Congenital Adrenal Hyperplasia Women Research Articles

Reproductive and perinatal outcomes in women with congenital adrenal hyperplasia: A population-based cohort study

CONTEXT Reduced fertility has been reported for women with congenital adrenal hyperplasia (CAH), especially for those with the salt-losing form. However, data are sparse on reproductive and perinatal outcomes in these women. OBJECTIVE To investigate reproductive and perinatal outcomes in women with CAH. DESIGN AND SETTING Population-based and nationwide study using the National CAH Register, the Total Population Register, and the Medical Birth Register of Sweden. PARTICIPANTS A total of 272 women with CAH due to 21-hydroxylase deficiency and 27 200 controls matched by sex, age, and place of birth. The median age was 31 years. MAIN OUTCOME MEASURES The proportion of CAH women that have given birth, and reproductive and perinatal outcomes. RESULTS Of the 272 women with CAH, 69 gave birth to at least 1 child (25.4%), which was a lower frequency than for the controls (45.8%) (P < .001). Furthermore, women with CAH had fewer children than controls and were slightly older at birth of their first child. More women with CAH were diagnosed with gestational diabetes than controls, 4.9% versus 1.4% (P < .05), and more women with CAH were delivered through cesarean section, 51.4% versus 12.3% (P < .05). There was no difference in Apgar score or frequency of small-for-gestational age between children born to mothers with CAH and controls. CONCLUSIONS This is, to our knowledge, the largest cohort designed to investigate reproductive and perinatal outcomes in women with CAH. We found the birth rate to be lower in women with CAH; gestational diabetes and cesarean section were more common, but perinatal outcomes were comparable with controls.

Reproductive and Perinatal Outcomes in Women with Congenital Adrenal Hyperplasia: A Population-based Cohort Study.

Reduced fertility has been reported for women with congenital adrenal hyperplasia (CAH), especially for those with the salt-losing form. However, data are sparse on reproductive and perinatal outcomes in these women. To investigate reproductive and perinatal outcomes in women with CAH. Population-based and nationwide study using the National CAH Register, the Total Population Register, and the Medical Birth Register of Sweden. A total of 272 women with CAH due to 21-hydroxylase deficiency and 27 200 controls matched by sex, age, and place of birth. The median age was 31 years. The proportion of CAH women that have given birth, and reproductive and perinatal outcomes. Of the 272 women with CAH, 69 gave birth to at least 1 child (25.4%), which was a lower frequency than for the controls (45.8%) (P < .001). Furthermore, women with CAH had fewer children than controls and were slightly older at birth of their first child. More women with CAH were diagnosed with gestational diabetes than controls, 4.9% versus 1.4% (P < .05), and more women with CAH were delivered through cesarean section, 51.4% versus 12.3% (P < .05). There was no difference in Apgar score or frequency of small-for-gestational age between children born to mothers with CAH and controls. This is, to our knowledge, the largest cohort designed to investigate reproductive and perinatal outcomes in women with CAH. We found the birth rate to be lower in women with CAH; gestational diabetes and cesarean section were more common, but perinatal outcomes were comparable with controls.

Sexual function in women with androgen excess disorders: classic forms of congenital adrenal hyperplasia and polycystic ovary syndrome

