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PubMed1976

[A case of testicular feminization with the karyotype 47, XXY (author's transl)].

A case of testicular feminization is described, who has the karyotype 47, XXY in all analysed metaphases from blood and skin cultures. The question is discussed whether the karyotype 47, XXY is compatible with the syndrome of testicular feminization and which conditions are required to allow the hitherto known transmission of testicular feminization in presence of the gonosomes XXY. A review of literature is given.

Adult↗
PubMed1985

Queen Elizabeth I: a case of testicular feminization?

The purpose of this paper is to provide support for the hypothesis that Queen Elizabeth I was a case of testicular feminization (male pseudohermaphroditism) and for the explanation of her contemporaries and of some historians, that she never married because of some congenital defect. The phenotypical characteristics of the testicular feminization syndrome are strikingly similar to descriptions of Elizabeth's appearance, personality, behaviour, and particularly, to those physical defects which her contemporaries believed made her sterile and unwilling to marry. Modern historians have rejected the "physical defect" explanation of Elizabeth's refusal to marry in favour of a "psychological" explanation. The basic premise of the "psychological" explanation, that Elizabeth was physically capable of bearing children is unsound for a number of reasons. Recent advances in our understanding of the process of sexual differentiation, particularly, the description of the testicular feminization syndrome, justify a re-evaluation of the "physical defect evidence" of Elizabeth's contemporaries.

Androgen-Insensitivity Syndrome↗
PubMed2003

The long term outcome of feminizing genital surgery for congenital adrenal hyperplasia: anatomical, functional and cosmetic outcomes, psychosexual development, and satisfaction in adult female patients.

BACKGROUND: There are only a few reports analyzing the long term outcome of feminizing surgery in females with congenital adrenal hyperplasia (CAH). Such analysis is crucial to evaluate the treatment and to make necessary adjustments. STUDY OBJECTIVES: To evaluate the adult outcome after feminizing surgery in adult females with salt wasting CAH. DESIGN: Retrospective observational followup investigation. SETTING: Outpatient clinic of a University Medical Center, in 2002. PARTICIPANTS: Eight patients (born 1973-1983) who underwent feminizing surgery in infancy by the same procedure and the same pediatric surgeon in our center, and 19 healthy female controls (for visual analog scales). METHODS: (a) Study of patients' records (n=8); (b) Systematic evaluation of the current situation (n=6): uroflowmetry, a written questionnaire to screen for psychopathology (Youth Adult Self Report, YASR), structured gynecologic examination and a structured psychosexual interview, including scoring on visual analog scales. RESULTS: (a) The first surgery (age 0.1-3.7 yr) consisted of clitoris reduction and vaginoplasty (single-stage) in 7 patients and clitoris reduction only in one patient. The latter patient had vaginoplasty in puberty. In puberty, 6 of the 7 patients with an initial single-stage procedure required re-vaginoplasty. All 6 patients who participated in this systematic evaluation had undergone (re-) vaginoplasty in puberty; (b) 2 of the 6 patients experienced some urinary incontinence, and in one of them, the uroflowmetry result was abnormal. The YASR showed no psychopathology, except for 1 patient with a slightly elevated externalizing score. Gynecologic examination (n=5) revealed vaginal strictures in 3 patients (1 severe, 2 mild). The 2 patients without vaginal strictures had coitus regularly. In the interview, 2 patients called themselves bisexual, the other 4 heterosexual. None of the patients had homosexual contacts. Sexual developmental milestones (romantic interest, falling in love, kissing and petting, coitus) had been reached by all, except for 1 patient who did not have coitus yet. In the patient group, satisfaction with height, body hair, and external genitalia and sexual fantasies and interest, measured with visual analog scales, was not different compared to the control group, except for satisfaction with total body appearance, which was significantly lower in the patients. CONCLUSION: Despite the poor outcome of the initial single-stage surgery in infancy and the inevitable re-operation in puberty, the adult outcome in our study population seems more positive than the findings in the few previous reports, especially with respect to sexual development and activity.

