Reversal of the hypogonadotropic hypogonadism of obese men by administration of the aromatase inhibitor testolactone.
Studies from this laboratory have shown that obese men have elevated serum estrogen levels and diminished levels of follicle-stimulating hormone (FSH) and free and total testosterone, all in proportion to their degree of obesity. The decreases in testosterone and FSH constitute a state of hypogonadotropic hypogonadism (HHG), and we have hypothesized that it results from feedback suppression of the pituitary by the elevated estrogen levels. We tested this hypothesis by lowering the serum estrogens of 6 health obese men (body mass index [BMI], 38 to 73) by administering the aromatase inhibitor testolactone (1 g daily for 6 weeks). Twenty-four-hour mean serum testosterone rose in every subject, from a mean of 290 +/- 165 ng/dL to a mean of 403 +/- 170 (P <.0003); 24-hour mean serum estradiol decreased in every subject, from a mean of 40 +/- 10.8 pg/mL to a mean of 29 +/- 6.7 (P <.004); and 24-hour mean serum luteinizing hormone (LH) increased in every subject, from a mean of 14.3 +/- 4.1 mIU/mL to a mean of 19.3 +/- 5.1 (P <.004). The rise in mean LH was due to an increase in the amplitude of the individual secretory pulses, especially at night. Twenty-four-hour mean serum estrone decreased nonsignificantly, from 48 +/- 14 pg/mL to 39 +/- 6.4, and 24-hour mean serum FSH increased nonsignificantly, from 13.5 +/- 5.3 mIU/mL to 15.0 +/- 5.4. The results are in accordance with the hypothesis, in that inhibition of estrogen biosynthesis (through administration of the aromatase inhibitor testolactone) results in alleviation of the HHG of our obese male subjects.
D000328:Adult; D047072:Aromatase Inhibitors; D015992:Body Mass Index; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D004958:Estradiol / Q000097:blood; D004967:Estrogens / Q000097:blood; D004970:Estrone / Q000097:blood; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D007006:Hypogonadism / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D009765:Obesity / Q000150:complications*; D013738:Testolactone / Q000627:therapeutic use*; D013739:Testosterone / Q000097:blood
D047072:Aromatase Inhibitors; D004791:Enzyme Inhibitors; D004967:Estrogens; D004970:Estrone; D013739:Testosterone; D004958:Estradiol; D013738:Testolactone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone