Identity, Sexuality, and Parenthood in Women with Congenital Adrenal Hyperplasia.

STUDY OBJECTIVE: To explore how women with congenital adrenal hyperplasia (CAH) describe their experiences of gender role behavior, psychosexual development, and intimate relationships. CAH results in increased androgen exposure in affected females, and is the most common reason for unclear sex at birth. Women with CAH have been studied to find answers to the role of androgens in psychosexual development. Nevertheless, factors that may account for the variability of outcomes in women with CAH are unclear. DESIGN, SETTING AND PARTICIPANTS: This was a qualitative study with 13 Swedish women (aged ≥18 years) with CAH. Semi-structured interviews were analyzed using inductive content analysis. MAIN OUTCOME MEASURES: Direct quotes of patients' experiences derived from interview transcripts were sorted in categories, subcategories, and according to latent theme. RESULTS: The main categories were "forming identity" and "establishing relationships." Forming identity encompasses that of a girl, a tomboy, and/or a woman. Establishing relationships focuses on intimate relationships, pregnancy, and parenthood. A latent theme was interpreted as "shifting perspectives," with CAH being the main focus of some participants' lives but a side issue for others. CONCLUSION: These women's experiences are varied and describe shifting perspectives on how much CAH affects their lives. Health care providers can play an important role in helping women with CAH to separate what is caused by the condition and what is not. The long-term goal is to help girls and women to feel in control of their condition across their whole life.

The experience of women living with Congenital Adrenal Hyperplasia: impact of the condition and the care given.

CONTEXT: Congenital adrenal hyperplasia (CAH) is caused most often by mutations in the CYP21A2 gene, resulting in cortisol and aldosterone deficiency and increased production of androgens. OBJECTIVE: To describe how women with CAH experience their condition and the care given. DESIGN, SETTING AND PARTICIPANTS: Semi-structured interviews with 13 adult Swedish women with CAH were transcribed. Data were analysed by qualitative content analysis to describe the variability in the experiences. MAIN OUTCOME MEASURES: Qualitative evaluation of the participants' life experiences. RESULTS: The participants' experiences of having CAH are described in four different categories. 1. Information comprises the experiences of interaction with healthcare providers, knowledge acquisition and information disclosure. 2. Exposure encompasses the experiences of genital examinations, the medical focus on the genitalia and of being photographed repeatedly. 3. Health covers the self-perceived experiences of having a medical condition that requires pharmacological treatment and sometimes surgery. 4. Research comprises the experiences of having a scientifically well-studied condition. Different experiences of shame reoccur in all categories, thus forming the latent theme. CONCLUSION: The experience of living with congenital adrenal hyperplasia can be facilitated by increased information and by acknowledging that women with CAH are a heterogeneous group with individual needs. Shame may be counterbalanced by increased parental support and increased knowledge among healthcare personnel aimed at providing children with continuous support and coping strategies during their upbringing. Based on the identified themes in this study, there are several research avenues to pursue in the future.

Voice problems due to virilization in adult women with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

OBJECTIVE: Congenital adrenal hyperplasia (CAH) is an autosomal recessive inherited disorder in which the lack of 21-hydroxylase results in cortisol and aldosterone insufficiency and an overproduction of adrenal androgens. High levels of androgens in women may cause virilization of the larynx and a masculine voice. The purpose of the present study was to investigate subjective voice problems due to virilization in women with CAH. DESIGN/PATIENTS: Participants were 42 women with CAH between 25 and 71 years of age, and 43 age-matched female healthy control subjects. All patients, but two, were in good disease control. MEASUREMENTS: A validated Swedish version of the Voice Handicap Index (VHI) and questions related to voice virilization were used. Endocrine data were obtained from medical files. RESULTS: Patients scored significantly higher on VHI when the results were divided into no/mild, moderate and severe voice handicap as compared with the control subjects. They rated significantly higher for 'dark voice' and for 'being perceived as a man on the phone' compared with controls. Seven per cent of the women with CAH had voice problems clearly related to voice virilization. High ratings of dark voice were significantly associated with long periods of under-treatment with glucocorticoids and higher bone mineral density but not with severity of mutation. CONCLUSION: Subjective voice problems due to voice virilization may occur in women with CAH. This further emphasizes the importance of avoiding long periods of increased androgen levels to prevent irreversible voice changes. For these patients, we recommend referral to voice assessment and treatment.