Adrenal Hyperplasia, Congenital↗
PubMed1993

Feminism: a concept analysis.

The purpose of this paper is to analyse the concept of feminism in order to clarify a sociological concept for its use in nursing theory and practice. This analysis is carried out using the Walker & Avant (1988) model. It includes: a literature review, an overview of the uses of the concept drawn from the literature, the defining attributes and the justification of their choice, the cases to demonstrate the concept, and the concept criteria. The concept was chosen out of an interest in developing a feminist nursing theory and desire to enhance nursing practice. The literature search proved most fruitful in the sociological literature. The nursing sources were fewer and concerned with practice rather than articulating any feminist nursing theory. Many of these sources were sociologists and nurses. The concept of feminism was defined as the concern with gender equality and the promotion of equal rights for men and woman, the expression of these concerns through theory or action, and the valuing of individuals for their contributions to society rather than their biological or sexual characteristics or roles. Although the concept of feminism was defined and analysed within the model suggested by Walker & Avant, the author found that the concept became oversimplified, losing much of the richness of the literature. The author felt that, for any development of theory or practice, this analysis would have to be expanded. It is argued that their model is too restrictive as it is based on positivist philosophy which seeks to establish divisions where, in fact, there is a blurring of meaning.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗
PubMed2003

Association with host mitochondrial haplotypes suggests that feminizing microsporidia lack horizontal transmission.

The amphipod crustacean Gammarus duebeni hosts two feminizing microsporidian parasites, Nosema granulosis and Microsporidium sp. Samples of G. duebeni were collected from three sites on the Scottish island of Great Cumbrae and screened for microsporidia using polymerase chain reaction. Associations between the prevalence of the two feminizing parasites and haplotypes of the host mitochondrial gene cytochrome oxidase I (COI) were investigated. The prevalence of both parasites varied significantly among the host's COI haplotypes, suggesting that horizontal transmission is rare or absent in the life cycles of the feminizing microsporidia and that all transmission must therefore be vertical. Life cycles in which all transmission is vertical are common among bacterial parasites but have never before been demonstrated in Eukaryotic parasites.

Amphipoda↗
PubMed2005

Passerini-glazel feminizing genitoplasty: a long-term followup study.

PURPOSE: We report our experience with early 1-stage Passerini-Glazel feminizing genitoplasty with special emphasis on long-term results of vaginoplasty. MATERIALS AND METHODS: A total of 66 patients with ambiguous genitalia underwent 1-stage Passerini-Glazel feminizing genitoplasty. Long-term followup included an outpatient visit at 1 year postoperatively and a genital assessment with the patient under general anesthesia performed before menarche courses in those operated on at age 6 months to 8 years, and at 2 years postoperatively for those operated on at 9 years or older. RESULTS: All patients underwent the first long-term followup evaluation and no major complications were observed. The second long-term followup evaluation was performed in 46 patients (70%). In all cases the vaginal introitus was located in the physiological position and was large and elastic. Vaginal caliber at the suture line between the tubularized flap and vaginal mucosa was the same size as the vaginal introitus and distal native vagina in 20 of 46 patients (43%), slightly smaller in 10 (22%) and stenotic in 16 (35%). Stenosis at the suture line was corrected with simple Y-V introitoplasty performed at the same followup visit. CONCLUSIONS: Early 1-stage Passerini-Glazel feminizing genitoplasty is a safe and effective procedure that allows total surgical correction of ambiguous genitalia in infancy and good cosmetic results. Incidence of vaginal stenosis at the suture line is high but it can be repaired with simple introitoplasty performed before menarche occurs. Good functional results are presumed.

Adolescent↗
PubMed1992

A case of testicular feminization syndrome with bulimia nervosa.

