Binding of Levonorgestrel, Norethisterone and Desogestrel to Human Sex Hormone Binding Globulin and Influence on Free Testosterone Levels

Abstract

The progestogens desogestrel, levonorgestrel, lynestrenol and norethisterone are known to display certain androgenic effects. Apart from direct androgen receptor interaction, binding to sex hormone binding globulin (SHBG) and displacement of testosterone could lead to an increase in free, metabolically active testosterone. The affinities for SHBG binding of some progestogens including levonorgestrel, norethisterone and the active metabolite of desogestrel, 3-keto-desogestrel, were compared using an equilibrium partition method, and the distribution between free and protein-bound testosterone during progestogen therapy was calculated with the use of a computer program. During treatment with desogestrel, levonorgestrel and norethisterone alone, testosterone displacement could account for a slight increase in free testosterone, though the decrease in serum SHBG following treatment was found to be more important in this respect. Also during treatment with combinations of ethinyl estradiol and levonorgestrel for oral contraception, testosterone displacement could theoretically have a slight influence on free testosterone levels. Combinations with ethinyl estradiol and desogestrel or norethisterone, on the other hand, cause an increase in SHBG concentration and as a result a fall in free testosterone which could not be compensated via testosterone displacement.