Dehydroepiandrosterone sulphate (DHEAS) and unconjugated dehydroepiandrosterone (DHEA) have been determined in the blood serum of normal subjects of both sexes from 1 month to 100 years of age. In total, 92 girls, 49 boys, 211 women and 110 men were investigated. The effects of age and sex on the levels of the hormones were measured. DHEAS levels declined rapidly during the first year of life and were maintained at a minimum level for 5 years. They increased significantly from 6 to 7 years of age and reached maximum levels in women at about 24 years and in men at about 30 years of age. They then declined rapidly in both sexes but the fall which occurred after 50 and 60 years of age respectively was only moderate. Age-related unconjugated DHEA levels were different. After the first month of life DHEA levels were relatively high and declined more slowly. The minimum level was observed in girls between 5 and 7 years and in boys between 5 and 9 years of age. A significant rise then began and levels reached a maximum in women as well as in men at about 20 years of age. In men levels then declined up to the age of 80. In women the DHEA levels declined during the next 15 years and from approximately 36 years of age they again rose significantly up to a second peak. A mild but significant decline then resumed. There was a difference in the levels of DHEA and DHEAS depending on sex. Unlike DHEAS, unconjugated DHEA was higher in women than in men. However, this difference was significant only in some age groups: during puberty (between 11 and 15 years of age), in the premenopausal period (between 36 and 45 years of age) and in the older group (after 60 years of age). Age- and sex-related dependencies were different between DHEAS and DHEA. They indicate the possible variable secretion and dynamics of their (inter)conversion. We have concluded that DHEA measurements cannot be a substitute for DHEAS and vice versa.

Objective: To evaluate adrenal and ovarian steroidogenesis before and after long-term treatment with metformin in women with polycystic ovary syndrome (PCOS). Design and Methods: Twenty-four women with PCOS were evaluated before and after treatment (27^4 weeks) with metformin (1000 mg/day) using adrenocorticotrophin (ACTH), GnRH analogue and oral glucose tolerance (oGTT) tests. For statistical evaluation, ANOVA and Wilcoxon's test were used. Results: In 58% of the women a significant improvement in menstrual cyclicity was observed. No significant change in basal steroid levels was found. After ACTH stimulation, a significant decrease in the activity of 3b-hydroxysteroid dehydrogenase in C 21 steroids P , 0X05 and in 17b-hydroxysteroid dehydrogenase P , 0X01 was observed, as was an increase in the activity of C17,20-lyase in the D 4 pathway P , 0X01X A significant growth in the dehydroepiandrosterone (DHEA)/DHEA-sulfate ratio P , 0X05 was detected. With regard to ovarian steroidogenesis, a significant decrease in the stimulated levels of testosterone P , 0X05Y index of free testosterone P , 0X01Y LH P , 0X05 and oestradiol P , 0X01Y and an increase in the levels of 17-hydroxypregnenolone P , 0X05 were detected. In the indices of ovarian enzyme activities, we observed a significant decrease in 3b-hydroxysteroid dehydrogenase in C 21 steroids P , 0X01Y in C17,20-lyase in the D5 pathway P , 0X01Y in 17b-hydroxysteroid dehydrogenase P , 0X05 and in aromatase. In glucose metabolism, a tendency towards reduction in the homeostasis model assessment (HOMA)-R (for insulin resistance) and HOMA-F (for b cell function) was detected. In addition, an increase in the levels of C peptide during oGTT was observed P , 0X01X Conclusions: Long-term metformin treatment reduced various steroid enzymatic activities both in the ovary and the adrenal glands, without apparent changes in basal steroid levels and in insulin sensitivity.

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17-Hydroxypregnenolone (3beta,17alpha-dihydroxypregn-5-en-20-one) and pregnenolone (3beta-hydroxypregn-5-en-20-one) were determined by radioimmunoassay following HPLC separation in serum of healthy subjects of both sexes from 2 to 66 years old (29 girls, 85 women, 30 boys, 89 men). The effects of age and sex on the levels of both steroids were investigated and the upper limits of normal in age groups were determined. The 17-hydroxypregnenolone levels as a function of age were characterized by a statistically significant maximum at the age of 18 and 20 years followed by a local minimum at the age of 39 and 37 years and by a statistically insignificant local maximum at the age of 55 and 49 years in men and women, respectively. Pregnenolone age-dependence was similar and the statistically significant maximum was reached at the age of 17 and 16 years, the local minimum occurred at the age of 37 and 38 years and the second, statistically insignificant, local maximum at the age of 48 and 47 years in men and women, respectively. Both 17-hydroxypregnenolone and pregnenolone in both sexes exhibited similarly shaped peaks with age. Both peaks of the polynomial fit in 17-hydroxypregnenolone were more pronounced in men than in women (13.0 and 9.20 nmol/l in the first peak; 7.72 and 4.78 in the second peak respectively). The situation with pregnenolone was the opposite. Both peaks of the polynomial fit in pregnenolone were lower in men than in women (2.29 and 3.21 nmol/l in the first peak; 0.92 and 1.78 in the second peak, respectively). The higher serum levels of pregnenolone at puberty and during fertile age and their wider variance in comparison with men could, be explained by the different gonadal steroidogenesis depending on the menstrual cycle, where the pregnenolone serves as a substrate for progesterone formation. The age dependencies of 17-hydroxypregnenolone and pregnenolone in women resembled that of unconjugated dehydroepiandrosterone. These results indicate that the increased metabolic activity in gonads in adolescence concerns not only dehydroepiandrosterone as the product of the 5-ene metabolic pathway but also its precursors.