Tag: TDS

EDCs among other health problems generate reproductive disorders in males, such as decreases in sperm count and quality, increases in testicular germ cell numbers, prostate and breast cancers, cryptorchidism and hypospadias, impaired fertility, and infertility.

2017 Abstracts

“The group of known EDCs is extremely heterogeneous and includes different groups of chemicals such as steroids (ethinyl estradiol, 17β-estradiol, estrone, mestranol and diethylstilbenstrol),…”

Testicular dysgenesis syndrome

“Cryptorchidism, hypospadias, poor semen quality, and testicular germ-cell cancers are defined as the testicular dysgenesis syndrome (TDS). They propose that the aetiology of TDS lies in the diminished androgen action in fetal developmental periods and has a negative impact on the proper functioning of Sertoli cells (the cells supporting germ cells) and Lydig cells (where androgen synthesis occurs). This hypothesis proposes a strong association between environmental exposures (e.g., to phthalates, polychlorinated biphenyls (PCBs), dioxins and non-resistant pesticides) and development of TDS. Identifying environmental causes of TDS in humans is difficult because developing fetal tissues are inaccessible for examination. Thus, the majority of mechanistic evidence linking EDCs to TDS comes from animal experiments.”

Cryptorchidism and hypospadias

“Several studies have shown that sons of mothers treated with diethylstilbestrol (DES) during pregnancy are at increased risk of cryptorchidism and hypospadias“.

Decreasing sperm counts and quality

” Several studies have shown that sons of mothers treated with DES during pregnancy are at increased risk of decreased sperm count.”

Testicular cancer

“During recent decades, there has been a significant increase in the incidence of testicular cancer, albeit with clear racial and geographical differences (the highest incidence is among white men in northern Europe) suggesting that both genetic and environmental factors are important in the development of testicular cancer. The main risk factor for testicular cancer is cryptorchidism, followed by hypospadias. Testicular cancer is most common among young men between the ages of 15–34 years. The origins of testicular cancer are elusive; however, many investigators are exploring the possibility that fetal and early-life EDCs exposures can disrupt the critical hormonal balance during development, and in turn contribute to the formation of testicular cancer later in life. It was found that men who have some form of gonadal dysgenesis are more likely to develop testicular cancer in conjunction with other male reproductive abnormalities such as hypospadias and cryptorchidism. The mechanisms behind the development of testicular cancer are still unknown, but both environmental and lifestyle factors have been associated with its development.”

References

• Endocrine-disrupting chemicals and male reproductive health: a review, University of Ljubljana, Slovenia, DOI: 10.6016/ZdravVestn.2456, 2017.
• Featured image allanmanning.

DES DIETHYLSTILBESTROL RESOURCES

• Source DES and testicular cancer studies.
• Diethylstilbestrol DES studies by topics.

Endocrine disruption: fact or urban legend? 2013

Abstract

“A current hypothesis has suggested that, in modern industrial societies, human male fertility is declining, whereas the incidence of diseases or birth defects of the male reproductive system is increasing. The hypothesis that human sperm count is declining whereas the incidence of testicular cancer, cryptorchidism (undescended testis) and hypospadias (abnormally placed urethral opening at the underside of the penis) is increasing and that these changes are associated with human exposure to hormonally active chemicals.

…, this hypothetical syndrome has been named the “Testicular dysgenesis syndrome” (TDS). It postulates that, in Western industrialised countries

• human male fertility, in particular sperm count, has declined and continues to decline,
• the incidence of human testicular cancer is increasing,
• the incidence of cryptorchidism
• and hypospadias in newborn male infants has increased.

An additional hypothesis is that the increased incidence in the TDS may be due to chemical EDC in the human environment.”

References

• Endocrine disruption: fact or urban legend?, Toxicology letters, DOI: 10.1016/j.toxlet.2013.10.022, 2013.
• Featured image techvibes.

DES DIETHYLSTILBESTROL RESOURCES

• Diethylstilbestrol DES studies by topics.

An increasingly common developmental disorder with environmental aspects, 2001

Abstracts

Numerous reports have recently focused on various aspects of adverse trends in male reproductive health, such as the rising incidence of testicular cancer; low and probably declining semen quality; high and possibly increasing frequencies of undescended testis and hypospadias; and an apparently growing demand for assisted reproduction.

Due to specialization in medicine and different ages at presentation of symptoms, reproductive problems used to be analysed separately by various professional groups, e.g. paediatric endocrinologists, urologists, andrologists and oncologists.

This article summarizes existing evidence supporting a new concept that poor semen quality, testis cancer, undescended testis and hypospadias are symptoms of one underlying entity, the testicular dysgenesis syndrome (TDS), which may be increasingly common due to adverse environmental influences.

Experimental and epidemiological studies suggest that TDS is a result of disruption of embryonal programming and gonadal development during fetal life. Therefore, we recommend that future epidemiological studies on trends in male reproductive health should not focus on one symptom only, but be more comprehensive and take all aspects of TDS into account. Otherwise, important biological information may be lost.

