Literary reports on dystonia date back to post-Medieval times. Medical reports are instead more recent. We review here the early descriptions and the historical establishment of a consensus on the clinical phenomenology and the diagnostic features of dystonia syndromes. Lumping and splitting exercises have characterized this area of knowledge, and it remains largely unclear how many dystonia types we are to count. This review describes the history leading to recognize that focal dystonia syndromes are a coherent clinical set encompassing cranial dystonia (including blepharospasm), oromandibular dystonia, spasmodic torticollis, truncal dystonia, writer’s cramp, and other occupational dystonias. Papers describing features of dystonia and diagnostic criteria are critically analyzed and put into historical perspective. Issues and inconsistencies in this lumping effort are discussed, and the currently unmet needs are critically reviewed. Bolgia four), by the divine law or retaliation for having looked too far forward, with their head twisted backwards . Into a similar infernal atmosphere, he described the healing of Epistemon, “who had his head cut off, was finely healed by Panurge, and brought news from the devils, and from the damned people in hell” … “Thus as they went seeking after him, they found him stark dead, with his head between his arms all bloody” … “Panurge took the head and held it warm foregainst his codpiece, that the wind might not enter into it. Eusthenes and Carpalin carried the body to the place where they had banqueted, not out of any hope that ever he would recover, but that Pantagruel might see it. … Then cleansed he his neck very well with pure white wine, and, after that, took his head, and into it synapised some powder of diamerdis, which he always carried about him in one of his bags. Afterwards he anointed it with I know not what ointment, and set it on very just, vein against vein, sinew against sinew, and spondyle against spondyle, that he might not be torticollis . This done, he gave it round about some fifteen or sixteen stitches with a needle that it might not fall off again; then, on all sides and everywhere, he put a little ointment on it, which he called resuscitative.”Rabelais (circa in 1532) introduced the French neologism torticollis , a condition he observed in four unrelated Jewish children who came to Berlin to be seen by him (dysbasia lordotica progressiva (progressive gait difficulty with lordosis), as he noted the occurrence of pronounced and progressive lordosis in his patients. A similar phenomenology had been previously observed in a Jewish kindred by Theodor Ziehen, professor of psychiatry in Berlin, who asked his resident Markus Walter Schwalbe to write a dissertation on this peculiar phenomenology. Ziehen presented his observations in Berlin in December 1910 and published the family in 1911 as well , we cannot be satisfied for the reason that in some, such as our two patients, the disease is as strong in the upper as in the lower extremities, and dysbasia is not the principal symptom. We have also shown that there is no hypotonia in our patients, and we also believe that the word ‘deformans’ contains something stable, which is not true in the case of the essentially mobile spasm.”The clinical descriptions in Flatau–Sterling publication are particularly interesting, probably because they have appeared later than Oppenheim’s publication. Oppenheim defended that: “the clonic jerks do indeed belong to the clinical picture,” “the hypotonia is a major element of the symptomatology,” and “the tonic cramps are very predominantly connected with the function of standing and walking.” Hence, he proposed to name the disease “dystonia”  or “dysbasia” . Flatau and Sterling reasoning led them to dispute this terminology. They stated: “With the name suggested by Oppenheim  selective systemic symptoms in the form of dystonic movements and postures; (b) gradual development, without recognizable etiological factors at the onset. He also distinguished early forms occurring shortly after birth, from the juvenile form with the onset between 5 and 15, and the late form after 15 years of age.Numerous reports followed. In a review of all published cases, Mendel summarized the significant clinical data and introduced the expression “torsion dystonia” to indicate a specific nosologic entity distinguished from other types of involuntary movements, such as hysteria, double athetosis, chorea, and myoclonus . During Notwithstanding these scholarly observations, torticollis and generalized dystonia were still considered two separate and distinct conditions. Craft neuroses  were also considered a distinct group of “functional disorders which are characterized by a difficulty in performing specific coordinated movements of certain occupations” . The besWriter’s cramp was another medical condition known since 1700 from the work of Bernardino Ramazzini, the father of occupational medicine , who staEye and facial spasms were a yet different condition. A notable artistic description of cranial dystonia was likely provided circa in 1558 by the vivid painting of an elderly woman made by Pieter Brueghel . The firSpasmodic dysphonia was probably first described by Traube in the second volume of his textbook  and lateThe first glimpse to a possible connection among different focal dystonia syndromes was the observation that two patients with “spasmodic torticollis” also had “functional spasms” in other body regions, including the right thigh, the upper limb while writing (writer’s cramp) and the left foot . A seconZeman et al.  summariz“Within this family there is a considerable variability of expressivity of the disease. For instance, V-14 shows symptoms of dystonia in a very mild form, manifested by temporary limping, torticollis and blepharospasm. At times this patient appears almost normal. On the other hand, three of his siblings are totally crippled and helpless. V-10 has neither spontaneous movements nor the typical dystonic posture. Yet, upon performing certain volitional movements, typical dystonic features can be easily elicited. Certainly in cases like these two, one could take the position that such manifestations do not justify the diagnosis of dystonia. Yet, it would be illogical to consider any other diagnosis in view of the fact that grandmother, father, siblings, and one child are so definitely affected by dystonia. Applying ‘Occam’s razor’ of scientific parsimony, it is certainly the most logical conclusion that this family exhibits ‘formes frustes’ as well as full-fledged cases of dystonia. Obviously, the strict diagnostic criteria as set forth by Herz  were notThe following years witnessed the development of stereotactic and functional neurosurgery, which was applied to dystonia as well as to Parkinson’s disease. At the same time, there were attempts to understand and classify the diverse causes of dystonia. Levodopa, the newly discovered treatment for Parkinson’s disease, was also tried in dystonia . Denny-BIn 1966, Jacob A. Brody, Chief of Epidemiology Branch at NINDS, and Irving S. Cooper, Head of Neurologic Surgery at St. Barnabas Hospital, discussed possible epidemiologic studies utilizing the large population of patients with neurological diseases seen at St. Barnabas Hospital over the years. During the course of their talks, Dr. Cooper mentioned that he had operated on approximately 200 patients with torsion dystonia. Dr. Roswell Eldridge, a trained medical geneticist, had just joined Dr. Brody’s staff, and he sensed a fertile ground for a genetic study of this disease. He then gathered a body of information on torsion dystonias, which provided important insights on the various genetic forms of the disease, their clinical presentation, and geographic and ethnic patterns. On January 9, 1970, Dr. Roswell Eldridge convened a conference on the torsion dystonias at NIH in Bethesda, MD, USA.When he moved from St. Thomas’s Hospital to King’s College in 1970, David Marsden was already interested in the pathophysiology of movement and had studied the physiology of human tremor. In 1973, he gave a lecture on drug treatment of diseases characterized by abnormal movements at a symposium on “Involuntary movements other than parkinsonism” . On thatIn his publication dedicated to the review of 42 patients with dystonia, Marsden recognized that “idiopathic torsion dystonia (dystonia musculorum deformans) is a rare and fascinating disease” . This paIn 1975, Marsden attended the first international conference on dystonia that was convened in New York by Roswell Eldridge and Stanley Fahn. Compared to the conference held in Bethesda 5 years before, this was called international as the faculty originated also from outside the United States. Stanley Fahn, who was at Columbia University in New York, had seen the daughter of Samuel and Frances Belzberg who was affected by generalized dystonia and consulted with Dr. Eldridge, who had extensively reviewed the genetic epidemiology of dystonia at the 1970 conference . The BelDe Gaper, by Pieter Brueghel the Elderly; but also because blepharospasm had not previously entered the spectrum of dystonia, and was not considered a phenomenology of formes frustes or a body part involved in generalized dystonia. Marsden concluded that “(1) blepharospasm and oromandibular dystonia are manifestations of a single illness or syndrome; (2) this is a physical illness, not a manifestation of a psychiatric disorder; (3) this syndrome is related to idiopathic torsion dystonia.”The founding of the modern concept of dystonia is considered to have occurred exactly 40 years ago, in 1976, when David Marsden published several reports on dystonia –53. One In the following years at Denmark Hill, the interest in myoclonus melted with that of dystonia and spanned from phenomenology to physiology and experimental animal models. Chorea and dystonia were recognized in patients with Parkinson’s disease , 55. Priad hoc committee established by the Research Group on Extrapyramidal Disorders of the World Federation of Neurology, chaired by André Barbeau  proposed that “hyperkinesias” encompassed tremors, tics, myoclonus, chorea, ballism, athetosis, and akathisia , oromandibular dystonia, spasmodic torticollis, truncal dystonia, writer’s cramp, and other occupational dystonias . SpecifiIs dystonia one or many diseases? The lucid effort of lumping together conditions that were previously considered separate diseases has greatly contributed to the modern era of movement disorders but has left unsolved the issue of whether dystonia is to be regarded today as a single disease entity, a syndrome, a collection of physical signs, or as a somehow heterogeneous collection of syndromes. The cases for lumping different dystonias into a unique disease entity, or by the contrary to split them into separate conditions, have been the object of a recent review . There iTable formes frustes of a same genetic condition.Ten papers considered the general features of dystonia, defined as a disease, a syndrome, or a collection of physical signs Table . Herz 2 was the Six publications defined the features and diagnostic criteria of blepharospasm. This focal form has different features from dystonia affecting the limbs or trunk. Diagnostic criteria for blepharospasm have been proposed only recently, and their specificity is a matter of discussion . Four puThe swing is currently moving back toward recognizing the specific identity of focal dystonia syndromes. A Delphi method approach is being used by the Movement Disorders Society Dystonia Task Force to identify specific criteria for blepharospasm and for cervical dystonia. In the time to come, general diagnostic criteria for dystonia as a whole and specific criteria for focal dystonia syndromes will probably coexist. Clinical trials on focal dystonias require the harmonic implementation of well-defined criteria in multicentric settings. A currently unmet need is the characterization of clinical subtypes of dystonias and the identification of diagnostic criteria for each of them Figure .Based on current knowledge, it remains hard to accept dystonia as a single disease: nosologically, it is a collection of syndromes ; phenomeThe author confirms being the sole contributor of this work and approved it for publication.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


