Comparison of anogenital distance and correlation with vulvo-vaginal atrophy: a pilot study on premenopausal and postmenopausal women

OBJECTIVES: Anogenital distance (AGD) represents the space between labia posterior commissure and anus. This was pilot study to investigate how menopause and so lack of oestrogens affects AGD. METHODS: A total of 109 patients were enrolled. AGD was measured in lithotomy position using sterile paper ruler. Anogenital index (AGI) was used to control 2 variables of height and weight (body mass index, kg/m2). Vaginal health index (VHI) was used to evaluate vaginal wellness. Female sexual function index (FSFI) questionnaire was administered to all women to evaluate the impact of menopause on their sexual function. RESULTS: AGD (30.87 ± 2.98 vs. 17.57 ± 2.18; P = 0.0001) and AGI (1.40 ± 0.21 vs. 0.70 ± 0.15; P = 0.0001) were both significantly lower in the postmenopausal group. Postmenopausal women were affected by vulvovaginal atrophy (VVA) significantly. Thus, VHI scores were dramatically worse in postmenopausal group (23.95 ± 1.28 vs. 10.75 ± 3.41; P = 0.0001) as well as FSFI results (32.68 ± 2.25 vs. 19.78 ± 5.46; P = 0.0001). CONCLUSIONS: This study confirms that AGD in post-menopausal women was significantly shorter than AGD in premenopausal women, correlating with an increase of VVA and sexual impairment. Changes of AGD and AGI demonstrated to predict hormonal changes that may occur after menopause

Growing Up Toxic: Chemical Exposures and Increases in Developmental Disease

Explains how exposure to toxic chemicals can harm health and impair development, causing premature birth, learning disabilities, behavioral disorders, asthma and allergies, and/or other problems. Suggests policy reforms

Meeting Report: Moving Upstream—Evaluating Adverse Upstream End Points for Improved Risk Assessment and Decision-Making

Background Assessing adverse effects from environmental chemical exposure is integral to public health policies. Toxicology assays identifying early biological changes from chemical exposure are increasing our ability to evaluate links between early biological disturbances and subsequent overt downstream effects. A workshop was held to consider how the resulting data inform consideration of an “adverse effect” in the context of hazard identification and risk assessment. Objectives Our objective here is to review what is known about the relationships between chemical exposure, early biological effects (upstream events), and later overt effects (downstream events) through three case studies (thyroid hormone disruption, antiandrogen effects, immune system disruption) and to consider how to evaluate hazard and risk when early biological effect data are available. Discussion Each case study presents data on the toxicity pathways linking early biological perturbations with downstream overt effects. Case studies also emphasize several factors that can influence risk of overt disease as a result from early biological perturbations, including background chemical exposures, underlying individual biological processes, and disease susceptibility. Certain effects resulting from exposure during periods of sensitivity may be irreversible. A chemical can act through multiple modes of action, resulting in similar or different overt effects. Conclusions For certain classes of early perturbations, sufficient information on the disease process is known, so hazard and quantitative risk assessment can proceed using information on upstream biological perturbations. Upstream data will support improved approaches for considering developmental stage, background exposures, disease status, and other factors important to assessing hazard and risk for the whole population

The epidemiologic evidence linking prenatal and postnatal exposure to endocrine disrupting chemicals with male reproductive disorders:a systematic review and meta-analysis

