Although estrogens are widely considered circulating “sex steroid hormones” typically associated with female reproduction, recent evidence suggests that estrogens can act as local modulators of brain circuits in both males and females. The functional implications of this newly characterized estrogen signaling system have begun to emerge. This essay summarizes evidence in support of the hypothesis that the rapid production of estrogens in brain circuits can drive acute changes in both the production and perception of acoustic communication behaviors. These studies (...) have revealed two fundamental neurobiological concepts: (1) estrogens can be locally produced in brain circuits, independent of levels in nearby circuits and in the circulation and (2) estrogens can have very rapid effects within these brain circuits to modulate social vocalizations, acoustic processing, and sensorimotor integration. This vertebrate‐wide span of research, including vocalizing fishes, amphibians, and birds, emphasizes the importance of comparative model systems in understanding principles of neurobiology. (shrink)

Estrogen receptor α (ERα) is a ligand‐dependent transcription factor that regulates the expression of estrogen‐responsive genes. Approximately 70% of patients with breast cancer are ERα positive. Estrogen stimulates cancer cell proliferation and contributes to tumor progression. Endocrine therapies, which suppress the ERα signaling pathway, significantly improve the prognosis of patients with breast cancer. However, the development of de novo or acquired endocrine therapy resistance remains a barrier to breast cancer treatment. Therefore, understanding the regulatory mechanisms of ERα (...) is essential to overcome the resistance to treatment. This review focuses on the regulation of ERα expression, including copy number variation, epigenetic regulation, transcriptional regulation, and stability, as well as functions from the point of view post‐translational modifications. (shrink)

New empirical evidence on the long-term effects of oestrogen treatment for tall adolescent girls has shown that the intended psychosocial benefit of the treatment may not have been realised. This paper describes recent trends in the prevalence of the treatment and the results of a large Australian cohort study evaluating girls assessed between 1959 and 1993 for excessive growth. The paper concludes that oestrogen treatment to prevent extreme tallness should belong to the past, not to the future.

Oestrogen treatment for girls, to prevent psychosocial problems due to extreme tallness, has been available for almost 50 years but uncertainty about its position prevails. The ethical problems of this treatment are focused on in this paper. After a brief overview on historical and medical aspects, ethical issues such as the general justification of oestrogen treatment, evaluation of its success and ethical concerns related to research in this subject are dealt with in detail.

The Estrogen Elixir: A History of Hormone Replacement Therapy in America by Elizabeth Siegel Watkins is a thoroughly documented cautionary tale of the information and advice offered to women in the perimenopausal period of their life, and the consequences of exposure to sexual hormones on their health and wellbeing.

The Estrogen Elixir: A History of Hormone Replacement Therapy in America by Elizabeth Siegel Watkins is a thoroughly documented cautionary tale of the information and advice offered to women in the perimenopausal period of their life, and the consequences of exposure to sexual hormones on their health and wellbeing.

The sequencing of the human genome has opened the way for using bioinformatics to identify sets of genes controlled by specific regulatory signals. Here, we review the unexpected diversity of DNA response elements mediating transcriptional regulation by estrogen receptors (ERs), which control the broad physiological effects of estrogens. Consensus palindromic estrogen response elements are found in only a few known estrogen target genes, whereas most responsive genes contain only low‐affinity half palindromes, which may also control regulation by (...) other nuclear receptors. ERs can also regulate gene expression in the absence of direct interaction with DNA, via protein–protein interactions with other transcription factors or by modulating the activity of upstream signaling components, thereby significantly expanding the repertoire of estrogen‐responsive genes. These diverse mechanisms of action must be taken into account in screening for potential estrogen‐responsive sequences in the genome or in regulatory regions of target genes identified by expression profiling. BioEssays 24:244–254, 2002. © 2002 Wiley Periodicals, Inc.; DOI 10.1002/bies.10066. (shrink)

Alzheimer's disease remains the most common form of dementia. Dementia symptoms vary depending on individual personality, life experience, and social and cultural influences. As dementia progresses, involvement of multi-disciplinary health care professionals is needed to manage the disease. Alzheimer research is progressing rapidly. While 5% of all Alzheimer's disease may be genetically determined, the majority is not. Susceptibility genes can reveal the risk of contracting Alzheimer's disease. Early life risk factors such as education, nutrition, and vascular disease may increase the (...) likelihood of dementia in later life. In the United States, two acetylcholinesterase inhibitors have been approved as cognitive enhancers. Possible prevention and symptomatic treatment interventions have focused on estrogen replacement therapy, antioxidants, and anti-inflammatory medications. Research advances have improved the clinical management of dementia. Ethical implications to the patient, family, and society are multiple and remain challenging. (shrink)

The classical estrogen receptor model does not sufficiently account for the tumor‐promoting activity of extrogens or for the antiproliferative effect of antiestrogens in estrogen‐dependent tumors. Particular difficulties not readily accommodated within the model are that hormonal autonomy can supervene without loss of the estrogen receptor and that antiestrogen effects are highly context‐dependent, without apparent differences in the estrogen receptor itself or in metabolic transformation of antiestrogens. Recent studies suggest that estrogens may promote cell proliferation, in part, (...) through the mediation of growth factors and that antiestrogens may exert some of their effects by mechanisms unrelated to the estrogen receptor. (shrink)

Since the 1970s, estrogen have sometimes been used in adolescent girls to reduce very tall adult expected height. Worries about long-term effects have led to a proposal to link treatment data with cancer registers. How should one deal with informed consent for such a study? We designed a qualitative study with semi-structured telephone interviews. From 1200 women who were to be followed-up in cancer registers, we randomly selected 22 women. Major themes were a wish to be involved and a (...) positive attitude to the proposed register research. The women did not express worry after reading the study protocol, but did convey considerable frustration that this research had not been initiated earlier. Active consent was not seen as crucial. We found strong interest in a high participation rate and a concern over missing data. The selection of information and consent or the decision to go ahead without consent in register follow-up is a delicate balancing act. Study participants wish to be contacted, but acknowledge the primary goal of answering important questions. Our study provides support for safeguarding privacy in epidemiological linkage studies and in follow-up of medical treatment without losing the scientific value by requesting for informed consent. (shrink)