In humans, both sexes sometimes show peculiar mating preferences that do not appear to increase their fitness either directly or indirectly. As humans may transmit their preferences and target culturally, and these may be artificially modifiable, I develop theoretical models where a preference and/or a trait are culturally transmitted with a restriction of the trait modification. I assume a monogamous population where some individuals fail to find a mate, and this affects the preference and the trait in the next time step. I show that a strong aversion to, or high tolerance of, failed individuals are necessary for the evolution of irrational preferences that neither seek good genes nor any direct benefit. This evolution is more likely to occur when the preference and/or the trait are cultural rather than genetic. These results may partly explain why humans sometimes show mating preferences for exaggerated physical and cultural traits. Fisher [Many mating behaviours and the associated physical traits are considered to have evolved through sexual selection. The most studied are the exaggerated male traits, such as the plumage of the peacock, as well as the female mating preferences for such traits. The theory of sexual selection was first proposed by Darwin , who arg. Fisher  suggeste. Fisher , where f. Fisher  consider. Fisher –7.However, theoretical models of sexual selection for non-human animals do not apply to humans without modification because of the unique characteristics of human mating behaviour. Although many human behaviours are unique, this study focuses on only three characteristics: monogamy, male mating preference and cultural transmission. As some animals also display these characteristics, how each one affects the sexual selection process has partly been studied, in theory, but there are no models that simultaneously assume these three characteristics.Although polygynous marriage is not totally prohibited in many  human societies, there are limited numbers of males with more than one wife, and the number of wives is often limited . Strong feminine traits , because choosy males can obtain a direct benefit through mating with more fertile females [As the number of offspring is limited in  females (the ‘Bateman's principle’ ), attrac females . These t females , a lower females , a more  females  and ligh females , althoug females . HoweverHuman behaviour is often influenced by culture, which is one of our most unique characteristics and forms the basis of our great prosperity. It may be difficult to identify a human complex behaviour that is completely independent of culture or social learning. Human mating behaviour is no exception; e.g. we dress in fashionable clothes to attract the opposite sex. Foot binding in ancient China and neck rings in the Kayan are extreme examples of this. Since so-called modern behaviour is often characterized by artistic ornaments, such as shell beads and the use of ochre –27, matiHere, I formulate and analyse models of sexual selection in monogamous species where a trait and a preference are continuously distributed and culturally transmitted. I assume that some individuals do not have a mate during each breeding season because of a shortage of available mating partners, and this affects the expression of trait and preference in the next time step (generation). I also consider the case when a trait or a preference is genetically transmitted. I assume that the mating system of the population is completely monogamous to ensure that the model applies to both female preferences for male traits and male preferences for female traits . Although a monogamous human population is implicitly assumed, the model may also apply to other animals, such as monogamous birds with culturally transmitted songs that attract the opposite sex. The model may also apply to human fashion cycles.2.2.1.y, is expressed in only a ‘choosy sex’ and the trait, z, is present in only a ‘decorative sex.’ Here, we do not specify which sex  is choosy or decorative because completely monogamous species are considered. The assumption of the mating system is explained later.In the first model, we assume that both a mating preference and a target trait are culturally transmitted. The preference, p(y) and t(z), with the means τ2 and σ2, respectively. Formally, the distribution of the preference isy for a decorative individual with trait z is denoted as y choosy individual prefers a decorative individual with trait value of y, and the preference decreases as the deviation from y increases. The choosiness is milder when ν2 is larger.On an appropriate scale of measurement, the preference and the (matured) trait are assumed to have normal distributions, eference ,2.3ψ is the ‘popularity’ of a z individual. Denoting the number of individuals of the choosy sex relative to that of the decorative sex in the breeding season as r (>0), the expected number of choosy individuals courting a z individual is rU(z). Provided each choosy individual decides on his/her courting target independently of other choosy individuals, the probability that a z individual is approached by 0, 1, 2, 3 … individuals follows a Poisson distribution with a mean of rU(z). Therefore, the probability that a z individual has a mate isThen the probability that a choosy individual with preference Individuals of the decorative sex can be classified into two groups, those with and those without a mate in the breeding season. These are the ‘popular’ and ‘unpopular’ individuals, respectively. The average trait of popular individuals (popular trait) isi isi, respectively. Parameter a describes the effect of each average trait (a > 0). When 0 < a ≤ 1, as a increases, the ideal trait approaches the average popular trait from the average unpopular trait. When a > 1, as a increases, the ideal trait deviates from the average popular trait to the opposite side of the average unpopular trait. In other words, parameter a describes an aversion to unpopular individuals.Individuals of the decorative sex in the next generation (or the next breeding season) observe the traits of popular and unpopular individuals and gain their ‘ideal’ traits. Assuming that the ideal trait of each individual is the weighted mean of the observed popular and unpopular traits, the ideal trait of individual κ reflects the sampling and observation errors. A small κ also implies a strong conformist bias in social learning, because conformity should decrease the variance.Although all individuals observe the traits in the same population, they may sample different individuals and incur an observation error. Therefore, the ideal traits for decorative individuals may distribute normally asθ (the easiest trait to express) increases. Formally, the ease with which to express z isω2 is larger. In other words, each individual originally  expresses trait θ and must make an effort to attain the ideal trait . This restriction is similar to viability selection in genetic sexual selection models. As shown in appendix B, assuming If there is a restriction to decorate (modify) the trait, the difficulty increases as the deviation from the plain trait i has the ideal trait to court asb describes his/her aversion to unpopular individuals (b > 0). Even if a choosy individual prefers unpopular traits to avoid competition with other choosy individuals, this equation is applicable if we consider a small value for b.Similarly, individuals of the choosy sex in the next generation (breeding season) observe the traits of popular and unpopular individuals and gain the ideal traits for courting. Note that the preferences of choosy individuals are invisible, so only the traits of the decorative sex affect the preferences in the next generation. As humans sometimes show so-called mate choice copying , and a pτ2, the average preference in the next generation (breeding season) isIn contrast with the trait expression, there is no restriction in preference, e.g. choosy individuals can prefer ‘Prince Charming’. Therefore, as shown in appendix B, assuming that sampling and observation errors entail variance a,b)-parameter space, and b), the equilibrium is unstable regardless of the properties of decorative individuals, and exaggerated traits and preferences evolve eventually. In this case, the equilibrium is more likely to be unstable as r increases when s ≤ 1/2. Even when 0 ≤ a ≤ 1 and 0 ≤ b ≤ 1, i.e. when both choosy and decorative individuals have the ideal trait that lies between the average popular and unpopular traits, the equilibrium can be unstable whenq), the choosiness is strong (large s) and the relative number of choosy individuals is large (large r). However, as shown in appendix C, the equilibrium is stable provided both choosy and decorative individuals have the ideal trait that lies between the average trait and the average popular trait, i.e. From (2.17) and (2.20), a recursive matrix can be drawn2.2.c (0 < c ≤ 1), i.e. even if he/she has a mate later on, the number of offspring is smaller than an individual with a mate acquired earlier, because of the late mating. Then, as shown in appendix D, the average trait of decorative individuals in the next generation before viability selection isz individual isNext, we consider a cultural mating preference for a genetic trait. The fitness (relative number of offspring) of a decorative individual without a mate in the breeding season  is 1 – 2.3.x individual isz from trait x isThird, we consider a cultural mating preference for a trait that is affected by both genes and culture. For example, skin colour is genetically transmitted, but it can be (slightly) modified by avoiding sunlight or by applying powder/cream. In this model, we assume the order of life-history events such as (i) birth, (ii) genetic trait expression, (iii) viability selection, (iv) trait modification, (v) mating and (vi) reproduction. The distribution of genetic trait (after viability selection) is2.4.Fourth, we consider a genetic mating preference for a cultural trait with assumptions as in the second model. As shown in appendix F, the average preference of individuals in the next generation is2.5.