ESSM Newsletter # 40

6 ESSM Today Introduction The term endocrine disrupters (EDC) was first coined in 1991 at the Wingspread Conference Centre in Racine, Wisconsin [1]. At this meeting researchers from several different disciplines came to the consensus that “a large number of man-made chemicals” have been released into the environment with the potential to “disrupt” the endocrine system of humans [1]. This fol- lowed on from several studies that had impli- cated environmental and household chemicals as contributing to adverse health effects in both humans and wildlife [2]. Recently, there has been a surge of research investigating the role of EDCs in human health and the Endocrine society stated in 2015 that this expansion of data “removes any doubt that EDCs are contributing to increased chronic disease burdens related to obesity, dia- betes mellitus, reproduction, thyroid, cancers, and neuroendocrine and neurodevelopmental functions”[3]. Endocrine disruptors have been linked with the rise in genital malformations, adverse pregnancy outcomes and global rates of endocrine related cancers. However, this view- point is controversial as a joint statement by the WHO and UNEP noted that “despite substantial advances in our understanding of EDCs, uncer- tainties and knowledge gaps still exist that are too important to ignore”[4]. The purpose of this review is to give an overview of the relationship of endocrine disruptors and sexual function in humans. Background and Limitations to Research Definition Endocrine disruptors have been defined as “an exogenous substance or mixture that al- ters function(s) of the endocrine system and consequently causes adverse health effects in an intact organism, or its progeny, or (sub) populations” [4]. Studies have demonstrated that EDCs can act at multiple sites in the hor- mone pathway including binding to the hormone receptor and acting on proteins that regulate hormone synthesis, metabolism and delivery [4]. Methodological Issues There are several factors that complicate the investigation of EDC exposure in human health. The potential pathological mechanisms of EDCs remain complicated and experimental studies have cited non-monotonic dose response rela- tionships [5]. This goes against the conventional toxicological risk stratification which attempts to calculate a “safe” level of a toxin [6] and hence further approaches are needed to assess EDCs. In addition to this, EDCs are ubiquitous within the environment and households with an estimated “1000” manufactured chemicals potentially having endocrine-acting properties [7]. Examples range from Phthalates used in children toys, food containers and household curtains to Dichlorodiphenyltrichloroethane (DDT) used in pesticides. The Endocrine society noted that biomonitoring shows nearly 100% of humans have a chemical body burden [8] and a study by Dodson et al demonstrated 50 potential EDCs in a range of cosmetics, per- sonal care products, cleaners, sunscreens, and vinyl products [9]. This highlights the difficulty in assessment of single exposures. Moreover, careful consideration needs to be given to the potential interaction of EDCs with each other or chemicals within the environment or the body. These interactions could be additive, synergistic or antagonistic [10]. Given there is a growing number of chemicals being identified as EDCs and many further unknown this highlights an- other evaluation issue. Several EDCs have short half lives meaning that there is large within-subject variability. As such even 24 hour urine collections have been deemed inaccurate in investigating EDC exposure [11]. Collectively, the aforementioned factors highlight the various methodological issues related to EDC assessment. Several studies have acknowledged this and there is an emerging movement towards EDC specific study protocols [10]. The number of suspected adverse health ef- fects of EDCs is vast and outside the remits of this review. We will focus on some of the wider publicised EDCs and the associations with sexual dysfunction. We have classified the EDCs based on examples of potential exposures to humans. Medications Diesthylstilbestrol (DES) is a high profile phar- maceutical example of endocrine disruptors that has resulted in developmental and repro- ductive abnormalities in humans. DES was the first synthetic non-steroidal oestrogen and was initially advertised to prevent miscarriage. How- ever, DES use was associated with an increased risk of clear cell vaginal carcinoma in females whose mothers had taken DES during preg- nancy [12]. Moreover, DES exposed daughters have been shown to have abnormalities in their genital tract [13] [14] and an increased risk of infertility [15]. Studies have demonstrated an association with in utero DES exposure and cryptorchid- ism in boys[16] [17] [18]. However, the current evidence linking DES to testicular cancer and infertility in exposed sons are conflicting [13]. Pesticides Tyrone Hayes studied the impact of low doses of Atrozene (a herbicide) on frogs and identi- fied that it produced sexual abnormalities. He Endocrine disruption and sexual dysfunction by Suks Minhas and Tharu Tharakan Suks Minhas, MD FRCS (Urol) Consultant Urologist and Andrologist Imperial College Healthcare NHS Trust London, UK suks.minhas@nhs.net Tharu Tharakan Department of Urology Imperial Healthcare NHS Trust Charing Cross Hospital Fulham Palace Road London, UK tharu.tharakan@nhs.net