Contribution of androgen receptor sensitivity to the relation between testosterone and sexual desire: An exploration in male-to-female transsexuals.

BACKGROUND: Low sexual desire is present in 1/3 of male-to-female transsexuals (post-operative male-to-female transsexual persons on estrogen replacement). Several studies report lower endogenous testosterone (T) levels in this group compared to community dwelling women. However, no relationship between T and sexual desire has been found in male-to-female transsexuals. Considering its role in androgen sensitivity, cytosine-adenine-guanine (CAG) trinucleotide repeat sequence in the androgen receptor (AR) might modify the relationship between T levels and sexual desire in male-to-female transsexuals. AIM: This study aims to assess the potential contribution of the number of CAG repeats in the association between T and sexual desire in male-to-female transsexuals. MATERIAL, SUBJECTS, AND METHODS: Thirty-four post-operative male-to-female transsexuals participated in a cross-sectional study. The Sexual Desire Inventory, a questionnaire measuring sexual desire, was completed. Serum levels of total (TT) and free T (FT), DHEA-S, SHBG, and LH were measured in morning blood samples. AR gene CAG repeat length was determined by automated DNA fragment analysis of exon 1 of the AR gene. RESULTS: The CAG repeat length ranged from 14 to 28 with a median of 21. CAG polymorphism was correlated with FT (r=0.389; p=0.023) but not with TT (r=0.191; p=0.280). The observed interaction between TT and CAG was significant only for solitary sexual desire (p=0.002). The interaction of CAG repeats and FT on sexual desire failed to reach significance. CONCLUSIONS: We could not establish that CAG repeat length is a consistent modulating factor in the relationship between TT or FT and sexual desire in male-to-female transsexuals.

Part of the interindividual variation in serum testosterone levels in healthy men reflects differences in androgen sensitivity and feedback set point: contribution of the androgen receptor polyglutamine tract polymorphism.

CONTEXT: There is a large interindividual variation in serum (free) testosterone (FT) levels in men, underlain in part by genetic components. OBJECTIVE: The objective of the study was to explore the hypothesis that this variability results in part from differences in androgen sensitivity and feedback loop set point and assess the role of the androgen receptor (AR) polyglutamine tract polymorphism encoded by a CAG repeat of variable length in exon 1 of the AR gene. DESIGN/SETTING/PARTICIPANTS: We performed a cross-sectional analysis in two independent populations of healthy men, consisting of 2322 men aged 35-59 yr (Belstress study) and 358 men aged 25-45 yr (Siblos study), respectively. MAIN OUTCOME MEASURES: Serum hormonal levels and the AR gene CAG repeat length were determined. RESULTS: In the Belstress population, serum testosterone and calculated FT showed a positive linear association with LH (P < 0.001). In the 200 men with lowest FT, CAG repeat number was lower than in the 200 men with highest FT (P = 0.004). As studied in a larger subset of the population consisting of 857 men covering the whole FT range, FT increased progressively with CAG repeat length (P = 0.003). These findings of a positive relation of FT with both LH and CAG repeat length were confirmed in the Siblos study population (both P < or = 0.001). Difference in FT between extreme quartiles of CAG repeat was 10 and 14% in the Belstress and Siblos study, respectively. In both study populations, CAG repeat length was also positively associated with serum total testosterone (P < or = 0.004). CONCLUSIONS: The data support the view that between-subject variability in serum FT in healthy men is underlain in part by differences in androgen sensitivity and feedback set point, with a contributory role of AR polymorphism. These findings have potential implications for the interpretation of epidemiological studies, diagnosis of hypogonadism, and pharmacogenetics of androgen treatment in men.