Following extensive examination of published and unpublished materials, we provide a history of the use of dexamethasone in pregnant women at risk of carrying a female fetus affected by congenital adrenal hyperplasia (CAH). This intervention has been aimed at preventing development of ambiguous genitalia, the urogenital sinus, tomboyism, and lesbianism. We map out ethical problems in this history, including: misleading promotion to physicians and CAH-affected families; de facto experimentation without the necessary protections of approved research; troubling parallels (...) to the history of prenatal use of diethylstilbestrol (DES); and the use of medicine and public monies to attempt prevention of benign behavioral sex variations. Critical attention is directed at recent investigations by the U.S. Food and Drug Administration (FDA) and Office of Human Research Protections (OHRP); we argue that the weak and unsupported conclusions of these investigations indicate major gaps in the systems meant to protect subjects of high-risk medical research. (shrink)

Disorders of sexual development are a heterogeneous group of disorders in which chromosomal, gonadal or anatomical sex development is atypical. The majority of these children are recognized at birth by ambiguous genitalia. Legal and societal pressures require the physician and parents to assign sex rapidly. Though sex assignment is undebated in several disorders of sexual development, many others need an individualized approach to gender-related concerns. Gender dysphoria is prevalent in disorders of sexual development, and early gender-defining surgeries have potentially lifelong (...) consequences. We use two cases, one of partial androgen insensitivity and another of simple virilizing congenital adrenal hyperplasia to illustrate that in disorders of sexual development, the ethical management principles remain the same at their core despite the vast differences in phenotypes. Sex assignment should maximize functional, psychological and sexual needs. Sex assigned should coincide with gender identity. We propose that we manage such children with the mutual participation of the physician, parents and the child. Though the parents and the physician have the child's best interests when making a decision, the child's developing autonomy should be protected. The communication of the health provider to the parent must be honest if early sex assignment is difficult. (shrink)

This article discusses the ethics of the use of preimplantation genetic diagnosis to prevent the birth of children with intersex conditions/disorders of sex development , such as congenital adrenal hyperplasia and androgen insensitivity syndrome . While pediatric surgeries performed on children with ambiguous genitalia have been the topic of intense bioethical controversy, there has been almost no discussion to date of the ethics of the use of PGD to reduce the prevalence of these conditions. I suggest that (...) PGD for those conditions that involve serious medical risks for those born with them is morally permissible and that PGD for other “cosmetic” variations in sexual anatomy is more defensible than might first appear. However, importantly, the arguments that establish the latter claim have radical and disturbing implications for our attitude toward diversity more generally. (shrink)