ω2 is large, ν2 is small, r is small, i.e. when viability selection is weak, choosiness is strong, heritability of the trait and the preference are large, and the relative number of choosy individuals is small. Interestingly, the effect of the relative number of choosy individuals on the stability of the equilibrium is opposite to that in the cultural model.Fifth, we consider a genetic mating preference for a genetic trait, which is equivalent to . In thisshown in , a runaw3.Ever since the time of Darwin , human sa and b) and conformist bias is strong when the trait and the preference distribute narrowly . It has also been assumed that there is a restriction on modifying the plain (genetic) trait (i.e. the easiest trait to express). Note that when a trait is culturally transmitted, reproductive success of individuals does not directly affect the generational change of the trait, but we can regard the process as sexual selection because mating success of individuals has the main influence on the trait evolution.In this study, I have theoretically analysed sexual selection models where a trait and/or a preference are culturally transmitted. Although humans adopt various social learning strategies , the mosω2 is large) and choosiness is strong , the equilibrium is more likely to be unstable. However, the equilibrium is always stable, provided that both the choosy and decorative sexes have the ideal trait that lies between the average trait and the average popular trait . In other words, a strong aversion to, or high tolerance of, unsuccessful individuals is necessary for exaggerated traits and peculiar preferences to evolve through cultural sexual selection. This result is unchanged even if we assume that either the trait or the preference is genetically transmitted.The presence of a unique equilibrium has been demonstrated where both the average trait of the decorative sex and the most preferable trait for the choosy sex are plain. Therefore, when this equilibrium is stable, the trait never evolves to be exaggerated. In other words, exaggerated traits and peculiar preferences can be observed only when sexual selection destabilizes the equilibrium favoured by natural  selection. As expected, when the restriction of trait modification is weak . When the trait or the preference is genetically transmitted, it should lie within a certain range in the next generation, while there is no restriction in cultural transmission. Therefore, we can suppose that genetic traits and preferences are less likely to be exaggerated (peculiar) compared with cultural traits. In humans, peculiar mating preferences, such as those for small feet (foot binding) or long necks (neck rings), are sometimes observed, and these may be transmitted culturally. On the other hand, many globally observed mating preferences, such as male preferences for female traits indicating reproductive capacity, are probably genetic (instinctive) and can be regarded as the equilibrium in genetic models . In shorHumans often give greater weight to negative entities than positive ones, known as ‘negativity bias’ . This birealists and prefer the unpopular traits to avoid mate competition with other individuals , the equilibrium can also be unstable. In this case, the trait and the preference oscillate to become exaggerated . In these cases, the destabilization is more likely to occur when the opposite sex prefers popular traits, i.e. disagreement between male and female ideal traits is important for destabilization. Interestingly, the destabilization can occur even when both choosy and decorative sexes have the ideal trait that lies between the average popular and unpopular traits (i.e. 0 ≤ a ≤ 1 and 0 ≤ b ≤ 1). In other words, even when male and female ideal traits are not extreme, the joint acceleration of trait and preference can occur if there is a large sexual difference in ideal traits. In humans, male preferences are often incomprehensible to females and vice versa [When individuals of the choosy sex are ggerated . A similce versa ,53, whicce versa .c). When males are choosy, and assuming that each male courts multiple (a fixed number of) females and each female randomly selects a mate from the males who court her, this is a polygynous mating system, but the model is essentially unchanged, provided that every female with a mate has the same number of offspring . In this case, we may redefine parameter r as the product of the adult sex ratio  and the number of females each male courts. It should be noted that the number of females without a mate may be smaller than that of males without a mate in polygynous populations, provided that the adult sex ratio is almost one, i.e. r is larger when males are choosy than when females are choosy. Therefore, we may suppose that exaggerated female cultural traits are more likely to evolve through sexual selection than those of the male because the equilibrium is more likely to be unstable when r increases. This may explain cultural evolution of female costly body modifications such as foot binding and neck rings. In short, although the model assumes monogamy, it is applicable to polygynous populations if minor modifications are made.Although the model assumes a completely monogamous population, this assumption can easily be relaxed to apply the model to a polygynous mating system. When females are choosy, and assuming that each male accepts every female who courts him, the mating system becomes one of polygyny. Then, if males with at least one mate and males without a mate are regarded as popular and unpopular, respectively, the model does not essentially change, provided that both the trait and the preference are culturally transmitted. Even if the trait or the preference is genetically transmitted, the model is unchanged if males with multiple mates have a smaller number of offspring by one mate than males with only one mate (this affects only parameter a and b are large) and conformist bias is weak (σ2 is large), which is similar to cultural evolution models [In the model, exaggerated traits are more likely to evolve when success bias is strong  compared with when they are genetically transmitted. However, when there is a strong restriction of trait modification, decorative individuals express the plain (genetic) trait, which is the most preferred by choosy individuals. A strong aversion to, or high tolerance of, individuals without a mate is necessary for exaggerated traits and peculiar preferences to coevolve. Although the model assumes cultural transmission of trait and preference in monogamous populations, it is applicable to genetic transmission and polygynous populations following the implementation of some minor modifications.


The 2006 ‘Consensus statement on management of intersex disorders’ recommended moving to a new classification of intersex variations, framed in terms of ‘disorders of sex development’ or DSD. Part of the rationale for this change was to move away from associations with gender, and to increase clarity by grounding the classification system in genetics. While the medical community has largely accepted the move, some individuals from intersex activist communities have condemned it. In addition, people both inside and outside the medical community have disagreed about what should be covered by the classification system, in particular whether sex chromosome variations and the related diagnoses of Turner and Klinefelter’s syndromes should be included. This article explores initial descriptions of Turner and Klinefelter’s syndromes and their subsequent inclusion in intersex classifications, which were increasingly grounded in scientific understandings of sex chromosomes that emerged in the 1950s. The article questions the current drive to stabilize and ‘sort out’ intersex classifications through a grounding in genetics. Alternative social and historical definitions of intersex – such as those proposed by the intersex activists – have the potential to do more justice to the lived experience of those affected by such classifications and their consequences. In 2005, a meeting of mainly medical professionals proposed a new classification system, one that would move away from taxonomies of ‘hermaphroditism’ and the terminology of intersex, to the new term, ‘disorders of sex development’ or DSD. The following year, the ‘Consensus statement on management of intersex disorders’ was published, in which DSDs were defined as ‘congenital conditions in which development of chromosomal, gonadal, or anatomical sex is atypical’ : ‘Sex chromosome DSD’; ‘46,XY DSD’; and ‘46,XX DSD’. Within these categories, individual diagnoses are further classified, based on hormonal, gonadal, chromosomal or other bodily variations or differences. In practice, however, the ideal of an Aristotelian classification system ‘gives way’ to ‘fuzzier’ classification systems populated by ‘heterogeneous objects linked by metaphor or analogy’ . Objects (including bodies and classification systems) are enacted in specific local practices, and thus become ‘heavy with meaning’, a meaning that has been attributed. Such attributions have a history, and they are culturally specific, opening them up for historical and social scientific investigation’ (p. 10).As I do not wish to argue that there is a ‘truth’ of either Turner or Klinefelter’s syndromes that different classification systems approach, but rather that classification systems are historically and culturally situated, enact sex chromosomes and bodies in different ways, and are thus open to critical investigation. I follow The stakes of this investigation are numerous, but I am particularly interested in three distinct issues. First, there are stakes for individuals named by diagnoses, taxonomies and classification systems. Scholarship on intersex has shown that individuals have different medical and non-medical experiences based on whether they accept DSD terminology. The description of symptoms, syndromes, genetic conditions or disorders is not just an issue of meanings; bodily and social realities shift depending on the meaning-making practice of classification. Second, there are stakes for medicine. As I will show, the efficacy and worth of the DSD classification system for medicine rests upon inclusion or exclusion of sex chromosome variations. The value of the system for medicine derives from its being grounded in genetics and the promissory, not in genitals and the assignment of gender as close to the moment of birth as possible; this grounding in genetics demands that sex chromosome variations are central to the DSD classification. And finally, there are wider stakes for democratic participation in practices of biomedical science, particularly around questions raised by intersex human-rights activism that foreground the power relations that prioritize genetic and molecular knowledge over lived experience. Whether Turner or Klinefelter’s syndromes are included or excluded from intersex classifications is not just an argument about numbers of intersex people. Rather, it is part of a broader argument about who gets to name what in biomedicine, and how scientific power can be appropriated and/or resisted through refusing classifications, or building alliances around alternatives.Recent debates about how many intersex people there are reveal how contested the category has been, and the centrality of Turner and Klinefelter’s syndromes to that question. In 2000, Anne Fausto-Sterling claimed a 1.7% incidence; this was based on a review of medical literature over a roughly 50-year period and suggested as ‘an order-of-magnitude estimate rather than a precise count’ . Fausto-Journal of Pediatric Endocrinology and Metabolism arguing for a change in clinician’s nomenclature and taxonomy. Significantly, they argued that intersex classifications do not represent natural kinds, but rather constitute practical taxonomies , and three medical professionals published an article in the xonomies : 730. Clxonomies . Dreger Later in 2005, Chase participated in a meeting on intersex in Chicago, jointly organised by Dr Peter Lee of