Is it loss of testosterone or estradiol that accounts for bone loss in men on ADT?

In this study, men were put on an LHRH agonist then given add-back testosterone with or without a drug that blocked the conversion of testosterone to estradiol. The study design allowed the researchers to determine whether the adverse effects of drugs, like Lupron and Zoladex, on bone mineral density is primarily due to loss of testosterone or estradiol (which in men is primarily derived from testosterone). The answer is clear—the problem is with the loss of estradiol.

The researchers don't go as far as recommending offering some add-back estradiol to men on ADT to protect their bones. Indeed, the study was not with prostate cancer patients or even older men, but rather with younger, healthy men between the ages of 20 and 50. Hopefully, the study will be extended to include men who are androgen-deprived to treat prostate cancer.


Finkelstein JS, Lee H, Leder BZ, Burnett-Bowie SM, Goldstein DW, Hahn CW, Hirsch SC, Linker A, Perros N, Servais AB, Taylor AP, Webb ML, Youngner JM, Yu EW. 2016. Gonadal steroid-dependent effects on bone turnover and bone mineral density in men. J Clin Invest [Epub ahead of print] 22 February 2016.