Hormone replacement treatment choices in complete androgen insensitivity syndrome: an audit of an adult clinic

OBJECTIVE: To review the treatment choices of women with complete androgen insensitivity syndrome (CAIS) at a single tertiary centre. DESIGN: Retrospective review. PATIENTS: Women with CAIS identified from our database. RESULTS: The study group comprised 141 women with CAIS. Eleven percent (16/141) of women had gonads in situ, 3 of whom were under workup for gonadectomy. The age of gonadectomy in the remainder 125 women was 17 (0.1-53) years. The most common form of HRT was oral oestrogen or transdermal oestrogen in 80% (113/141). 13/141 (9%) women used vaginal oestrogens alone or together with other forms of HRT. Testosterone preparations had been used by 17% (24/141) of women and were currently used in 10% (14/141). Of those who had used testosterone, 42% (10/24) had chosen not to continue after a therapeutic trial. CONCLUSIONS: In a clinic offering individualised multidisciplinary care for women with CAIS, we found that the majority of women chose oestrogen-based treatment while a significant minority used testosterone

Next generation sequencing reveals novel genetic variants (SRY, DMRT1, NR5A1, DHH, DHX37) in adults with 46,XY DSD

Context: The genetic basis of human sex development is slowly being elucidated and more than 40 different genetic causes of differences (or disorders) of sex development (DSD) have now been reported. However, reaching a specific diagnosis using traditional approaches can be difficult, especially in adults where limited biochemical data may be available. / Objective: We used a targeted next-generation sequencing approach to analyze known and candidate genes for DSD in individuals with no specific molecular diagnosis. / Partcipants and Design: We studied 52 adult 46,XY women attending a single-center adult service, who were part of a larger cohort of 400 individuals. Classic conditions such as17β-hydroxysteroid dehydrogenase deficiency type 3, 5α-reductase deficiency type 2 and androgen insensitivity syndrome were excluded. The study cohort had broad working diagnoses of complete gonadal dysgenesis (CGD) (n=27) and partially-virilised 46,XY DSD (pvDSD) (n=25), a group that included partial gonadal dysgenesis (PGD) and those with a broad ”partial androgen insensitivity syndrome” label. Targetted sequencing of 168 genes was undertaken. / Results: Overall a likely genetic cause was found in 16/52 (30.8%) individuals (22.2% CGD; 40.0% pvDSD). Pathogenic variants were found in SRY (n=3), DMRT1 (n=1), NR5A1/SF-1 (n=1) and DHH (n=1) in the CGD group, and in NR5A1 (n=5), DHH (n=1) and DHX37 (n=4) in the pvDSD group. / Conclusions: Reaching a specific diagnosis can have clinical implications and provides insight into the role of these proteins in sex development. Next-generation sequencing approaches are invaluable, especially in adult populations or where diagnostic biochemistry is not possible