegetation. Most of the radioactive material that was widely deposited was strontium 90 (90Sr), a high-energy beta emitter with a half-life of nearly 29 years, which readily enters the food chain and becomes deposited in bone. Although the resulting exposure of the general population to radiation was below the levels known to be toxic or mutagenic, I suggest that exposure to these low doses, especially during embryonic and fetal development, may have impacted adult testicular function and cancer risk. In the context of this hypothesis, it is of interest that the particularly striking reductions in sperm count and increases in the incidence of testicular cancer were reported from Denmark and other northern European countries, where relatively rainy weather is conducive to removal of solid particles from the atmosphere, and a dairy industry creates favorable conditions for the transfer of 90Sr from radioactive fallout via vegetation, cows, and milk to humans. However, other etiological factors may have also been involved, because incidence of testicular cancer in Denmark increased before the period of intensive testing of nuclear weapons (Moller, 1993). From the available information, it is difficult and perhaps impossible to know what stages of male development are most vulnerable to the exposure to low radiation doses and whether mutagenic or epigenetic effects in women and transgenerational effects of radiation could have also been involved (Barber et al, 2002). Men who are currently diagnosed with reduced sperm count and/or quality or develop testicular cancer include children of individuals who have been exposed in utero to the radioactive fallout and grandchildren of individuals who were exposed as adults. It is hoped that the hypothesis proposed in this letter may encourage novel directions of research. Sincere thanks to Dr Serge Volovik for his assistance and most helpful discussions.

Endocrine disruptors and estrogenic effects on male reproductive axis

Endocrine disruptors (e.g., polychlorinated biphenyls [PCBs], dichlorodiphenyl-trichloroethane [DDT], dioxin, and some pesticides) are estrogen-like and anti-androgenic chemicals in the environment. They mimic natural hormones, inhibit the action of hormones, or alter the normal regulatory function of the endocrine system and have potential hazardous effects on male reproductive axis causing infertility. Although testicular and prostate cancers, abnormal sexual development, undescended testis, chronic inflammation, Sertoli-cell-only pattern, hypospadias, altered pituitary and thyroid gland functions are also observed, the available data are insufficient to deduce worldwide conclusions. The development of intra-cytoplasmic sperm injection (ICSI) is beyond doubt the most important recent breakthrough in the treatment of male infertility, but it does not necessarily treat the cause and may inadvertently pass on adverse genetic consequences. Many well-controlled clinical studies and basic scientific discoveries in the physiology, biochemistry, and molecular and cellular biology of the male reproductive system have helped in the identification of greater numbers of men with male factor problems. Newer tools for the detection of Y-chromosome deletions have further strengthened the hypothesis that the decline in male reproductive health and fertility may be related to the presence of certain toxic chemicals in the environment. Thus the etiology, diagnosis, and treatment of male factor infertility remain a real challenge. Clinicians should always attempt to identify the etiology of a possible testicular toxicity, assess the degree of risk to the patient being evaluated for infertility, and initiate a plan to control and prevent exposure to others once an association between occupation/toxicant and infertility has been established.

Does Relaxed Reproductive Selection Explain the Decline in Male Reproductive Health? A New Hypothesis

One hypothesis that has been advanced to explain this decline in male reproductive health is that some environmental exposures act as endocrine disruptors. These endocrine-disrupting chemicals are hypothesized to exert antiandrogenic effects on developing male fetuses and children. Although we have no evidence to offer against this hypothesis we offer here an alternative hypothesis for a decline in male reproductive health. Our hypothesis is based on the proposition that until recent times there has been strong natural selection against poor reproductive health but in the past few decades this selective pressure has been relaxed. (authors)

Gonadal function in men with testicular cancer: biological and clinical aspects.

This paper reviews current knowledge about the effect of testicular germ cell cancer (TGCC) on gonadal function and of cancer treatment on spermatogenesis and Leydig cell function. It is well documented that testicular cancer is associated with impaired spermatogenic function and some patients already have impairment of Leydig cell function before orchidectomy. The degree of spermatogenic dysfunction is higher than what can be explained by local tumour effect and by a general cancer effect, since patients with other malignant diseases have normal, or only slightly decreased, semen quality. Furthermore, sperm counts after orchidectomy are further reduced to less than half of the values in healthy men, even in patients cured from the cancer disease after orchidectomy alone. These observations are supported by histological investigations which have shown a high prevalence of abnormalities of spermatogenesis in the contralateral testis in patients with unilateral TGCC. The association between testicular cancer and poor gonadal function is very interesting both from a biological and from a therapeutic point of view. Firstly, the increase in incidence of testicular cancer has been suggested to be associated with a general decline in male reproductive health and it seems likely that the development of TGCC shares common aetiologic factors with development of other types of testicular dysfunction. This suggestion is supported by the observation that men with various types of gonadal dysfunction such as testicular dysgenesis, androgen insensitivity syndrome, and cryptorchidism have increased risk of testicular cancer. Secondly, the general cure rate in patients with testicular cancer exceeds 90% and the quality of life, including fertility aspects, is therefore important in the management of these patients. Spermatogenesis is already so severely impaired before treatment that fertility is lower than in healthy men. Moreover, radiotherapy and chemotherapy both induce dose-dependent impairment of spermatogenesis and recovery of spermatogenesis after treatment may be long lasting even more than five years in some patients. Sufficient androgen production is seen in the majority of the patients, but some patients suffer from testosterone deficiency. The effect of chemotherapy on Leydig cell function also seems to be dose-dependent. In conclusion there is no doubt that testicular cancer is associated with poor gonadal function even before treatment. Furthermore, the treatment of testicular cancer may have a serious impact on the gonadal function in these patients, most of whom are in the reproductive age. Moreover, the epidemiological and clinical data indicate a common aetiology between testicular germ cell cancer and other abnormalities in male reproductive health (such as infertility and cryptorchidism). These observations are in agreement with the suggestions of hormonal involvement in the aetiology of testicular cancer. Generally, men with TGCC need counselling about their reproductive function with respect to semen cryopreservation, chance of recovery of spermatogenesis, fertility, and the possible need for androgen replacement.

Do environmental estrogens contribute to the decline in male reproductive health?

Several observations suggest that male reproductive health has been declining since World War II in many countries. The incidence of testicular cancer, hypospadias, and cryptorchidism has been increasing and semen quality has been decreasing, and these may have a common etiology. Treatment of several million pregnant women with the synthetic estrogen diethylstilbestrol led to an increase in these conditions among the sons of these women. These abnormalities probably arise during fetal development. The similarity between these effects and the adverse change in male reproductive development and function raised the question of whether the adverse changes are attributable to altered exposures to estrogenic and other endocrine-disrupting agents during fetal development. We speculate that alteration in exposure to estrogen in the past half-century may have caused the changes in male reproductive health.