46,XY性发育异常的诊断和外科治疗研究进展

性发育异常(disorders of sex development,DSD)是一种表型和遗传高度异质的先天性疾病,其中46,XY性发育异常的病因和临床表现最为复杂多样,不及时治疗可能会给患者和家庭带来深远的影响.应综合患者病史、体格检查、实验室检查、影像学检查和分子遗传学检查进行诊断.目前DSD的治疗方式仍以手术治疗...     

Two Males with SRY-Positive 46,XX Testicular Disorder of Sex Development

The 46,XX testicular disorder of sex development (46,XX testicular DSD) is a rare phenotype associated with disorder of the sex chromosomes. We describe the clinical, molecular, and cytogenetic findings of a 16- and a 30-year-old male patient with sex-determining region Y (SRY)-positive 46,XX testicular DSD. Chromosomal analysis revealed 46,XX karyotype. Fluorescence in situ hybridization (FISH) showed the SRY region translocated to the short arm of the X chromosome. The presence of the SRY gene was also confirmed by polymerase chain reaction (PCR). The X chromosome inactivation (XCI) assay showed that both patients have a random pattern of X chromosome inactivation. This report compares the symptoms and features of the SRY-positive 46,XX testicular DSD patients.     

46,XY女性性发育异常的遗传学病因研究进展

46,XY女性性发育异常(46,XY DSD)是一种罕见的先天性遗传学疾病,根据发生机制主要包括性腺分化发育异常和雄激素合成或功能障碍两方面。其遗传背景复杂,与多种遗传因素相关,性腺分化发育异常与SRY、WT1、SF1、SOX9、DAX-1、DMRT1等基因相关;CYP17A1、SRD5A2等基因突变可引起参与雄激素合成的酶发育异常,从而导致雄激素合成障碍;雄激素功能障碍主要与雄激素受体(AR)基因相关。该病在临床表现有很大的异质性,包括完全性性腺发育不良、部分性性腺发育不良及睾丸退化综合征。早期发现、明确病因对患者的治疗选择、预后和遗传咨询具有重要的意义,本文对引起46,XY DSD的相关基因及临床表现进行综述。     

45,X/46,XY嵌合体性发育异常诊治进展

45,X/46,XY嵌合体性发育异常是临床上比较少见的疾病,其发生机制可能与Y染色体微缺失、Y染色体性别决定基因(SRY)或其他性别决定基因发生突变或调节异常有关。患者的临床表型特点主要为外生殖器及性腺发育异常、身材矮小伴或不伴Turner综合征相关表型异常。细胞及分子遗传学检查可明确诊断,外生殖器男性化评分、激素水平测定、影像检查、腹腔镜探查及性腺活检等对指导后续治疗具有重要意义。在患者的性别分配、激素补充治疗、是否行性腺切除、手术干预的时机及方式等方面仍有很多争议。多学科综合诊断及个体化的治疗原则虽已逐渐成为共识,还应更好地实施。     

Psychological Distress,Self-Harming Behavior,and Suicidal Tendencies in Adults with Disorders of Sex Development

Evaluation of psychological distress has received relatively little attention in research on persons with disorders of sex development (DSD). Results of previous studies varied considerably, but most studies did not find increased levels of psychological distress. We conducted a pilot study based on a sample of 37 persons with diverse forms of DSD recruited via various strategies. The Brief Symptom Inventory (BSI) was used to assess self-reported psychological distress. Psychological distress varied broadly across all diagnostic subgroups. Overall, the BSI Global Severity Index indicated higher distress in the sample of persons with DSD compared to a non-clinical norm population of women, with an effect size of d = 0.67. According to predefined BSI criteria, 59% of participants were classified as a clinical case. Self-harming behavior and suicidal tendencies were also assessed and compared to a community based sample of women, including subgroups of traumatized women with a history of physical or sexual abuse. The prevalence rates of self-harming behavior and suicidal tendencies in the DSD sample exceeded the rates of the non-traumatized comparison subgroup, with rates comparable to the traumatized comparison groups of women with physical or sexual abuse. As possible explanations for the higher distress found here compared to most previous studies, differences in measures and sample recruitment are discussed. Our results suggest that adults with DSD are markedly psychologically distressed with rates of suicidal tendencies and self-harming behavior on a level comparable to non-DSD women with a history of physical or sexual abuse, but sample recruitment procedures do not permit a firm generalization.     