the US-based Lawson Wilkins Pediatric Endocrine Society and Dr Ieuan Hughes of the European Society for Paediatric Endocrinology. The meeting was attended by 50 experts, only two of whom (Chase included) were not medical professionals. The suggestion of a nomenclature change to ‘disorders of sexual differentiation’ was raised . In ChasTerms such as intersex, pseudohermaphroditism, hermaphroditism, sex reversal, and gender based diagnostic labels are particularly controversial. These terms are perceived as potentially pejorative by patients, and can be confusing to practitioners and parents alike. The term ‘disorders of sex development’ (DSD) is proposed, as defined by congenital conditions in which development of chromosomal, gonadal, or anatomical sex is atypical. : 554The ‘Consensus Statement on Management of Intersex Disorders’ was published the following year, in 2006. The change to a DSD taxonomy was justified as follows:The consensus statement therefore followed Dreger and Chase’s suggestions, particularly in moving away from the hierarchical categorization of pseudo and true hermaphroditism, and in broadening the medical classification system beyond the gonads.The 2006 consensus statement includes ‘45,X (Turner syndrome and variants)’ and ‘47,XXY (Klinefelter syndrome and variants)’ as ‘Sex Chromosome DSD’. However, discussion about these variations is limited and estimates of intersex in the consensus statement are reserved for a statement that ‘genital anomalies occur in 1 in 4500 births’ : 554. ThSome individuals and organizations have been critical of the shift to DSD terminology; many organizations used the term ‘intersex’ to reframe variations in sex characteristics as a social issue, not a medical emergency. The term ‘disorder’ structures the classification around the normal and the abnormal – a fact implicitly recognized by medical professionals when they suggested using ‘differences’ or ‘variations’ (rather than ‘disorders’) of sex development when speaking with individuals and family members . At the I turn to the original descriptions of Turner and Klinefelter’s syndromes, to historicize the difficult business of ‘sorting out’ intersex classifications. In 1938, Henry H Turner first described what would become known as Turner syndrome. Turner was an endocrinologist running his own practice and working as assistant professor of medicine and as consulting endocrinologist at the University of Oklahoma’s College of Medicine. He thus saw a large number of individuals with developmental variations. In 1942, Harry Klinefelter, along with the endocrinologists Fuller Albright and Edward Reifenstein, described what would become known as Klinefelter’s syndrome . KlinefeThe initial description of Turner and Klinefelter’s syndromes illustrate what While the definition of Turner’s and Klinefelter’s as syndromes made up new categories of people and gave classificatory meaning to particular symptom clusters, these categories bore no relationship yet to older categories of hermaphroditism or the emerging category of ‘intersex’. Despite the reproductive issues and effects on sex characteristics associated with these two syndromes, their original descriptions did not suggest that these bodies were in any way ‘in doubt’, with regards to gender and sexuality . Originathe new science of sex, structured around the sex hormone, was firmly established, institutionally and intellectually. An expectation of a dynamically interacting two-tiered structure of explanation for sex at the genetic and hormonal levels fuelled new biological models of sex and irresistibly pulled theorists toward the consistent and parallel terminology of ‘sex hormones’ and ‘sex chromosomes’ .Sex chromosome variations would be central to developments in intersex classifications, and to the development of what In the first half of the twentieth century, the concept of a sex chromosome was becoming increasingly established. However, the general view was that the X chromosome was determinative of biological sex, and the Y was not determinative, or was even inert : 72. BotDrosophila melanogaster.2Drosophila studies began in the early twentieth century , with more X chromosomes producing female fruit flies . With Margaret Graham and Keith Moore, he argued that the disjunction between medical theory and clinical practice was a pressing problem. They stated that cases of ‘hermaphroditism’ were a tragedy and a ‘developmental error’ that demanded correction through medical action, informed by the ability to test for Barr bodies (Lancet. As coarctation (narrowing) of the aorta  is most commonly described in male individuals, The classification of individuals based on karyotypes, as identified by presence or absence of Barr bodies, led to the assumption that individuals with Turner and Klinefelter’s syndromes were ‘sex-reversals’ : 126. WiIn the case of Klinefelter’s syndrome, it was discovered in 1956 that some individuals with Klinefelter’s Syndrome were chromatin-positive; that is, a Barr body was identified and the individual was assumed to have an XX karyotype . After tDuring the 1950s, the diagnosis of Turner and Klinefelter’s syndromes shifted from describing a cluster of symptoms to enacting those described as examples of ‘sex-reversal’. The discovery of Barr bodies and associated karyotyping technologies thus allowed for new classifications of populations of individuals as well as new forms of intersex to be imagined and enacted, beyond those previously identified in clinical practice see . With thLancet, Polani presented 25 case studies of female individuals diagnosed with Turner syndrome. He reported that: ‘Twenty of the patients had chromatin-negative nuclei  and four had chromatin-positive nuclei ’  as the best marker of sex and the best grounding for a classification of intersex, the sex-reversal hypothesis was not universally accepted. In 1956 in an article in the erence)’ : 119. ThSupport for this speculation would come in 1959, with the publication of two key articles that provided evidence for more sex chromosome constitutions than just XX or XY. First, British researchers published evidence that individuals diagnosed with Klinefelter’s syndrome could have an XXY karyotype, rather than the assumed XX . Later tThis history of sex chromosome variations intersects with Britain’s post-war investment in atomic energy research, a national atomic bomb project, and research into the biological and medical aspects of radiation, which was the responsibility of Britain’s Medical Research Council (MRC) : 710. BrLancet in 1959, just three months after the Jacobs and Strong paper on Klinefelter’s syndrome.The description of XXY karyotypes in some individuals diagnosed with Klinefelter’s syndrome was significant. Indeed, as These ‘startling’ discoveries led to a proliferation of discoveries of chromosome ‘abnormalities’ or ‘aberrations’ soon after, including XXXY, XXXXY and mosaicism . Turner the marker of male sex. Jacobs and other researchers within the growing field of human medical genetics thus turned their attention to the recently described XYY karyotype. Jacobs recounts reading a piece of research in 1960 that found an over-representation of XXY individuals in security facilities, and also noticed that ‘a very significant proportion were XYY’  gender roles. A striking example of this is the research into the XYY ‘supermale’ : 84. Theere XYY’ : 89. SheYY male’ . FollowiYY male’ : 84 reseNarratives that associated the extra Y with an extra and problematic dose of masculinity were so influential that even the observation that individuals with XXY karyotypes were also over-represented in the same facilities could not seriously challenge the hypothesis. As Richardson notes, this apparent contradiction of the XYY theory was resolved through the reproduction of cultural norms about the differences between men and women, interpreting any XXY criminality as resulting from ‘feminine ineffectiveness and passivity’ and any XYY criminality as resulting from ‘a masculine overactive personality’ (p. 95). Richardson describes XYY ‘supermale’ research as an ‘embarrassing episode in the history of genetics’ (p. 82); a large-scale study in 1976 found that there was ‘no evidence … that men with either of these sex chromosome complements are especially aggressive’, and that there was therefore no social benefit in screening for these chromosomal variations . HoweverThe example of XYY ‘supermale’ research is informative. XYY would seem to fit the current DSD classification definition of ‘congenital conditions in which development of chromosomal, gonadal, or anatomical sex is atypical’ : 554; hoThe idea that all disease is genetic disease is not an abstraction. It is a social experience manifest in language, technology, emotion, and policy. Increasingly, it plays a role in the legal system, in the practices of hospitals, in the research priorities of the armed forces, in the treatment of people with mental retardation, and in medical education. It has become an idea with social force. (p. 2)The significant publications of 1959 and the first half of the 1960s established human medical genetics as an important field, compared to its previous status as a ‘sleepy subspecialty’ : 1. GeneXYY is a striking example of this, as social assumptions about masculinity and criminality came to define a population classified together through a shared karyotype. From 1959 through the 1960s, Turner and Klinefelter’s Syndrome also seemed to fit the pattern Lindee describes. Prior to the 1950s, a diagnosis of either Turner or Klinefelter’s syndrome was a description of a symptom cluster in one individual body. During the 1950s, this shifted, as the diagnosis began to mean ‘sex-reversal’ – a shift that enacted individuals in such a way that doubt was cast on their sex, gender and sexuality.The Intersexual Disorders, published in 1969, is a significant exception; whereas the other books published at this time gave sex chromosome variations precedence and thus centrality in the classification of intersex, Dewhurst assigned them a peripheral position. Turner and Klinefelter’s syndromes did get a chapter in the book: ‘Sex chromosome abnormalities’. However, this was a short chapter, mainly focussed on diagnostic criteria. Furthermore, this chapter came after a chapter on ‘Transvestism and transsexualism’ even though in a later interview Dewhurst would make it clear that he did not consider ‘transvestism’ or ‘transsexualism’ to be intersex variations, but rather included them to cover as wide an area as possible, and because they were often confused with intersex The debate within the medical profession about the categorical inclusion or exclusion of Turner and Klinefelter’s syndromes illustrates an ambiguity at the heart of the DSD classification system. The classification system is constructed differently depending upon whether Turner and Klinefelter’s syndromes are considered the ‘mainstream’ that is central to the DSD classification system, or peripheral and excludable. Indeed, Eric Vilain and David Sandberg (both present at the Chicago meeting) argued in 2009 that excluding Turner and Klinefelter’s syndromes from DSD ‘implies that atypical genital appearance is the sine qua non of DSD’ : 9. For If Turner and Klinefelter’s syndromes are included as DSDs or intersex variations, estimates of frequency are necessarily higher than if they are not (as demonstrated by the debate between Fausto-Sterling and Sax). But if they are excluded it seems the very nature of the classification system changes, from a classification that is seemingly about multiple aspects of sexual development, to a classification that is focused on genitals and gender assignment. Accordingly, for Vilain and Sandberg, the very ‘value’ of the DSD nomenclature is undermined by the exclusion of Turner and Klinefelter’s syndromes. This is a particularly strong statement of the stakes for medicine in the inclusion or exclusion of these syndromes from classifications or taxonomies of intersex or DSD.The DSD classification system is ‘fuzzier’ than it first appears. There is a certain incoherence or messiness within the logic of the consensus itself. After the ‘example of a DSD classification’, the statement suggests: ‘While consideration of karyotype is useful for classification, unnecessary reference to karyotype should be avoided; ideally, a system based on descriptive terms  should be used wherever possible’ : 555. ThThese obstacles are likely to be overcome in the future, and next-generation sequencing is likely to become one of the first methods used for the diagnosis of DSD.  genetic science will facilitate clarity in intersex classifications, rapid and definitive diagnoses, and better treatments.In both the 2006 consensus statement and the 2016 update, biomedical classifications and data are framed as promising more than psychosocial or cultural approaches. This is not only true of DSD, but of a recent interest in what attention to ‘rare diseases’ can reveal, both about these conditions and about non-affected populations. Indeed, iDSD, a contemporary international biomedical registry for intersex variations, is modelled on the rare disease approach, allowing medical professionals to access and study intersex biology on remote, despite perhaps never knowingly meeting an intersex person.in infancy by a relatively simple procedure’ . iDSD  is the successor project of EuroDSD, funded by the European Union. This network enacts intersex variations/DSDs as rare genetic diseases, with the assumption that bodily difference is best understood through more and better, ongoing, future-focused genetic and molecular knowledge production. Once again, it remains to be seen whether this faith in increasing biomedicalization of the intersex experience will improve the health and lives of those affected.Hughes emphasized the fact that the 2006 consensus statement led to a focus on genetics when he identified the Chicago meeting as the ‘starting point’ that ‘spawned a classification system that recognised the impact molecular genetics could have, literally at the cot-side’ : 160. CoMedical classifications are socially and historically situated, as well as determined by scientific and technological possibilities of the time. DSD is explicitly a future-oriented classification system, aiming to be ‘sufficiently flexible to incorporate new information but robust enough to maintain a consistent framework’ : 554. BuChrysalis, edited by intersex activists Cheryl Chase and Martha Coventry. In this ironic glossary, Klinefelter’s syndrome is defined: ‘One of that large class of syndromes named for people who did not have the syndromes. Even Lou Gehrig’s Disease has been renamed for some doctor who probably couldn’t even hold a bat’  the move to the DSD classification system. This is activism in the face of widespread acceptance of DSD in the medical community . Indeed,d a bat’ : 10. NamEarlier I discussed another example of resistance, the creation of a different classification that is not structured around genitals, gender assignment or even the ‘truth’ of sex to be found in gonads or chromosomes, but instead in the social consequences of biomedical classifications. This ‘post-medicine definition’ defines intersex as ‘the lived experience of the socio-cultural consequences of being born with a body that does not fit with normative social constructions of male and female’ . Bowker Classifications are always historically and socially situated, which allows for subversive reimaginings of medical classifications. Resistance can also take the form of new and different orders of classification, for example those that prioritise the lived experience and shifting social consequences of being classified. The 1950s provided an example of a previous attempt to ground the difficult business of sorting out intersex classifications in genetics (at the level of the chromosome). However, grounding intersex in chromosomes in the 1950s did not improve clinical care for individuals with variations of their sex characteristics. The current DSD classification system is insufficiently attentive to the social and ethical needs of the present and relies on a vague promise that, sometime in the future, classification, diagnosis, and clinical practice will be sorted out for the benefit of both the medical profession and for individuals affected by classification. The history of the shifting understandings of Turner and Klinefelter’s syndromes illustrates that this faith in promissory genetic classifications may be misplaced. Instead, resistant social and historical classifications  of bodily difference and the situated experience of the medicalization of difference may be more useful to do justice to the historical and contemporary lived experience of those affected by classifications of intersex.


Space matters. We read space like we read people’s faces. Space is an instrument of collaboration and innovation. At the University of Michigan’s Institute for Clinical and Health Research (MICHR), a team was created to creatively and economically enhance our operating space into a flexible workspace that supports privacy, innovation, creativity, and most important, a culture of collaboration.The team used a human-centered design process to creatively engage the staff at large into analyzing our existing space, identifying latent needs, proposing solutions, generating feedback, and economically building the rethought process.The redesigned workspace embraces the differences among MICHR’s teams while encouraging collaboration and teamwork and keeping costs at a minimum. It has resulted in a flexible space that includes co-located teams, spaces dedicated to different work goals, an open area for collaboration, quiet zones for focused work, and better wayfinding.Through our Rethink Space project, we hope to have demonstrated that, by initiating the project internally and by engaging the users of the space themselves in an empathetic, visual, and human-centered way, a space redesign can be undertaken economically while also leading to improved levels of employee and team satisfaction. The poll results showed a majority backed the proposal.This phase involved planning and building, economically and within the given timeframe, the new space that we had proposed in the “Create” phase.To meet our new proposal, we had to move a total of 70 staff members. We planned the moves so as to not disrupt any MICHR services. MICHR was not closed for the moves and the moves took place on weekdays during regular business hours. The moves were distributed sequentially across 30 days, with every staff member having an average of 2 days to move. The plan was based on already available open spaces, availability of construction crews, construction noise, and program-specific considerations like large meetings that would cause staff to be out of the office. To lighten the stress of moving, on the first day in their new space, the staff member would find welcoming them a thank you note attached to a bag of candies.To keep the costs to a minimum, most of the needed furniture was reclaimed from unused buildings in the immediate research complex or from the University of Michigan’s Property Disposition Center.Signs were placed at strategically important locations to help with wayfinding, branding, and team morale.The majority of our $35 000 budget was spent on construction, whiteboards, monitors, and furniture for the open space. Notably, we were able to repurpose unwanted furniture from other units housed at our complex.Our staff-led redesign processes led us to the new spaces shown in Organizational culture has been variously defined. Little agreement exists over a precise definition of organizational culture, how it should be observed or measured, or how different methodologies can be used to inform routine administration or organizational change . It follThat being said, in the short time following the opening of the new space, the Rethink Space team has received positive anecdotal feedback from MICHR staff and guests suggesting that the new space is “more functional,” “matches their style of work,” “is more collaborative,” “is less intrusive,” “has more natural light,” and “is friendlier.” The project was nominated for a Medical School Administration team award by the staff. The team also won an Ergo Hero award from the University of Michigan for our creative efforts in building a multiple purpose open space, thus improving communication and collaboration among staff. In terms of usage, we have observed that the open space is almost always occupied, either by a single large group or by multiple smaller teams. Attendance seems to have increased at MICHR events like the monthly all-staff meetings, lunchtime enrichment presentations, and celebrations, which are now all held in the open space. The quiet area is also occupied often and the dedicated team rooms are in use.Six months after the reconfiguration of our space, we surveyed staff to get their direct feedback on the changes. Through observation and anecdotal collection, we felt the changes were overall positive and successful. The survey gave us more concrete information on how things were really going.The 10-question survey was taken anonymously with an option to leave contact information at the end. The survey included both ratings and open-ended questions. We had a 60% response rate. Overall satisfaction with the new collaboration space was good, with an average rating of 4.26 out of 5. Responders commented, “It’s a flexible space that no one ‘owns.’” “This creates a more inviting and welcoming atmosphere where people can come together to visit, collaborate and create synergy” and “It has really helped with team dynamics.” Satisfaction with individual workspaces was an average of 3.83 out of 5 and satisfaction with team rooms was 3.61 out of 5, noting that not everyone has a team room.We also asked about satisfaction with the process itself. Responses average 4.13 out of 5. Numerous comments were left, providing positive feedback and suggestions for improvements.Flexibility, collaboration, and staff engagement are important characteristics that define successful organizations of the 21st century. Space is the platform on which face-to-face social interactions and the networks that result from them are enacted [We believe that we have the beginnings of a framework for exploration, experimentation, and trial and error that can help solve complex problems that have fuzzy goals. Whether you are redesigning your workspace, rethinking a service that you offer, or reimagining a more just world, we believe the empathetic, visual, human-centered process we have experienced deserves consideration. More detailed information on our process is outlined on the Rethink Space Web site at http://www-personal.umich.edu/~aalapd/new-website/index.htmlFinally, we as the Rethink Space team have found immense joy and satisfaction working on this project and have learned a lot about how to approach problems that have nebulous goals.


In recent years, compounded bioidentical hormone therapy (CBHT) has emerged as a popular alternative to manufactured, FDA approved hormone therapy (HT)—despite concerns within the medical community and the availability of new FDA approved “bioidentical” products. This study aims to characterize the motivations for using CBHT in a U.S. sample of ordinary midlife women.We analyze data collected from 21 current and former users of CBHT who participated in a larger qualitative study of menopausal decision-making among U.S. women. Interviews and focus groups were audio-recorded, transcribed verbatim, and analyzed thematically using an iterative inductive and deductive process.safety of conventional HT, (2) an aversion to conjugated estrogens in particular, and (3) and overarching distrust of a medical system perceived as dismissive of their concerns and overly reliant on pharmaceuticals. Participants also voiced dissatisfaction with the effectiveness of herbal and soy supplements. Participants were attracted to CBHT because they perceive it to be (1) effective in managing menopausal symptoms, (2) safer than conventional HT, (3) tailored to their individual bodies and needs, and (4) accompanied by enhanced clinical care and attention.Although women’s individual motivations varied, two overarching themes emerged: “push motivations” that drove women away from conventional HT and from alternative therapies, and “pull motivations” that attracted women to CBHT. Push motivations focused on (1) fear and uncertainty about the This study finds that women draw upon a range of “push” and “pull” motivations in their decision to use CBHT. Importantly, we find that women are not only seeking alternatives to conventional pharmaceuticals, but alternatives to conventional care where their menopausal experience is solicited, their treatment goals are heard, and they are engaged as agents in managing their own menopause. The significance of this finding goes beyond understanding why women choose CBHT. Women making menopause treatment decisions of all kinds would benefit from greater shared decision-making in the clinical context in which they are explicitly invited to share their experiences, priorities, and preferences. This would also provide an opportunity for clinicians to discuss the pros and cons of conventional HT, CBHT, and other approaches to managing menopause. Since the discovery of sex hormones in the late nineteenth century, women’s relationship with hormone therapy (HT) for menopause has endured a series of paradigm shifts , 2. It hnot regulated and approved by the FDA because it is not a standardized pharmaceutical product; thus, CBHT does not carry the safety warnings mandated by the FDA for estrogen-products after the discontinuation of the Women’s Health Initiative , or even consider [it]. … I knew several women who were on it. And I know people who are still on it, who are starting on it and taking it. But I never really, even if I had really bad symptoms, I don’t think I would have rushed for HRT. Just because of my thoughts about biomedicine. And especially natural biological processes, I am not sure that we need to change them.Seventeen (80.9%) of the 21 current or former CBHT users described their treatment decision within the context of fear or uncertainty about the safety of conventional (manufactured and FDA-approved) hormone therapy. Like those in the overall study, many women choosing CBHT were concerned about the safety of HT, and WHI results confirmed those fears. Susan,Like other women in this study, Susan suggests that she was never inclined to seek out conventional HT to manage menopausal symptoms, and media coverage of conventional HT reinforced this belief.Many CBHT users specifically mentioned increased cancer risk as a reason to avoid conventional HT. This concern stemmed from the media attention to increased rates of breast cancer among HT users, the FDA’s “boxed warning” required for estrogen products, and the overall salience of breast cancer as a major health risk for women beginning in midlife. For example, Patricia, a 54-year-old federal employee who used compounded estrogen and progesterone lozenges for about 4 months, explained, “the [symptoms of menopause] for me have not been severe enough to the point where I would consider taking hormone supplements on a regular basis. Because I don’t, I don’t trust the side effects. The risk of the damage I don’t think outweighs the benefit.” When we follow-up on this point, she continues, “I have personally avoided the synthetic hormones because of the side effects for cancer. And sought the bioidentical in as low a strength as I could have compounded.”equine-sourced products as way to differentiate conventional, manufactured HT from the CBHT they used. Consider the following focus group conversation between Dorothy, a 61-year-old postmenopausal registered nurse, and Lisa, a 49-year-old manager just entering perimenopause.DOROTHY: Well, I make a big distinction between the compounding, that’s not made from Premarin, it’s not made from mare urine, versus the pharmaceutical. And it’s very different, very different base, so I’m not afraid of that -- whereas I never wanted to go on the other, and refused for years to go on anything.LISA: So, what’s the difference between them?DOROTHY: Well, the base is just entirely different. It has nothing to do with animals whatsoever. […].[T]he pharmaceutical ones that you would get from a regular gynecologist who just sends you to the regular pharmacy, are made from mare urine and all kinds of different things. And, not just for the conditions of the animals, is one reason I refuse, but also because the side effects are so much more horrendous.Although many of the CBHT users in this study categorically ruled out using manufactured HT, nearly half  singled out conjugated estrogens (CE) by brand name: Wyeth products Premarin (CE) and Prempro (CE and medroxyprogesterone acetate). In fact, many CBHT users referenced these As this exchange illustrates, for some women, CE becomes a symbol of all they perceive to be wrong with conventional HT—from its animal source, which carries both a visceral disgust and concern about animal cruelty, to its questionable safety and side effects. Further, by focusing their concerns about HT on their particular distaste for and avoidance of CE, women are able to make a distinction between conventional HT and the CBHT they use.It makes me really angry that they’ve pushed hormones for so long. I mean, for 30 years. And they touted it as “you must be young forever.” I think it had a lot to do with the way our culture is biased, maybe more now—much more now—against aging. And then they find out, “Oop! We were wrong!” It just pisses me off. It … confuses and frustrates me when they have conflicting things—three or four articles in a week that say different things. If I can’t sort it out, how can the rest of the world? It’s very frustrating. Get it together. Figure it out.Nearly every CBHT user in this study  expressed frustration and distrust toward biomedicine or the pharmaceutical industry that shaped their overall desire to avoid conventional HT. In particular, CBHT users in this study describe feeling like women had been repeatedly misled by a pharmaceutical industry that promoted HT as the route to longer, healthier, more youthful lives Bev, a 49-year-old certified nurse midwife who prescribes CBHT and uses it herself, put it this way:Although uncertainties are ever-present in medicine, these women express aggravation with a pharmaceutical industry that many feel has tirelessly promoted HT to women despite real concerns about its safety.[My doctor], she’s really knowledgeable, but she’s not listening to what I want from her, and I emphasize, you know, what my lifestyle is. She doesn’t consider my lifestyle to what she prescribes to me. … She’s got a certain line of medication, and she prescribes that to every patient. She doesn’t change her therapy for different patients, I think.Other participants asserted strong critiques of an overly-interventionist medical system, too heavily dependent on pharmaceuticals as a “quick fix.” Embedded in this critique was the perception that many clinicians were too ready to prescribe conventional HT, rather than work more collaboratively with patients to identify a treatment approach that would effectively manage their symptoms in ways aligned with their overall approach to health and wellness. Women described being disappointed by clinicians who they felt were dismissive of their experiences, the particularities of their treatments goals, and their ongoing uncertainty about whether the risks of HT outweighed the clinical benefits. Sandra, a 50-year-old, highly educated immigrant to the U.S., had spent several thousands of dollars out-of-pocket seeking the “right” treatment for her menopausal symptoms. She says, “So, the health professionals, I’m not very happy with they way they’re doing it right now. I mean, all they do [is] give you medications and go, ‘Come back and see how you feel.’” Instead, Sandra says she’s looking for a clinician who considers her as an individual. She continues:I try to be as informed as I can, cuz I don’t trust the medical field to be informed... And I don’t trust them to necessarily care—unless I know the doctor personally, and I know that they’re really intelligent, and that they really have integrity. Cuz a lot of them will throw anything at you. And in this culture, they will still do it to women way, way, way more than men. And I work in medicine, and I know that.Finally, several participants suggested that clinicians’ dismissal of women’s concerns and their reliance on pharmaceuticals should be understood as implicit gender-bias or racial-/ethnic-bias in health care. Peg, a 61-year-old physical therapist, who had been using CBHT for twelve years at the time of our interview, emphasized the relationship between implicit gender bias in medicine and the necessity for self-advocacy, saying:The healthcare system creates doctors who have an arrogance about them, and so that arrogance translates into patient care. … [Substandard care] happens all the time, and that has to do with the arrogance. But also being a woman of color, racism is so ingrained, it is so innate, that a lot of times, people don’t even realize that they’re operating from that basis, because it is so much a part of who they are and their frame of reference. It’s just what they do.Sheree, a 58-year-old working in city government, focused on implicit racial bias and its consequences for the quality of care for women of color. She explained:The critiques levied by women like Peg and Sheree were not specific to HT, but they signified an overall mistrust of the medical system that has tangible effects on women’s willingness to seek care and trust the recommendations coming through conventional channels.Although the particular critiques differed, nearly every woman who used CBHT in this study expressed some level of distrust and frustration aimed at clinicians, the broader medical system, or the pharmaceutical industry. Some of this frustration stemmed from ongoing uncertainties about the risk of HT, but they also voiced broader frustrations—about a medical system too quick to dismiss women’s concerns and resort to pharmaceuticals, thus serving up massive profits for the pharmaceutical industry. Together, women’s distrust of the medical system, along with their particular concerns about the safety of conventional HT, and distaste for CE in particular, provide a very strong motivation pushing them away from conventional HT—thus driving them to seek an alternative.Widely available over the counter, dietary supplements like soy, red clover, and black cohosh are a convenient alternative for women seeking to avoid conventional HT; nevertheless, for the most part, these products have not proven themselves efficacious in clinical trials , 80. EigHowever, like Sandra, many participants did not find long-term symptom relief from dietary supplements, and this pushed them to seek CBHT as a more effective alternative. For example, when Patricia first began experiencing symptoms early in her perimenopause, she tried a number of over-the-counter herbal supplements on the recommendation of a friend. When we asked her to tell us about that experience, she said, “I didn’t notice any positive effects with them. I didn’t have any negative effects but as far as assisting … the hot flashes during the day and the night sweats, they didn’t help at