PurposeWe compared the sexual function in women with classic forms of congenital adrenal hyperplasia (CAH) and polycystic ovary syndrome (PCOS) to find if the cause of androgen excess determines sexual functioning.MethodsHundred and four women (21 with CAH, 63 with PCOS and 20 healthy controls) aged 18–40 years were included into the study. All participants completed a questionnaire regarding their sociodemographic background and underwent anthropometric and basic biochemical measurements. Plasma levels of total testosterone, androstenedione, and 17-hydroxyprogesterone were measured with immunoassay. To assess the sexual functions, the Female Sexual Function Index (FSFI) questionnaire was applied.ResultsApart from the higher physical activity in PCOS patients (P = 0.017), we found no significant sociodemographic differences between the studied groups. In clinical assessment, women with CAH had a lower incidence of acne (P = 0.006). Their plasma levels of 17OHP (P = 0.005) and insulin resistance index (P = 0.0248) were higher, while total testosterone (P = 0.0495) and glucose (P = 0.0061) was lower compared to the PCOS group. Significantly more women with CAH were homosexual (P = 0.003) and bisexual (P = 0.006). CAH group showed a lower total FSFI score (P = 0.0043) and lower scores in three domains: lubrication (P = 0.0131), sexual satisfaction (P = 0.0006), and dyspareunia (P < 0.0001). Higher physical activity was associated in all women with higher total FSFI score (P = 0.009) and scores in the domain of desire (P = 0.034) and sexual satisfaction (P = 0.01), while in CAH women apart from the total score (P = 0.03) and sexual satisfaction (P = 0.002) also in the domains of orgasm (P = 0.005), and pain (P = 0.03).ConclusionsCAH women present more often homosexual and bisexual orientation, while their sexual functions are impaired compared to PCOS patients.

Steroid 17-Hydroxyprogesterone in Hair Is a Potential Long-Term Biomarker of Androgen Control in Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency

Introduction: To evaluate scalp hair steroid concentrations as a monitoring tool for androgen control and metabolic outcomes in adults with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. Methods: 17-hydroxyprogesterone (17-OHP), androstenedione, testosterone, cortisol, cortisone, progesterone, prednisolone, and prednisone concentrations were measured in scalp hair by means of LC-MS/MS in 27 women and 15 men with CAH and controls (37 women, 42 men). Results: In CAH men and women, 17-OHP levels in hair showed a significant positive correlation with corresponding levels in serum (ρ = 0.654; p = 0.01; ρ = 0.553, p = 0.003 respectively), while total testosterone levels were only significantly correlated in CAH men (ρ = 0.543; p = 0.036). Androstenedione levels did not show a significant correlation. Receiver-operating characteristic (ROC) curve analysis indicated that a cutoff value of 21.7 pg/mg for 17-OHP in hair provided a sensitivity of 100% and a specificity of 88.9% for identifying men with elevated serum androstenedione. Hair 17-OHP in women showed a poorer performance in terms of identifying those with elevated androstenedione serum levels. However, when applying a cutoff value of 5.5 for the free androgen index as a marker of significant hyperandrogenism in CAH women, 17-OHP >27.6 pg/mg in hair provided a sensitivity of 100% and a specificity of 95.8% (AUC 0.986, 95% CI 0.945–1.000; p < 0.001). Neither hair cortisol nor markers of adrenal androgen control in hair showed significant associations with cardiometabolic outcome or bone health. Conclusion: This study shows that scalp hair 17-OHP concentrations may be a promising noninvasive long-term parameter for treatment monitoring in adult patients with CAH.

Effect of androgen excess and glucocorticoid exposure on metabolic risk profiles in patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency

Data on cardiovascular morbidity in adults with congenital adrenal hyperplasia (CAH) is sparse. We therefore aimed to determine the role of androgen control and glucocorticoid therapy on metabolic health. For that purpose, we included 90 patients (N = 39 men, N = 51 women) with classic CAH due to 21-hydroxylase deficiency (N = 61 salt wasting, N = 29 simple virilizing) and an equal number of controls matched for age, sex, BMI and smoking-habits. We could show that there was no difference in intima-media-thickness between patients and controls and only one patient fulfilled all criteria of the metabolic syndrome. CAH men presented with an increased relative body fat mass in comparison to controls (25.6 % vs. 22.1 %; p = 0.011) while this was not true for CAH women. Body fat was lower in those taking hydrocortisone instead of synthetic glucocorticoids (B = -3.27; p = 0.048). While arterial hypertension was rare, 54 % of patients had an impaired systolic drop at night or were classified as non-dippers (17 %). Impaired dipping was not associated with evening glucocorticoid and fludrocortisone intake but mediated by sodium levels. Insulin resistance was more common in CAH women (B = 1.689; p = 0.036) and in those with poor androgen control (B = 0.823; p = 0.046). In summary, we could show that good cardiovascular health outcome in adult CAH patients can be achieved. Hydrocortisone is superior in terms of body composition. It is yet unclear how non-dipping will translate into cardiovascular morbidity in the long-term.