Since the 1970s, estrogen have sometimes been used in adolescent girls to reduce very tall adult expected height. Worries about long-term effects have led to a proposal to link treatment data with cancer registers. How should one deal with informed consent for such a study? We designed a qualitative study with semi-structured telephone interviews. From 1200 women who were to be followed-up in cancer registers, we randomly selected 22 women. Major themes were a wish to be involved and a (...) positive attitude to the proposed register research. The women did not express worry after reading the study protocol, but did convey considerable frustration that this research had not been initiated earlier. Active consent was not seen as crucial. We found strong interest in a high participation rate and a concern over missing data. The selection of information and consent or the decision to go ahead without consent in register follow-up is a delicate balancing act. Study participants wish to be contacted, but acknowledge the primary goal of answering important questions. Our study provides support for safeguarding privacy in epidemiological linkage studies and in follow-up of medical treatment without losing the scientific value by requesting for informed consent. (shrink)

We argue that estrogen feminization of the brain is the result of a series of events initiated by differential androgen exposure. There is no need to postulate a feminizing process parallel to androgen-induced masculinization to explain the findings.

Does life have meaning? What is flourishing? How do we attain the good life? Philosophers, and many others of us, have explored these questions for centuries. As Eva Feder Kittay points out, however, there is a flaw in the essential premise of these questions: they seem oblivious to the very nature of the ways in which humans live, omitting a world of co-dependency, and of the fact that we live in and through our bodies, whether they are fully abled or (...) disabled. Our dependent, vulnerable, messy, changeable, and embodied experience colors everything about our lives both on the surface and when it comes to deeper concepts, but we tend to leave aside the body for the mind when it comes to philosophical matters. Disability offers a powerful challenge to long-held philosophical views about the nature of the good life, what provides meaning in our lives, and the centrality of reason, as well as questions of justice, dignity, and personhood. These concepts need not be distant and idealized; the answers are right before us, in the way humans interact with one another, care for one another, and need one another--whether they possess full mental capacities or have cognitive limitations. We need to revise our concepts of things like dignity and personhood in light of this important correction, Kittay argues. This is the first of two books in which Kittay will grapple with just how we need to revisit core philosophical ideas in light of disabled people's experience and way of being in the world. Kittay, an award-winning philosopher who is also the mother to a multiply-disabled daughter, interweaves the personal voice with the philosophical as a critical method of philosophical investigation. Here, she addresses why cognitive disability can reorient us to what truly matters, and questions the centrality of normalcy as part of a good life. With profound sensitivity and insight, Kittay examines other difficult topics: How can we look at the ethical questions regarding prenatal testing in light of a new appreciation of the personhood of disabled people? What do new possibilities in genetic testing imply for understanding disability, the family, and bioethics? How can we reconsider the importance of care, and how does it work best? In the process of pursuing these questions, Kittay articulates an ethic of care, which is the ethical theory most useful for claiming full rights for disabled people and providing the opportunities for everyone to live joyful and fulfilling lives. She applies the lessons of care to the controversial alteration of severely cognitively disabled children known as the Ashley Treatment, whereby a child's growth is halted with extensive estrogen treatment and related bodily interventions are justified. This book both imparts lessons that advocate on behalf of those with significant disabilities, and constructs a moral theory grounded on our ability to give, receive, and share care and love. Above all, it aims to adjust social attitudes and misconceptions about life with disability. (shrink)

The case of Ashley X involved a young girl with profound and permanent developmental disability who underwent growth attenuation using high-dose estrogen, a hysterectomy, and surgical removal of her breast buds. Many individuals and groups have been critical of the decisions made by Ashley's parents, physicians, and the hospital ethics committee that supported the decision. While some of the opposition has been grounded in distorted facts and misunderstandings, others have raised important concerns. The purpose of this paper is to (...) provide a brief review of the case and the issues it raised, then address 25 distinct substantive arguments that have been proposed as reasons that Ashley's treatment might be unethical. We conclude that while some important concerns have been raised, the weight of these concerns is not sufficient to consider the interventions used in Ashley's case to be contrary to her best interests, nor are they sufficient to preclude similar use of these interventions in the future for carefully selected patients who might also benefit from them. (shrink)

The hypothesis that foreseeable developments in interventions directed to forestall and to treat the disabilities of aging might result in the extension of the human lifespan may be further supported by the “evolutionary theory of aging.” Besides caloric restriction, several hormone supply or replacement strategies are considered to contrast the functional decline associated with aging. Hormone treatments may include growth hormone (GH), insulin‐like growth factor I (IGF‐I) signaling, dehydroepiandrosterone (DHEA), melatonin, testosterone, progesterone, and estrogen. In the 1990s, DHEA was (...) exalted as a possible candidate for the “fountain of youth.” Several experiments on animals have shown that DHEA is a multifunctional adrenal steroid with immune function enhancement, anti‐diabetic, anti‐cancer, and anti‐aging effects. The ethical questions concerning the extension of the lifespan belong to two distinct areas: the area of individual morality and the area of social morality. (shrink)

Expression of sexually dimorphic behaviors critical for reproduction depends on the organizational actions of steroid hormones on the developing brain. We offer the new hypothesis that transcriptional activities in brain regions executing these sexually dimorphic behaviors are modulated by estrogen‐induced modifications of histone proteins. Specifically, in preoptic nerve cells responsible for facilitating male sexual behavior in rodents, gene expression is fostered by increased histone acetylation and reduced methylation (Me), and, that the opposite set of histone modifications will be found (...) in females. Conversely, in ventromedial hypothalamic neurons that are responsible for coordinating female sexual behavior, transcriptional activities in genetic females are fostered by increased histone acetylation and reduced Me, and, further, that the opposite set of histone modifications will be found in males. Thus, these epigenetic events will guarantee that effects of sex hormone exposure during the neonatal critical period will be translated into lasting sex differences in adult reproductive behaviors. (shrink)