Evidence from animal studies and wildlife

There is a wealth of data showing that male animals exposed in utero or perinatally to exogenous oestrogens (diethylstilbo-estrol, ethinyl oestradiol, bisphenol A) and anti-androgens [flutamide, vinclozolin, 1,1-dichloro-2, 2-bis(p-chlorophenyl)ethylene (DDE), 1,1,1-trichloro-2, 2-bis(4-chlorophenyl)ethane(DDT)] develop hypospadias, undescended testis, low sperm counts or, in the worst case, intersex conditions, teratomas and Leydig cell tumours. A recent report provided experimental evidence that ubiquitous phthalates, can also hamper testicular descent in rats when administered prenatally.

References

• Testicular dysgenesis syndrome: an increasingly common developmental disorder with environmental aspects, Endocrinology, Human reproduction (Oxford, England), NCBI PubMed, PMID: 11331648, 2001 May.

DES DIETHYLSTILBESTROL RESOURCES

• Source DES and testicular cancer studies.
• Diethylstilbestrol DES studies by topics.

Possible role of endocrine disrupters, 2006

Abstracts

The testicular dysgenesis syndrome (TDS) hypothesis proposes that the four conditions cryptorchidism, hypospadias, impaired spermatogenesis and testis cancer may all be manifestations of disturbed prenatal testicular development. The TDS hypothesis is based on epidemiological, clinical and molecular studies, all suggestive of an interrelation between the different symptoms. The aetiology of TDS is suspected to be related to genetic and/or environmental factors, including endocrine disrupters.

…Important insight into the effect of in utero exposure to compounds with oestrogenic activity in humans comes from the former widespread use of diethylstilboestrol (DES), a synthetic oestrogen. …
… The effect of DES on sperm concentration and risk of development of testis cancer is unclear, as some studies have found a reduced sperm concentration in men exposed to DES in utero, whereas others have not. For testis cancer, only a slight increase in risk has been cautiously suggested (1996), (2001). …

Few human studies have found associations/correlations between endocrine disrupters, including phthalates, and the different TDS components. However, for ethical reasons, evidence of a causal relationship between prenatal exposure and TDS is inherently difficult to establish in human studies, rendering the recently developed animal TDS model an important tool for investigating the pathogenesis of TDS. Clinically, the most common manifestation of TDS is probably a reduced sperm concentration, whereas the more severe form may include a high risk of testis cancer. Clinicians should be aware of the interconnection between the different features of TDS, and inclusion of a programme for early detection of testis cancer in the management of infertile men with poor semen quality is recommended.

References

• Testicular dysgenesis syndrome: possible role of endocrine disrupters, Best practice & research. Clinical endocrinology & metabolism, NCBI PubMed PMID: 16522521, 2006 Mar.

DES DIETHYLSTILBESTROL RESOURCES

• Source DES and testicular cancer studies.
• Diethylstilbestrol DES studies by topics.

It is clear that hypospadias, cryptorchidism, and testicular cancer are all positively associated with prenatal exposure to DES

2008 Study Abstract

Background
Male reproductive tract abnormalities such as hypospadias and cryptorchidism, and testicular cancer have been proposed to comprise a common syndrome together with impaired spermatogenesis with a common etiology resulting from the disruption of gonadal development during fetal life, the testicular dysgenesis syndrome (TDS). The hypothesis that in utero exposure to estrogenic agents could induce these disorders was first proposed in 1993. The only quantitative summary estimate of the association between prenatal exposure to estrogenic agents and testicular cancer was published over 10 years ago, and other systematic reviews of the association between estrogenic compounds, other than the potent pharmaceutical estrogen diethylstilbestrol (DES), and TDS end points have remained inconclusive.

Objectives
We conducted a quantitative meta-analysis of the association between the end points related to TDS and prenatal exposure to estrogenic agents. Inclusion in this analysis was based on mechanistic criteria, and the plausibility of an estrogen receptor (ER)-α–mediated mode of action was specifically explored.

Results
We included in this meta-analysis eight studies investigating the etiology of hypospadias and/or cryptorchidism that had not been identified in previous systematic reviews. Four additional studies of pharmaceutical estrogens yielded a statistically significant updated summary estimate for testicular cancer.

Conclusions
The doubling of the risk ratios for all three end points investigated after DES exposure is consistent with a shared etiology and the TDS hypothesis but does not constitute evidence of an estrogenic mode of action. Results of the subset analyses point to the existence of unidentified sources of heterogeneity between studies or within the study population.

Sources

• Full study (free access) : Testicular Dysgenesis Syndrome and the Estrogen Hypothesis: A Quantitative Meta-Analysis, Environmental Health Perspectives, PMC2235228, 2008 Feb.

DES DIETHYLSTILBESTROL RESOURCES

• Source DES and cryptorchidism studies, DES and hypospadias studies.
• Source DES and testicular cancer studies.
• Diethylstilbestrol DES studies listed by topics and date of publication.