An Unusual Case of Triazophos Poisoning Presenting with New-Onset Refractory Status Epilepticus.

Background:There is equipoise regarding the status of bone mineral density (BMD) in patients with congenital adrenal hyperplasia (CAH), where patients need to be on long-term low-dose steroids.Objective:We aimed to evaluate BMD at the hip, spine and forearm in women with CAH and compare it to healthy young adult women of the same age range.Subjects and Methods:Fifteen adult women with CAH with age ranging from 18 to 40 years (mean ± standard deviation = 27.5 ± 6.2 years) underwent dual-energy X-ray absorptiometry along with laboratory evaluation. BMD at lumbar spine, hip, forearm along with T-scores were measured. Serum total calcium, phosphate, alkaline phosphatase, 25 hydroxy Vitamin D, intact parathyroid hormone, total testosterone, and dehydroepiandrosterone were assayed. History of any fractures in the past was taken. Fifteen healthy women in the same age range were taken as controls for comparison.Results:The BMD at hip (0.85 ± 0.02 g/cm2) in CAH was significantly lower as compared with controls (0.92 ± 0.03 g/cm2, P = 0.029). BMD at lumbar spine was also reduced (0.96 ± 0.02 vs. 1.03 ± 0.03, P = 0.057). The BMD at forearm was not significantly different between CAH and controls. The mean Vitamin D was 9.8 ng/ml (deficient range). There was no history of fractures in CAH.Conclusion:Young adult CAH women had lower BMD at spine and hip than healthy young adult women of the same age range. The forearm BMD was not different from controls. No change in fracture frequency was present. Patients with CAH being treated with steroids are at increased risk of osteopenia, and their bone health needs to be monitored.

An unusual case of triazophos poisoning presenting with New-Onset refractory status epilepticus

Background: There is equipoise regarding the status of bone mineral density (BMD) in patients with congenital adrenal hyperplasia (CAH), where patients need to be on long-term low-dose steroids. Objective: We aimed to evaluate BMD at the hip, spine and forearm in women with CAH and compare it to healthy young adult women of the same age range. Subjects and Methods: Fifteen adult women with CAH with age ranging from 18 to 40 years (mean ± standard deviation = 27.5 ± 6.2 years) underwent dual-energy X-ray absorptiometry along with laboratory evaluation. BMD at lumbar spine, hip, forearm along with T-scores were measured. Serum total calcium, phosphate, alkaline phosphatase, 25 hydroxy Vitamin D, intact parathyroid hormone, total testosterone, and dehydroepiandrosterone were assayed. History of any fractures in the past was taken. Fifteen healthy women in the same age range were taken as controls for comparison. Results: The BMD at hip (0.85 ± 0.02 g/cm2) in CAH was significantly lower as compared with controls (0.92 ± 0.03 g/cm2, P = 0.029). BMD at lumbar spine was also reduced (0.96 ± 0.02 vs. 1.03 ± 0.03, P = 0.057). The BMD at forearm was not significantly different between CAH and controls. The mean Vitamin D was 9.8 ng/ml (deficient range). There was no history of fractures in CAH. Conclusion: Young adult CAH women had lower BMD at spine and hip than healthy young adult women of the same age range. The forearm BMD was not different from controls. No change in fracture frequency was present. Patients with CAH being treated with steroids are at increased risk of osteopenia, and their bone health needs to be monitored.