Sexual function and surgical outcome in women with congenital adrenal hyperplasia due to CYP21A2 deficiency: clinical perspective and the patients' perception.

CONTEXT: Females with congenital adrenal hyperplasia (CAH) due to a CYP21A2 deficiency are exposed to androgens during fetal development, resulting in virilization of the external genitalia. Little is known about how these women feel that the disease has affected their lives regarding surgery and psychosexual adaptation. OBJECTIVE: Our objective was to investigate the correlation between the surgical results, the self-perceived severity of the disease, and satisfaction with sexual life and relate the results to the CYP21A2 genotype. DESIGN AND PARTICIPANTS: Sixty-two Swedish women with CAH and age-matched controls completed a 120-item questionnaire, and a composite score for sexual function was constructed. The surgical outcome, including genital appearance and clitoral sensitivity, was evaluated by clinical examination. The patients were divided into four CYP21A2 genotype groups. RESULTS: The sexual function score, but not for genital appearance, was higher in the patients satisfied with their sexual life. This was also true of the patients who were satisfied with the surgical result. There were discrepancies between the patients' perception of the impact of the condition on their sexual life and what health professionals would assume from clinical examination. The patients in the null genotype group scored lower on sexual function and satisfaction with their sexual life and had more surgical complications, also compared with the slightly less severe I2-splice genotype group. CONCLUSION: Our data show that the null genotype group was considerably more affected by the condition than the other groups and should be regarded as a subgroup, both psychologically and from a surgical perspective. Genotyping adds clinically valuable information.

Gender role behavior, sexuality, and psychosocial adaptation in women with congenital adrenal hyperplasia due to CYP21A2 deficiency.

CONTEXT: Gender-atypical behavior has been described in young girls as well as in women with congenital adrenal hyperplasia (CAH) due to a CYP21A2 deficiency. OBJECTIVE: The aim of the study was to assess health-related, psychosexual, and psychosocial parameters and correlate the results to CYP21A2 genotype. DESIGN AND PARTICIPANTS: Sixty-two Swedish women with CAH and age-matched controls completed a 120-item questionnaire and a validated quality of life instrument [psychological general well-being (PGWB) formula] to identify psychosexual and psychosocial parameters. The patients were divided into four CYP21A2 genotype groups. RESULTS: The women with CAH held more male-dominant occupations (30%) compared to controls (13%) (P = 0.04), especially those in the null genotype group (55%) (P = 0.006). They also reported a greater interest in rough sports (74%) compared to controls (50%) (P = 0.007). Eight women with CAH (14%) reported a prime interest in motor vehicles, compared to none of the controls (P = 0.002). Non-heterosexual orientation was reported by 19% of women with CAH (P = 0.005), 50% in the null genotype group (P = 0.0001), 30% in I2 splice (NS), and 5% in I172N (NS). PGWB total score did not differ between patients and controls. CONCLUSION: We identified increased gender-atypical behavior in women with CAH that could be correlated to the CYP21A2 genotype. This speaks in favor of dose-dependent effects of prenatal androgens on the development of higher brain functions. The impact of the disease on upbringing and interpersonal relationships did not correlate with disease severity, indicating that other factors, such as coping strategies, are important for psychosocial adaptation. This illustrates the need for psychological support to parents and patients.

Reduced bone mineral density in adult women diagnosed with menstrual disorders during adolescence.