all.”Patricia’s response was typical of the CBHT users in this study, many of whom had tried dietary supplements out of a desire to avoid hormones but eventually sought out CBHT as a more effective intervention. Thus herbal and dietary supplements, can begin as a kind of “pull” toward something perceived to be more “natural,” safer, convenient, and less expensive than biomedical and pharmaceutical interventions. However, if they do not provide adequate relief for menopausal symptoms, they become their own “push” motivation—away from an ineffective treatment and toward a treatment similarly framed as “natural” and often perceived as safer, yet something certainly more effective for symptom management: CBHT.both mainstream and alternative. Four key themes emerged in the way women characterized their attraction to CBHT: (1) it is effective in managing their menopausal symptoms, (2) they perceive it to be “safer” than conventional HT, (3) it is tailored to their individual bodies and needs, and (4) it was accompanied by enhanced clinical care and attention.It is within the context of the “push” motivations discussed above that participants framed their attraction to CBHT. In short, for many of the CBHT users in this study, CBHT represented a therapeutic approach that was A key draw for CBHT users was simply that it worked. As a hormonal approach, most women found that CBHT was effective in managing their menopausal symptoms. Although a large number of women in the overall research project were able to weather menopausal symptoms without hormones, other women—including those using CBHT—found their symptoms disruptive enough that they actively sought remedy. And for those who wanted to avoid conventional HT, finding a way to effectively manage disruptive symptoms was no easy task. Over three-quarters of the CBHT users in this study  emphasized that one of their primary reasons for using CBHT was that was effective in managing the symptoms they associated with menopause, where lifestyle approaches, herbal remedies, and sometimes other pharmaceuticals fell short.this works.” At the end of the interview, when we asked what helped her best cope with menopause, Peg says, “the natural hormones!” She continues, “Without them, I think I’d be dead. I mean, I’m not kidding. I really don’t think I’d be alive. I think I’da become so psycho from not sleeping, my brain might’ve exploded, or I might’ve thrown myself in front of a truck, I don’t know.”For example, in an effort to manage the symptoms she associates with menopause, including hot flashes, short-term memory loss, and insomnia, Peg tried a number of over-the-counter products, including hormonal creams, Black Cohosh dietary supplements, and soy products. She also tried CE—despite a strong aversion to the very idea. Both the soy and the conventional HT made her sick, and nothing alleviated her symptoms. Eventually, Peg found a naturopathic physician who prescribed CBHT. Within a week, Peg felt that her symptoms were manageable: her short-term memory improved, her sleep improved, she felt calmer, and she regained bladder control. She’s been on the same dose ever since—for the last twelve years. Peg says that she’s “afraid to try anything else because very next day I felt better. It was just like the cloud had lifted. It was amazing. And I don’t think it was in my head, either. I’d been so, just like, [sharp intake of breath] and I had energy and I was happy.I mean, I was depressed for a couple months. I was like, “This isn’t me. This isn’t me. This isn’t who I am. I’ve never been like this.” But once [my naturopathic physician] started me on the [CBHT], the Similarly, Deborah, a 53-year-old pre-school teacher in perimenopause, describes her transition to menopause as a “scary time” marked by a number of physical and emotional symptoms, including anxiety, memory loss, insomnia, and night sweats that made her worry that something was “seriously” wrong with her. She says,In short, for women like Peg and Deborah, who are facing severe symptoms they associate with menopause yet wish to avoid conventional HT, CBHT becomes a compelling approach to treatment because, as a form of hormone therapy, it is very effective.Over three quarters of the CBHT users in this study  described CBHT as safer than conventional HT. The remainder either characterized the safety as equivocal, or did not make any statements about safety. No one characterized CBHT as less safe than conventional HT. Participants based this perception on a couple of key qualities of CBHT: (a) because it is plant-based, it is “natural”; (b) because it is “bioidentical,” it is a more precise chemical match to their bodies’ endogenous hormones; and (c) because it is tailored to their individual needs, they could use the lowest dose possible to achieve their treatment goals.I knew I didn’t wanna take chemical hormones, you know, and so some friends of mine were telling me that they were taking the bioidentical hormones, and you know, so I started researching it online, and reading books, … and you know, I know hormones are hormones, but it just seemed to me that if you could take something that was plant-based and more easily recognized by your body, that that would be a safer alternative.Ann best illustrates this perception—and how this pull motivation is embedded in the push motivations discussed above. When describing her experience of perimenopause, Ann described experiencing hot flashes, heavy bleeding, and most significantly, insomnia. Because of her work as a fitness instructor, Ann feels a responsibility to keep her body fit as she ages—for her business, but also because she is a role model for her clients who are aging along side her. Nevertheless, she entered perimenopause with a positive attitude, “I figured, ah, it’s not gonna be such a big deal, and it wasn’t until the lack of sleep … because when you don’t sleep, you’re really cranky.” In response, she tried several herbal and soy supplements, which she says “worked for a while, probably.” Finally, she says, “the lack of sleep … that was what prompted me to seek other treatments.” She continues:Here, Ann echoes the push motivations discussed above: dissatisfaction with alternative therapies and a desire to avoid conventional HT. She worked with a local physician specializing in “anti-aging” medicine, and takes a compounded regimen of estrogen troches, progesterone pills, and DHEA and testosterone cream. Although she recognizes that “hormones are hormones,” she believes that CBHT might be “a safer alternative” because it is “plant-based and more easily recognized by your body.” When we follow up on this point, Ann indexes the idea that her compounded regimen is safer because it is a closer chemical match to her body’s endogenous hormones. She says, “Well, the way I understand it is that it’s plant based and that it seems to be identical to the hormones that your body produces, or at least that’s the way that your body recognizes it.”uncritically confident about the safety of CBHT. She continues, “like I say, hormones are hormones, and if you’re not supposed to be on hormones for long periods of time, it probably doesn’t matter whether it’s bioidentical versus the chemical, the manmade, whatever.” In the end, however, Ann has stuck with CBHT because it works—saying, “Within a month I was sleeping. You know, no more mood swings, no more hot flashes, no more night sweats.”Nevertheless, it is important to point out that Ann—like several of the CBHT users in this study—is not Very familiar with all of this. Very knowledgeable. Did the saliva test. In a week, I had what my body needed—you know, what level it would actually need, so that they didn’t just throw a bulk amount at you. They actually calibrated it for your system, the levels that were in your system or not in your system.CBHT users in this study were also attracted to a treatment approach that they perceived to be tailored, or individualized, for their bodies and their treatment goals. Twelve (57.1%) women made this point, framing it in several different ways: First, women indexed a kind of biological tailoring in CBHT—both in terms of a chemical match to their bodies’ endogenous hormones and in terms of tailoring hormone dosages based in either blood or saliva tests for hormone levels, or symptom profiles. For example, when we asked Peg whether the naturopathic physician she found was familiar with compounded HT, she responded:there they have tests that you can buy and send in to some lab. … And so then it was very confusing to know is she right? Are they right? Is there anything such as a bioidentical hormone anyway?[My gynecologist] said, doing blood work and all that doesn’t work. Because, she said, there’s so much fluctuations, daily fluctuations …  “I want to start you on the lowest dose and then see if there’s any change. And then go up from there.” And then … I got that feedback from the compounder [that the dose was too low to be effective], and then Here, Peg makes a controversial point, one frequently raised in our interviews with women and in the literature on CBHT, about the value of blood or saliva testing for determining CBHT doses. Overall, women in this study held varied perspectives on the value of blood and saliva testing—often reflecting on conflicting ideas picked up through media, or from their clinicians. Susan illustrates this point:idea that compounded hormones were tailored to accurately supplement deficits in particular hormones.Despite their uncertainties about the value or accuracy of these tests for calibrating hormone dosages, many women were enticed by the your goals?” Which I just find awesome. And, like, my goal was never to have a period again. And she said, “Well, if I do this right, you won’t.” I mean, but some people do want to. They like that up and down thing. And they-- she can compound that, too. And they figure it out, and then they check in with you once a month for several months to make sure everything’s good, and if it’s not, then they reformulate, and they give you something a little different. They tweak it until you’re happy with what you have.OK, here’s how I do it. Somebody comes to me and tells me that they’re having these symptoms, and I offer them … a range of options, and it depends on whether they’re perimenopausal or postmenopausal, as well. If they decide they wanna go to [a local compounding] pharmacy, as an option, I draw their a detailed [blood] hormone panel, … [then] send you to [the compounding] pharmacy with a referral form, where they take, like, two trees’ worth of paper of a history and a symptom diary, and [the pharmacist] there talks to you for-- I mean she spends a hour and a half with you. And then they decide exactly what your goals are. I mean, not only just, here are my symptoms, and here’s, you know, what my hormone levels are, but, “What are Perhaps more importantly, women reported feeling like their CBHT regimen was tailored to meet their individualized treatment goals—that is, to specifically address the symptoms women found most bothersome . Bev describes this from her dual perspective of certified nurse midwife and CBHT user:We discuss the importance of this kind of clinical care in the section below, but here we highlight the attention to women’s treatment goals and women’s attraction of the idea that CBHT regimens are tailored to meet these goals.[group laughter]… Yeah, yeah, they do, they make ‘em taste good.