Transition of Care. Группа авторов

these patients, 46% stated being unhappy about their sexual life. A French cross-sectional study showed that 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 [23]. In this study, 37% of CAH women said they never had heterosexual intercourse with vaginal penetration, and for those who had, 81% experienced pain during vaginal penetration. Sexual functioning was much lower in CAH women than controls and lowest in CAH women with high Prader stages. In a more recent review including 151 patients with genitoplasty, assessments of cosmetic results have shown that the majority of patients (between 60 and 94%) reported good or excellent outcomes [26]. When the physician was the person who assessed the cosmetic outcomes, 59–94% reported satisfactory results [26].

The fertility rate, i.e. live births per woman, is significantly lower in CAH women than in the general female population [30]. On the other hand, pregnancy estimates are more encouraging when examined only in the patients actively trying to conceive [31]. In a UK cohort of 103 CAH women among whom 25% wanted to conceive, the pregnancy estimate was 54% [15]. Pregnancies were most often spontaneous, obtained after a good hormonal control with optimized GC and MC regimens. Recently, a large population-based epidemiological study on psychosocial outcomes in CAH patients was conducted in Sweden that showed that women with the SW form were less often married (OR 0.5, CI 0.2–1.1) and had fewer partnerships compared with controls. CAH patients were less likely to have biological children than controls (OR 0.3, CI 0.2–0.3) and when assessing women with the SW and SV forms, it was still significantly decreased (SW OR 0.05, CI 0.0–0.1; SV OR 0.4, CI 0.2–0.7) [32].

      The transition period from pediatric to adult health care is the time of sexual maturation that occurs during adolescence. Thus, provision of detailed CAH-related education by the pediatric practitioner to the patient before the transfer to an adult practitioner is of importance. In particular, for women with CAH, comprehension of their genital anatomy and surgical history is essential. Better sexuality, fertility, and fecundity in CAH women will be largely dependent on surgical advances in genital reconstruction, earlier treatment, optimized compliance to therapy, availability of psychological support, organization of transition from pediatric to adult specialist care, procuration of menstrual cycle control and sexual well-being.

      Male-Specific Issues

Male patients with CAH may also present impaired gonadic function and infertility. It appears that adult males with CAH face a dual problem. Adrenal steroid overproduction, especially androgen and progesterone, might interfere with follicle-stimulating hormone and LH production, resulting in gonadotropic deficiency. In addition, testicular adrenal rest tumors (TARTs) may develop in some CAH patients and impact both endocrine and exocrine testicular functions [33]. TARTs have been identified with a prevalence of 30–95% depending on age and modality of diagnosis, i.e. palpation or ultrasound [34]. The prevalence of TARTs increases with age, after onset of puberty [35, 36]. Some studies report the development of TARTs despite good hormonal control, suggesting that undertreatment is not the only cause for their growth [37, 38]. Indeed, a recent study about the molecular characterization of TARTs has shown that these tumors have multiple steroidogenic properties, including the expression of adrenal cortex and typical Leydig cell markers [39]. Because of their central localization near the rete testis, TARTs can lead to compression of the seminiferous tubules that may finally lead to obstructive azoospermia and irreversible damage of the surrounding testicular tissue [40]. In patients with and without TARTs, inhibin B levels differ significantly, and there are higher total sperm counts and concentrations in patients without TARTs [34]. 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,