OBJECTIVE: To evaluate the long-term effects on bone mineral density (BMD) in women diagnosed with menstrual disorders in their adolescence. DESIGN: Prospective follow-up study six years after the initial investigation. SETTING: A youth clinic that is part of the school health system in Stockholm. POPULATION: Eighty-seven women diagnosed with secondary amenorrhea or oligomenorrhea in adolescence. METHODS: Subjects underwent gynecological examination, evaluation of eating behavior and physical activity. Whole body Dual Energy X-ray Absorptiometry was used for measurement of BMD. MAIN OUTCOME MEASURES: BMD. RESULTS: The overall frequency of osteopenia/osteoporosis was 52%, and three girls had osteoporosis. Women with previous secondary amenorrhea had significantly lower BMD in the pelvis and lumbar spine than those with previous oligomenorrhea. The strongest predictor of low BMD was a restrictive eating disorder in adolescence and the most important counteraction was high physical activity at follow-up and a body mass index (BMI) > or = 22. Persistent menstrual dysfunction at follow-up was associated with polycystic ovary syndrome and lower frequency of osteopenia. CONCLUSIONS: This clinical follow-up study has demonstrated a high frequency of osteopenia in women diagnosed with menstrual disorders in adolescence. Previous anorectic behavior was the strongest negative predictor of BMD. It is important to pay attention to an underlying eating disorder in young women with menstrual dysfunction in order to promote bone health.

Increased liver enzymes in adult women with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

The aims were assessing liver function tests (LFT) in women with congenital adrenal hyperplasia (CAH) on glucocorticoids. Sixty-one women with genetically verified CAH due to 21-hydroxylase deficiency, aged 18-63 years were compared to 61 controls. Serum alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transpeptidase (GGT), anthropometry and fat mass (dual energy X-ray absorptiometry) were measured. ALT and GGT were higher in the entire patient group (p=0.01 and 0.002); AST, GGT and ALP in patients > or =30 years (p=0.007-0.045); all LFT in salt-wasting (p<0.001-0.042); GGT in simple virilizing (p=0.008); ALT, GGT and ALP in Null/Null genotype (p=0.018-0.040); ALT and GGT in I2splice genotype (p<0.001 and 0.011). Using a recently proposed cut-off level for ALT (>0.317 microkat/L), 54% of patients vs 23% of controls had elevated levels (p=0.028). In patients, GGT and ALP correlated with waist circumference and with total body and trunk fat (r=0.274-0.406, p=0.001-0.043). However, ALT, GGT and ALP were increased even in non-obese patients (waist circumference < or =88 cm and body mass index <30 kg/m(2)) (p=0.012-0.045) mainly attributed to the patients > or =30 years who also demonstrated elevated insulin levels and HOMA-indices. In conclusion, compared with controls, women with CAH have higher LFT, in particular patients > or =30 years and those with severe forms, probably reflecting a higher lifetime glucocorticoid exposure. LFT were positively correlated to measurements of body fat. These women might have increased frequency of NAFLD. The finding of higher LFT also in non-obese patients suggests that not only central obesity but also glucocorticoids per se may influence.

Voice characteristics in women with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

OBJECTIVE: Congenital adrenal hyperplasia (CAH) is an autosomal recessive inherited disorder resulting in lack of cortisol and often aldosterone and overproduction of androgens. Raised levels of androgens can lead to increased mass in the laryngeal tissues, which may lower the fundamental frequency (F0) of the voice. DESIGN/PATIENTS: A follow-up study of voice characteristics in 38 women with CAH and 24 age-matched controls between 18 and 63 years of age using subjective self-ratings of voice symptoms and acoustic and perceptual analyses. The results were correlated to mutation and treatment. MEASUREMENTS: The subjects rated degree of hoarseness, dark voice, voice problems and vocal fatigue on visual analogue scales. Audio recordings were made of a standard reading passage in a sound treated booth. Acoustic analyses were made of the subjects' mean, minimum and maximum F0 in the habitual speech range. Three voice clinicians made perceptual evaluations of dark voice in terms of timbre. RESULTS: Women with CAH rated higher values than controls with regard to the statement 'my voice is a problem in my daily life'. They spoke with significantly lower mean, lower minimum and lower maximum F0, as well as darker voice quality as compared with the controls. Affected voice symptoms were associated with a late diagnosis or problems with medication. CONCLUSION: The voices in women with CAH can be virilized because of late diagnosis or suboptimal treatment with glucocorticoids. These voice problems may need referral for voice assessment and should be considered when treating CAH.