Aggressive and Mating Behaviors in Two Types of Sex Reversed Mice: XY Females and XX Males

Aggressive and mating behaviors were assessed in XX females, XY females, and XY males of the C57BL/6/J/Ei (“C57BL/6” or “B6”) strain of mouse. The Y chromosome of the XY females derives from Mus domesticus poschiavinus and the Y chromosome of the XY males derives from Mus musculus. The poschiavinus Y in the C57BL/6 background results in XY mice with either ovaries or ovotestes. Only those with ovaries were tested. These XY females appear to be endocrinologically identical to XX females. Aggressive and mating behaviors were also tested in XX males and XY males of the FVB/NtacfBR Odsex (“FVB”) strain of mouse. The XX males have a transgene inserted 1 Mb upstream of the SOX9 gene, resulting in gonadal differentiation as a testis in the absence of a Y chromosome. C57BL/6 mice were tested for aggression in an instigated resident intruder paradigm and FVB/NtacfBR Odsex mice were tested for aggression in a neutral cage paradigm. Mice of both strains were tested with opponents of the same sex chromosome complement and gonadal sex. On the C57BL/6 background, the XY males were more aggressive than the XY and XX females, but there was no significant difference between the XX and XY females in aggression. On the FVB background, the XY and XX males were equally aggressive. Mice from both C57BL/6 and FVB backgrounds were tested for mating behaviors with females in hormonal estrus. On the C57BL/6 background, the XY males mounted more than the XY females, but there was no significant difference between the XY and XX females in mounting. On the FVB background, mounting, intromissions, and ejaculations were the same in XY and XX males. The implications of these findings for the effect of sex chromosome complement on sex differences in aggression and mating in mice are discussed.     

Gender Incongruity in a Person with 46,XY and Complete Androgen Insensitivity Syndrome Raised as a Female

We present the case of a patient with female sex assignment at birth whose parents consulted with a pediatrician when the child was 12 years old, indicating that despite female sex assignment, she felt that she (henceforth “he”) had a male gender identity and was gynephilic. Medical examination revealed a 46XY karyotype, a primary amenorrhea and an appropriate testosterone increase after HCG stimulation test. The patient was diagnosed then with a 46,XY disorder of sex development with androgen insensitivity syndrome, but then he missed subsequent appointments. At the age of 24, he resumed medical follow-up to reaffirm his male gender identity through sex reassignment surgery. His physical examination showed a Tanner stage III-IV breast development, vulva, clitoris, normal-sized vagina, absence of uterus and ovaries on transvaginal ultrasound, bilateral cryptorchidism on abdominal-pelvic MRI and osteoporosis on bone densitometry. The results of the blood tests were LH 24.5 mIU/mL [normal range, 1.7–8.6 mIU/mL for men] and testosterone 8.8 nmol/L [8.7–33 nmol/L]; conversely, FSH, estradiol, progesterone, and prolactin levels were normal. The molecular genetic analysis revealed an androgen receptor gene mutation associated with complete androgen insensitivity syndrome. At present, the patient has undergone bilateral orchiectomy and has initiated treatment with topical testosterone and bisphosphonates. We have yet to evaluate the effects and decide the best therapy taking into account that he has a male gender identity but complete androgen insensitivity syndrome.

     

The Influence of Gender on Sex: A Study of Men's and Women's Self-Reported High-Risk Sex Behavior

An investigation is presented of the relationship between gender and five self-reported high-risk sex behaviors: ever having had casual sex, the lifetime number of vaginal sex partners, the lifetime number of anal sex partners, having had multiple vaginal sex partners over the short term, and having had multiple anal sex partners over the short term. The analysis was guided by a conceptual model that emphasized the constraints and opportunities for high-risk sex behavior that arise from an individual's structural position and cultural context. Gender differences in high-risk sex behaviors were predicted to be due to differences in men's and women's family roles, work roles, religious behaviors, and past sex experience. In addition, the effects of certain sociocultural factors on the high-risk sex behaviors were expected to be dependent on an individual's gender. The hypotheses were evaluated using national data from the United States on self-reported sex behaviors for men ages 20 to 39 years old and women ages 20 to 37 years old. Data analyses were conducted using ordinary least-squares regression and logistic regression. Findings provided mixed support for the predictions. Gender was not significantly related to short-term, self-reported high-risk sex behaviors once social and cultural factors were included in the statistical models. But it continued to predict lifetime behaviors. Several variables, including race, age, age at first sex, and marital status, had gender-specific effects on the self-reported high-risk sex behaviors. The study demonstrates how the effects of structural and cultural factors on sex behavior differ for men and women.     

Gender Identity Outcome in Female-Raised 46,XY Persons with Penile Agenesis,Cloacal Exstrophy of the Bladder,or Penile Ablation

This review addresses the long-term gender outcome of gender assignment of persons with intersexuality and related conditions. The gender assignment to female of 46,XY newborns with severe genital abnormalities despite a presumably normal-male prenatal sex-hormone milieu is highly controversial because of variations in assumptions about the role of biological factors in gender identity formation. This article presents a literature review of gender outcome in three pertinent conditions (penile agenesis, cloacal exstrophy of the bladder, and penile ablation) in infancy or early childhood. The findings clearly indicate an increased risk of later patient-initiated gender re-assignment to male after female assignment in infancy or early childhood, but are nevertheless incompatible with the notion of a full determination of core gender identity by prenatal androgens.     

