Differential Effect of Oral Dehydroepiandrosterone-Sulphate on Metabolic Syndrome Features in Pre- and Postmenopausal Obese Women

Cecilia Gómez-Santos; Juan José Hernández-Morante; Francisco Javier Tébar; Esteban Granero; Marta Garaulet


Clin Endocrinol. 2012;77(4):548-554. 

In This Article

Subjects and Methods

Subject Characteristics

Sixty-one postmenopausal women were recruited from the 'Community Health Centre of Espinardo' (Murcia, Spain). Subjects were randomly divided into two groups: 'placebo' (n = 20, 51 ± 2y) receiving a placebo and 'treated' (n = 41, 52 ± 1y) receiving a daily oral dose of 100 mg DHEA-S. The study design was a double-blind placebo-controlled trial. In a second study, the results obtained in the 'postmenopausal treated' group (n = 41, 52 ± 1y) were compared with a 'premenopausal treated' group (n = 20, 28 ± 1y) receiving the same dose of DHEA-S. Placebo and hormonal treatment lasted 3 months. Capsules were made with 100 mg of DHEA-S and cellulosum microcristallinum as filling agent. The dose was selected after revising the bibliography for the physiological dose that influenced weight loss with the fewest adverse effects.[13] Placebo capsules contained just the filling substance.

Inclusion criteria were as follows: overweight women, obesity type I or II and without changes in their normal diet during treatment. Exclusion criteria were as follows: women following any special diet, steroid or thyroid medication, or diagnosed with diabetes mellitus, chronic renal failure, hepatic disease or cancer.

Premenopausal women were defined as those having regular menstrual cycles during the last 12 months. Menopause was defined as the date of the last menses followed by 12 months of no menses and a follicle-stimulating hormone level higher than 30 mIU/ml.[20]

Subjects were monitored monthly during the 3 months of treatment. Patients followed their normal diet during the study. This was corroborated by the 7-day dietary record provided at both the beginning and at the end of the treatment, no significant differences being found during treatment. Moreover, these were no major changes in the physical activity of the participants during the treatment.

All the protocols were approved by the University of Murcia Ethics Committee and were conducted according to the guidelines of the Declaration of Helsinki. Subjects signed a written informed consent before treatment.

Anthropometric and Clinical Characteristics

Obesity assessment was carried out according to the criteria proposed by the Spanish Society for the Study of Obesity (SEEDO).[21] Body weight was measured to the nearest 0·1 kg, while subjects were dressed in their underwear, and height was measured to the nearest centimetre. From these data, the body mass index was calculated. Total body fat (%) was analyzed by means of a bioimpedance technique, using a TANITA TBF-300 (TANITA Corporation of America, Arlington Heights, IL, USA).[22]

Blood samples were collected at the beginning and at the end of the treatment and immediately centrifuged, for 10 min at 4000 g to isolate the plasma content. These samples were stored at −80 °C until analysis. Venous blood samples were obtained after overnight fasting. Plasma insulin was determined by immunoradiometric assays with reagents from Diasource (Fleurus, Belgium). The sensitivity of the method was 1 μU/ml. The intra-assay coefficient of variation (CV) was 4·5% at a serum insulin concentration of 6·6 μU/ml and 2·1% at 53 μU/ml.

The homoeostasis model assessment (HOMA), an index of insulin resistance, was calculated with the accepted formula:[23] HOMA = fasting glucose (mm) × fasting insulin (μUI/ml)/22·5.

Dehydroepiandrosterone-sulphate was determined by radioimmunometric assay (RIA) with reagents purchased from Diagnostic Systems Laboratories Inc. (Webster, TX, USA). The assay had a sensitivity of 1·7 mg/100 ml for DHEA-S. The intra-assay CV was 9·4% at a mean DHEA-S concentration of 20·3 mg/100 ml and 6·3% at 593·3 mg/100 ml.

In addition, leptin, adiponectin and ghrelin were measured. Plasma adiponectin levels were measured by RIA using a Millipore Laboratory Kit (Billerica, MA, USA) with a sensitivity of 2 ng/ml and intra-assay CV of 6·6%. Plasma leptin and grhelin levels were measured using a RIA from Mediagnost Laboratory (Reutlinge, Germany) with a sensitivity of 0·5 ng/ml and intra-assay CV of 8·3%. A gamma counter (DPC Gambyt) was used for the quantification of these hormones.

Metabolic Syndrome Score

To determine the presence or absence of metabolic syndrome (MetS), the definition proposed by the International Diabetes Federation (IDF)[5] was followed. Waist circumference was measured between the lower rib margin and the iliac crest. Plasma concentrations of glucose, triacylglycerides, total cholesterol and high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol were determined with commercial Kits (Roche Diagnostics GmbH, Mannheim, Germany), following the manufacturer's guidelines. Arterial pressure was also measured.

To be able to analyze the effect of DHEA-S replacement on MetS, a MetS score was developed in each woman by adding one unit for each of the MetS components (waist, fasting glucose, triacylglycerides, HDL-c, and systolic or diastolic blood pressure) with a maximum value of five points.

Statistical Analysis

Statistical differences in the baseline characteristics of the groups (a: placebo vs treated and b: postmenopausal treated vs premenopausal treated) were analyzed by Student's t-test. The effects, before and after 3 months of treatment, were evaluated using a paired t-test, comparing within-subject differences. To confirm these data, a general linear model test with both 'treatment' and 'menopausal status' as independent factors was performed. More specifically, a general linear model test for placebo vs treated women was performed and another for postmenopausal treated vs premenopausal treated women.

Significance level was always set at P < 0·05. All analyses were performed using statistical software spss v15.0 (SPSS Inc, Chicago, IL, USA).