Prise en charge à l’âge adulte des hyperplasies congénitales des surrénales par déficit en 21-hydroxylase

Congenital adrenal hyperplasia (CAH) is the commonest genetic endocrine disorder. Mutations in the 21-hydroxylase gene account for 95% of cases. CAH is classified according to symptoms and signs and to age of presentation. The clinical phenotype is typically classified as classic, the severe form, or nonclassic (NCF), the mild or late-onset form. Classic CAH is a life-long chronic disorder. In childhood, treatment focuses on genital surgery and optimization of growth and pubertal development. Priorities change with increasing age, typically focusing on fertility in early adult life and prevention of metabolic syndrome and osteoporosis in middle and older age. Recent studies highlight the importance of long-term follow-up of these patients and of transitional care between childhoods to adult life. In nonclassic CAH women, subfertility is mild compared with the classic form and seems to be mainly due to hormonal imbalance. Menstrual cycle or ovulation disorders observed in these women who consulted for infertility are in most cases corrected by hydrocortisone treatment, which led to simultaneous lowering of plasma androgen levels and rapid occurrence of pregnancy. Hydrocortisone also reduces the incidence of miscarriages. Several studies have reported that near 60% of nonclassic CAH patients are carriers of a severe mutation. These patients may therefore give birth to a child with the classical form of CAH if their partner is also carrying a severe mutation. Due to the high frequency of CYP21A2mutations in the general population, it is essential to genotype the partner of NC-CAH patients with one severe mutation to offer genetic counselling.

Chapter Eight - The Biological Basis of Human Sexual Orientation: Is There a Role for Epigenetics?

Sexual orientation is one of the largest sex differences in humans. The vast majority of the population is heterosexual, that is, they are attracted to members of the opposite sex. However, a small but significant proportion of people are bisexual or homosexual and experience attraction to members of the same sex. The origins of the phenomenon have long been the subject of scientific study. In this chapter, we will review the evidence that sexual orientation has biological underpinnings and consider the involvement of epigenetic mechanisms. We will first discuss studies that show that sexual orientation has a genetic component. These studies show that sexual orientation is more concordant in monozygotic twins than in dizygotic ones and that male sexual orientation is linked to several regions of the genome. We will then highlight findings that suggest a link between sexual orientation and epigenetic mechanisms. In particular, we will consider the case of women with congenital adrenal hyperplasia (CAH). These women were exposed to high levels of testosterone in utero and have much higher rates of nonheterosexual orientation compared to non-CAH women. Studies in animal models strongly suggest that the long-term effects of hormonal exposure (such as those experienced by CAH women) are mediated by epigenetic mechanisms. We conclude by describing a hypothetical framework that unifies genetic and epigenetic explanations of sexual orientation and the continued challenges facing sexual orientation research.

Cognitive outcome of offspring from dexamethasone-treated pregnancies at risk for congenital adrenal hyperplasia due to 21-hydroxylase deficiency

To test whether dexamethasone (DEX) treatment in pregnancies at risk for congenital adrenal hyperplasia (CAH) impairs cognitive functioning in the offspring. Observational follow-up of prenatally DEX-exposed offspring and controls. Study 1 included 140 children aged 512 years: 67 DEX-exposed (long-term: eight CAH girls) and 73 unexposed (with 15 CAH girls). Study 2 included 20 participants aged 11-24 years: seven DEX-exposed (long-term: one CAH woman) and 13 unexposed (with four CAH women). Neuropsychological testing was done in hospital settings or at patients' homes. Data analysis aimed at maximizing detection of the effects of DEX exposure. The vast majority of group comparisons were not marginally or conventionally significant. The few significant findings on short-term prenatal DEX exposure suggested more positive than adverse outcomes. By contrast, few significant findings in females with CAH and long-term DEX exposure indicated slower mental processing than in controls on several neuropsychological variables, although partial correlations of DEX exposure duration with cognitive outcome did not corroborate this association. Although our studies do not replicate a previously reported adverse effect of short-term prenatal DEX exposure on working memory, our findings on cognitive function in CAH girls with long-term DEX exposure contribute to concerns about potentially adverse cognitive after effects of such exposure. Yet, our studies are not definitive, and replications in larger samples are required.

