Gundela Holmdahl

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.

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

BACKGROUND Low pregnancy rate has been reported in women with congenital adrenal hyperplasia (CAH) and little information on pregnancy and children is known. METHODS 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. RESULTS 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. CONCLUSIONS 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.

Four-Hour Voiding Observation in Healthy Infants

PURPOSE We present the 4-hour voiding observation as a method for basic assessment of bladder function in infants and nontoilet trained children. MATERIALS AND METHODS Voiding pattern, including number of voidings, voided volume, bladder capacity and residual urine for 4 hours, was determined noninvasively in 43 healthy infants. RESULTS The infants voided an average of 1 time per hour but with great variability. Bladder capacity increased with age according to the formula, 38 + 2.5 x age (months). Mean residual urine plus or minus standard deviation was 4.6 +/- 3.0 ml. In all infants residual volume was less than 5 ml. at least once during observation. CONCLUSIONS The 4-hour voiding observation is an easy noninvasive method of characterizing the voiding pattern, focusing especially on emptying difficulties, in infants and nontoilet trained children.

The Swedish Reflux Trial in Children: II. Vesicoureteral Reflux Outcome

PURPOSE We compared reflux status in children with dilating vesicoureteral reflux treated in 3 groups, including low dose antibiotic prophylaxis, endoscopic therapy and a surveillance group on antibiotic treatment only for febrile urinary tract infection. MATERIALS AND METHODS A total of 203 children 1 to younger than 2 years with grade III-IV reflux were recruited into this open, randomized, controlled trial. Endoscopic treatment was done with dextranomer/hyaluronic acid copolymer. The main end point was reflux status after 2 years. Data were analyzed by the intent to treat principle. RESULTS Reflux status improved in all 3 treatment arms. Of patients in the prophylaxis, endoscopic and surveillance groups 39%, 71% and 47%, respectively, had reflux resolution or downgrading to grade I-II after 2 years. This was significantly more common in the endoscopic than in the prophylaxis and surveillance groups (p = 0.0002 and 0.0030, respectively). After 1 or 2 injections 86% of patients in the endoscopic group had no or grade I-II reflux but recurrent dilating reflux was seen in 20% after 2 years. CONCLUSIONS Endoscopic treatment resulted in dilating reflux resolution or downgrading in most treated children. After 2 years endoscopic treatment results were significantly better than the spontaneous resolution rate or downgrading in the prophylaxis and surveillance groups. However, of concern is the common reappearance of dilating reflux after 2 years.

Bladder Dysfunction in Boys with Posterior Urethral Valves before and after Puberty

PURPOSE We characterized bladder dysfunction in boys with posterior urethral valves during childhood and adolescence. MATERIALS AND METHODS A total of 12 prepubertal boys with posterior urethral valves presenting before age 1 year was followed from ages 4 to 14 years and compared to 6 postpubertal boys with posterior urethral valves. Urodynamic evaluations and renal function studies were performed repeatedly. RESULTS Patients had a changing urodynamic pattern with instability decreasing with time, increasing bladder capacity and commonly an unsustained voiding contraction causing emptying difficulties. Postpubertal boys had high capacity bladders with low contractility. CONCLUSIONS We suggest that previously described urodynamic patterns of the valve bladder (unstable, poorly compliant and over distended bladders) are variations of the same basic pattern that changes with time toward decompensation.

The Changing Urodynamic Pattern in Valve Bladders During Infancy

Bladder dysfunction in boys with posterior urethral valves is well documented in studies of long-term followup. These reports suggest that dysfunctional bladders can be divided into 3 main types, including unstable, low compliant and over distended. To our knowledge urodynamic findings at presentation during infancy have not been described previously. We report on 16 male patients born between 1989 and 1993 who presented with symptoms of posterior urethral valves between birth and age 5 months, and who were followed with repeated urodynamic evaluations for a mean of 19 months. At presentation the bladder was hypercontractile with low capacity. During the first 3 years of life, the urodynamic pattern changed with vanishing hypercontractility and increasing bladder capacity, although instability remained unchanged with emptying difficulties. Thus, the 3 patterns of bladder dysfunction reported in older boys after resection of posterior urethral valves could not be found in infants and small children.

