Aim
To assess testicular volume at puberty for boys who underwent orchidopexy at 9 or at 36 months compared to boys with spontaneous postnatal descent.
Methods
At age 6 months, boys with congenital ...unilateral cryptorchidism were randomised to surgery at 9 or 39 months of age and followed to 16 years in parallel with boys with spontaneous postnatal descent. Ultrasound was done at 11 and 16 years to determine testicular volume. The ratio of the initially undescended testis to its scrotal counterpart was used to assess testicular growth.
Results
At age 16, the ratio was lower (p < 0.00) in the late group compared to the early group. At 16 years, the spontaneously descended testes were significantly smaller than their scrotal counterparts but larger than the operated groups (early p < 0.01 and late p < 0.00).
Conclusion
Our data at 16 years show that orchidopexy at 9 months results in better testicular growth compared to 3 years but did not reach the corresponding volumes of their scrotal counterparts. This indicates that earlier surgery is beneficial to testicular growth. At age 16, the postnatally descended testes were not only larger than the surgically treated testes but also exhibited impaired testicular growth.
Context:
Congenital adrenal hyperplasia (CAH) is lethal in its most severe forms if not treated with glucocorticoids. However, glucocorticoids may increase the risk of cardiovascular and metabolic ...morbidity.
Objective:
This study aimed to study cardiovascular and metabolic morbidity in CAH.
Design, Setting, and Participants:
Patients with CAH due to 21-hydroxylase deficiency (n = 588; >80% with known CYP21A2 mutations) were compared with controls matched for sex, year, and place of birth (n = 58 800). Data were obtained by linking national population-based registers. Subgroup analyses were performed regarding sex, clinical severity (salt wasting, simple virilizing, nonclassic), CYP21A2 genotype (null, I2 splice, I172N, P30L), and stratified by the introduction of neonatal screening, age groups, and nonobesity.
Main Outcome Measures:
To study cardiovascular and metabolic morbidity in CAH.
Results:
In CAH, both any cardiovascular and metabolic disorders (OR odds ratio, 3.9; 95% CI confidence interval, 3.1–5.0), and cardiovascular disease (OR, 2.7; 95% CI, 1.9–3.9) were increased. Separate analyses of the individual diseases showed higher frequencies in CAH of hypertension, hyperlipidemia, atrial fibrillation, venous thromboembolism, obesity, diabetes (mainly type 2), obstructive sleep disorder, thyrotoxicosis, and hypothyroidism. Similar results were seen in the stratified groups. On the subgroup level, females were generally more affected (especially I172N and the nonclassic group), as were males with the null genotype.
Conclusions:
CAH was associated with excess cardiovascular and metabolic morbidity but the mechanism is not certain as the glucocorticoids were not assessed. Hypothyroidism and obesity may be an effect of close observation. However, more severe conditions were presumably detected equally in patients and controls. Screening for diabetes and other metabolic disorders that increase cardiovascular risk is important.
Purpose We studied the incidence of hypospadias in Sweden during a 40-year period to determine if changes were associated with known risk factors. Materials and Methods We analyzed prospective data ...from nationwide health care and demographic registers collected for all males (1,948,591 total) born in Sweden between 1973 and 2009. The incidence of hypospadias per 1,000 live-born boys was calculated as number of cases divided by total number of births yearly. The association between hypospadias and risk factors was estimated using logistic regression, expressed as odds ratios. Results The nationwide incidence of boys diagnosed with hypospadias was approximately 4.5 per 1,000 live-born boys until 1990, increasing to 8 per 1,000 boys during the following decade. Mild and severe phenotypes comprised the increase. Boys born small for gestational age (OR 4.34), as a twin (OR 1.8), as a result of in vitro fertilization (OR 1.15), or with parents from Asia (OR 1.45) or continental Europe (OR 1.41) were at increased risk for hypospadias. Multivariate analyses revealed that changes in risk factors did not explain the increased incidence. However, a systematic change in the classification of the diagnosis in registers could not be ruled out. Conclusions This nationwide study demonstrates an increased incidence of hypospadias diagnoses in Sweden from 1990 to 1999 that is not attributable to previously known risk factors. The increase includes mild and severe phenotypes, suggesting that shifts in the diagnostic criteria are not the underlying cause.
Congenital malformations often have a genetic background associated with a recurrence risk and may be part of a syndrome. Therefore, for children with a congenital malformation, the parents should be ...offered genetic counseling, and the child should also be offered the same when they reach adulthood. Hypospadias is a common malformation in boys that arises during genital development in weeks 8 to 16. This results in an underdevelopment of the ventral aspect of the penis with a misplacement of the urethral opening somewhere along the penis, scrotum, or in the perineum and with different degrees of penile curvature. The cause can be monogenic, but generally it is regarded as a complex disorder caused by both genetic and environmental factors. Severe hypospadias and familial cases should be genetically investigated, as for other forms of disorders of sex development, according to current guidelines with sequencing of relevant genes. Hypospadias associated with another independent malformation may be part of a syndrome and should be investigated. Fortunately, boys born with milder hypospadias generally have a good outcome and thus the clinical value of finding a disease-causing mutation appears to be limited especially in light of the present cost of genetic analysis. However, all men born with hypospadias should be advised on the recurrence risk and risk for reduced fertility.
Highlights • We conducted a cohort study based on Swedish nationwide registers linked with the national Swedish Congenital Adrenal Hyperplasia (CAH) register. • We assessed the risks of psychiatric ...outcomes in girls and women with CAH born between January 1915 and January 2010 compared with age-matched controls. • The risk of any psychiatric diagnoses in general and substance misuse in particular was more frequent in girls and women with CAH. • Prenatal androgens and/or cortisol deficiency could be contributing factors to psychiatric morbidity.
Context:
Reports on mortality in patients with congenital adrenal hyperplasia (CAH) are lacking.
Objective:
This study sought to study mortality and causes of death in CAH.
Design, Setting, and ...Participants:
We studied patients with CAH (21-hydroxylase deficiency, n = 588; CYP21A2 mutations known, >80%), and compared them with controls (n = 58 800). Data were derived through linkage of national population-based registers.
Main Outcome Measures:
Mortality and causes of death.
Results:
Mean age of death was 41.2 ± 26.9 years in patients with CAH and 47.7 ± 27.7 years in controls (P < .001). Among patients with CAH, 23 (3.9%) had deceased compared with 942 (1.6%) of controls. The hazard ratio (and 95% confidence interval) of death was 2.3 (1.2–4.3) in CAH males and 3.5 (2.0–6.0) in CAH females. Including only patients born 1952–2009, gave similar total results but only patients with salt wasting (SW) or with unclear phenotype had an increased mortality. The causes of death in patients with CAH were adrenal crisis (42%), cardiovascular (32%), cancer (16%), and suicide (10%). There were seven additional deaths in CAH individuals with incomplete or reused personal identification number that could not be analyzed using linkage of registers. Of the latter, all except one were deceased before the introduction of neonatal screening in 1986, and most of them in the first weeks of life, probably in an adrenal crisis.
Conclusions:
CAH is a potentially lethal condition and was associated with excess mortality due to adrenal crisis. The SW phenotype also seemed to have worse outcome in children and adults due to adrenal crisis and not only before the introduction of neonatal screening.
Controversy continues over a proposed moratorium on elective genital surgery in childhood for disorders/differences of sex development (DSD). Empirical evidence on patient preference is needed to ...inform decision-making. We conducted a multicentre survey by cross-sectional questionnaire in 14 specialized clinics in six European countries. The sample comprised 459 individuals (≥ 16 years) with a DSD diagnosis, including individuals with congenital adrenal hyperplasia (CAH) (
n
= 192), XY DSD with prenatal androgen effect (A) (
n
= 150), and without (nA) (
n
= 117). Main outcome measures were level of agreement with given statements regarding genital surgery, including clitoris reduction, vaginoplasty, and hypospadias repair. A total of 66% of individuals with CAH and 60% of those with XY DSD-A thought that infancy or childhood were the appropriate age for genital surgery. Females with XY DSD were divided on this issue and tended to prefer vaginoplasty at a later age (XY DSD-A 39%, XY DSD-nA 32%). A total of 47% of males preferred early hypospadias surgery. Only 12% (CAH), 11% (XY DSD-A), and 21% (XY DSD-nA) thought they would have been better off without any surgery in childhood or adolescence. Individuals who had early genital surgery were more likely to approve of it. Outcome data failed to support a general moratorium on early elective genital surgery. Participant perspectives varied considerably by diagnostic category, gender, history of surgery, and contact with support groups. Case-by-case decision-making is better suited to grasping the ethical complexity of the issues at stake.
Trial registration
: German Clinical Trials Register DRKS00006072.
