In a large cohort of male CAH patients, 70% had severe oligospermia or azoospermia when TARTs were found versus only 3.6% when they were not [34]. The profile of the gonadotropic-testicular axis in these patients will primarily show testicular failure and eventually reveal endocrine and exocrine testicular dysfunctions. Treatment options for male patients with TARTs are still limited and mainly based on a good hormonal control with GC [40]. However, in some patients, treatment is poorly tolerated, and the medical response is disappointing. Surgery can be proposed but there are no data on fertility preservation. Prevention has therefore a real important place in the management of male CAH fertility. A systematic ultrasound evaluation is recommended at puberty to detect lesions at an early stage.
Besides these somatic causes of impaired fertility in CAH males, there might be aspects of psychosocial adaptation and sexual well-being. Very few data have been reported on sexual satisfaction in CAH males. Two recent studies have shown that fewer CAH patients than controls had an active sexual life and that they had fewer lifetime partners [41, 42]. In a Swedish cohort, erectile dysfunction was found in about half of these patients [42] as was described in the study from Dudzińska et al. [43]. A sexual well-being study of CAH males has revealed impairments in sexual drive, erections, and ejaculations [43], associated with a reduced sexual drive. However, in the recent Swedish follow-up study described above, although the reason is unknown, men were more often married than controls (OR 1.6, CI 1.0–2.5) but, as the CAH women, they had fewer biological children than controls (OR 0.4, CI 0.2–0.6) [44]. Further studies are needed to properly assess these psychosocial outcomes, in order to improve the care given to the patients.
Therefore, prevention of TART development and progression and a good hormonal control of the disease are a major concern in male CAH patients at the time of the transition. Sexuality has to be considered with the patient. Patients should be informed of CAH disease and a control’s consequences on testicular function and fertility; a semen analysis should also be realized as soon as possible, and the question of systematic sperm cryopreservation seems fully justified [45].
Long-Term Consequences of Glucocorticoid Treatment
CV Risk and Risk Factors
Cohorts of adults with CAH due to 21-OHD from Europe and the USA have been described in recent years [15–17]. They have shown an increased risk for metabolic disorders in adults. Overweight and obesity have been reported in adult patients with CAH [15], but sometimes with a prevalence similar to that found in the general population [16, 17]. Some studies reported normal resting [46] and 24-hour BP profiles [47] and others a slight increase in either diurnal or both diurnal and nocturnal systolic BP, compared to matched controls [15, 48]. Classic CAH children have been shown to have a higher prevalence of elevated systolic BP and an absent physiological nocturnal systolic BP nadir on 24-h ambulatory monitoring [46]. Careful fludrocortisone dosing, assessment of renin or plasma renin activity and accurate BP measurement are indispensable to avoid iatrogenic hypertension in children with CAH. There are minimal data available on the prevalence of hypertension in adult patients with CAH. In a recent epidemiological Swedish registry study, an increased frequency of hypertension in CAH patients has been shown, but when analyzing the different subgroups, only SV females had an increased BP [21]. This was in accordance with a recent study showing that adult males with classic CAH have a rather low BP compared with healthy men [34].
In this intricate scenario, it is reasonable to expect a high CV risk profile in CAH patients. However, the impact of these risk factors on the vascular system has never been systematically ascertained. The long-term outcomes in CAH patients have recently been studied using the Swedish national CAH registry [20]. The hazard ratio of death was 2.3 (1.2–4.3) in males and 3.5 (2.0–6.0) in females. The causes of death were adrenal crisis (42%), CV diseases (32%), cancer (16%), and suicide (10%). Interestingly, the same team analyzed CV and metabolic morbidity in CAH patients [21]. This study showed an increase in both CV and metabolic disorders. Separate analyses of the individual diseases showed higher frequencies of hypertension, dyslipidemia and atrial fibrillation in CAH patients [21]. Obesity was consistently increased in all subgroups. However, the nonobese patients with CAH were similarly affected as the entire CAH cohort. There was also an increased frequency of obstructive sleep apnea in this CAH cohort. Similarly, the frequency of diabetes was increased, especially in females with the SV (I172N genotype) or nonclassic phenotype. An increased frequency of venous thromboembolic events was also reported. CAH is therefore associated with higher CV risk factors and probably with excess CV and metabolic morbidity. Some subgroups of patients seem to be more affected.
Thus, a regular and long-term follow-up of CAH patients is needed, along with lifestyle interventions, which must be introduced from childhood and continued into adulthood, to limit the onset of weight gain and obesity, to screen for diabetes, other metabolic disorders, and CV risk factors. Close monitoring of GC doses is important during the whole life, to avoid these complications.
Bone Mineral Density
Osteoporosis has been an understandable concern for children and adult patients with CAH who may receive or have received supraphysiological doses of GCs [49–51]. Chronic GC therapy is known to generate bone loss in many ways: a direct suppression of osteoblastic activity and an inhibition of digestive calcium absorption with secondary hyperparathyroidism and increased bone resorption by osteoclasts [50]. GCs also lead to an inhibition of intestinal calcium absorption and an increase in renal calcium excretion leading to secondary hyperparathyroidism [50]. Some previous reports on BMD in adult CAH patients showed no significant differences in BMD between patients with CAH and controls, but others found a lower BMD in all or certain subpopulations of CAH patients [49–51]. These reports differ with respect to age selections and GC regimens. In reports documenting the BMD reduction, this outcome has been attributed to an accumulated effect of prolonged exposure to excess GCs during infancy and
