Partial reversal of the hypogonadotropic hypogonadism of obese men by administration of corticosuppressive doses of dexamethasone

Obese men have hyperestrogenemia-induced hypogonadotropic hypogonadism (HHG), due, we believe, to increased aromatization of adrenal androgens by the increased bulk of aromatase-containing adipose tissue. We studied the effects of corticosuppressive doses of dexamethasone (D) on 24-h mean plasma total and free estradiol (E₂), estrone (E₁), LH, FSH, total and free testosterone, Δ⁴-androstenedione (Δ⁴), and sex-hormone-binding globulin (SHBG) in nine obese men and five normal-weight controls. In the obese men, the following hormones fell: E₂ [59 ± 19 to 39 ± 11 pg/ml (P < 0.01)], E₁[93 ± 41 to 50 ± 25 pg/ml; (P < 0.01)], Δ4-androstenedione [120 ± 80 to 55 ± 27 ng/dl; (P < 0.02)]; free E₂ [1.6 ± 0.4 to 1.1 ± 0.2 pg/ml; (P < 0.01)], SHBG [12.8 ± 5.3 to 8.2 ± 3 nM/l; (P < 0.04)]. ESH rose from 4.8 ± 3.2 to 7.6 ± 4.2 miu/ml (P < 0.01). LH, total and free testosterone showed no significant change. In the nonobese men, there were decreases in total E₂ [(34 ± 6.8 to 25 ± 10 pg/ml; P < 0.04)], SHBG [16.8 ± 7,5 to 10.4 ± 2.0 nM/l: P < .05], free E₂ [0.9 ± 0.2 to 0.7 ± 0.3 pg/ml: P < 0.05], Δ⁴ [91.4 ± 3.6 to 33.4 ± 16.7 ng/dl: P < .01] and total T [492 ± 44 to 393 ± 121 ng/dl; P < 0.04]. There was no significant change in E₁, FSH, LH or free T. Of the three components of hyperestrogenemia-induced HHG in the obese men, two (elevated estrogens and diminished gonadotropins) were normalized by D. The testosterone did not rise, possibly because of counteractive direct suppression of testosterone secretion by D, as shown in the control men.