Arterial Stiffness in Transgender Men Receiving Long-term Testosterone Therapy.

Context: The effects of androgen therapy on arterial function in transgender men (TM) are not fully understood, particularly concerning long-term androgen treatment. Objective: To evaluate arterial stiffness in TM receiving long-term gender-affirming hormone therapy by carotid-femoral pulse wave velocity (cf-PWV). Methods: A cross-sectional case-control study at the Gender Dysphoria Unit of the Division of Endocrinology, HC-FMUSP, Sao Paulo, Brazil. Thirty-three TM receiving intramuscular testosterone esters as regular treatment for an average time of 14 ± 8 years were compared with 111 healthy cisgender men and women controls matched for age and body mass index. Aortic stiffness was evaluated by cf-PWV measurements using Complior device post-testosterone therapy. The main outcome measure was aortic stiffness by cf-PWV as a cardiovascular risk marker in TM and control group. Results: The cf-PWV after long-term testosterone therapy was significantly higher in TM (7.4 ± 0.9 m/s; range 5.8-8.9 m/s) than in cisgender men (6.6 ± 1.0 m/s; range 3.8-9.0 m/s, P < .01) and cisgender women controls (6.9 ± .9 m/s; range 4.8-9.1 m/s, P = .02). The cf-PWV was significantly and positively correlated with age. Analysis using blood pressure as a covariate showed a significant relationship between TM systolic blood pressure (SBP) and cf-PWV in relation to cisgender women but not to cisgender men. Age, SBP, and diagnosis of hypertension were independently associated with cf-PWV in the TM group. Conclusion: The TM group on long-term treatment with testosterone had higher aging-related aortic stiffening than the control groups. These findings indicate that aortic stiffness might be accelerated in the TM group receiving gender-affirming hormone treatment, and suggest a potential deleterious effect of testosterone on arterial function. Preventive measures in TM individuals receiving testosterone treatment, who are at higher risk for cardiovascular events, are highly recommended.

Premature Pubarche due to Exogenous Testosterone Gel or Intense Diaper Rash Prevention Cream Use: A Case Series.

BACKGROUND/AIMS: Premature pubarche is associated with conditions such as virilizing congenital adrenal hyperplasia, androgen-secreting tumors, and exogenous exposure to androgen products. We describe the clinical and hormonal features of a series of children who were referred to endocrine evaluation due to premature pubarche. METHODS: This is a retrospective case series study of 14 children with premature pubarche and/or virilization. Five were unintentionally exposed to testosterone gel (parental use). Nine patients were intensely exposed to diaper rash prevention creams. Clinical and laboratory data were revised. RESULTS: Moderate to severe virilization was detected in the 5 patients (2 boys and 3 girls) who were exposed to testosterone gel. These patients had pubic hair development associated with clitoromegaly (3/3), penile enlargement (2/2), and accelerated growth (5/5). Testosterone levels were elevated in 4/5 patients associated with normal prepubertal gonadotropin levels and adrenal androgen precursors. The 9 children who were intensely exposed to diaper rash prevention creams had mild pubarche (intermediate hair) without any other clinical manifestation of pubertal development. Three of them exhibited pubic hair thinning after cream withdrawal. CONCLUSION: Unintentional topical androgen exposure or the intense use of diaper rash prevention cream should be ruled out in children with precocious pubarche and/or virilization signs to avoid misdiagnosis and expendable investigation.

Trp28Arg/Ile35Thr LHB gene variants are associated with elevated testosterone levels in women with polycystic ovary syndrome.

INTRODUCTION: Polycystic Ovary Syndrome (PCOS) is a complex endocrine disorder, of multifactorial etiology, which affects 6-10% of women of reproductive age. It is considered the leading cause of anovulatory infertility, menstrual disorders and hyperandrogenism in this population. The genetic basis of PCOS is still largely unknown despite significant family clustering; determining its mode of inheritance is particularly difficult given the heterogenic presentation of the disease. MATERIALS AND METHODS: 130 Brazilian women, aged 14-42 years, who met the 2003 Rotterdam criteria for PCOS diagnosis, were included, and 96 healthy women constituted the control group. Presence of hirsutism was classified using the modified Ferriman-Gallwey score (F-G score) as absent (≤7), mild (8-14), and severe (≥15). Blood levels of luteinizing hormone (LH), total testosterone (TT), dehydroepiandrosterone sulfate (DHEA-S) and androstenedione were determined. The coding region of the luteinizing hormone beta-subunit (LHB) gene was amplified and sequenced. Differences in allelic and genotypic frequency distribution of each polymorphism across controls and cases were estimated by the Mantel-Haenszel chi-square or Fisher's exact test (p<0.05), and the probability of an association between the detection of a polymorphism and presence of a diagnosis of PCOS, by logistic regression. RESULT(S): Sequencing detected 8 polymorphisms in the LHB gene coding region. Two polymorphisms in linkage disequilibrium were significantly more prevalent in the presence of hyperandrogenemia: rs1800447/rs34349826 (Trp28Arg/Ile35Thr) (p=0.02). CONCLUSION(S): In this series, a modulatory effect of LHB polymorphisms on hyperandrogenemia phenotype of PCOS was observed; however, this finding needs to be replicated in other populations.