Ovarian epithelial neoplasia after hormonal infertility treatment: long-term follow-up of a historical cohort in Sweden.

OBJECTIVE: To study the association between hormonal infertility treatment and ovarian neoplasia. DESIGN: Historical cohort study. SETTING: Three university hospitals in Sweden. PATIENT(S): A total of 2,768 women assessed and treated for infertility and infertility-associated disorders between 1961 and 1975. INTERVENTION(S): Exposed women received clomiphene citrate and/or gonadotropins. MAIN OUTCOME MEASURE(S): Incidence of ovarian neoplasia. RESULT(S): No overall excess risk of invasive ovarian cancer emerged compared with the general population. In women with gonadotropin treatment for non-ovulatory disorders, the risk was elevated (standardized incidence ratio [SIR] = 5.89; 95% confidence interval [CI] 1.91-13.75); four of the five cases reported hCG treatment only, rendering the biological plausibility uncertain. Multivariate analysis within the cohort indicated that treatment with gonadotropins only was associated with an increased risk of invasive cancer (relative risk = 5.28; 95% CI 1.70-16.47). For borderline tumors, a more than threefold overall increase of tumors (SIR = 3.61; 95% CI 1.45-7.44) was noted; women exposed to clomiphene because of ovulatory disorders showed the highest risk (SIR = 7.47; 95% CI 1.54-21.83). CONCLUSION(S): Our findings of increased risk of ovarian cancer after gonadotropins and of borderline tumors after clomiphene treatment need to be interpreted with caution. However, concern is raised, and further research on the long-term safety particularly of modern hormonal infertility treatment in IVF programs is warranted.

Prospective follow-up of menstrual disorders in adolescence and prognostic factors.

OBJECTIVE: Clinical follow-up of menstrual status and eating behavior in grown-up women diagnosed with menstrual disturbance in adolescence. DESIGN: Prospective follow-up study six years after the initial study. SETTING: A youth clinic that is part of the school health system in Stockholm. POPULATION: Eighty-seven women diagnosed with secondary amenorrhea or oligomenorrhea in adolescence. METHODS: Subjects underwent gynecological examination, evaluation of eating behavior and endocrine status. MAIN OUTCOME MEASURES: Menstrual status and eating behavior changes. RESULTS: Menstrual disturbances were still present in 62% of the subjects not using hormonal contraception, 59% of which fulfilled the criteria for polycystic ovary syndrome (PCOS). The frequency of persistent menstrual disturbance was significantly more common in women with previous oligomenorrhea than secondary amenorrhea. The occurrence of eating disorders was decreased by half to 31% in women diagnosed with secondary amenorrhea at the initial study, whereas it was unchanged (40%) in women with previous oligomenorrhea. Recovery from anorectic behavior, primarily in the group of secondary amenorrhea, significantly predicted resumption with menses. CONCLUSION: Menstrual disturbances and eating disorders were still frequent after six years in a follow-up of women who had menstrual disturbance in adolescence. PCOS was the main cause explaining persistent menstrual disorder, whereas recovery of anorectic eating disorders predicted resumption of menses. The findings call for a continued follow-up of women diagnosed with menstrual disturbance in their teens.

Type of mutation and surgical procedure affect long-term quality of life for women with congenital adrenal hyperplasia.