[Most doctors] essentially give all women the same dosage, which I think is like, what, .625 [mg CE]? And, you know, they give us all the same, but what Dr. C was saying is that we’re not the same. So, by looking at our hormone levels, that gives you an idea of what it is that you are deficient in, and so, the compounding formula is specific to your hormonal levels. So, I was over there taking those blackberry and cream troches-- Women also liked that administration method for their CBHT could also be individualized to their preference . Sheree good-naturedly makes this point during a focus group, while also indexing her critique of the quality of mainstream medicine and the biological tailoring of CBHT:Although the delivery is clearly less important than the safety and efficacy of treatment, it demonstrates that women feel like CBHT  is finely tuned—both to their bodies’ needs and to their personal preferences.Many of the CBHT users in this study  described clinicians and compounding pharmacists who were willing spend significant time establishing and building trust with women, listening to them as they describe their symptoms and often intimate experiences with menopause, counseling women around their treatment options, and enlisting them as partners in treatment decisions. Above, Bev described this kind of enhanced clinical experience in which the compounding pharmacist takes significant time to talk with women about their menopausal experiences, work with them to identify treatment goals and preferences, and provide follow-up care to ensure that women are satisfied with their CBHT regimens.Similarly, Liz, a 51-year-old high school teacher, describes the central roles played by her clinicians and compounding pharmacist in assuaging her concerns about hormones and addressing the symptoms she associates with menopause. Liz described her symptoms as a vicious circle of hot flashes, night sweats, insomnia, and anxiety, saying, “It was so awful, it was insane.” To help break the cycle, Liz tried a series of over-the-counter products, including vitamins, herbal supplements, and progesterone cream; she eventually sought treatment from her midwife and primary care provider (PCP) from whom she requested sleeping pills. When we asked her why she requested sleeping pills rather than something to stop the hot flashes, Liz indexed a common push motivation, saying she was avoiding estrogen because “I’m terrified of getting cancer. … My grandmother died of cancer, and my sister-in-law died of breast cancer. My mom had [cancer and] a mastectomy. … It’s a horrible way to die and I don’t want to do anything that would be conducive to inviting that dysfunction to my own body.”After a consultation with a compounding pharmacist, Liz refused estrogen but decided to try compounded bioidentical progesterone. Nevertheless, when we asked Liz if there is anything she is reserving in case the symptoms become unbearable again, she indexes another push motivation, stressing that “horse estrogen” is completely off the table but that she might be persuaded to try plant-based estrogen. Liz says that she prefers a “holistic kind of approach” to taking a pill. In the end, however, it is the clinical experience  that matters. Liz says, “I guess it really basically comes down to this, I want to be able to describe my experience to somebody who has a vested interest in our relationship continuing, and have them know like anything there is to know and be able to offer that without agenda.”In a follow-up conversation, Liz reported that she had started using CBHT  soon after our original interview. When we asked her how she decided to use estrogen despite her concerns, she told us that had been “feeling psychotic from nights and nights of not sleeping.” Her PCP told her that “you have to sleep. You cannot function without sleeping.” Liz discussed her reluctance to use estrogen, her family history of cancer, and her overall concerns with her midwife, who explained that compounded estrogen was “different from pharmaceutically-produced hormones.” Like her PCP, her midwife also stressed that Liz needed to get some rest. While she still has some concerns about the safety of using estrogen, Liz says that the time, attention, and care the compounding pharmacist brought to their interaction was “important in feeling like my decision was OK.” The other factor was pragmatic: the CBHT worked immediately. Within two weeks the hot flashes were gone and the sleeping followed.Central to this point is that women sought clinicians who take time to listen and to develop trust with their patients. Across the broader study, the most satisfied women regardless of treatment type were those that felt that they had a trusting relationship with a clinician who they felt was personally invested in their well-being. This is a lesson for all clinicians.As of 2004, the FDA has recommended that HT be used at the “lowest effective dose of for the shortest duration to reach treatment goals” . With thformer users—meaning that they had discontinued CBHT use prior to participating in this study. The former users tried CBHT for the same push and pull reasons discussed above. What is different about the former users is that they generally described menopause symptoms in less distressing terms than the current users, and many only used CBHT for a short period when symptoms became more disruptive to their lives. The motivations that women described for discontinuing CBHT were largely same reasons women in the overall study gave for discontinuing conventional HT: the treatment was ineffective or had too many side effects, they were concerned about the risks of HT, or their symptoms abated and did not return.As we discussed above, nearly half  of the CBHT users in this study were The hot flashes disappeared; the light-headedness came. And at first I was just concerned maybe … I wasn’t doing it correctly, or I need to up the dosage, or lower something. I talked to the pharmacist because then I had the spotting and I thought, oh, well maybe this is because I missed a dose and-- But I didn’t like the feeling of light-headedness.The most common reasons women gave for discontinuing CBHT were that they were either ineffective or that the side effects of treatment did not outweigh the benefits. For example, having prescribed CBHT for her patients, Karen, a 52-year-old naturopathic physician, tried CBHT when she noticed her mild hot flashes increasing in frequency and intensity. She also started having night sweats. Karen tried a compounded bi-estrogen (estradiol and estriol) and progesterone for only three weeks before discontinuing the therapy due to the side effects she was experiencing. She explained:After discontinuing the CBHT, Karen’s light-headedness subsided. At the time of our interview, minor hot flashes had resumed, and she was trying to manage them through dietary changes and stress management techniques.don’t do that anymore!” As we saw with Ann, above, and as Joan illustrates here, although the CBHT users in this study perceive CBHT to be a better choice than conventional HT, they do not view it as wholly different when assessing risk. In light of new information, women reconsidered their CBHT use, just as women were reassessing HT overall.A few women discontinued CBHT in response to research highlighting the risks of long term HT. Joan, a 56-year-old behavioral health counselor, started using CBHT in 2000 to be proactive about her sexual health and osteopenia; she quit two years later, along with a wave of women who discontinued hormone therapy when the risks were in the news. She explains, “I think that when that study first came out, it was alarming, and I was part of that trend of women that were deciding Finally, several women described passively discontinuing CBHT simply by not refilling their prescription, only to find that their symptoms were bearable without treatment. Sheree said, “So, and I did that [CBHT] probably for about a year, maybe a year and a half, and then … it was time to go back and you know, I didn’t … and you know, there really wasn’t a need for me to go back.” In other words, many women have taken the FDA admonition to use hormones at the lowest dose for the shortest period seriously, and thus it was common for women to report experimenting with reducing hormone dosage or frequency, or stopping altogether to determine whether they could manage symptoms with less. This kind of experimentation, which we saw among women using CBHT as well as those using conventional HT, is similar to the trend we previously identified among dietary supplement users , in whicwhy women choose CBHT is essential. Yet, few studies have actually examined women’s experiences with CBHT or their rationales for using it. This study aimed to characterize the motivations for using CBHT in a U.S. sample of ordinary midlife women. Analyzing interview and focus group data collected with current and former users of CBHT, we identified motivations that drive women away from conventional approaches to managing menopause, and those that attract women to CBHT in particular.Recent data suggests that over one-third of U.S. women currently using menopausal HT are using CBHT . Given tequine estrogens), with many identifying these products by brand name and using emotional language to index their equine-source. This may reflect the effectiveness of decades of public awareness campaigns against these products e.g., [A cross-cultural meta-synthesis of qualitative and quantitative studies of women’s attitudes toward HT found that women generally have a positive view of the efficacy of HT for treating the symptoms of menopause and improving quality of life, but they have concerns about the potential side effects  and about the uncertainty of evidence for HT .4 These ts e.g., , 89, as ts e.g., , 84.Women in this study also voiced frustration with a medical system that they perceive to be dismissive of their concerns and overly reliant on pharmaceuticals in place of clinical attention. They were even more critical of a pharmaceutical industry that they feel has tirelessly promoted HT to generations of women , 90, 91 is the most effective way to manage the vasomotor symptoms of menopause [In contrast, our participants were attracted to CBHT because—as a form of HT—they viewed it as effective for managing the symptoms of menopause and thus for supporting their quality of life. The importance of this point cannot be overstated. It is the efficacy of HT that has allowed it to weather multiple crises of confidence. Clinicians continue to prescribe HT, and women continue to use HT because it enopause , 100. Thperceptions about the safety and individualization of CBHT—not because we view this as a straightforward example of patient misunderstanding driving the need for patient education, but because it speaks volumes about the kinds of treatments women desire, and because these perceptions are influencing women’s real world treatment decisions.Our research corroborates previous studies indicating that women are attracted to CBHT because they perceive it to be “safer” or more “natural” than conventional HT, and more individualized to their treatment priorities and preferences , 51, 52.Finally, perhaps the most significant appeal of CBHT may not be the pharmaceutical itself, but the kind of clinical care that surrounds it. Research has demonstrated the interpersonal value of clinical care for patient wellness and satisfaction –104. ManIn recent years, CBHT has emerged as a popular alternative to manufactured, FDA-approved hormone therapy—despite concerns within the medical community and the availability of new FDA-approved “bioidentical” products. This study investigated the motivations for choosing and using CBHT in a U.S. sample of ordinary midlife women. Although women’s individual motivations varied, several themes emerged across CBHT users that can broadly be categorized as “push motivations” driving women away from conventional hormone therapy and “pull motivations” that attracted women to compounded hormone therapy, in particular.some of women’s concerns about conventional HT may be allayed, and some of the characteristics women seek may be met with non-hormonal and manufactured bioidentical HT. Yet an important take home message of this study is that women are not only seeking alternatives to conventional pharmaceuticals, but alternatives to conventional care. This study demonstrates that many women chose CBHT because they want a different kind of clinical experience, in which their experiences of menopause are validated and they are listened to, where their treatment objectives are solicited and prioritized, and where they are invited to play an active role in determining their treatment. In short, the clinical context of CBHT appears to explicitly invite women to participate shared decision-making in ways the standard clinical context does not [As clinical decision-support tools for menopause symptom management are released  and moredoes not , 105.The significance of this finding goes beyond understanding why women choose CBHT. We argue that women making menopause treatment decisions of all kinds would benefit from a clinical context in which they are explicitly invited to share their experience of menopause, and voice their treatment preferences and priorities. This would also provide an opportunity for clinicians to discuss the pros and cons of conventional HT, CBHT, and other approaches to managing menopause. Certainly, there are often structural barriers  that make shared decision-making difficult in the standard clinical context ; neverth