High Fetal Testosterone and Sexually Dimorphic Cerebral Networks in Females

Active masculinization by fetal testosterone is believed to be a major factor behind sex differentiation of the brain. We tested this hypothesis in a 15O-H2O positron emission tomography study of 11 women with congenital adrenal hyperplasia (CAH), a condition with high fetal testosterone, and 26 controls. Two indices of cerebral dimorphism were measured--functional connectivity and cerebral activation by 2 putative pheromones (androstadienone [AND] and estratetraenol [EST]), previously reported to activate the hypothalamic networks in a sex-differentiated manner. Smelling of unscented air was the baseline condition, also used for measurements of functional connectivity from the amygdala. In CAH women and control women AND activated the anterior hypothalamus, and EST the amygdala, piriform, and anterior insular cortex. The pattern was reciprocal in the male controls. Also the functional connections were similar in CAH women and control women, but different in control men. Women displayed connections with the contralateral amygdala, cingulate, and the hypothalamus, men with the basal ganglia, the insular and the sensorimotor cortex. Furthermore, the connections were in CAH and control women more widespread from the left amygdala, in men from the right amygdala. Thus, we find no evidence for masculinization of the limbic circuits in women with high fetal testosterone.

The sex ratio of offspring of women with congenital adrenal hyperplasia

Sir, We have with great interest read the comments made by Dr James concerning our paper ‘Fertility and pregnancy outcome in women with congenital adrenal hyperplasia due to 21-hydroxylase deficiency’ recently published in Human Reproduction (Hagenfeldt et al., 2008). We have also enjoyed reading some of his extensive work in the area concerning sex ratio in mammals. We appreciate that Dr James is confirming the data we presented in our paper on the sex of children born to women with congenital adrenal hyperplasia (CAH). In addition to the data given in Table 1 in Dr James’ comments, another 22 girls and 11 boys were reported by Lo and Grumbach (2001). Hence, including our own data, the number so far reported in the literature (apart from cases that are reported twice) are 68 girls and 34 boys (sex ratio 0.33). Dr James proposes that the reason for this difference in sex ratio of children born to women with CAH could be depressed androgen levels in the women at conception. This is an interesting hypothesis and seems reasonable since most women with CAH need to have depressed androgen levels in order to ovulate regularly. Concerning the effect of gonadotrophin stimulation, only one of our patients needed this treatment; she delivered one girl after each of these treatments. As far as we know the sex ratio in women who underwent IVF is normal. In our material, only one woman needed IVF. We are looking forward to a future discussion concerning the possible explanation to the unequal sex ratio in children born to CAH women.

Fertility and pregnancy outcome in women with congenital adrenal hyperplasia due to 21-hydroxylase deficiency

Low pregnancy rate has been reported in women with congenital adrenal hyperplasia (CAH) and little information on pregnancy and children is known. In a Swedish study, 62 adult women with CAH, aged 18-63 years, and 62 age-matched controls were followed-up. Medical records, including those concerning pregnancies and deliveries, were examined and the 21-hydroxylase genotype of patients was noted. All women answered a questionnaire concerning sexual and reproductive health including health of the children. Pregnancy and delivery rates were significantly lower in women with CAH (P < 0.001, P < 0.0056, respectively), and the severity of the 21-hydroxylase-mutation correlated with the reduced number of children born. More women with salt-wasting CAH were single and had not attempted pregnancy. Pregnancies were normal except for a significantly increased incidence of gestational diabetes in CAH patients (P < 0.0024). The children had normal birthweight and no malformations were observed. A later follow-up of the children showed a normal intellectual and social development. The sex ratio of the offspring differed significantly, with 25% boys in the CAH group compared with 56% among controls (P < 0.016). CAH women had more gynaecological morbidity during menopause. Pregnancy and delivery rates are reduced in women with CAH mainly due to psychosocial reasons. The outcome of children did not differ from controls. The unexpected sex ratio in children born to mothers with CAH warrants further research.