CONTEXT: In congenital adrenal hyperplasia (CAH) caused by different mutations, feminizing surgery is mostly performed in childhood, and many patients are lost to follow-up. OBJECTIVE/PATIENTS: A follow-up study on 62 CAH women aged 18-63 yr and 62 age-matched controls to correlate findings of both operative method and mutation was performed. DESIGN: Semistructured interviews were performed in cases and controls, as well as a gynecological examination in the cases. The results were correlated with disease-causing mutations and earlier surgical procedures if performed. SETTING: The study was conducted at university hospital referral clinics. MAIN OUTCOME MEASURES: Gynecological examination in all cases correlated to previous surgery (n = 49), type of mutation, and questionnaire responses. RESULTS: Half of the CAH women claimed that the disease affected their sex life. The women were less satisfied with their genitals, whether operated or not. Clitoris size and functions were affected by the surgical method. Five women had a clinically evident vaginal stenosis on examination. However, almost half of patients experienced a narrow vagina. The overall psychosexual aspects of life were affected in these patients with later sexual debut, fewer pregnancies and children, and an increased incidence of homosexuality. These quality of life factors were correlated to the severity of the mutations. CONCLUSIONS: The overall quality of life in adult women with CAH is affected both by the type of mutation and operative procedure. Indications for clitoroplasty should be restrictive. Medical, surgical, and psychological treatment should be centralized.

Fractures and bone mineral density in adult women with 21-hydroxylase deficiency.

CONTEXT: Patients with classical congenital adrenal hyperplasia (CAH) receive lifelong, often supraphysiological, glucocorticoid therapy. Pharmacological doses of glucocorticoids are an established risk factor for osteoporosis. OBJECTIVE: Our objective was to evaluate bone mineral density (BMD), fracture prevalence, and markers of bone metabolism in adult females with CAH. DESIGN: This was a cross-sectional observational study. SETTING: Tertiary care referral centers were used in this study. PARTICIPANTS: We studied 61 women, aged 18-63 yr, with genetically verified CAH due to 21-hydroxylase deficiency. They were patients with salt wasting (n = 27), simple virilizing (n = 28), and nonclassical 21-hydroxylase deficiency (n = 6). A total of 61 age-matched women were controls. MAIN OUTCOME MEASURES: History of fractures was recorded. Total body, lumbar spine, and femoral neck BMD were measured by dual-energy x-ray absorptiometry. The World Health Organization criteria for osteopenia and osteoporosis were used. Serum marker of bone resorption, beta-C telopeptide was studied. RESULTS: The mean glucocorticoid dose in hydrocortisone equivalents was 16.9 +/- 0.9 mg/m2. Patients had lower BMD than controls at all measured sites (P < 0.001). In patients younger than 30 yr old, 48% were osteopenic vs. 12% in controls (P < 0.009). In patients 30 yr or older, 73% were osteopenic or osteoporotic vs. 21% in controls (P < 0.001). BMD was similar in the two classical forms and had no obvious relationship to genotypes. beta-C-telopeptide was decreased in older patients. More fractures were reported in patients than controls (P < 0.001). The number of vertebrae and wrist fractures almost reached significance (P = 0.058). CONCLUSIONS: Women with CAH have low BMD and increased fracture risk. BMD should be monitored, adequate prophylaxis and treatment instituted, and glucocorticoid doses optimized from puberty.

Menstrual disorders and associated factors among adolescent girls visiting a youth clinic.