A 19-year-old patient with a female appearance visited our department for treatment of bulimia nervosa. The patient had primary amenorrhea. Chromosomal studies revealed a 46XY karyotype, and the plasma testosterone level was in the range of normal adult males. The patient was diagnosed as having testicular feminization syndrome. The psychological background, such as severe anxieties concerning her body, was behind the eating disorders. Examinations revealed intraabdominal testes. A bilateral gonadectomy was performed, and no androgen receptors were detected in the suprapubic skin. After the gonadectomy, the patient's mental status became much more stable, and the ability to control her eating pattern was restored. Testicular feminization with bulimia nervosa is rare in Japan. The importance of mental support and a careful follow-up to people with testicular feminization is being discussed.

Adult↗
PubMed2000

Estrogens and estrogen-like non-feminizing compounds. Their role in the prevention and treatment of Alzheimer's disease.

The present position paper is intended to provide evidence that estrogen deprivation contributes to the occurrence and course of Alzheimer's disease (AD) and that currently available estrogen preparations may be useful in the prevention and treatment of AD in women. Additionally, there is now substantial preclinical evidence to support the development of novel non-feminizing estrogens for use in male and female subjects for the protection of neurons from damage and death that underlies the neuropathology of AD. Estrogens and non-feminizing estrogen-like compounds may exert their beneficial effects in AD through a variety of mechanisms, directly through their neuroprotective actions and indirectly through their neurotrophic effects. Inasmuch as estrogens are comparatively free of both acute and chronic toxicities, and non-feminizing estrogens are expected to be even safer, their use for years to decades for the prevention or treatment of AD is possible.

Alzheimer Disease↗
PubMed1995

Genetic feminization of brain structures and changed sexual orientation in male Drosophila.

The neural basis of sexual orientation in Drosophila was studied by the production of males with regionally feminized brains. Such flies express the female form of the sex determination gene transformer in a limited number of neurons under the control of GAL4 enhancer trap inserts. This method facilitated the creation of lines with a stable pattern of feminization. In tests of sexual preferences, flies that were feminized in a portion of the antennal lobes or in a subset of the corpora pedunculata (mushroom bodies) courted both males and females. These two brain structures, both of which are involved in olfactory processing, may function in the recognition of sex-specific pheromones, in the control of sex-specific behaviors, or both.

Animals↗
PubMed1972

Studies on the pathogenesis of the pseudohermaphroditism in the mouse with testicular feminization.

The pathogenesis of the male pseudohermaphroditism in the mouse with X-linked testicular feminization (Tfm) has been investigated by comparing testosterone formation, the effects of androgen administration, and the metabolism of testosterone-1,2-(3)H in normal mice and Tfm mice of varying ages. First, it was established that the adult Tfm animal, in contrast to the human with testicular feminization, has both a low serum testosterone and a low rate of testosterone formation as assessed in slices of testes utilizing a variety of precursors. However, the formation of testosterone from pregnenolone-7alpha-(3)H was shown to be normal in newborn Tfm testes, suggesting that a defect in testosterone synthesis may not be primary to this mutation. Second, to establish that the pseudohermaphroditic state is due to androgen resistance rather than to diminished androgen biosynthesis during fetal life, the effect of the administration of dihydrotestosterone to pregnant animals was studied in male, female, and Tfm offspring. Whereas normal and carrier female littermates demonstrated striking virilization of the internal genital tract after such treatment, there was no sign of virilization in the Tfm animals. This finding provides direct experimental evidence in support of the view that male pseudohermaphroditism in testicular feminization is the result of resistance to androgen action during androgen-mediated sexual differentiation in embryos. Third, the metabolism of testosterone-1,2-(3)H was investigated both in tissue slices and in functionally hepatectomized animals. Dihydrotestosterone formation in tissue slices of the fetal anlage of the male organs of accessory reproduction is normal in the Tfm animal, suggesting that the primary defect in this disorder involves an intracellular event subsequent to this step and that the deficient dihydrotestosterone formation observed in the adult genital tract of the Tfm mouse is secondary to the failure of differentiation in these tissues. Finally, deficient binding of testosterone in the nuclei of the submandibular gland of adult Tfm animals, a known testosterone target tissue, was demonstrated in functionally hepatectomized mice. This finding could either be a manifestation of the primary genetic defect in this disorder or might reflect another acquired abnormality due to incomplete differentiation of adrogen-sensitive cell lines.