Fertility among women with classical congenital adrenal hyperplasia: Report of seven cases where treatment was started after 9 years of age

Background and aim. Androgen excess is believed to be one of the major factors responsible for poor fertility outcomes in females with congenital adrenal hyperplasia (CAH). Some believe that the adverse effect of androgens on fertility could have its origins as early as the antenatal years. To assess the impact of prolonged androgen exposure on fertility in CAH patients, we compiled the data of females with CAH followed in our clinic during the last 25 years who were sexually active and had not been initiated on steroids until age 9 years.Study design and patients. This was an observational case study on seven patients with classical CAH who fulfilled the inclusion criteria. The age at initiation of therapy in these females ranged from 9 years to 29 years.Results. All patients had varying degrees of genital ambiguity. The most common presenting complaints were genital ambiguity, non-development of secondary sexual characteristics, hirsutism and primary amenorrhea. Genital surgery was performed in all patients at ages ranging from 12 to 29 years, except for one patient who underwent surgery at age 5 years without a diagnosis of CAH being made. Breast development ensued within 2 to 12 months and periods started in all patients within 2–24 months of steroid initiation. There were 13 pregnancies (seven normal vaginal deliveries, two spontaneous abortions and four pregnancies were medically terminated).Conclusions. Late initiation of steroid therapy did not affect fertility in our cohort of CAH women. Androgen excess in situations of subnormal cortisol may not adversely affect fertility in females with CAH.

Type of Mutation and Surgical Procedure Affect Long-Term Quality of Life for Women with Congenital Adrenal Hyperplasia

In congenital adrenal hyperplasia (CAH) caused by different mutations, feminizing surgery is mostly performed in childhood, and many patients are lost to follow-up. 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. 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. The study was conducted at university hospital referral clinics. Gynecological examination in all cases correlated to previous surgery (n = 49), type of mutation, and questionnaire responses. 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. 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.

Impaired Sexual and Reproductive Outcomes in Women with Classical Forms of Congenital Adrenal Hyperplasia

The objectives of the study were 2-fold: 1) a detailed description of sexual and reproductive outcomes in adult women with congenital adrenal hyperplasia (CAH) of different phenotypic severity at birth; and 2) comparisons of these outcomes among CAH subtypes and between CAH women and non-CAH control women. This was a cross-sectional study using a face-to-face interview, a written questionnaire, the Female Sexual Function Index, and a gynecological examination. Patients included 35 women with CAH, representing Prader stages I-V at birth, aged 18-43 yr, who had been treated from birth to adolescence in the same pediatric endocrine clinics. Sixty-nine non-CAH healthy control women were selected from hospital-staff families. None of the CAH women expressed doubts about their gender assignment. Twenty percent (seven of 35) had homosexual inclinations; 23% (eight of 35) were married; three reported a complete lack of sexual activity; and 37% (13 of 35) said they never had heterosexual intercourse with vaginal penetration. Sexual functioning as assessed by the Female Sexual Function Index was much lower in CAH women than controls and lowest in CAH women with high Prader stages. Eighty-one percent (18 of 22) experienced pain during vaginal penetration. Only eight women became pregnant, and 17% (six of 35) had children. Despite expert medical and surgical care by physicians dedicated to this rare disease, women with CAH still suffer major limitations in their sexual function and reproductive life.

Metabolic Profile and Body Composition in Adult Women with Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency

The chronic, often supraphysiological glucocorticoid doses used in congenital adrenal hyperplasia (CAH) might increase morbidity in cardiovascular disease and diabetes. 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. Body composition and cardiovascular risk factors were the main outcome measures. 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. 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.

Impaired Cognitive Function in Women with Congenital Adrenal Hyperplasia

Congenital adrenal hyperplasia (CAH) is a disorder with a wide spectrum of severity. The objective of this study was to investigate cognitive function in CAH women. This was a case-control study. This study was conducted at a tertiary center for pediatric endocrinology at the University Hospital of Copenhagen. Thirty-five Danish CAH women (age 17-51 yr) were included, and participation rate was 84%. Control women were recruited through the Danish Civil Registration System and matched on age and education. An abbreviated form of the Wechsler Adult Intelligence Scale was used, i.e. full-scale intelligence quotient (IQ; five of 11 subtests), which included three of six verbal IQ subtests and two of five performance IQ subtests. A significantly lower IQ was found in CAH patients compared with controls with respect to mean full-scale IQ (84.5 vs. 99.1; P < 0.001), mean verbal IQ (86.6 vs. 97.3; P < 0.001), and mean performance IQ (85.7 vs. 101.3; P < 0.001). The salt-wasting CAH group had lower IQ scores than the simple-virilizing CAH group, which reached significance for mean total IQ (81.2 vs. 92.8, P = 0.04) and mean verbal IQ (84.7 vs. 95.5, P = 0.05), and additionally, lower scores than the late-onset CAH group, which reached significance for performance IQ (mean 81.5 vs. 96.2, P = 0.02). Impaired cognitive function was observed in patients with CAH, especially in salt-wasting CAH. These intriguing findings may reflect adverse effects of hyponatremic episodes, suboptimal postnatal hormone replacement therapy or prenatal adrenal androgen excess, and the potential psychosocial consequences of the disorder.