Anatomical and functional outcomes of feminizing genitoplasty for ambiguous genitalia in patients with virilizing congenital adrenal hyperplasia.

UNLABELLED: The ideal surgical technique and appropriate age for performing feminizing genitoplasty are debatable, and few long-term outcome studies have been reported. PURPOSE: To report a retrospective study on anatomical and functional outcomes of feminizing genitoplasty in patients with virilizing congenital adrenal hyperplasia. METHODS: We selected 34 patients (mean age = 3.4 +/- 2.5 yr) with genital ambiguity classified according to Prader stage. Follow-up ranged from 2 to 16 years. Clitoral length ranged from 1.9 to 5.0 cm; 28 patients had a single perineal orifice, and 6 had a double orifice. The surgical technique included clitorovaginoplasty in a single procedure and was carried out before 2 years of age in 18 patients. Clitoroplasty was performed with glans preservation in all patients. Blood supply was exclusively maintained by the frenular pedicle in 97% of the cases, whereas clitoral dorsal nerves and vessels were preserved in the remaining 3%. The opening of the urogenital sinus was performed using either the Y-V perineal flap procedure (25 patients) or the cut-back incision procedure (8 patients). RESULTS: Good morphological and functional results were achieved in 68% of the patients; 21% of the patients had surgical complications, such as incision bleeding (2 cases), glans necrosis (1 girl with Prader V), and vaginal introitus stenosis (4 cases). Three of the latter underwent dilation with acrylic molds in the post-pubertal period with good functional results. CONCLUSIONS: We conclude that single-stage feminizing genitoplasty consisting of vulvoplasty, clitoroplasty, and Y-V perineal flap produced good cosmetic and functional results in virilized girls with congenital adrenal hyperplasia, with few complications. In addition, this surgical approach prevented the need for neovaginaplasty even in patients with high vaginal insertion.

Anatomical and functional outcomes of feminizing genitoplasty for ambiguous genitalia in patients with virilizing congenital adrenal hyperplasia

OBJETIVO: Apresentar um estudo retrospectivo sobre os resultados cosméticos e funcionais da genitoplastia feminizante em pacientes com hiperplasia adrenal congênita virilizante. MÉTODOS: Trinta e quatro pacientes com idade média de 3,35 ± 2,5 anos com ambigüidade genital classificada de acordo com os estádios de Prader foram selecionados. O seguimento pós-operatório foi de 2 a 16 anos. O tamanho do clitóris variou de 1,9 a 5,0 cm; 28 pacientes tinham orifício único perineal e 6 tinham dois orifícios. A técnica cirúrgica incluiu clitorovaginoplastia em tempo único e foi realizada antes dos dois anos de idade em 18 pacientes. A clitoroplastia preservou a glande, a qual teve seu suprimento sanguíneo mantido em 97% dos casos pela mucosa do freio e no demais casos com a manutenção do feixe vasculo-nervoso dorsal. Duas técnicas foram utilizadas para a ampliação do seio urogenital: o retalho perineal em "Y-V" em 25 pacientes e a incisão longitudinal posterior em 8 pacientes.RESULTADOS: As complicações cirúrgicas ocorreram em 20,5% dos casos: sangramento, necrose da glande e estenose vaginal. Foram necessárias dilatações vaginais com moldes de acrílico no período pós puberal em 3 das pacientes com estenose, com bons resultados funcionais. CONCLUSÃO: As técnicas utilizadas seguidas pelas dilatações, permitiram bons resultados cosméticos e funcionais em 67% dos casos apresentando poucas complicações e evitando a necessidade de neovagina inclusive nos pacientes com inserção alta do intróito vaginal.