Androgen-Insensitivity Syndrome↗
PubMed1979

Testicular feminization associated with a thermolabile androgen receptor in culutred human fibroblasts.

Evidence for a qualitative abnormality in the androgen receptor was obtained by studies of temperature sensitivity. The binding of [(3)H]dihydrotestosterone (17beta-hydroxy-5alpha-androstan-3-one) was studied in monolayers of cultured genital skin fibroblasts from genetic males with abnormal sexual differentiation resulting from androgen resistance. Binding in cells from eight patients with a female phenotype (complete and incomplete testicular feminization) fell from half-normal levels at the usual assay temperature of 37 degrees C to levels <20% of normal when cells were incubated at 42 degrees C. This thermal inactivation was rapidly reversed when the assay temperature was lowered to 37 degrees C, was not associated with altered dihydrotestosterone metabolism, and was also demonstrable with [(3)H]methyltrienolone as the binding ligand. Binding increased to overlap the normal range when the assay temperature was lowered to 26 degrees C. The patients with receptor-deficient testicular feminization include three pairs of siblings; the pedigrees in two of these families are compatible with X-linkage. Only minor changes in the amount of binding at elevated temperatures were observed in cells from 10 control subjects and from 2 male pseudohermaphrodites with normal levels of androgen receptors. In 10 patients with androgen resistance and partial receptor deficiency associated with a predominantly male phenotype (Reifenstein syndrome and infertile men), dihydrotestosterone binding also did not change consistently with elevated temperature. Binding was approximately half-normal at 37 degrees C and either increased or decreased slightly at 42 degrees C. The thermal instability in receptor-deficient testicular feminization represents a new molecular defect associated with hereditary male pseudohermaphroditism that appears to be caused by an alteration in the tertiary structure of the androgen receptor protein.

Androgen-Insensitivity Syndrome↗
PubMed1992

Incomplete testicular feminization syndrome: studies of 17 beta-oestradiol-binding activity and aromatase activity in cultured genital fibroblasts showing impaired dihydrotestosterone-binding.

Dihydrotestosterone (DHT) and 17 beta-oestradiol binding, and aromatase activity were measured in cultured genital skin fibroblasts from two siblings with the incomplete testicular feminization syndrome. Whole-cell and nuclear DHT binding in the cells from both patients were reduced to 80% and 60%, respectively of those in a normal male subject. The nuclear oestradiol binding was not impaired in the fibroblasts from the patients whose plasma oestradiol was normal or a little elevated. Although gonadectomy led to a decrease in plasma testosterone concentration, the concentration of testosterone-binding globulin showed no change suggesting no apparent effect on testosterone-binding globulin synthesis by testicular steroids. There was no significant difference in aromatase activity of the fibroblasts between the patients and the normal male subjects. The relatively increased oestrogen concentration in the syndrome might result from oestrogen production in testes, but is unlikely to be from peripheral tissues such as fibroblasts. This is the first report to examine oestradiol binding and aromatase activity in the cells from the incomplete testicular feminization associated with impaired DHT binding. These findings may give new insight into the pathogenesis of abnormal male sexual differentiation in the patients with testicular feminization syndrome.

Adult↗
PubMed2003

Feminizing chicks: a model for avian sex determination based on titration of Hint enzyme activity and the predicted structure of an Asw-Hint heterodimer.

