Doris Hübler

Timetable of effects of testosterone administration to hypogonadal men on variables of sex and mood.

Introduction. The effects of testosterone have been extensively characterized, but little attention has been given to the timetable of occurrence of the various effects of testosterone. Methods. The timetables of effects on sexual and psychological variables in 40 hypogonadal men receiving treatment with either parenteral testosterone enanthate (TE) or undecanoate (TU). Results. Sexual thoughts/fantasies and sexual interest/desire/spontaneous morning erections emerged quickly and plateaued after 3 weeks. Total erections rose to a maximum over 9 weeks and then plateaued. Ejaculations per week/satisfaction with sex life rose over the first 3 weeks, increasing steadily to a plateau at 12 weeks. Depression scores decreased to reach a plateau after 6 weeks. Aggressiveness did not change. Scores of concentration improved and reached a plateau after 3 weeks in the group treated with TE and after 9 weeks in the group treated with TU. Good mood improved after 6–9 weeks. Positive effects on self-confidence appeared between 3–6 weeks and on fatigue after 9–12 weeks. Conclusion. Insight into the emergence of effects may be useful information for the patient and for the attending physician in monitoring clinical effects of testosterone treatment of hypogonadal men.

A four-year efficacy and safety study of the long-acting parenteral testosterone undecanoate

Introduction. This is a four-year follow-up of 25 men who received parenteral testosterone undecanoate (TU), 1000 mg every 12 weeks for at least four years. This study was a continuation of a 30-week study wherein the effects of TU had been compared to those of parenteral testosterone enanthate. Methods & Results. Plasma testosterone (T) trough values of the injection interval of 12 weeks): median 11.9 – 15.9 nmol/L (N 10.0–30.0). E2 and SHBG were stable. Body weight, BMI, waist-to-hip ratio remained stable. Total cholesterol, and triglycerides were unchanged but plasma LDL declined while HDL, after an initial reduction over the first 30 weeks, had increased significantly after three years. Leptin levels, bone mineral density, blood pressure, liver function tests, haemoglobin and haematocrit levels remained stable without values above the upper limit of normal. Over the first 12 months of the study there was an increase in prostate volume from 19.7 ± 8.8 mL to 22.0 ± 8.4 mL (p < 0.05) but thereafter volumes remained stable, paralleled by an increase in PSA from 0.67 ± 0.38 µg/dL to 0.75 ± 0.35 µg/dL (p < 0.05) without any further changes after 12 months. Conclusion. TU appears to be a stable and safe treatment modality of hypogonadal men.

Influence of oral dehydroepiandrosterone (DHEA) on urinary steroid metabolites in males and females

Oral dehydroepiandrosterone (DHEA) replacement therapy may have a multitude of potential beneficial effects and exerts its action mainly via peripheral bioconversion to androgens (and estrogens). A daily dose of 50-mg DHEA has been shown by us and others to restore low endogenous serum DHEA concentrations to normal youthful levels followed by an increase in circulating androgens and estrogens. As the hepatic first-pass effect may lead to a non physiological metabolism of DHEA after oral ingestion we studied the influence of two single DHEA doses (50 and 100 mg) on the excretion of steroid metabolites in 14 elderly males [age 58.8+/-5.1 years (mean +/- SEM)] with endogenous DHEAS levels <1500 ng/ml and in 9 healthy females (age 23.3+/-4.1 years) with transient suppression of endogenous DHEA secretion induced by dexamethasone (dex) pretreatment (4x0.5 mg/day/4 days). Urinary steroid profiles in the elderly males were compared to the steroid patterns found in 15 healthy young men (age 28.9+/-5.1 years). In the females the results were compared to their individual baseline excretion without dex pretreatment. Urinary steroid determinations were carried out by semiautomatic capillary gas-liquid chromatography. In both genders DHEA administration induced significant increases in urinary DHEA (females: baseline vs. 50 mg vs. 100 mg: 361+/-131 vs. 510+/-264 vs. 1541+/-587 microg/day; males: placebo vs. 50 mg vs. 100 mg: 434+/-154 vs. 1174+/-309 vs. 4751+/-1059 microg/day) as well as in the major DHEA metabolites androsterone (A) and etiocholanolone (Et). Fifty mg DHEA led to an excretion of DHEA and its metabolites only slightly above baseline levels found in young females and in young men, respectively, whereas 100 mg induced clearly supraphysiological values. After 50 mg DHEA the ratios of urinary DHEA metabolites (A/DHEA, Et/DHEA) were not significantly different between elderly males vs. young male volunteers and young healthy females versus their individual baseline levels. In conclusion, an oral dose of 30 to 50 mg DHEA restores a physiological urinary steroid profile in subjects with DHEA deficiency without evidence for a relevant hepatic first-pass effect on urinary metabolites.

Selected aspects of endocrine pharmacology of the aging male

This minireview explores the endocrinology and the clinical consequences of age-related hypogonadism (hypotestosteronemia). In addition, pharmacological and clinical applicability of new androgen formulations is described briefly. Other topics include selective androgen receptor modulators, non-feminizing estrogens, and the possible use of selective aromatase modulators. Finally, a theoretical concept of hormone displacement (i.e. excessive hormone production) is introduced using cortisol as an example.

Scavenging and antioxidant effects of estrogen derivatives in cholesterol-fed rabbits.

It is well establish that many estrogens are naturally occurring antioxidant1.Some Δ8.,9-dehydro derivatives of 17α-estradiol and 17β-estradiol are effective scavengers of free oxygen radicals2. These estrogens are called scavestrogens because their radical scavenging effect is higher than those of the parent compounds. There are the experimental data on estrogens attenuating the progression of atherosclerosis3. Oxidation of low-density lipoproteins (LDL) is believed to play an important role in atherogenesis4. A supplementation with different antioxidants is widely used for the treatment and prevention of atherosclerosis5. We studied the antioxidative effect of Δ8,9-dehydro derivative of 17α-estradiol, 14α, 15α-methylene-8-dehydro-17α-estradiol (J861) in a comparison with 17α-and 17β-estradiols in the liver of cholesterol-fed rabbits. We also evaluated radical scavenging properties of scavestrogens and estrogens in vitro using spin-trapping techniques.