Metabolic effects of estradiol versus testosterone in complete androgen insensitivity syndrome

Purpose: To study differences in metabolic outcomes between testosterone and estradiol replacement in probands with complete androgen insensitivity syndrome (CAIS). Methods: In this multicentre, double-blind, randomized crossover trial, 26 women with CAIS were included of whom 17 completed the study. After a two-months run in phase with estradiol, probands either received transdermal estradiol followed by crossover to transdermal testosterone or vice versa. After six months, differences in lipids, fasting glucose, insulin, hematocrit, liver parameters and blood pressure between the treatment phases were investigated. Results: Linear mixed models adjusted for period and sequence did not reveal major group differences according to treatment for the investigated outcomes. In each treatment group, there were however significant uniform changes in BMI and cholesterol. BMI increased significantly, following six months of estradiol (+ 2.7%; p = 0.036) as well as testosterone treatment (+ 2.8%; p = 0.036). There was also a significant increase in total (+ 10.4%; p = 0.001) and LDL-cholesterol (+ 29.2%; p = 0.049) and a decrease in HDL-cholesterol (−15.8%; p < 0.001) following six months of estradiol as well as six months of testosterone treatment (total cholesterol: + 14.6%; p = 0.008; LDL-cholesterol: + 39.1%; p = 0.005, HDL-cholesterol: −15.8%; p = 0.004). Other parameters remained unchanged. Conclusion: Transdermal estradiol as well as testosterone treatment in women with CAIS results in worsening in lipid profiles. Given the relatively small sample size, subtle group differences in other metabolic parameters may have remained undetected.