BACKGROUND: More than 20 years ago, it was hypothesized that exposure to prenatal and early postnatal environmental xenobiotics with the potential to disrupt endogenous hormone signaling might be on the causal path to cryptorchidism, hypospadias, low sperm count and testicular cancer. Several consensus statements and narrative reviews in recent years have divided the scientific community and have elicited a call for systematic transparent reviews. We aimed to fill this gap in knowledge in the field of male reproductive disorders. OBJECTIVE AND RATIONALE: The aim of this study was to systematically synthesize published data on the risk of cryptorchidism, hypospadias, low sperm counts and testicular cancer following in utero or infant exposure to chemicals that have been included on the European Commission's list of Category 1 endocrine disrupting chemicals defined as having documented adverse effects due to endocrine disruption in at least one intact organism. SEARCH METHODS: A systematic literature search for original peer reviewed papers was performed in the databases PubMed and Embase to identify epidemiological studies reporting associations between the outcomes of interest and exposures documented by biochemical analyses of biospecimens including maternal blood or urine, placenta or fat tissue as well as amnion fluid, cord blood or breast milk; this was followed by meta-analysis of quantitative data. OUTCOMES: The literature search resulted in 1314 references among which we identified 33 papers(28 study populations) fulfilling the eligibility criteria. These provided 85 risk estimates of links between persistent organic pollutants and rapidly metabolized compounds (phthalates and Bisphenol A) and male reproductive disorders. The overall odds ratio (OR) across all exposures and outcomes was 1.11 (95% CI 0.91–1.35). When assessing four specific chemical subgroups with sufficient data for meta-analysis for all outcomes, we found that exposure to one of the four compounds, p,p′-DDE, was related to an elevated risk: OR 1.35 (95% CI 1.04–1.74). The data did not indicate that this increased risk was driven by any specific disorder. WIDER IMPLICATIONS: The current epidemiological evidence is compatible with a small increased risk of male reproductive disorders following prenatal and postnatal exposure to some persistent environmental chemicals classified as endocrine disruptors but the evidence is limited. Future epidemiological studies may change the weight of the evidence in either direction. No evidence of distortion due to publication bias was found, but exposure–response relationships are not evident. There are insufficient data on rapidly metabolized endocrine disruptors and on specific exposure–outcome relations. A particular data gap is evident with respect to delayed effects on semen quality and testicular cancer. Although high quality epidemiological studies are still sparse, future systematic and transparent reviews may provide pieces of evidence contributing to the narrative and weight of the evidence assessments in the field

Anogenital distance as a marker of androgen exposure in humans.

Abnormal foetal testis development has been proposed to underlie common disorders of the male reproductive system such as cryptorchidism, hypospadias, reduced semen quality and testicular germ cell tumour, which are regarded as components of a 'testicular dysgenesis syndrome'. The increasing trends and geographical variation in their incidence have been suggested to result from in utero exposure to environmental chemicals acting as endocrine disruptors. In rodents, the anogenital distance (AGD), measured from the anus to the base of genital tubercle, is a sensitive biomarker of androgen exposure during a critical embryonic window of testis development. In humans, several epidemiological studies have shown alterations in AGD associated with prenatal exposure to several chemicals with potential endocrine disrupting activity. However, the link between AGD and androgen exposure in humans is not well-defined. This review focuses on the current evidence for such a relationship. As in rodents, a clear gender difference is detected during foetal development of the AGD in humans which is maintained thereafter. Reduced AGD in association with clinically relevant outcomes of potential environmental exposures, such as cryptorchidism or hypospadias, is in keeping with AGD as a marker of foetal testicular function. Furthermore, AGD may reflect variations in prenatal androgen exposure in healthy children as shorter AGD at birth is associated with reduced masculine play behaviour in preschool boys. Several studies provide evidence linking shorter AGD with lower fertility, semen quality and testosterone levels in selected groups of adults attending andrology clinics. Overall, the observational data in humans are consistent with experimental studies in animals and support the use of AGD as a biomarker of foetal androgen exposure. Future studies evaluating AGD in relation to reproductive hormones in both infants and adults, and to gene polymorphisms, will help to further delineate the effect of prenatal and postnatal androgen exposures on AGD.The CBGS studies referred to in this review were supported by a European Union Framework V programme, the World Cancer Research Fund International, the Medical Research Council (UK), the Newlife Foundation, the Mothercare Foundation, the Evelyn Trust and the NIHR Cambridge Biomedical Research Centre.This is the author accepted manuscript. The final version is available from Wiley via http://dx.doi.org/10.1111/andr.1215