The Swedish Reflux Trial in Children: V. Bladder Dysfunction

PURPOSE We investigated the prevalence and types of lower urinary tract dysfunction in children with vesicoureteral reflux grades III and IV, and related improved dilating reflux, renal damage and recurrent urinary tract infection to dysfunction. MATERIALS AND METHODS A total of 203 children between ages 1 to less than 2 years with reflux grades III and IV were recruited into this open, randomized, controlled, multicenter study. Voiding cystourethrography and dimercapto-succinic acid scintigraphy were done at study entry and 2-year followup. Lower urinary tract function was investigated by noninvasive methods, at study entry with 4-hour voiding observation in 148 patients and at 2 years by structured questionnaire and post-void residual flow measurement in 161. RESULTS At study entry 20% of patients had lower urinary tract dysfunction, characterized by high bladder capacity and increased post-void residual urine. At 2 years there was dysfunction in 34% of patients. Subdivision into groups characteristic of children after toilet training revealed that 9% had isolated overactive bladder and 24% had voiding phase dysfunction. There was a negative correlation between dysfunction at 2 years and improved dilating reflux (p = 0.002). Renal damage at study entry and followup was associated with lower urinary tract dysfunction at 2 years (p = 0.001). Recurrent urinary tract infections were seen in 33% of children with and in 20% without dysfunction (p = 0.084). CONCLUSIONS After toilet training a third of these children with dilating reflux had lower urinary tract dysfunction, mainly voiding phase problems. Dysfunction was associated with persistent reflux and renal damage while dysfunction at study entry did not predict the 2-year outcome.

The Swedish Reflux Trial in Children: I. Study Design and Study Population Characteristics

PURPOSE We compared the rates of febrile urinary tract infection, kidney damage and reflux resolution in children with vesicoureteral reflux treated in 3 ways, including antibiotic prophylaxis, endoscopic therapy and surveillance with antibiotics only for symptomatic urinary tract infection. MATERIALS AND METHODS Children 1 to younger than 2 years with grade III-IV reflux were recruited into this prospective, open, randomized, controlled, multicenter study and followed for 2 years after randomization. The main study end points were recurrent febrile urinary tract infection, renal status on dimercapto-succinic acid scintigraphy and reflux status. Outcomes were analyzed by the intent to treat principle. RESULTS During a 6-year period 128 girls and 75 boys entered the study. In 96% of cases reflux was detected after urinary tract infection. The randomization procedure was successful and resulted in 3 groups matched for relevant factors. Recruitment was slower than anticipated but after patients were entered adherence to the protocol was good. Of the children 93% were followed for the intended 2 years without a treatment arm change. All except 2 patients completed 2-year followup scintigraphy. CONCLUSIONS Recruitment was difficult but a substantial number of children were entered and randomly assigned to 3 groups with similar basic characteristics. Good adherence to the protocol made it possible to address the central study questions.

Long-term followup of men born with hypospadias: urological and cosmetic results.

PURPOSE We present data on long-term functional and cosmetic results after hypospadias surgery. MATERIALS AND METHODS Males older than 18 years with hypospadias treated in Sweden were asked to participate in the study, as well as age matched controls and circumcised men. All participants answered questionnaires, and a subgroup was examined during an outpatient visit. Relationships with outcome were analyzed using analysis of variance and regression analysis. RESULTS A total of 167 patients with a mean age of 34 years and 169 controls with a mean age of 33 years answered the questionnaire. Of the patients 63% had distal, 24% mid and 13% proximal hypospadias. A total of 46 patients and 49 controls presented for physical examination. Patients were significantly less satisfied with the penile cosmetic outcome regarding all parameters of the Penile Perception Score. There was a difference in penile length between patients and controls (mean 9.7 vs 11.6 cm, p <0.001). More patients than controls reported voiding dysfunction symptoms (p = 0.003). Patients had a lower maximum urinary flow rate than controls (p = 0.001). These differences were most prominent between patients with proximal hypospadias and controls. CONCLUSIONS Men operated on for hypospadias were less satisfied with the cosmetic result than controls, and had a shorter penile length. Patients presented with more symptoms of voiding dysfunction and displayed a lower maximum urinary flow rate. Patients with proximal hypospadias were more affected than those with milder hypospadias. Our results indicate that patients with hypospadias can be subgrouped and that those with severe phenotypes should be followed more closely during childhood as well as later in adulthood.

Hypospadias repair with tubularized incised plate: Does the obstructive flow pattern resolve spontaneously?

OBJECTIVE The aim of this prospective study was to evaluate whether urinary flow improves with time after tubularized incised plate (TIP) repair. PATIENTS AND METHOD Between 1999 and 2003, primary TIP was performed in 126 boys. In patients old enough (48 boys, mean age at surgery 46 months, range 18-103), uroflowmetry was performed 1 year and 7 (median, range 3-10) years post surgery. Miskolc nomograms were used to compare results from the two follow ups (Q(max) in relation to voided volume and age). RESULTS Eleven boys had symptoms of obstruction resulting in intervention. For the other 37 boys, the mean Q(max) was 13.6 ± 5.6 ml/s 1 year postoperatively (mean voided volume 107 ± 43 ml) and 49% had flows below the 5th percentile. Seven years postoperatively the mean Q(max) was 19.0 ± 8.1 ml/s (mean voided volume 235 ± 112 ml) and 32% had flows below the 5th percentile. In the group with flows below the 5th percentile at 1 year, all improved and 28% improved to above the 25th percentile. Proximal hypospadias was more often associated with obstructive flow than distal (75%/75% compared to 43%/21% 1/7 years postoperatively). CONCLUSION We found spontaneous improvement (P = 0.00022) 7 years after TIP repair, although many boys still had a Q(max) in the low normal or obstructive range.