CoChat
Sign Up
Cited by 189Adrenal Hormones and DisordersHormonal and reproductive studiesHormonal Regulation and Hypertension

Long-Term DHEA Replacement in Primary Adrenal Insufficiency: A Randomized, Controlled Trial

Open access
Gurnell, Eleanor M., Hunt, Penelope J., Curran, Suzanne E., Conway, Catherine L., Pullenayegum, Eleanor M., Huppert, Felicia A., Compston, Juliet E., Herbert, Joseph +1 more·2008·The Journal of Clinical Endocrinology & Metabolism
DOI 10.1210/jc.2007-1134PMC PMC2729149
Open this paper in CoChat — free accountOpen PDF

Abstract

CONTEXT: Dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) are the major circulating adrenal steroids and substrates for peripheral sex hormone biosynthesis. In Addison's disease, glucocorticoid and mineralocorticoid deficiencies require lifelong replacement, but the associated near-total failure of DHEA synthesis is not typically corrected. OBJECTIVE AND DESIGN: In a double-blind trial, we randomized 106 subjects (44 males, 62 females) with Addison's disease to receive either 50 mg daily of micronized DHEA or placebo orally for 12 months to evaluate its longer-term effects on bone mineral density, body composition, and cognitive function together with well-being and fatigue. RESULTS: Circulating DHEAS and androstenedione rose significantly in both sexes, with testosterone increasing to low normal levels only in females. DHEA reversed ongoing loss of bone mineral density at the femoral neck (P < 0.05) but not at other sites; DHEA enhanced total body (P = 0.02) and truncal (P = 0.017) lean mass significantly with no change in fat mass. At baseline, subscales of psychological well-being in questionnaires (Short Form-36, General Health Questionnaire-30), were significantly worse in Addison's patients vs. control populations (P < 0.001), and one subscale of SF-36 improved significantly (P = 0.004) after DHEA treatment. There was no significant benefit of DHEA treatment on fatigue or cognitive or sexual function. Supraphysiological DHEAS levels were achieved in some older females who experienced mild androgenic side effects. CONCLUSION: Although further long-term studies of DHEA therapy, with dosage adjustment, are desirable, our results support some beneficial effects of prolonged DHEA treatment in Addison's disease.

Integrity signals

Registry

Crossref · 10.1210/jc.2007-1134

Cites

61 of 61 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

10 of 63 cited sources checked · 8 supported · 0 flagged · accuracy not yet measured

  • Findingcitation

    Using SF-36, Addison's disease subjects had lower scores at baseline, denoting worse health status than a normal U.K. population.

    “As with GHQ status, using the SF-36 questionnaire as a tool to assess a broad range of physical symptomatology as well as psychological morbidity, the Addison's disease subjects had lower scores at baseline, denoting worse health status than a normal U.K. population (36) (Table 6).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [36] Jenkinson, 1999, Assessment of the SF-36 version 2 in the United Kingdom., J Epidemiol Community Health source
  • Premisecitation

    The improvement in lean muscle mass mirrors that seen in previous studies with DHEA supplementation in aging or postmenopausal women.

    “The improvement in lean muscle mass mirrors that seen in previous studies with DHEA supplementation in aging or postmenopausal women (7,8).”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [7] Morales, 1998, The effect of six months treatment with a 100 mg daily dose of dehydroepiandrosterone (DHEA) on circulating sex steroids, body composition and muscle strength in age-advanced men and women., Clin Endocrinol (Oxf) source

      The Body composition, muscle strength and BMR section reports a trend toward increased lean body mass in women taking DHEA (0.7 ± 0.4 kg, P = 0.08), but not a statistically significant improvement; it reports no increase in men. Thus this study offers limited support for the comparison, but does not establish the claimed improvement in lean muscle mass in aging or postmenopausal women. A page number is not available for the indexed passage. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [8] Diamond, 1996, Metabolic effects of 12-month percutaneous dehydroepiandrosterone replacement therapy in postmenopausal women, J Endocrinol

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Premisecitation

    Other studies of DHEA therapy in postmenopausal women or aging have also shown selective improvement in BMD at the femoral neck.