Summary Objectives To investigate effects of testosterone treatment regarding voice virilization, voice problems, and voice satisfaction in transsexual female-to-male individuals, referred to as ...trans men. Study Design Longitudinal. Methods Fifty trans men, diagnosed with transsexualism, 18–64 years, met the inclusion criteria. Voice data before treatment and after 3, 6, or 12 months were available from 49 participants, and for 28 participants also after 18 and/or 24 months of treatment. Digital audio recordings of speech range profiles and voice range profiles were carried out in a sound-treated booth following clinical routines. Acoustic analyses of fundamental frequency (F0) and sound pressure level were made. Endocrine data and answers from questionnaires concerning voice function and voice problems were collected from medical records. Results Mean F0 and mode F0 of the habitual voice decreased significantly after 3 months, 6 months, and up to 12 months, when group data were congruent with reference data for males. Mean F0 was 125 Hz after 12 months with a large interindividual variation. Sound pressure level values did not change significantly. Voice satisfaction correlated with lower F0 values. Twenty-four percent of the participants reported voice symptoms, for example, vocal instability and fatigue, and had received voice therapy. F0 values did not correlate with androgen levels. Conclusions Most trans men developed a male voice and were satisfied. However, it is important to detect the substantial group of trans men with voice problems and with insufficient voice virilization and who may need voice therapy. Therefore, we recommend systematic voice assessments during testosterone treatment.
Abstract
Context
It has been suggested that injuries and accidents are increased in females with congenital adrenal hyperplasia (CAH), but the prevalence is unclear.
Objective
To study the prevalence ...of injuries and accidents in females and males with CAH.
Design, Setting, and Participants
Patients with CAH (n = 714, all 21-hydroxylase deficiency) were compared with matched controls (n = 71 400). Data were derived by linking National Population-Based Registers.
Main Outcome Measures
Prevalence of injuries and accidents.
Results
Mean age was 29.8 ± 18.4 years. Injuries were more prevalent in patients with CAH than in controls (relative risk, 1.34; 95% CI, 1.24-1.44), and this was found in both sexes (females: 1.43; 1.29-1.58; males: 1.25; 1.12-1.38). In the classical phenotype, the prevalence of injuries was higher, especially in females but not in the nonclassic phenotype. In the genotype groups, injuries were mainly increased in females. Head injuries were increased in all patients with CAH and in the different phenotypes and were mainly driven by females. More patients with CAH born before the introduction of neonatal screening had had an injury compared with controls (1.48; 1.35-1.62); this was seen in both sexes. In patients with CAH born after the introduction of screening, the prevalence of injuries was overall increased (1.20; 1.07-1.35), and in females with CAH but not in males. Accidents showed a similar pattern to injuries in all comparisons.
Conclusion
Patients with CAH had an increased prevalence of both injuries and accidents, especially in females and in those born before the neonatal screening program. Patients with nonclassic phenotype were hardly affected.
Abstract
Context
Fertility in males with 21-hydroxylase deficiency (21OHD) is unclear.
Objective
Study fertility outcome in males with congenital adrenal hyperplasia.
Design, Setting, and ...Participants
Males ≥15 years old with 21OHD (n = 221) were compared with controls matched for sex and year and place of birth (n = 22,024). Data were derived by linking national population-based registers. Subgroup analyses were performed regarding phenotype salt-wasting (SW), simple virilizing (SV), and nonclassic (NC) and CYP21A2 genotype (null, I2 splice, I172N, and P30L) and stratified by the introduction of neonatal screening.
Main Outcome Measures
Number of biological and adopted children.
Results
Males with 21OHD were less likely to be fathers of biological children odds ratio (OR), 0.5; 95% confidence interval (CI), 0.4 to 0.7; after adjusting for socioeconomic characteristics: OR, 0.4; 95% CI, 0.2 to 0.5. This was true for SW, SV, I2 splice, and I172N, but not for NC, null, and P30L groups (all adjusted). Among patients born before the neonatal screening introduction, fewer were fathers (adjusted OR, 0.3; 95% CI, 0.2 to 0.5), but this normalized in those born afterward. Adoption was more common in the 21OHD males (OR, 2.9; 95% CI, 1.0 to 7.9) and the SV and I172N subgroups. Age at becoming a father, marriage, region of residence, and education were similar, but fewer patients had high incomes. NC and I172N groups had, however, higher academic degrees and NC patients were more often married, whereas SW and I2 splice patients were more often divorced.
Conclusions
21OHD was associated with a reduced frequency of biological children and an increased frequency of adopted children, suggesting impaired fertility, although some subgroups had normal fertility.
21OHD was associated with reduced frequency of biological children and increased frequency of adopted children, indicating impaired fertility, but some subgroups had normal fertility.
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