Alpha‐fetoprotein (AFP)AFP, alpha‐fetoprotein; T3R, thyroid hormone (triiodothyronine) receptor; RAR, retionic acid receptor; erbA, putative thyroid hormone receptor proto‐oncogene products; VDR, vitamin D receptor; MR, mineralocorticoid receptor; GR, glucocorticoid receptor; PR, progesterone receptor; AR, androgen receptor; HRE, hormone response element on DNA; RXR, retionic‐X‐receptor; RAP, receptor auxiliary (accessory) proteins; E, estrogen. is a tumor‐associated fetal marker, associated both with tumor growth and with birth defects. AFP, whose precise function is unknown, has been classified as belonging to a protein superfamily together (...) with albumin and vitamin D‐binding (Gc) protein. AFP has been shown to bind various ligands in vitro including fatty acids, estrogens, thyroid hormones and retinoic acids. The steroid/thyroid nuclear receptor superfamily of proteins has recently become a major focus of biomedical investigation regarding regulation of gene expression. These receptors are thought to bind to DNA‐hormone response elements (HRE) that affect growth, development, differentiation, reproduction and homeostasis. The HREs are known to share DNA sequences with the various members of the nuclear receptor superfamily. In the present report, the possibility of a leucine‐zipper dimerization (heptad) motif in the carboxy‐terminal third domain of both rodent and human AFP is postulated. The presence of nine such hydrophobic repeats in the third domain of the AFP molecule mimics the heptad dimerization repeats found in the retinoic acid, thyroid, e‐erbA and other members of the nuclear receptor superfamily. Computer analysis revealed that the most conservative matching occurred between AFP and the retinoic acid class of receptors. However, other superfamily members displayed 40–60% homology with 5 of 9 AFP heptads. These findings could provide a possible mechanism for explaining the growth‐regulatory properties (both inhibition and enhancement) that have been ascribed to AFP in the last decade. (shrink)

The use of contraceptives has become prevalent among females in Thailand in the past 20 years, and oral contraceptive use has been suggested to trigger changes in fat intake, energy expenditure, fat metabolism and blood pressure. Based on field investigations of 391 married women aged 20 years or over in Yasothon Province, North-east Thailand, this study aims to elucidate the effects of oral contraceptive use on body mass index (BMI: kg/m2 ) and blood pressure, taking into account reproductive histories and (...) socioeconomic conditions. The proportion of obese (BMI> 25) subjects was high in the age groups 3049 and 5049, 5069 age groups. Current contraceptive practices in the studied population included sterilization by operation, oral contraception and injection. These methods accounted for 43·0%, 12·8% and 8·2% of the population, respectively. Sociodemographic factors such as reproductive history, years of education and household income were not significantly related to BMI or to blood pressure (ANOVA with age adjustment). In contrast, oral contraceptive users had significantly higher BMIs and diastolic blood pressures (p<0·01, ANOVA with age adjustment). Multiple regression analysis also revealed that oral contraceptive use was a weak but significant contributing factor to both high BMI and blood pressure when sociodemographic factors were taken into account and controlled for statistically. It can thus be concluded that the use of contraceptive pills, which contain oestrogen and progestin and are provided free of charge to Thai women, tend to increase BMI and to elevate blood pressure. (shrink)

IT sounds like something out of the satirical journal Annals of Improbable Research: a team of Swedish neuroscientists scanned people's brains as they smelled a testosterone derivative found in men's sweat and an estrogen-like compound found in women's urine. In heterosexual men, a part of the hypothalamus (the seat of physical drives) responded to the female compound but not the male one; in heterosexual women and homosexual men, it was the other way around. But the discovery is more than (...) just a shoo-in for that journal's annual Ig Nobel Prize - it raises provocative questions about the science and ethics of human sexuality. (shrink)

For individuals pursuing medically assisted gender transition, gender-affirming surgical treatments, such as oophorectomy (removal of the ovaries) and orchiectomy (removal of the testicles), cause sterility, and gender-affirming hormone treatment with medications (i.e., testosterone and estrogen) may negatively impact infertility. The major United States (US) medical associations already endorse fertility preservation (FP) through cryopreservation (i.e., “freezing” egg and sperm) for transgender individuals. Despite these endorsements from the relevant medical societies, medical insurance coverage for FP remains very limited in the US. (...) Given the high out-of-pocket costs for FP services, fertility preservation remains financially out of reach for many transgender individuals who may desire it. We present an ethical justification for universal FP coverage for all transgender and gender diverse (TGD) individuals who request this option during medically assisted gender transition. First, we argue that gender-affirming medical care is analogous to other medical interventions and treatment regimens that compromise fertility, such as cancer care, and that both types of interventions need to be afforded the same medical benefits and assistance in pursuing fertility goals. Second, we argue that the lack of FP for transgender individuals contributes to the ongoing and profound transphobia and anti-trans bias that has been exacerbated in the past several years across the healthcare landscape in the United States. We argue that the provision of FP coverage for transgender individuals is necessary for clinicians and third-party payers to state their unequivocal support for TGD patients and their healthcare needs. (shrink)

This “current controversies” contribution describes the recent case of a severely disabled six year old girl who has been subjected to a range of medical interventions at the request of her parents and with the permission of a hospital clinical ethics committee. The interventions prescribed have become known as “the Ashley treatment” and involve the performance of invasive medical procedures (eg, hysterectomy) and oestrogen treatment. A central aim of the treatment is to restrict the growth of the child and thus (...) make it easier for her parents to care for her at home. The paper below discusses the main objections to the treatment. It concludes that the most serious concern raised by the case is that it may set a worrying precedent if the moral principle employed in justification of the treatment is applied again to endorse it in similar circumstances. Finally, it raises the possibility that that same moral principle may even be invoked to justify more radical interventions than those that were actually performed in the Ashley treatment. (shrink)

In Phillip Kerr’s 1994 spellbinding novel A Philosophical Investigation, the medical test to which the protagonist refers is a functional brain scan based on positron emission tomography. It is used to run large studies of male and female brains and, following a lead suggested by animal studies, has been used to identify rare cases of human male subjects who lack the ventral medial nucleus. This nucleus, in the experiment, is hypothesized to inhibit the activity of the sexually dimorphic nucleus, a (...) preoptic area of the male brain believed to be a repository of male aggressive response. Prior research, we learn from the plot, shows that 3 in 100,000 human males are VMN-negative. Thirty percent of those affected are believed to be in prison or to have a criminal record; 70% are believed to stabilize levels of aggression by producing increased levels of estrogen. Identities of subjects participating in the brain scan studies are protected through the conversion of real names to those of famous figures of the past — Bertrand Russell, Charles Dickens. Those for whom results are unfavorable are recontacted, and they are offered counseling. (shrink)