Clinical studies on testicular growth and descent

Recent population-based cohort studies indicate that semen quality is declining and simultaneously the incidence of testicular germ-cell cancer is increasing globally. A failure of testicular descent i.e. cryptorchidism and reduced testicular volume are risk factors both for testicular germ-cell cancer and reduced semen quality. Epidemiological and experimental studies suggest that these disorders may originate from testicular dysgenesis and reduced intratesticular androgen action during fetal period, which may be caused by genetic factors or exposure to antiandrogen endocrine disrupters. In this study, we explored postnatal testicular descent and the physiological significance of the so-called ‘minipuberty’, the transient activation of the hypothalamic-pituitary-gonadal axis after birth for postnatal testicular position. In addition, we assessed whether the levels of persistent organic pollutants such as polychlorinated biphenyl (PCBs), polychlorinated dibenzo-p-dioxins and furans (PCDD/Fs, or ‘dioxins’) and polybrominated diphenyl ethers (PBDEs) are associated with congenital cryptorchidism. Finally, we assessed the testicular development during puberty among boys with a history of congenital cryptorchidism. We observed that testicular descent continued until the age of three months, and was followed by a ‘physiological’ testicular ascent, which coincided with the decline in circulating reproductive hormones. We also discovered that the circulating concentration of insulin-like growth factor 1 and hormonal indices reflecting Sertoli and Leydig cell function correlated with testicular position. Our results also suggest that the exposure to dioxins may increase the risk of congenital cryptorchidism. Furthermore, we showed that boys who had a history of congenital cryptorchidism display poor testicular growth during puberty in comparison to controls, which may predispose them to reduced semen quality and subfertility.Kliinisiä tutkimuksia kivesten kasvusta ja laskeutumisesta Viimeaikaisten tutkimusten mukaan siemennesteen laatu on heikentynyt ja kivessyövän esiintyvyys lisääntynyt ympäri maailmaa. Laskeutumaton kives eli piilokives ja kivesten pieni koko altistavat sekä kivessyövälle että heikentyneelle siemennesteen laadulle. Epidemiologisten tutkimusten sekä eläinmallien tulosten perusteella nämä häiriöt saattavat johtua kiveksen kehityshäiriöstä ja vähentyneestä sikiökautisesta kiveksensisäisestä androgeenivaikutuksesta. Tämä puolestaan saattaa johtua perintötekijöiden lisäksi altistuksesta ympäristön antiandrogeenisille hormonaalisille haitta-aineille. Tässä väitöskirjassa selvitimme syntymän jälkeisen ohimenevän hypotalamus-aivolisäke-kives –akselin aktivoitumisen eli niin sanotun minipuberteetin merkitystä kivesten laskeutumiselle syntymän jälkeen. Väitöskirjassani myös selvitettiin altistavatko ympäristön pysyvät hormonaaliset haitta-aineet kuten polyklooratut bifenyylit (PCB), dioksiinit (PCDD/F) tai polybromatut difenyylieetterit (PBDE) piilokiveksisyydelle. Lisäksi tutkimme piilokiveksisten ja verrokkien kiveskasvua murrosiässä. Tutkimustulostemme mukaan kivekset laskeutuvat kolmen kuukauden ikään asti, minkä jälkeen kivekset nousevat samaan aikaan kun sukupuolihormonien pitoisuus verenkierrossa vähenee. Väitöskirjani mukaan insuliinin kaltaisen kasvutekijä 1:n pitoisuus sekä Leydigin ja Sertolin solujen toimintaa kuvaavat sukupuolihormoni- indeksit olivat yhteydessä kiveksen laskeutumiseen syntymän jälkeen. Lisäksi altistuminen pysyville hormonaalisille haitta-aineille, erityisesti dioksiineille, näyttää olevan yhteydessä synnynnäiseen piilokiveksisyyteen. Lisäksi synnynnäinen piilokives kasvaa verrokkien kiveksiä heikommin murrosiän aikana, mikä ennustaa heikompaa siemennesteen laatua ja hedelmällisyyttä

Endocrine Disrupting Chemicals' Effects in Children: What We Know and What We Need to Learn?

Thousands of natural or manufactured chemicals were defined as endocrine-disrupting chemicals (EDCs) because they can interfere with hormone activity and the endocrine system. We summarize and discuss what we know and what we still need to learn about EDCs' pathogenic mechanisms of action, as well as the effects of the most common EDCs on endocrine system health in childhood. The MEDLINE database (PubMed) was searched on 13 May 2022, filtering for EDCs, endocrine diseases, and children. EDCs are a group of compounds with high heterogeneity, but usually disrupt the endocrine system by mimicking or interfering with natural hormones or interfering with the body's hormonal balance through other mechanisms. Individual EDCs were studied in detail, while humans' "cocktail effect" is still unclear. In utero, early postnatal life, and/or pubertal development are highly susceptible periods to exposure. Human epidemiological studies suggest that EDCs affect prenatal growth, thyroid function, glucose metabolism, obesity, puberty, and fertility through several mechanisms. Further studies are needed to clarify which EDCs can mainly act on epigenetic processes. A better understanding of EDCs' effects on human health is crucial to developing future regulatory strategies to prevent exposure and ensure the health of children today, in future generations, and in the environment