BACKGROUND: In birds and some lizards, females are heterogametic with a ZW karyotype, while males are ZZ homogametes. The molecular basis for sexual differentiation in birds is unknown: arguments exist for doses of Z masculinizing chicks and for W information feminizing. ASW was identified as a tandemly repeated gene conserved on avian W chromosomes that is expressed in early female development and appears to be an inactive form of avian Z-encoded HINT. Hint is a dimeric enzyme that hydrolyzes AMP linked to lysine, whose enzyme activity is required for regulation of the Cdk7 homologous Kin28 kinase in yeast. Of 16 residues most conserved across all life forms for AMP interactions, 15 are sexually dimorphic in birds, that is, altered in the female-specific Asw protein. Genomic and expression data suggest that Asw may feminize chicks, dominantly interfering with Hint function by heterodimerization. RESULTS: We consider whether positive cooperativity could explain how Hint heterodimerization with an inert enzyme might reduce specific activity by more than 50% and provide data sufficient to reject this model. Instead, we hypothesize that Asw carries a signal for mislocalization and/or proteolysis, and/or dominantly suppresses the remaining Hint active site to function as a dominant negative. CONCLUSIONS: Molecular modeling suggests that Asw and Hint can heterodimerize and that Gln 127, an Asw-specific alteration for Trp123, dominantly interferes with the Hint active site. An extra dose of HINT in ZZW chicks, and thus more Hint homodimer, may partially overcome the feminizing influence of ASW and lead to the observed intersexual characteristics of ZZW triploids.

Animals↗
PubMed1975

Clinical and endocrinologic characterization of a patients with the syndrome of incomplete testicular feminization.

A 46 XY individual with male pseudohermaphroditism was investigated. The phenotype was distinctive in that the habitus was female in character, but partial fusion of the labioscrotal folds, testes, and male wolffian duct structures that terminated in the vagina were present. Müllerian structures were absent. At the expected time of puberty both feminization (breast development) and virilization (clitoral enlargement) took place. Studies of estrogen and androgen dynamics revealed plasma testosterone levels and production rates characteristic of normal men. Plasma estrogen levels and production rates were greater than those of normal men. Plasma gonadotropin levels were also high. These findings suggest that the fundamental defect in this patient is androgen resistance rather than defective androgen synthesis. Dihydrotestosterone formation from testosterone slices of epididymis and perineal skin was normal. The family history was uninformative. On endocrinologic, genetic, and phenotypic grounds the syndrome of incomplete testicular feminization can be separated from the complete form of testicular feminization and from familial incomplete male pseudohermaphroditism, Type 2. Additional studies will be required to determine whether this disorder is also distinct from the Type 1 form of familial incomplete male pseudohermaphromditism.

Androstenedione↗
PubMed1976

[Sexually differentiated metabolism of testosterone in liver slices of mouse, and its alteration by a mutation in the X-chromosome that results in testicular feminization].

1. Sexual differentiation of the metabolism of testosterone in liver slices of normally developed, sexually mature mice: Sexual differentiation in the mouse, unlike that in the rat, shows a high degree of uniformity: Where the formation of metabolites with the composition C19O2 is markedly greater in one sex, then this is invariably the male. The formation of C19O3 steroids and 4-androstene-3,17-dione, and the turnover of testosterone show no marked sexual differences, although the sum of the C19O2-type delta4-hydrogenation products of testosterone is significantly greater in the male. This apparent discrepancy is explained by the fact that the sum of the delta4-hydrogenation products represents no more than 10% of testosterone turnover. Thus, sexual differences in the formation of individual delta4-hydrogenation products are not apparent from a consideration of the overall turnover of testosterone. 2. Sexual differentiation of testosterone metabolism studied in genetically male litter mates, carrying the X-chromosome-bound mutation and showing testicular feminization (Tfm): The Tfm mutation (genotype XTfm Blo/Y; Blo = coat colour gene Blotchy) results in a feminization of testosterone metabolism. Where the level of testosterone metabolites is significantly higher in the normal male than in the normal female, the Tfm mutation shows a level that is significantly lower than in the normal male, and which, in most cases, is the same as that in the normal female. The concentration of three metabolites (3alpha- and 3beta-hydroxy-5beta-androstan-17-one, and 5beta-androstane-3,17-dione), which do not show sex-based differences, were significantly increased in the Tfm mutation. The Tfm mutation therefore effects the formation of all ring A hydrogenation products of type C19O2 (with the single exception of 5bets-androstane-3alpha,17beta-diol). It does more than simply equalize sexual differences by feminization. It has no effect on the hydroxylation of testosterone, or on its 17beta-dehydrogenation to 4-androstene-3,17-dione. The consequences of the Tfm mutation for the liver are irreversible: The formation of 5alpha-androstane-3,17-dione, which is a representative parameter for the sexual differentiation of testosterone metabolism, is not influenced by the injection of testosterone (15 mg i.p. 6 days before investigation).