In this critical, feminist account of the management of intersex conditions under 2006's controversial “Disorders of Sex Development” (DSD) treatment model, I argue that like the “Optimal Gender of Rearing” (OGR) treatment model it replaced, DSD aims at securing a cisgendered future for the intersex patient, referring to a normalized trajectory of development across the lifespan in which multiple sexed, gendered, and sexual characteristics remain in “coherent” alignment. I argue this by critically analyzing two ways that intersex management has changed (...) between OGR and DSD: 1) regarding sex‐assignment recommendations for three patient populations and, 2) with the prenatal treatment of pregnant individuals at risk of conceiving a fetus with congenital adrenal hyperplasia with the steroid hormone dexamethasone. I conclude that like OGR before it, DSD also unjustifiably presumes that typical genitalia are necessary for cisgendered development. However, unlike OGR, it appeals to the empirically inadequate, theoretically suspect, and biologically determinist model of gender development known as brain‐organization theory. Given this, I conclude that the treatment of intersex people under DSD continues to be driven by problematically heterosexist and transphobic assumptions regarding the value and normalcy of cisgendered life, while practically and discursively constituting it as such. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Finding My Compass*Laura Inter+I was born in the 1980s, and much to my parents surprise, the doctors could not say whether I was a boy or a girl because my body had ambiguous genitalia. They then conducted a chromosome test and the result was XX chromosomes. I was assigned female and only later was diagnosed with congenital adrenal hyperplasia (CAH). Fortunately for me the endocrinologist who (...) treated me did not mention the option of surgery, so my medical treatment consisted only of taking cortisol. Apart from this, from the time I turned one, I was subjected to genital examinations twice a year, during which the endocrinologist would touch my genitals and look to see how they were developing.These unnecessary and intrusive examinations had a profound effect on me. As a young child, I did not understand why I had to lower my pants in front of a stranger—the endocrinologist—and let him touch me. The fact that my mother was present, and approved of this was something that made me feel completely helpless. All this seemed very strange to me; I found it confusing, and terribly uncomfortable, and I just felt it wasn’t right.I remember the doctor always spoke as if I wasn’t right there, and I did not always understand everything the doctor said when I was young, because of all the medical terms he used. I grew up with a feeling of being “inadequate,” of having a sense that something was wrong with me, though I didn’t know exactly what. These exams lasted until I was about 12 years old. Years later, as I began my adult, sexual life, I realized how much those displays had affected me emotionally.I discovered what was “wrong” with me during sex education classes in the first year of high school. There was a class session in which two images were shown: one displaying the external female sex organs, and the other the male sex organs. I noticed that my body was not like either of them. I was very distressed, thinking “I have deformed genitals!” I feared I could not perform sexually as either a man or a woman. I became very depressed. I was sure nobody would want me, that I would never have a relationship. I was unacceptable, “abnormal,” or at least that is what the doctors had said. And in any case my parents never spoke of it, and I didn’t know that I had CAH.Skip forward a few years: I was still looking for answers, I found my medical file and read in the documents “pseudo–hermaphrodite,” and [End Page 95] “congenital adrenal hyperplasia.” I searched the internet, but only found medical opinions that said that in the case of genital ambiguity, the best option was surgery. I wondered to myself: “Why didn’t they operate on me?”I put the question to my parents, and, at fifteen, I found myself being examined once more in the doctor’s office, this time to consider the possibility of a genital surgery which might once and for all, I believed, make me a “normal” person.I have never told anyone outside my family before, but one of those exams was the most humiliating experiences of my life. One doctor wanted to speak with me alone, so she made my mother wait outside the exam room. My mother agreed, thinking that after the doctor talked with me, my mother would be able to be present during the rest of the exam. The doctor asked me questions, some of which made me very uncomfortable: “Do you feel good about being a woman”? Did you ever feel like a man? Why don’t you dress up more, use more makeup? Are you a lesbian? Have you ever had sex? She then said she wanted to see my genitals. I felt awful and wanted my mother present, but I also wanted it to be over quickly, and said nothing. Examining my genitals, the doctor told me they “would not be adequate for sex,” and that she needed to “perform surgery.” Something else that made me uncomfortable was the presence of another doctor in... (shrink)

The two provocative essays in this issue of the Hastings Center Report should stimulate debate not only about female genital cutting, fetal dexamethasone, and clitoral reduction surgery, but also about our fierce commitment to particular cultural norms about the body. Under what conditions may adults irreversibly modify a child's body because they think the change is in her best interest? Certainly, parents who opt for female genital cutting or for surgical reduction of an enlarged clitoris in a girl with (...) class='Hi'>congenital adrenal hyperplasia want to make choices that will contribute to their child's potential happiness. If cutting in Africa—or mitigating CAH symptoms here—upholds a girl's gender identity, which will translate into a fulfilled life as an adult, some argue that a parent's refusal to abide by social prescriptions does the child a serious disservice. (shrink)

In a series of essays and letters published in 2010, commentators in bioethics debated the ethics of two interventions that aim to prevent or treat a symptom of a genetic condition called congenital adrenal hyperplasia, which can cause “virilization” in affected baby girls—the development of atypical, sometimes masculine‐appearing, genitals. Surgeries are often performed to try to “normalize” both the appearance and the function of affected girls’ genitals, and a drug thought to prevent virilization is sometimes prescribed to (...) pregnant women who are likeliest to be carrying an affected fetus. The CAH debates suggest that there is profound disagreement in the field about whether preventing or treating virilization is an appropriate goal of medicine—or, indeed, parenting. Of course, that disagreement has its roots in ongoing debates about how to understand and react to a range of anatomical and behavioral differences, from short stature to deafness to hyperactivity, as well as ongoing debates about the limits of autonomy—in this case, parental autonomy, which is all the more complex. These issues are at the heart of bioethics. Yet it can be very difficult for us to talk and write respectfully and clearly about them. Here, I recount the debates, show how they lost focus, and attempt to explain why the question about how parents and physicians should respond to atypical genitalia in children is so important and difficult. I argue that it is not a question that should be answered based on a single principle or philosophical commitment. No one principle can do all of the work. For each individual or family that faces it, the question is shaped by details about particular interventions aimed at altering a particular difference and offered in a particular social and family context. Scholars in bioethics who hold an especially strong commitment to any one principle should advocate for their views, but they must also make room for and respect the kind of pragmatic, particularized decision‐making that parents sometimes engage in. (shrink)