BACKGROUND: Menstrual disturbances are common among teenagers and are often explained by immaturity of the hypothalamic-pituitary-gonadal axis. However, little is known about the underlying causes. The aim of this study was to evaluate endocrine mechanisms of menstrual disturbances and associated factors among adolescent girls visiting a Swedish youth clinic. METHODS. All adolescent girls visiting the youth clinic during a five-year period due to menstrual disturbances, except those with primary amenorrhea, were included in this retrospective study. These 203 girls were evaluated in a standardized manner by the same gynecologist. One third also met a psychologist and/or a dietician at the clinic. RESULTS: Secondary amenorrhea was diagnosed in 117 girls (58%) and oligomenorrhea in 86 girls (42%). Menarcheal age was 13 in both groups. Hypothalamic inhibition of the gonadal axis was more frequent in the girls with secondary amenorrhea, whereas a hyperandrogenic hormonal pattern as a feature of polycystic ovary syndrome was more common in the oligomenorrheic girls. Different types of eating disorders were diagnosed in 68% of the amenorrheic girls and in 38% of the oligomenorrheic girls. CONCLUSIONS: We found hypothalamic amenorrhea and hyperandrogenism to be frequent endocrine mechanisms of menstrual disorders in teenagers. Concomitant eating disorder was highly frequent and secondary amenorrhea was associated with anorectic behavior. It is important to evaluate endocrine patterns and eating behavior in adolescents with menstrual disturbances to ensure adequate medical care and treatment.

Metabolic profile and body composition in adult women with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

CONTEXT: The chronic, often supraphysiological glucocorticoid doses used in congenital adrenal hyperplasia (CAH) might increase morbidity in cardiovascular disease and diabetes. OBJECTIVE: Our aim was to assess risk factors for cardiovascular disease and diabetes in CAH women. SUBJECTS, METHODS, AND DESIGN: We compared 61 women, 18-63 yr, with CAH due to 21-hydroxylase deficiency with 61 age- and sex- matched controls. Twenty-seven were younger than 30 yr, and 34 were 30 yr or older. Anthropometry, fat and lean mass measured by dual-energy x-ray absorptiometry, serum lipids, insulin, and adrenocortical steroids were studied. MAIN OUTCOME MEASURE: Body composition and cardiovascular risk factors were the main outcome measures. RESULTS: Younger patients and controls had similar waist to hip ratio, lean and fat mass, and insulin. Older patients had higher waist to hip ratio, lean mass, and insulin than controls. Fat mass was similar to controls but higher than in younger patients. Lipid profiles were slightly more favorable in older patients than controls. Gestational diabetes was more common in patients (21% of pregnancies vs. 0, P < 0.026). Few older patients had hypertension, cardiovascular disease, or diabetes. Despite moderate glucocorticoid doses, most patients had suppressed androgens. CONCLUSIONS: No clear evidence of unfavorable cardiovascular risk factors were found. Increased fat mass and higher insulin levels were, however, found in patients older than 30 yr. High frequency of gestational diabetes is a risk marker for future diabetes. Lifelong follow-up, lifestyle modifications, and attempts to adjust and reduce the glucocorticoid doses seem important.

Congenital adrenal hyperplasia due to 21-hydroxylase deficiency--the adult woman.

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is a disease with a varying phenotype depending on the mutation(s) present and the severity of the disease. All children with CAH need to be continuously cared for from birth or early infancy by specialists in paediatric endocrinology and surgery. Complications due to over- or under-treatment with corticosteroids are often seen during adolescence, and these problems often continue into adulthood. For the young woman with CAH, questions about menstruation, sexuality, fertility and the possible necessity of complementary surgery are always important issues that need to be discussed. To meet the needs of the young woman with CAH, it is important that the transition from paediatric to adult care be a process of parallel consultations over several years, always involving an experienced gynaecologic endocrinologist.

[End-of-life sedation--definition and clinical guidelines needed]. / Sedering i livets slutskede--definition och kliniska riktlinjer behövs.

End-of-life sedation is not well defined in clinical medicine. The Swedish Society of Medicine, Delegation for Medical Ethics, arranged a Nordic expert workshop to discuss issues of terminology, indications, information and consent, follow up and teaching. It was concluded that the following issues must be part of the decision-making process: the diagnosis and prognosis must be correct, all other treatment options including psychological and existential support must have been tried, there must be consensus between the patient, the family and the staff about the situation and the proposed treatment. These discussions will be followed by clinical guidelines issued by the Society.