[Adrenopause and dehydroepiandrosterone: pharmacological therapy versus replacement therapy]

Adrenopause is an age-related, partial insufficiency of the adrenal cortex characterized by its low blood levels of dehydro-epiandrosterone (DHEA) and DHEA sulfate (DS) in the presence of undiminished cortisol levels. A great number of effects in the CNS and in the periphery are known, partially due to DHEA as an independent hormone, partially due to its influence as a precursor of sex hormones. Positive epidemiological data about DHEA on morbidity and mortality in males as well as clinical reports about promising effects of a DHEA supplementation in elderly people suggest that controlled replacement therapy might be useful in the prevention and treatment of degenerative processes in humans. In studies sofar a fixed daily DHEA dose of 50-100 mg in men and 25-50 mg in women was used irrespective of the individual extent of the adreno-pause. This regimen raised serum levels of DS to and mostly above the upper normal range, thus leading to pharmacological effects.

We report about our experiences in DHEA dose finding in 100 men and 100 women with adrenopause, aged between 46 and 74 years, over a period of 6-12 weeks in order to find a suitable daily oral DHEA dose. The aim was to raise the daily DS peak level between 3 and 5 h after the intake in the morning to 2.0-2.8 pg/ml in women and 4.0-5.0 gg/ml in males, levels that are thought to be in the optimal range of healthy adults in the third decennium of their life (controls).

There were 5, 10, 15, 25 or 50 mg DHEA in 18, 26, 34, 19 or 3% of the women and 15, 25, 50, 75 or 100 mg DHEA in 5, 13, 51, 17 or 14% of the males suitable for that purpose. This adjusted dose regimen raised serum levels (mean values +/- SD) significantly (p < 0.01): (a) in women in the case of DS from 0.7 +/- 0.4 to 2.4 + 0.5 microg/ml, free testosterone from 0.4 +/- 0.4 to 0.9 +/- 0.5 pg/ml and androstenedione from 0.8 +/- 0.4 to 1.4 +0.4 ng/ml, and (b) in males in the case of DS from 1.4 +/- 0.5 to 4.1 +0.7 microg/ml, free testosterone from 10.9 + 4.1 to 14.7 +/- 4.5 pg/ml,androstenedione from 1.2 +/- 0.5 to 2.0 +/- 0.6 ng/ml, estrone from 28 +/- 14 to 41 +/- 19 pg/ml and estradiol from 16 +/- 8 to 31 +/- 15 pg/ml. In cases of inadequate dosage there were side effects like sleepiness,restlessness, headache, acne/hirsutism, effluvium or odors in a percentage of 34, 17, 9, 31, 21 and 11% of the women, respectively.After having adjusted the individual dosage to meet the proper serum levels of DS, these side effects were significantly reduced (p <0.05; p < 0.2 in cases with headache) and found only in 8, 2, 4, 6, 7 and 0%, respectively. In males, such symptoms occurred only occasionally.

We suggest replacement therapy in cases of adrenopause with an "individually adjusted" low DHEA dose between 5 and 50 mg for women and 15 and 100 mg for men in order to raise DS peak levels into the physiological range of younger adults. This procedure has here been applied routinely for the last 5 years, leading to an excellent compliance of the patients. In contrast,a high-dose pharmacological DHEA administration seems to be suit-able for patients with systemic lupus erythematosus and other related diseases.