The objectives of this cross sectional study «Miller KK, Lawson EA, Mathur V ym. Androgens in wo...»1 were to determine whether endogenous androgen and dehydroepiandrosterone sulfate (DHEAS) levels:

1. are reduced in women with anorexia nervosa (AN) and normal-weight hypothalamic amenorrhea
2. are reduced further by oral contraceptives in women with AN, and
3. are predictors of weight, body composition, or bone density in such women.

Women (N = 217) were divided in four groups: Those (N = 137) with AN not receiving oral contraceptives, those (N = 32) with AN receiving oral contraceptives, normal-weight women (N = 21) with hypothalamic amenorrhea, and healthy eumenorrheic controls (N = 27). Testosterone, free testosterone, DHEAS, bone density, fat-free mass, and fat mass were assessed. Endogenous total (22.6 ± 1.0 vs 32.3± 2.7 ng/dl, p < 0.05) and free testosterone (0.32 ± 0.03 vs 0.47 ± 0.05 ng/dl, p < 0.05), but not DHEAS, were lower in women with AN than in controls. More marked reductions in both free testosterone (0.13 ± 0.03 ng/dl) and DHEAS (113.4 ± 19.1 vs 175.5 ± 11.3 µg/dl) were observed in women with AN receiving oral contraceptives. In contrast, normal-weight women with hypothalamic amenorrhea had normal androgen and DHEAS levels. Lower free testosterone, total testosterone, and DHEAS levels predicted lower bone density at most skeletal sites measured, and free testosterone was positively associated with fat-free mass.

• Tutkimuksen laatu: kelvollinen
• Sovellettavuus suomalaiseen väestöön: hyvä

The hypothesis of this placebo-controlled randomized study «Miller KK, Grieco KA, Klibanski A. Testosterone ad...»2 was that bone formation increases and that depressive symptoms and spatial cognition improve with short-term physiological testosterone administration in subjects with AN. Thirty-three women with AN and relative testosterone deficiency were randomised to transdermal testosterone 150 µg, 300 µg, or placebo, for 3 wk. At baseline, free testosterone correlated with L4 bone density, body mass index, depressive symptoms and spatial cognition. C-terminal propeptide of type 1 collagen levels were higher during testosterone administration than placebo (% change +15 %, P = 0.03). The change in propeptide of type 1 collagen correlated with change in free testosterone over 3 weeks, as a marker of increased bone formation. The other markers of bone formation (osteocalcin and bone-specific alkaline phosphatase), however, did not change. Depressed patients receiving testosterone improved from severely depressed to moderately depressed; the placebo group was unchanged (P = 0.02). Spatial cognition improved in the testosterone group, compared with placebo (P = 0.0015).

• Tutkimuksen laatu: kelvollinen
• Sovellettavuus suomalaiseen väestöön: hyvä

A double-blind, placebo-controlled, randomized trial «Divasta AD, Feldman HA, Giancaterino C ym. The eff...»3 studied whether the combination of dehydroepiandrosterone (DHEA) + estrogen/progestin is superior to placebo in preserving skeletal health over 18 months in AN. Ninety-four subjects (mean age 18.1 ± 2.7, range 13.3, 27.1 years; BMI 18.0 ± 1.5, range 14.8, 22.9 kg/m²) were randomized, and 80 completed baseline assessments and received either study drug (oral micronized DHEA 50 mg + 20 µg ethinyl estradiol/0.1 mg levonorgestrel combined oral contraceptive pill [COC] daily; n = 43, duration of AN median 12 mths (6–40)) or placebo (n = 37, duration of AN 9 mths (4–18). Serial measurements of areal bone mineral density (aBMD), bone turnover markers, and serum hormone concentrations were obtained. Sixty subjects completed the 18-month trial. Spinal and whole-body aBMD z scores were preserved and showed even a modest upward trend in the DHEA + COC group, but decreased in the placebo group comparing trends, P = 0.008 and P = 0.001, respectively). Bone turnover markers initially declined in subjects receiving DHEA + COC and then returned to baseline. The decrease in bone resorption markers exhibited by the treatment arm provides a potential synerdistic mechanism of effect for the DHEA+COC treatment (anabolic effect of DHEA on bone formation. No differences in body composition, adverse effects of therapy, or alterations in biochemical safety parameters were observed. The rate of change in body mass and composition measures did not differ between groups and the advantageous effect of DHEA+COC persisted even after controlling for weight gain. The authors conclude that combined therapy with DHEA + COC appears to be safe and effective for preventing bone loss in young women with AN, whereas placebo led to decreases in areal BMD.

• Tutkimuksen laatu: tasokas
• Sovellettavuus suomalaiseen väestöön: hyvä

In further analyses «DiVasta AD, Feldman HA, Beck TJ ym. Does hormone r...»4 in this same study population, the authors studies the effects of DHEA+COC vs placebo on changes in bone geometry. They used the Hip Structural Analysis (HSA) Program to determine BMD, cross-sectional area (CSA), and section modulus at the femoral neck and shaft. Each measurement was expressed as a percentage of the age-, height-, and lean mass-specific mean from an independent sample of healthy adolescent females. Over the 18 months, DHEA+COC led to stabilization in femoral shaft BMD (change/year ± SE -0.0 ± 0.5, p = 0.94) compared with decreases in the placebo group (change/year ± SE -1.1 ± 0.5, p = 0.03). Subjects receiving placebo treatment developed thinner bone cortical thickness -0.7 ± 0.3 % per year, p = 0.02). The subjects receiving DHEA+COC did not demonstrate changes at these sites during 18 months. These longitudinal changes in bone geometry estimates led to declines in bone bending strength, estimated by both the sectional modulus and the bone strength index, in the placebo group and a significant difference from the subjects receiving DHEA + COC by 18 months (DHEA + COC 1.1 ± 0.7 %/year versus placebo -1.1 ± 0.7 %/year, p = 0.04 for both). These results indicate that this combination treatment has a beneficial impact on surrogate measures of bone strength, and not only bone density, in young women with AN.

• Tutkimuksen laatu: tasokas
• Sovellettavuus suomalaiseen väestöön: hyvä

In this RCT «Bloch M, Ish-Shalom S, Greenman Y ym. Dehydroepian...»5 the effects of the administration of dehydroepiandrosterone (DHEA) were investigated on weight, bone metabolism, bone density and clinical mood symptoms in outpatient Anorexia Nervosa (AN) patients. Patients (n = 26) were double-blindly randomized to receive DHEA (100 mg, n = 15, mean age 26.6 ± 8.9 years, BMI 17.75 ± 1.53 kg/m²) or placebo (n = 11, mean age 27.4 ± 7.4 years, BMI 17.76 ± 0.92 kg/m²) for 6 months. Outcome measures were bone mineral density (BMD) and bone mineral content (BMC) measured by dual energy X-ray absorptiometry (DXA) and metabolism indexes, steroid hormones, and mood and eating disorder symptoms measured at baseline and at the 3 and 6 months follow-up visits. Mood and eating disorder symptoms were assessed monthly by the Beck Depression Inventory, Eating Disorder Inventory and Clinical Global Improvement Scales. No treatment or treatment by time interaction was observed for any bone density measures. An increase in body mass index (BMI) in the DHEA group was significantly higher (8.9 % vs 0.2 %, p = 0.05) at 4 months (but not anymore at 6 months) compared to the control group. This weight gain may reflect a specific DHEA effect. Moreover, improvement of mood was significantly correlated with weight only in the DHEA group (p < 0.01). No improvement in bone mineral density was detected.

• Tutkimuksen laatu: tasokas
• Sovellettavuus suomalaiseen väestöön: hyvä