There is some very limited evidence for a role of estrogens in human psychosexual masculinization; its interpretation is uncertain. Fitch & Denenberg's demonstration of a role for estrogens in the behavioral feminization of nonhuman mammals implicitly suggests an answer to a riddle posed by the syndrome of congenital adrenal hyperplasia in women.

This article is the first indepth ethical analysis of empirical studies that support the claim that children born without major parts of their cerebral cortex are capable of conscious experiences and have a rudimentary capacity for agency. Congenitally decorticate children have commonly been classified as persistently vegetative, with serious consequences for their well-being and opportunities to flourish. The paper begins with an explication of the rights-based normative framework of the argument, including conceptual analysis of the terms ‘agency’, ‘potentiality for agency’ (...) and ‘gradual approach of agency’. It critically examines Alan Gewirth’s account of the criteria for being a rights bearer and principles for settling rights conflicts between agents and potential agents. It then applies the rights-based normative framework to the ethical challenges associated with care for congenitally decorticate children. It argues that recent empirical studies support the claim that the concepts ‘potential for agency’ and ‘capacity for rudimentary agency’ apply to children who are born without major parts of their cerebral cortex. The article finally discusses important medical ethical implications of these results. It specifically focuses on congenitally decorticate children’s preparatory rights to a stimulating intellectual and social environment. (shrink)

Chagas disease or American trypanosomiasis is an important health problem in Latin America. Due to the mobility of Latin American population around the world, countries without vector presence started to report disease cases. We developed a deterministic compartmental model in order to gain insights into the disease dynamics in a scenario without vector presence, considering congenital transmission and transmission by blood transfusion. The model was used to evaluate the epidemiological effect of control measures. It was applied to demographic data (...) from Spain and sensitivity analysis was performed on model parameters associated with control strategies. (shrink)

I take the phrase ‘congenital transcendentalism’ from Santayana who defined it as ‘the spontaneous feeling that life is a dream’. ‘The loneliness which is the truth about things’ is a phrase of Virginia Woolf's. The thesis I will advance is that many expressions of doubt or denial of the shareable world are self-misunderstood manifestations of the state indicated by Woolf's expression. But the loneliness of which Woolf speaks must not be construed as the kind of loneliness which can be (...) assuaged by family, friends, lovers or company. Nor is it the loneliness which a convinced solipsist might experience. It is rather the loneliness of ‘that “I” and that “life of mine'” which is ‘untouched whichever way the issue is decided whether the world is or is not’. (shrink)

Phenomenology has contributed to healthcare by providing resources for understanding the lived experience of the patient and their situation. But within a burgeoning literature on the characteristic features of illness, there has not yet been an account appropriate to describe congenital illnesses: conditions which are present from birth and cause suffering or medical threat to their bearers. Congenital illness sits uncomfortably with standard accounts in phenomenology of illness, in which concepts such as loss, doubt, alienation and unhomelikeness presuppose (...) prior health. These accounts reflect, in different ways, Maurice Merleau-Ponty’s assumption that the ways of living of the ill contain allusions to fundamental, healthy functions. The originality of congenital illness complicates this assumption and demands its own original phenomenology. In this paper, I sketch my personal experience living with a single-ventricle heart condition. While some of this story may reflect my own idiosyncratic experience, I hope that much of it will resonate with the congenital illness experience. I argue that the phenomenological literature on illness, grounded in the notion of loss, does not describe the congenital illness experience. I show how a number of other patient-centred theories of health and illness which have been influential on phenomenology can and cannot elucidate congenital illness. In particular, I consider Georges Canguilhem’s account of the normal and the pathological; debates in disability; and the notion of illness as biographical disruption. I show that congenital illness results in the preadmission of its patients to a paradoxical logic of medical palliation, one product of which is existential maturity. (shrink)