Gender destinies: assigning gender in Disorders of Sex Development‐Intersex clinics

Based on audio recordings of consultations in three U.S. paediatric multidisciplinary Disorders of Sex Development‐Intersex clinics, we examine the process of gender assignment of children with “atypical” genitalia. Rather than fully determined by the presence of biological sex traits, the gender assignment discussion hinges on how clinician and parent collaboratively imagine different aspects of what constitutes being a gendered person. They orient towards the potential for sexual intimacy, fertility, gender dysphoria, stigma, and gonadal cancer risk. While these futures remain inherently uncertain, clinicians and parents plan to mobilise gender socialisation and medical interventions to render their choice of gender a self‐fulfilling prophecy. Gender destinies capture that the child always had a specific, innate gender awaiting discovery, and presumes a project for medical and social monitoring, intervention, correction, and optimisation.     

Sexual Self-Concept in Women with Disorders/Differences of Sex Development

Many women born with disorders or differences of sex development (DSD) report sexual problems, in particular women who have undergone extensive genital reconstruction. Examining cognitions and emotions that hinder or promote sexuality may facilitate understanding these sexual problems and may contribute to the development of specific interventions. In this study, sexual self-concept, body image, and sexual functioning were investigated in relation to genital surgery. To conduct the study, the women’s Sexual Self-Concept Scale was translated to Dutch. Evaluation of psychometric properties was conducted in a sample of healthy Belgian and Dutch women participating in an anonymous web-based survey (N?=?589, Mdn age, 23 years). The resulting three-factor structure corresponded largely to that of the original version. Compared to control women, women born with a DSD who were included in the Dutch DSD study (N?=?99, Mdn age, 26 years) described themselves as being less interested in sex and less sexually active. These women also harbored more negative emotions and cognitions regarding their sexuality and were less satisfied with their external genitalia. In women with a DSD, sexual self-concept was associated with compromised outcomes on sexual functioning and distress. Women who were in a steady relationship, and/or had been sexually active in the past 4 weeks had a more positive sexual self-concept, took a more active role in their sexual relationship, experienced more sexual desire and arousal and less sexual distress than women who were not involved in a partner relationship. Findings in this study indicate that cognitions and emotions related to sexual self-concept play a role in sexual functioning of women with a DSD. A cognitive behavioral counseling approach with focus on coping and exploration of their own sexual needs could prove useful in this group.

     

Common Genetic Effects of Gender Atypical Behavior in Childhood and Sexual Orientation in Adulthood: A Study of Finnish Twins

The existence of genetic effects on gender atypical behavior in childhood and sexual orientation in adulthood and the overlap between these effects were studied in a population-based sample of 3,261 Finnish twins aged 33–43 years. The participants completed items on recalled childhood behavior and on same-sex sexual interest and behavior, which were combined into a childhood gender atypical behavior and a sexual orientation variable, respectively. The phenotypic association between the two variables was stronger for men than for women. Quantitative genetic analyses showed that variation in both childhood gender atypical behavior and adult sexual orientation was partly due to genetics, with the rest being explained by nonshared environmental effects. Bivariate analyses suggested that substantial common genetic and modest common nonshared environmental correlations underlie the co-occurrence of the two variables. The results were discussed in light of previous research and possible implications for theories of gender role development and sexual orientation.     

Gender Nonconformity, Childhood Rejection, and Adult Attachment: A Study of Gay Men

Several childhood factors are reported to be associated with a homosexual orientation in men, including gender nonconformity and rejection by parents and peers. The purpose of this study was to explore the associations between these childhood factors and attachment anxiety (the tendency to experience anxiety regarding potential loss and rejection in close relationships) and attachment avoidance (the tendency to avoid versus seek out closeness in relationships) in gay and bisexual men. A community sample of 191 gay and bisexual men completed questionnaires and an attachment interview. Gender nonconformity was significantly associated with paternal, maternal, and peer rejection in childhood. In addition, paternal and peer rejection, but not maternal rejection, independently predicted attachment anxiety. Peer rejection and, to a lesser extent, paternal rejection mediated the association between gender nonconformity and attachment anxiety. Finally, peer rejection mediated the association between paternal rejection and attachment avoidance. Findings highlight the role of gender nonconformity in contributing to childhood rejection and the importance of peer relationships in the socialization of gay men.