The case of Ashley X involved a young girl with profound and permanent developmental disability who underwent growth attenuation using high-dose estrogen, a hysterectomy, and surgical removal of her breast buds. Many individuals and groups have been critical of the decisions made by Ashley's parents, physicians, and the hospital ethics committee that supported the decision. While some of the opposition has been grounded in distorted facts and misunderstandings, others have raised important concerns. The purpose of this paper is to (...) provide a brief review of the case and the issues it raised, then address 25 distinct substantive arguments that have been proposed as reasons that Ashley's treatment might be unethical. We conclude that while some important concerns have been raised, the weight of these concerns is not sufficient to consider the interventions used in Ashley's case to be contrary to her best interests, nor are they sufficient to preclude similar use of these interventions in the future for carefully selected patients who might also benefit from them. (shrink)

Many clinicians are experiencing consumer resistance to the prescription of equine HRT (that is hormone replacement therapy which has been manufactured from mare's urine). In this paper I consider the ethical implications of prescribing these preparations. I decide that patients should have a right to refuse such treatment but also ask whether a prescribing doctor should choose one preparation over another on moral grounds. I determine that there is prima facie evidence to suggest that mares may suffer and that prescription (...) of equine HRT (instead of synthetic oestrogen-oestriol) would therefore have to be justified in terms of either offering greater benefits to the women or offering greater value for money to the health service. I find that there is no substantial evidence to suggest that equine HRT offers unique advantages over and above oestriol. I conclude that it would be preferable for a doctor to recommend the synthetic oestrogen to women who want relief from the symptoms of the menopause and protection from osteoporosis and cardiovascular disease. (shrink)

In this paper we provide a critical review of research concerned with social/environmental mechanisms that modulate human neuroendocrine function. We survey research in four behavioral systems that have been shaped through evolution: competition, partnering, sex, and pregnancy/parenting. Generally, behavioral neuroendocrine research examines how hormones affect behavior. Instead, we focus on approaches that emphasize the effects of behavioral states on hormones (i.e., the “reverse relationship”), and their functional significance. We focus on androgens and estrogens because of their relevance to sexually selected (...) traits. We conclude that the body of research employing a reversed or bidirectional perspective has an incomplete foundation: participants are mainly heterosexual men, and the functionality of induced shifts in neuroendocrine factors is generally unknown. This area of research is in its infancy, and opportunities abound for developing and testing intriguing research questions. (shrink)

Researches over many years have examined whether levonorgestrel emergency contraception has a postfertilization effect. In a recent article in the Catholic Health Association’s journal Health Progress, Sandra Reznik, MD, asserts that “levonorgestrel acts to prevent pregnancy before, and only before, fertilization occurs.” A companion article by Ron Hamel, PhD, argues for the moral certainty that Plan B is not an abortifacient. Reznik fails to address the principal model supporting a potential postfertil­ization mechanism of action, specifically, that preovulatory administration of levonorgestrel (...) disrupts the delicate ratio of estrogen and progesterone essential to healthy endometrial development and induces the equivalent of luteal phase insufficiency, thereby jeopardizing implantation. Hamel’s argument for moral certitude is similarly inadequate. This article critically reviews both articles and the sources on which they rely. National Catholic Bioethics Quarterly 10.4 : 741–772. (shrink)

In Testo Junkie, Preciado briefly introduces the figure of the ‘techno-Barbie’. Contrasted with his own Testogel-fuelled pornographic experiments, the possibilities of oestrogen or progesterone seem somewhat uncharitably foreclosed upon. Though Preciado draws our attention to the gendered politics of chemical enhancement and hormonal justice, it begs the question: where do we draw the line between experimentation and chemical domination? We engage with the figure of the techno-Barbie to explore our own experiments with hormones and gendered agency in the boundaries of (...) advanced biocapitalism. Drawing on a range of allied texts, we explore the ambivalences of our own hormonal experimentation. What kinds of hormonal experiments are allowed to be cast as such? In response to this all-encompassing theory of domination, we ask: how might the techno-Barbie speak back? (shrink)

Female sex steroids can affect the motor system, modulating motor cortex excitability as well as performance in dexterity and coordination tasks. However, it has not yet been explored whether FSS affects the cognitive components of motor behavior. Mu is a sensorimotor rhythm observed by electroencephalography in alpha and beta frequency bands in practices such as motor imagery and action observation. This rhythm represents a window for studying the activity of neural circuits involved in motor cognition. Herein we investigated whether the (...) alpha-mu and beta-mu power in the sensorimotor region and the alpha and beta power over frontal, parietal, and occipital regions are modulated differently in the menstrual, follicular, and luteal phases of menstrual cycles in right-handed dominant women. To do so, these women underwent MI and AO in the three menstrual cycle phases. The spectral activity of the cortical regions for the alpha and beta bands were compared between phases of the menstrual cycle and a correlation analysis was also performed in relation to estrogen and progesterone levels. For the hypothesis-based approach, beta-mu event-related desynchronization was significantly stronger in the C3 channel in the follicular phase than in the menstrual and luteal phases. For the data-driven approach, beta ERD during MI was higher in the follicular phase than in the menstrual and luteal phases in the frontal region. These findings suggest the effect of FSS on executive movement control. No effect of menstrual cycle phases was observed in cortical areas investigated during OA, but alpha and beta bands correlated positively with the follicular phase plasma estradiol level. Thus, the attenuation of alpha and beta bands referring to mirror neuron activities appears to be associated with inhibition of cortical activity when estradiol levels are lower, improving cognitive processing of motor action. (shrink)