Androgen-Insensitivity Syndrome↗
PubMed2006

Anatomical and functional outcomes of feminizing genitoplasty for ambiguous genitalia in patients with virilizing congenital adrenal hyperplasia.

UNLABELLED: The ideal surgical technique and appropriate age for performing feminizing genitoplasty are debatable, and few long-term outcome studies have been reported. PURPOSE: To report a retrospective study on anatomical and functional outcomes of feminizing genitoplasty in patients with virilizing congenital adrenal hyperplasia. METHODS: We selected 34 patients (mean age = 3.4 +/- 2.5 yr) with genital ambiguity classified according to Prader stage. Follow-up ranged from 2 to 16 years. Clitoral length ranged from 1.9 to 5.0 cm; 28 patients had a single perineal orifice, and 6 had a double orifice. The surgical technique included clitorovaginoplasty in a single procedure and was carried out before 2 years of age in 18 patients. Clitoroplasty was performed with glans preservation in all patients. Blood supply was exclusively maintained by the frenular pedicle in 97% of the cases, whereas clitoral dorsal nerves and vessels were preserved in the remaining 3%. The opening of the urogenital sinus was performed using either the Y-V perineal flap procedure (25 patients) or the cut-back incision procedure (8 patients). RESULTS: Good morphological and functional results were achieved in 68% of the patients; 21% of the patients had surgical complications, such as incision bleeding (2 cases), glans necrosis (1 girl with Prader V), and vaginal introitus stenosis (4 cases). Three of the latter underwent dilation with acrylic molds in the post-pubertal period with good functional results. CONCLUSIONS: We conclude that single-stage feminizing genitoplasty consisting of vulvoplasty, clitoroplasty, and Y-V perineal flap produced good cosmetic and functional results in virilized girls with congenital adrenal hyperplasia, with few complications. In addition, this surgical approach prevented the need for neovaginaplasty even in patients with high vaginal insertion.

Adrenal Hyperplasia, Congenital↗
PubMedDate not supplied

Ultrastructure of feminizing testicular Leydig cell tumors.

The ultrastructure of a feminizing testicular Leydig cell tumor was analytically compared with that of the five reported feminizing neoplasms and with that of the eight published masculinizing or hormonally inactive tumors. Certain observations were noteworthy but of uncertain significance. In the current case, nuclear outlines tended to be irregular, nuclear pores were relatively few, chromatin was often uniformly dispersed, and nucleoli were frequently multiple. Membranous whorls and "myelin figures" were common. Collectively, the nuclear aberrations were noted only in the two feminizing neoplasms studied by us. Other findings in the present case included abundant endoplasmic reticulum, swollen pleomorphic mitochondria, numerous lysosomes, "dark" and "light" Leydig cell nuclei, and specialized modifications of the plasma membrane. These observations were inconstantly present in the group as a whole, irrespective of hormonal activity. Employing present methods it is not feasible to correlate the fine anatomy of testicular Leydig cell tumors with their capability of hormonal function.

Adult↗
PubMed2000

[Testicular feminization syndrome associated with acute hydramnios: apropos of 1 case].

We describe the first, to our knowledge, case of a feminizing testicle associated with acute polyhydramniosis observed at 21 weeks 3 days gestation. There was no fetal malformation or maternal disease that would explain the polyhydramnios. Prenatal diagnosis of feminizing testicle can now be made but is very difficult to suspect without similar family history or a suggestive ultrasonographic sign. Many fetal malformations have been directly linked to different causes of feminizing testicle, but for other malformations such as acute polyhydramnios, the pathogenesis remains unknown.

Adult↗