Reduced conversion of dehydroepiandrosterone into estrogens in women having hypogonadotropic hypogonadism associated with weight loss.
The purpose of this study was to evaluate, without using radioisotopes, the peripheral contribution of dehydroepiandrosterone (D) to estrogens and to androstenedione (A) in patients with hypogonadotropic hypogonadism associated with weight loss (HH) and in normal menstruating women (N). Unlabelled D was infused for 48 h in 12 normal women and in 12 women affected by HH. Plasma levels of D, dehydroepiandrosterone sulfate (DS), A, estrone (E1), estrone sulfate (E1s) and estradiol (E2) were measured before and after 48 h of infusion. Metabolic clearance rates of D (MCRD), production rates of D (PRD), and increases in plasma concentration of DS, A, E1, E1s and E2, relative to the corresponding increase in plasma concentration of D, were determined. The baseline plasma levels of all steroids studied were found to be significantly lower in the patient group than in the control. The MCRD in the normal and the HH groups were similar (1420 +/- 340 l/day versus 1670 +/- 569 l/day, P greater than 0.05). No significant difference was found in PRD between the 2 groups (mean +/- SD 10.3 +/- 5 versus 13.3 +/- 5.5 mg/day, P greater than 0.05). Administration of D increased the levels of estrogen in the normal group but not in the HH group. The relative increase in plasma levels of DS resulting from infusion of D (delta cDS/delta cD) was found to be larger in the HH group than in the normal group (40.4 +/- 17 versus 26.3 +/- 11.8, P less than 0.05). Furthermore, relative increases in plasma levels of A derived from infusion of D were larger in the HH group than in the normal group (0.0495 +/- 0.0021 versus 0.192 +/- 0.0071, P less than 0.001). We conclude from these results that in the HH patients there is a blockage of the peripheral conversion of D to E1 and E1s and an enhancement of the peripheral conversions of D to DS and to A. These metabolic changes may account for the androgenization of the patients under study.
D000328:Adult; D000568:Amenorrhea / Q000378:metabolism; D000735:Androstenedione / Q000097:blood; D001835:Body Weight; D003687:Dehydroepiandrosterone / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism*; D019314:Dehydroepiandrosterone Sulfate; D004958:Estradiol / Q000097:blood; D004967:Estrogens / Q000096:biosynthesis* / Q000172:deficiency; D004970:Estrone / Q000031:analogs & derivatives / Q000097:blood; D005260:Female; D006801:Humans; D007006:Hypogonadism / Q000378:metabolism*; D007986:Luteinizing Hormone / Q000172:deficiency; D008657:Metabolic Clearance Rate
D004967:Estrogens; D004970:Estrone; D000735:Androstenedione; D003687:Dehydroepiandrosterone; D004958:Estradiol; D019314:Dehydroepiandrosterone Sulfate; D007986:Luteinizing Hormone; C017296:estrone sulfate