Osteoporosis, a disease of bone loss associated with aging and estrogen loss, can be crippling but is ‘silent’ prior to bone fracture. Despite its disastrous health effects, high prevalence, and enormous associated health care costs, osteoporosis lacked a universally accepted definition until 1992. In the 1980s, the development of more accurate medical imaging technologies to measure bone density spurred the medical community’s need and demand for a common definition. The medical community tried, and failed, to resolve these differing definitions (...) several times at consensus conferences and through published articles. These experts finally accepted a standard definition at an international consensus conference convened by the World Health Organization in 1992. The construction of osteoporosis as a disease of quantifiable risk diagnosed by medical imaging machines reflects contemporary trends in medicine, including the quantification of disease, the risk factor model, medical disciplinary boundaries, and global standardization of medical knowledge. (shrink)

Abstract11β‐hydroxysteroid dehydrogenases regulate glucocorticoid concentrations and 17β‐hydroxysteroid dehydrogenases regulate estrogen and androgen concentrations in mammals. Phylogenetic analysis of the sequences from two 11β‐hydroxysteroid dehydrogenases and four mammalian 17β‐hydroxysteroid dehydrogenases indicates unusual evolution in these enzymes. Type 1 11β‐ and 17β‐hydroxysteroid dehydrogenases are on the same branch; Type 2 enzymes cluster on another branch with β‐hydroxybutyrate dehydrogenase, 11‐cis retinol dehydrogenase and retinol dehydrogenase; Type 3 17β‐hydroxysteroid dehydrogenase is on a third branch; while the pig dehydrogenase clusters with a yeast multifunctional (...) enzyme on a fourth branch. Pig 17β‐hydroxysteroid dehydrogenase appears to have evolved independently from the other three 17β‐hydroxysteroid dehydrogenase dehydrogenases; in which case, the evolution of 17β‐hydroxysteroid dehydrogenase activity is an example of functional convergence. The phylogeny also suggests that independent evolution of specificity toward C11 substituents on glucocorticoids and C17 substituents on androgens and estrogens has occurred in Types 1 and 2 11β‐ and 17β‐hydroxysteroid dehydrogenases. (shrink)

Contemporary hormonal therapy for the menopause has its conceptual origins in the ancient tradition of organotherapy. The popular but pharmacologically inactive precursors of hormonal therapy were developed as part of a resurgence of interest in organotherapy in the 19th century, which coincided with increasing medicalization of the menopause and the view that the ovaries were responsible for the ‘feminine’ identity and wellbeing of women. The subsequent chemical identification of oestrogens allowed the development of pharmacologically active hormonal therapy for the menopause, (...) which was probably first used clinically in the late 1920s. Around this time, emphasis shifted from the ovaries to oestrogen as being responsible for femininity and health, with the menopause and ageing increasingly defined as oestrogen deficiency diseases. Hormonal therapy for the menopause was first used predominantly for women who had a premature menopause. In the 1960s, universal prescription was increasingly promoted as a way of preventing diseases of later life and the perceived ‘defeminization’ of women by menopause. Scientific evidence regarding the risks and benefits of hormonal therapy for the menopause has been accruing over the last 70 years; its interpretation has been affected by background beliefs regarding the effects of oestrogen and the menopause on women. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Feminist Studies 41, no. 3. © 2015 by Feminist Studies, Inc. 571 Moving through Cancer: An Interview with Carol Collins Artist Carol Collins spoke with Feminist Studies editorial collective member Stephanie Gilmore about her experience of cancer, treatment, and recovery and how it gave rise to an art series that examines what nature means in the midst of unnatural treatments. SG: Carol, thank you for the opportunity to speak (...) with you about your artwork. Having just lost my sister to cancer, your work reminds me of much pain and loss, but also of love and the desire to survive. Before we discuss the work itself, I would like to hear about your journey through cancer, treatment, and recovery. CC: The breast cancer patient’s journey is complex and perilous. When I was healthy, I was ignorant about the magnitude of suffering many cancer patients undergo. And, although I am a private person, I’m now publicly sharing my cancer experience in order to be a voice for those who have suffered through similar treatments—and worse—and those who sadly are no longer with us to tell their story. Being bald and nauseated are not the most awful possible side effects of the treatments, although they are the most well known. Some women survive the cancer but can die from the treatments, or others suffer through the treatments and die anyway. Often, it seems many believe patients can overcome their 572 Carol Collins adversity solely with positive thinking and persistence. However, not discussing the array of physical and psychological damage that even those with good prognoses incur propagates ignorance about this malady. I hope that my artwork and story will promote a deeper understanding of a breast cancer patient’s plight and will encourage more support for research for individualized therapies and prevention. My cancer journey began when I received a breast cancer diagnosis in January 2014. Life just before that point was good; the future was bright. Tendon pain, caused by my flat feet and a lot of exercising, was my only known ailment. But one day a routine mammogram revealed three tumors in my right breast. The radiology oncologist said the masses were highly likely to be cancerous, so he immediately did painful core biopsies at the sites of my three tumors. The