Various explanations have been proposed to account for complex differentiation and development in humans, despite the human genome containing only two to three times the number of genes in invertebrates. Ignored are the actions of adrenal and sex steroids—androgens, estrogens, glucocorticoids, mineralocorticoids, and progestins—which act through receptors that arose from an ancestral nuclear receptor in a protochordate. This ligand‐based mechanism is unique to vertebrates and was integrated into the already robust network of transcription factors in invertebrates. Adrenal and (...) sex steroids influence almost all aspects of vertebrate differentiation and development. I propose that evolution of this ligand‐based mechanism in a primitive vertebrate was an important contribution to vertebrate complexity. Sequencing of genomes from a cephalochordate, such as amphioxus, and from hagfish and lamprey will establish early events in the evolution of steroid hormone signaling, and also allow genetic studies to elucidate how vertebrate complexity depends on steroid hormones. BioEssays 25:396–400, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

To test if dreams contain remote or never-experienced motor skills, we collected during 6 weeks dream reports from 15 paraplegics and 15 healthy subjects. In 9/10 subjects with spinal cord injury and in 5/5 with congenital paraplegia, voluntary leg movements were reported during dream, including feelings of walking , running , dancing , standing up , bicycling , and practicing sports . Paraplegia patients experienced walking dreams just as often as controls . There was no correlation between the frequency (...) of walking dreams and the duration of paraplegia. In contrast, patients were rarely paraplegic in dreams. Subjects who had never walked or stopped walking 4–64 years prior to this study still experience walking in their dreams, suggesting that a cerebral walking program, either genetic or more probably developed via mirror neurons is reactivated during sleep. (shrink)

Reports of phantom limbs amongst aplasics have often been presented as evidence that body image is ‘hard-wired’ in the brain and that neither sensory input nor proprioceptive feedback are essential to its formation. Although attempts have been made to account for these phantoms by other means, these have been on a case by case basis and no satisfactory alternative framework has been proposed. This paper collates the accounts of aplasic phantoms and presents them as compatible with a four-part hypothesis, in (...) which body image is learnt from experience during both pre- and post-natal development, and in which cross-cortical connections and mirror neurons play prominent roles. This model unites several previously disparate theories to offer a viable solution to several longstanding phantom limb mysteries and serves to highlight avenues worthy of further inquiry. (shrink)

A large number of previous reports described an effect of the pituitary hormone prolactin (PRL) on steroid hormone production by the adrenal cortex. However, those studies remained anecdotal and were never converted into a conceptual and mechanistic framework, let alone being translated into clinical care. In the light of our recently published landmark study where we described PRL signalling as a pivotal regulator of the sexually dimorphic adrenal phenotype in mouse and of adrenal androgen production in humans, (...) we present here the overarching hypothesis that PRL signalling increases the activity of Steroidogenic Factor‐1 (SF‐1/NR5A1), a transcription factor that has an essential role in adrenal gland development and function, to regulate adrenal cortex growth and hormonal production in physiological and pathological conditions. PRL can then be considered as a bona fide adrenocorticotropic hormone synergizing with ACTH in the endocrine control of adrenal cortex function. (shrink)

This target article considers the ethical implications of providing prenatal diagnosis (PND) and antenatal screening services to detect fetal abnormalities in jurisdictions that prohibit abortion for these conditions. This unusual health policy context is common in the Latin American region. Congenital conditions are often untreated or under-treated in developing countries due to limited health resources, leading many women/couples to prefer termination of affected pregnancies. Three potential harms derive from the provision of PND in the absence of legal and safe (...) abortion for these conditions: psychological distress, unjust distribution of burdens between socio-economic classes, and financial burdens for families and society. We present Iran as a comparative case study where recognition of these ethical issues has led to the liberalization of abortion laws for fetuses with thalassemia. We argue that physicians, geneticists and policymakers have an ethical and professional duty of care to advocate for change in order to ameliorate these harms. (shrink)

This article investigates the emergence of the concept of stress in the 1930s and outlines its changing disciplinary and conceptual frames up until 1960. Originally stress was a physiological concept applied to the hormonal regulation of the body under stressful conditions. Correlated closely with chemical research into corticosteroids for more than a decade, the stress concept finally became a topic in cognitive psychology. One reason for this shift of the concept to another discipline was the fact that the hormones previously (...) linked to the stress concept were successfully transferred from laboratory to medical practice and adopted by disciplines such as rheumatology and dermatology. Thus the stress concept was dissociated from its hormonal context and became a handy formula that allowed postindustrial society to conceive of stress as a matter of individual concern. From a physiological phenomenon stress turned into an object of psychological discourse and individual coping strategies. (shrink)

Oncogenic hyperplasia is the first and inevitable stage of formation of a (solid) tumor. This stage is also the core of many other proliferative diseases. The present work proposes the first minimal model that combines homeorhesis with oncogenic hyperplasia where the latter is regarded as a genotoxically activated homeorhetic dysfunction. This dysfunction is specified as the transitions of the fluid of cells from a fluid, homeorhetic state to a solid, hyperplastic-tumor state, and back. The key part of the (...) model is a nonlinear reaction-diffusion equation (RDE) where the biochemical-reaction rate is generalized to the one in the well-known Schlögl physical theory of the non-equilibrium phase transitions. A rigorous analysis of the stability and qualitative aspects of the model, where possible, are presented in detail. This is related to the spatially homogeneous case, i.e. when the above RDE is reduced to a nonlinear ordinary differential equation. The mentioned genotoxic activation is treated as a prevention of the quiescent G0-stage of the cell cycle implemented with the threshold mechanism that employs the critical concentration of the cellular fluid and the nonquiescent-cell-duplication time. The continuous tumor morphogeny is described by a time-space-dependent cellular-fluid concentration. There are no sharp boundaries (i.e. no concentration jumps exist) between the domains of the homeorhesis- and tumor-cell populations. No presumption on the shape of a tumor is used. To estimate a tumor in specific quantities, the model provides the time-dependent tumor locus, volume, and boundary that also points out the tumor shape and size. The above features are indispensable in the quantitative development of antiproliferative drugs or therapies and strategies to prevent oncogenic hyperplasia in cancer and other proliferative diseases. The work proposes an analytical-numerical method for solving the aforementioned RDE. A few topics for future research are suggested. (shrink)

Previous studies of Zika virus (ZIKV) pathogenesis have focused primarily on virus‐driven pathology and neurotoxicity, as well as host‐related changes in cell proliferation, autophagy, immunity, and uterine function. It is now hypothesized that ZIKV pathogenesis arises instead as an (unintended) consequence of host innate immunity, specifically, as the side effect of an otherwise well‐functioning machine. The hypothesis presented here suggests a new way of thinking about the role of host immune mechanisms in disease pathogenesis, focusing on dysregulation of post‐transcriptional RNA (...) editing as a candidate driver of a broad range of observed neurodevelopmental defects and neurodegenerative clinical symptoms in both infants and adults linked with ZIKV infections. The authors collect and synthesize existing evidence of ZIKV‐mediated changes in the expression of adenosine deaminases acting on RNA (ADARs), known links between abnormal RNA editing and pathogenesis, as well as ideas for future research directions, including potential treatment strategies. (shrink)

ObjectivesThis study aimed to describe the experiences and challenges faced by adolescents with moderate and severe congenital heart defects or Chronic Rheumatic Heart Disease and to determine their needs in order to develop an Adolescent Transition Psychoeducational Program.MethodsThe study involved seven adolescents with moderate to severe CHD/CRHD, six parents, and four health care providers in Institute Jantung Negara. Participants were invited for a semi-structured interview. Qualitative data were analyzed through the Atlas.ti 7 program using triangulation methods.Results/conclusionsWe identified five themes (...) concerning the experience and challenges of adolescents relating to: emotional/psychological issues; the progress of the illness; relationship issues; future preparation; and, school and community. These themes were identified together with eleven subcategories. The staff expressed support for the development of the Adolescent Transition Psychoeducational Program and adolescents with CHD/CRHD and their parents were willing to participate in the program if their schedule allowed. Their suggestions to improve the program were classified into six categories, with two main themes, the self-management of illness in life and the future; and, social support. In conclusion, the findings from the situation analysis act as a basis for a conceptual framework that will contribute to the development of an Adolescent Transition Psychoeducational Program that aims to empower adolescents with CHD/CRHD, enabling them to manage challenges during the transition phase between childhood and adulthood. (shrink)