Testosterone to Estradiol Ratios in Fertile and Subfertile Men: A Large Cohort Analysis.

Objective: To validate the established normal testosterone to estradiol ratio and characterize the distribution of testosterone to estradiol ratios in a large cohort of fertile and subfertile men.

Materials and methods: Retrospective review of adult men (≥18 years of age) presenting for fertility evaluation between 2002 and 2021 who underwent evaluation by a reproductive urologist, had two separate semen analyses and had hormonal testing within six months of their index semen analysis. Men were dichotomized into fertile and subfertile groups based on total motile sperm count on two semen analyses. The subfertile cohort included men with a total motile sperm count <20 million on both semen analyses. The main outcome measures were serum testosterone, serum estradiol, and serum testosterone to estradiol ratio.

Results: Among 816 men, 651 (79.8%) were classified as fertile and 165 (20.2%) as subfertile. Median testosterone (ng/dL) to estradiol (pg/mL) ratios were similar between the groups (14.48 vs 15.00, p=0.5). The 20^th percentile testosterone to estradiol ratio for the fertile group was 9.77.

Conclusions: This is the largest study to date characterizing testosterone to estradiol ratios in men presenting for fertility evaluation. We validated the 10/1 ratio that was previously established as the 20^th percentile for fertile men. We found no difference in testosterone to estradiol ratios between fertile and subfertile men defined by total motile sperm count, highlighting the need for further investigation to better define the cohort of men with infertility who could benefit from aromatase inhibitor therapy.