next day, it became clear that we needed to act quickly. The biopsy results revealed I had a very aggressive invasive breast cancer with estrogen, progesterone, and HER2 receptors. Breast cancer in premenopausal women grows quickly due to the high level of hormones present. The oncologists and surgeons said I would, at a minimum, need a mastectomy and possibly lymph node resection, and they warned that I would likely need chemotherapy, which would destroy my eggs and ovaries. After learning of my limited options, I approved the removal of one breast and my sterilization. I knew I needed to think rationally and face the giant raven before me head on. However, I did not realize the magnitude and multitude of physical and psychological pains, illnesses, and losses that were soon to come. The first year of cancer treatments inflicted much physical pain. I received three extremely painful injections into my right breast with a radiolabeled colloid just prior to the mastectomy. The pain came from the injected dye, not from the needle. The modified radical mastectomy was more excruciatingly painful than I anticipated, even with painkillers and overnight hospitalization. Breast reconstruction was an option that added more pain and discomfort from weekly fillings of the installed “expander” and additional surgeries. Extreme pain after the mastectomy prevented me from lying down for months. Foolishly, I did not get an injection port installed in my chest. Instead, I endured numerous deep (and often unsuccessful) needle pricks into the seemingly few veins of my left arm (which still had its lymph nodes) that were appropriate for infusions over the period of a year. Shooting pains across my chest and arm were the norm. Carol Collins 573 In addition to the surgically induced physical pain, the chemotherapy quickly caused a myriad of undesirable physical side effects. It is scary to realize that the medical community does not often fully understand... (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Game ChangeMaximo CortezOn November 17, 1983, I was born with a condition called mixed gonadal dysgenesis, and ambiguous genitalia. My gender was not of a big concern at that time. The more urgent matter was that I had a heart murmur, which was repaired when I was twelve months old. [End Page E5]It was not until I turned five, and by issue of the Texas Children’s Protective Services (CPS), (...) that my mother was forced to authorize providers to perform normalization surgeries on me. An anonymous caller tipped the CPS that my mother was raising a boy as a girl. The state intervened and explained to my mother that she would have to consent to these surgeries or else she would lose custody of me. This included a gonadectomy and a clitorectomy. Without any consent, these surgeries were performed “in my best interests.” My mother was an epileptic, Hispanic, Mormon, single parent.I was raised to be a socially acceptable female, though as early as five, I played with “boy” toys and enjoyed TV programs aimed at male youth, like Teenage Mutant Ninja Turtles. It was not until I had those normalization surgeries performed on me that I felt different. I knew that something major had happened to me. I woke up in a hospital bed in a gown. I raised the covers and noticed that I had an “X” carved in my groin area. Doctors mutilated my clitoris by reducing its size, which made me feel alienated and angry that something was wrong with my body.I had a surgery performed on me that was to be kept secret and never talked about. This sense of fear and shame was instilled in me shortly after the surgery. I do not recall any psychological evaluations or counseling to help me cope with such surgeries. Seeing everyone else my age going through puberty during my teenage years, I felt behind. I wasn’t becoming a boy with a deep voice or facial hair. Instead, I visited the doctor’s office with my mom and was told that I would be taking oral estrogen to become a woman. I wasn’t until that moment that I understood I was seeing a doctor to foster the development of female secondary characteristics. I felt betrayed by the medical community and by my own mother.Just a few years later, I saw a urologist to find out whether I was ready for a vaginal construction surgery (vaginoplasty). Thankfully the urologist suggested that I was not ready to move forward with an invasive and irreversible vaginal construction surgery. I never pursued it as an adult, as I have always felt male gendered.Social sexual relationships have always been difficult for me but more so with my attraction to women. I first realized my attraction to women in early middle school. Being raised Mexican and a Mormon and knowing that I was homosexual created a lot of conflict for me. I felt that I was a male–gendered person forced into a castrated, mutilated, and medically created female body. I suffered through depression from an early age and it continues today. My conservative Mormon upbringing brought me much shame. The Mormon religion, as most people understand it, expresses a great intolerance to homosexuals and transgender people. I felt like I was a heterosexual male in a female’s body, but the Mormons would never accept me.My later teenage years and mid–twenties were a dark time in my life. I even attempted suicide in my early twenties. My depression was treated with antidepressants and talk therapy. Once I began testosterone, I gradually stopped taking antidepressants. When I was only on estrogen, I felt very moody, angry, and in an emotional funk. I would cry easily and would become very irritable and emotional without cause. With testosterone therapy, I began to think more clearly, had balanced emotions, and began to think more logically.I began to research intersex online and found a women’s androgen insensitivity (AIS) support group. At one of their national conferences, I met another intersex individual who was raised as a female and who had transitioned to male. Like me... (shrink)