Self-Reported Sexual Arousability in Women with Congenital Adrenal Hyperplasia

As part of a larger study of psychosexual development and sexual functioning in women with congenital adrenal hyperplasia (CAH), we assessed self-reported sexual arousability with the Sexual Arousability Inventory-Short Form (SAI-SF; Hoon & Chambless, 1998). Compared to their unaffected sisters/female cousins (n = 15), women with CAH (n = 30) reported significantly lower sexual arousability on the SAI, with an effect size, using Cohen's d, of 1.16. For both the CAH women alone and combined with the controls, higher self-reported sexual arousability was significantly associated with (a) relationship status (married or cohabitating with a man versus being single or not in a relationship); (b) higher levels of sexual attraction to men in fantasy in the past 12 months on the Erotic Response and Orientation Scale (Storms, 1980); (c) higher Kinsey interview ratings of a heterosexual orientation in behavior in the past 12 months; and (d) more sexual experiences with men, according to a modified version of the Zuckerman (1973) Heterosexual Experience Scale (HES), in the past 12 months and lifetime (all ps < .001–.05). CAH women who were simple virilizers (versus salt-wasters) and those assigned female at birth (versus delayed or male) tended to report higher levels of sexual arousability (p < .10). Self-reported degree of satisfaction with genital surgery and genital function was also associated with higher levels of arousability. For CAH women and both groups combined, multiple regression analysis showed that the sole predictor of self-reported sexual arousability was HES lifetime sexual experiences with men. We discuss the results in the context of assessing sexual function and dysfunction in women with CAH.

Psychosexual Development of Women with Congenital Adrenal Hyperplasia

Women with congenital adrenal hyperplasia (CAH) (N= 31) and their unaffected sisters or female cousins (N= 15) participated in a study of psychosexual development. All participants were ≥18 years of age (mean age, 25 years; range, 18–40). Comparisons were also made between the CAH women with the salt-wasting (SW) form of the disorder and those with simple virilization (SV). A psychosexual assessment protocol examined six variables: (1) sex assignment at birth (probands only); (2) recalled sex-typed behavior during childhood; (3) gender identity and gender role identification in adulthood; (4) relationship status; (5) sexual orientation in fantasy; and (6) sexual orientation in behavior. Salt-wasting status and sex assignment at birth were also ascertained for the CAH women who either refused to participate in the study (N= 10) or could not be traced (N= 13). Compared to the controls, the women with CAH recalled more cross-gender role behavior and less comfort with their sense of “femininity” during childhood. The two groups did not differ in degree of gender dysphoria in adulthood, although the probands showed more cross-gender role identification. Three of the nonparticipant probands were living, as adults, in the male social role (2 reared from birth as boys and 1 who changed from the female to the male social role during adolescence). The CAH women and the controls did not differ in relationship status (married/cohabiting vs. single). The CAH women had lower rates of exclusive heterosexual fantasy and fewer sexual experiences with men than the controls; however, the CAH women did not have more sexual experiences with women than the controls. Comparisons between the SW and SV revealed several differences: the SW were less likely to be assigned to the female sex at birth, recalled more cross-gender role behavior during childhood, were less likely to be married or cohabiting, and had lower rates of sexual experiences with men. The results were discussed in relation to the effects of prenatal androgens on psychosexual differentiation.