The transforming growth factors beta are a family of peptides which are involved in the regulation of cell growth and differentiation. It has been suggested that the loss of sensitivity to growth inhibition by endogenous TGF‐β may contribute to the process of carcinogenesis in epithelial systems. However, many breast cancer cells remain sensitive to the growth inhibitory effects of these peptides, suggesting that the local induction of TGF‐β could provide a pharmacological approach to chemoprevention. Triphenylethylene anti‐oestrogens, synthetic progestins and retinoids (...) all offer potential as chemopreventative agents. A common feature of their mechanism of action is the ability to locally increase the production of the transforming growth factors beta. (shrink)

A number of commentators agree that the evidence reviewed in the target article supports a previously unrecognized role for ovarian hormones in feminization of the brain. Others question this view, suggesting that the traditional model of sexual differentiation already accounts for ovarian influence. This position is supported by various reinterpretations of the data presented (e.g., ovarian effects are secondary to the presence/absence of androgen, ovarian effects are smaller than testicular effects, ovarian effects are not organizational). We discuss these issues, and (...) reiterate our position that evidence of neurobehavioral ovarian effects is incompatible with the currently accepted model of sexual differentiation. Other points regarding species generalizations, the direct versus indirect action of estrogen, and nonhormonal mechanisms of sexual differentiation are also discussed. Finally, we address the controversial issue of using ratio scores in the assessment of the human corpus callosum (where CC scores are divided by an index of brain size). Future applications to human research are also discussed. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Transgressive Translations:Parrhesia and the Politics of Being UnderstoodTim R. JohnstonAuthor And Activist Julia Serano’s spoken word poem “Performance Piece” is a smart and passionate polemic against people who say that “all gender is performance” (Serano 2010, 85). In response to those who treat gender as an endlessly mutable fiction, performance, or facade Serano says:Sure, I can perform gender: I can curtsy, or throw like a girl, or bat my (...) eyelashes. But performance doesn’t explain why certain behaviors and ways of being come to me more naturally than others. It offers no insight into the countless restless nights I spent as a pre-teen wrestling with the inexplicable feeling that I should be female. It doesn’t capture the very real physical and emotional changes that I experienced when I hormonally transitioned from testosterone to estrogen. (Serano 2010, 85–86)My first reaction to this understanding of performativity was to get defensive, immediately thinking of all the ways in which it reflects a poor reading of Judith Butler and is an incorrect use of the concept. Yet, to make that argument would mean arriving late to the party. Many theorists, notably Jay Prosser and Viviane Namaste, have made similar arguments about performativity to which Butler and many others have responded. I am not interested in joining this debate by defending or critiquing performativity; instead, I want to take seriously Serano’s criticism of the way performativity functions as a “mantra” for [End Page 84] “queerer-than-thou hipsters” (Serano 2010, 87). The fact is, concepts that help people make sense of their experience are often taken up piecemeal. They gain traction, get printed on posters, discussed in safe-spaces, taught in intro classes, and yelled at parents. They take on a life of their own and are queered again and again. It may not be anyone’s fault that performativity has come to signify a kind of insincerity, detachment from the body, linguistic constructionism, or a play of surfaces, but for many people this is exactly what it means. What follows is inspired by the questions at the heart of Serano’s poem: “Can’t we find new ways of speaking? Shouldn’t we be championing new slogans that empower all of us, whether trans or non-trans, queer or straight, female and/or male and/ or none of the above?” (Serano 2010, 87). I depart slightly from Serano insofar as I am not interested in replacing performativity as a concept. Instead, I am interested in locating other concepts that could be useful in understanding and communicating our multiple experiences of gender.Serano’s concern is not only the depth and conviction with which she experiences gender, but also the communicability of this conviction. We are social beings. We seek out the company of other people, animals, and objects. In order to flourish we need to feel understood by our surroundings. We are creatures that need to be connected, and connection requires translating our subjective experiences into a communicable, socially understandable register. How does this translation occur? How do we make ourselves understandable? What external forces regulate or influence this translation? And, crucially, how can we construct philosophical concepts that do justice to our need to feel that our interior selves are understood? What concept could we cast out into the world that might answer Serano’s call for new ways of speaking? What follows is an attempt to think through this question by looking at the relationship between the medicalization of trans people, Michel Foucault’s writings on parrhesia, and coming out.The first half of this essay examines the ways in which the medical apparatus that manages transitioning attempts to control transsexual coming-out narratives, an example of what Foucault calls biopower. I argue that the medicalization of transitioning has created a legible transsexual identity structured on the distance between our interiority and the world external to the self. The trans person’s claims about their interior sense of self are the only evidence needed to access medical technologies such as hormone therapy or surgery. But oftentimes such claims are only accepted as valid if they conform to certain scripts—scripts that are... (shrink)

Developmental counts of axons in the splenium of the rat corpus callosum are compatible with the hypothesis that estrogen may be acting late in development to sculpt the female nervous system.

Open science hardware (OSH) are prototypes of laboratory instruments that use open source hardware to extend the purely epistemic (improving knowledge about nature) and normative (improving society) ideals of science and emphasize the importance of technology. They remind us of Zilsel’s 1942 thesis about the artisanal origins of science and instrument making that bridged disciplinary and social barriers in the 16th century. The emphasis on making, tinkering, and design transcends research, reproducibility, and corroboration in science and pushes to the forefront (...) educational, emancipatory, and aesthetic and exploratory uses. I will use two recent projects, OpenDrop electrowetting platform and Open Source Estrogen that make but also reflect OSH’s playful, expressive, and performative strategies and define the present practices as “artisanal science.” These hybrid and ambiguous practices bridge divides between present disciplines and skills but they also define science as an everyday activity directly connected to the private and public interests of the citizens. To describe this epistemic and normative ambiguity of artisanal science, I employ Hannah Arendt’s 1958 critique of homo laborans and homo faber and claim that science artisans (citizen scientists, geeks, makers, and hackers) offer an alternative to professionalization of science as practiced in the university and R&D laboratories. Science artisans design and build instruments to engage in civic “vita activa” over instruments but also leisurely “otium” outside of the work and science labor. OSH in this sense empowers individuals and communities to explore new connections between scientific practices, public actions, and private interests (leisure). The science artisans strive for and explore sovereignty, dignity, and freedom in an age immersed in science and technology controversies by bridging the divides between art, science, engineering, and humanities. (shrink)

Retinoids play an important role in development and differentiation(1,2). Their effect is mediated through nuclear receptors, RAR (α, β and γ) and RXR (α, β and γ),Abbreviations. RAR: retinoic acid receptor; RXR: retinoid X receptor; T3:thyroid hormone receptor; VD3R: vitamin D3 receptor; PPAR: peroxisome proliferator activated receptor; EcR ecdycsone receptor; USP, ultraspiracle; NGFI‐B: also referred to as nur77a; ELP: embryonal long terminal repeat‐binding protein; FTZ‐F1: positive regulator of the fushi tarazu gene in blastodermstage embryos of Drosophila melanogaster; GR: glucocorticoid receptor; (...) ER: estrogen receptor; RARE, retinoic acid response element; PR: progesterone receptor; DR+x: direct repeat with a spacing of x nucleotides; DBD: DNA‐binding domain; CRABP I and II: cellular retinoic acid binding protein type I and II, respectively; MoMLV: Moloney Murine Leukemia Virus; TBP: TATA‐binding protein; TAF: TBP associated factor. which are members of a distinct subclass (hereafter referred to as type II) of the nuclear receptor superfamily that includes the thyroid hormone receptor (T3R), the vitamin D3 receptor (VD3R) and the peroxisome proliferator activated receptor (PPAR). Type II receptors transactivate through binding sites composed of closely related half‐sites (consensus sequence AGG/T TCA) arranged as direct repeats and, with the possible exception of RXR, do not bind to their cognate binding sites as homodimers but require RXR for high affinity binding. RXR thus provides a link between biologically distinct ligand induced pathways and is a potential target for cross‐regulation. In addition, RAR can utilize alternative routes to enhance transcription initiation mediated through transcriptional co‐activators which are expressed in a cell‐type specific manner. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Promoting Health and Social Progress by Accepting and Depathologizing Benign Intersex TraitsHida ViloriaI was born with ambiguous genitalia and it was a doctor who, by honoring my bodily integrity and not “fixing” me, gave me the greatest gift I’ve ever received. Because my body and its sexual traits are a positive, fundamental part of my experience and identity as a human being, I know that having my genitals removed (...) or altered according to someone else’s vision would have deeply damaged me, both physically and psychologically.The doctor who protected my autonomy was, unsurprisingly, my father. I say “unsurprisingly” because in my experience parents are typically more protective of their children than doctors are of their patients. Also, doctors do not discuss cases with other doctors in the same way they do with laypeople, as doctors know more about medical issues such as the risks involved in infant genital surgery.Other than having clitoromegaly (a large clitoris), my reproductive anatomy is typically female, and so I was assigned female and raised as such without incident. My parents didn’t discuss my intersex traits with me, and I grew up thinking of myself and being accepted as, a girl.When I began menstruating, my father told me I’d need to take pills to “grow taller.” I thought this unusual, as I wasn’t short, and later overheard my mother arguing with him, saying that the pills were “experimental”. I was reminded of this discussion years later, when she told me that the pills had actually been hormones to make my breasts grow. I never took them though as she convinced my father not to make me.Article 7 of The International Covenant on Civil and Political Rights states that, “No one shall be subjected without his free consent to medical or scientific experimentation,” and I’m grateful to both my parents for protecting my civil rights as they protected my health.Due to my Catholic upbringing and schooling, I had no opportunity to compare my genitals to other girls’, and it wasn’t until the age of twelve that I realized, while perusing magazines with friends, that I have atypical sex anatomy. Contrary to common speculation however, this awareness didn’t make me question being female. I simply assumed there must be some genital variation in humans.I feel my parents made the wisest decision possible by registering me as one of the two accepted, available genders but allowing me to live, physically and behaviorally, as who I am. Despite not having developed a stereotypically curvaceous female figure, I was popular and excelled in typically feminine social activities, as well as sports and academics. For example, I was one of four girls selected out of one hundred twenty–five that competed for a spot on my high school cheerleading [End Page 114] squad when I tried out to help a friend who needed a tryout partner.Other than escaping IGM (Intersex Genital Mutilation) and estrogen therapy, I’ve had only a few experiences pertaining to my medical care around being intersex. These experiences fall into two categories: seeing medical doctors who treated me the same after discovering that I have ambiguous genitalia, and seeing ones who didn’t. I feel incredibly blessed that my experiences in the former category vastly outweigh the latter.My first experience came at the age of twenty, when a gynecologist asked me if my clitoris had always been as large as it is. I responded that it had, and she said, while looking at me disapprovingly, that she’d like to do some tests. When I asked her what they were for though, she wouldn’t respond directly. She said I’d reported having some upper lip hair, and acne, on my intake forms. I replied that neither were above average, and asked if there were health issues I should be concerned about. She reluctantly said no. I asked what reason there was then for undergoing tests because of the size of my clitoris.She finally responded, “It’s just not normal.”Fortunately, I’d had positive reactions to my sex traits from the people I’d dated. For example, the first... (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Removing the Mask: Hopeless Isolation to Intersex AdvocacyAlexandra von KlanStrangers undoubtedly perceive me as female, but I identify as an intersex woman. My karyotype is 46,XY, a typically defined marker of male biological sex, and I was born with undeveloped, non–functioning gonads. As an intersex person, I know firsthand the negative consequences of pathologizing intersex people’s lived experience by categorizing otherwise healthy, functioning organs and bodies as abnormal. The (...) following narrative recounts conversations and interactions with medical providers during my diagnosis and subsequent treatment of pure XY gonadal dys-genesis, sometimes referred to as Swyer Syndrome. I hope to elaborate upon emotionally significant actions and inactions of medical care providers to expose consequential effects on my emotional processing, physical health, and self–actualization.In December 1988, I was born with “typical” female genitalia. No one knew I was an intersex woman with 46,XY karyotype. Thus, there was no hesitation in the announcement of the birth of a girl in the delivery room or later, on my birth certificate. My parents raised me as a girl and dressed their firstborn in culturally normative feminine garments and accessories: lace frilly frocks, oversized bows, white stockings, and black patent leather Mary Jane’s. I embraced femininity and expressed this gender identity throughout my childhood and adolescence. I’m the eldest of six children split between two households.In January 2005, a month after my sixteenth birthday, delayed puberty and absent menstruation prompted an appointment to a local women’s health center. Nurses collected blood samples and administered an MRI scan on my pelvic region. A week later, my father received a perplexing phone call. An inexperienced doctor told him “there must be something wrong” with me, because lab results revealed I was “chromosomally male.” My father recalls the information presented like, based on the evidence, “your daughter may not be completely female,” and that is that. His impression was that she knew little about the subject and was a bit clueless. She did not mention Swyer Syndrome, or any diagnosis for that matter.Up to this point, I was unaware that a member of my extended family also had Swyer Syndrome. Born in the 1950s, secrecy engulfed her medical treatment and doctors warned her parents against revealing her true chromosomal sex in order to prevent the hysterical panic and depression they [End Page E14] thought the truth would bring. Years later, she sought her medical records and unearthed the truth. Shortly after my father received that dubious phone call, my relative’s endocrinologist provided a referral to his mentor, “Doctor A,” a clinical reproductive endocrinologist.Under Doctor A’s care, I experienced the first of many pelvic exams. Much to my discomfort, Doctor A inspected my semi–clothed body with a male resident in the room. As a people–pleasing teen, I granted permission for his presence; I didn’t voice my preference for a female alternative. Doctor A’s cold hands pressed around each undeveloped breast, pulled a gown away from my hips to inspect a sparse patch of pubic hair, and conducted an examination of my vaginal canal.Shortly after the examination, Doctor A charted Swyer Syndrome as the official diagnosis. Speaking to my father and me, he described my condition as an extremely rare genetic mutation. He told us that Swyer Syndrome was an intersex condition, a group of congenital disorders impacting a person’s internal or external reproductive systems, including endocrine function and genitalia. He explained I had atypical streak gonads instead of ovaries and that, despite having typical male sex chromosomes, I was still very much a girl. He disclosed that my vaginal canal was moderate in length, perhaps further evidence—or consolation—that my body possessed normative female reproductive attributes after all.Next, Doctor A identified a pressing medical concern—golf–ball–sized benign tumors had developed on each streak gonad; if allowed to remain, they would pose an increasing risk of malignancy. We scheduled an appointment for laparoscopic gonadectomy six months later. I left his office with a 3–month prescription for estrogen and progesterone oral tablets. On the way home, we drove to an electronics store where my father... (shrink)