    “second, other studies of DHEA therapy in postmenopausal women (9) or aging (40,47) have also shown selective improvement in BMD at this site.”
    Quote in the paperNot a substantial claim2 of 3 sources checked
    • cites [9] Labrie, 1997, Effect of 12-month dehydroepiandrosterone replacement therapy on bone, vagina and endometrium in postmenopausal women., J Clin Endocrinol Metab source

      The Bone density section (page unavailable) reports a significant BMD increase at the total hip after DHEA treatment, but not at the femoral neck specifically. Ward’s triangle, an area near the femoral neck, increased without reaching statistical significance. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [40] Baulieu, 2000, Dehydroepiandrosterone (DHEA), DHEA sulfate, and aging: contribution of the DHEAge Study to a sociobiomedical issue., Proc Natl Acad Sci USA source
    • cites [47] Nair, 2006, DHEA in elderly women and DHEA or testosterone in elderly men., N Engl J Med source
  • Findingown data

    At baseline, subscales of psychological well-being in questionnaires (Short Form-36, General Health Questionnaire-30) were significantly worse in Addison's patients vs control populations (P < 0.001).

    “At baseline, subscales of psychological well-being in questionnaires (Short Form-36, General Health Questionnaire-30), were significantly worse in Addison's patients vs. control populations (P Ͻ 0.001),”
    Quote in the paperNot a substantial claim
  • Findingown data

    Supraphysiological DHEAS levels were achieved in some older females who experienced mild androgenic side effects.

    “Supraphysiological DHEAS levels were achieved in some older females who experienced mild androgenic side effects.”
    Quote in the paperNot a substantial claim
  • Classified as probably not a substantial claim. 25
  • May combine two claims. 39
  • The quote only partly states this claim. 1

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    A 9-month, parallel group trial of DHEA replacement in 39 patients showing no benefit in health status may have been underpowered.

    “A 9-month, parallel group trial of DHEA replacement in 39 patients showing no benefit in health status (25) may have been underpowered (26).”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [25] Lovas, 2003, Replacement of dehydroepiandrosterone in adrenal failure: no benefit for subjective health status and sexuality in a 9-month, randomized, parallel group clinical trial., J Clin Endocrinol Metab source
    • cites [26] Arlt, 2003, DHEA replacement in adrenal insufficiency, J Clin Endocrinol Metab 88:4001; author reply source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Positive effects of DHEA replacement have been described on psychological well-being, body composition, and bone mineral density in older, normal adults.

    “positive effects of DHEA replacement have been described on psychological well-being (6), body composition (7,8), and bone mineral density (BMD) (9) in older, normal adults.”
    Quote in the paperNot a substantial claim2 of 4 sources checked
    • cites [6] Morales, 1994, Effects of replacement dose of dehydroepiandrosterone in men and women of advancing age., J Clin Endocrinol Metab source
    • cites [7] Morales, 1998, The effect of six months treatment with a 100 mg daily dose of dehydroepiandrosterone (DHEA) on circulating sex steroids, body composition and muscle strength in age-advanced men and women., Clin Endocrinol (Oxf) source
    • cites [8] Diamond, 1996, Metabolic effects of 12-month percutaneous dehydroepiandrosterone replacement therapy in postmenopausal women, J Endocrinol

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [9] Labrie, 1997, Effect of 12-month dehydroepiandrosterone replacement therapy on bone, vagina and endometrium in postmenopausal women., J Clin Endocrinol Metab source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    The SF-36 questionnaire is a tool that has been validated in population studies.

    “The Short Form-36 (SF-36) questionnaire examined symptoms relating to physical and mental health and is a tool that has been validated in population studies (35,36).”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [35] Keller, 1998, Use of structural equation modeling to test the construct validity of the SF-36 Health Survey in ten countries: results from the IQOLA Project. International Quality of Life Assessment., J Clin Epidemiol source
    • cites [36] Jenkinson, 1999, Assessment of the SF-36 version 2 in the United Kingdom., J Epidemiol Community Health source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Another androgen (testosterone) improves sexual function in surgically menopausal women.

    “Another androgen (testosterone) also improves sexual function in surgically menopausal women (55,56).”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [55] Shifren, 2000, Transdermal testosterone treatment in women with impaired sexual function after oophorectomy., N Engl J Med source
    • cites [56] Simon, 2005, Testosterone patch increases sexual activity and desire in surgically menopausal women with hypoactive sexual desire disorder., J Clin Endocrinol Metab source

  • May combine two claims.

    Interpretationown data

    The absence of changes in sexual function after DHEA treatment is in keeping with observations in some short- and longer-term trials but differs from observations in women with primary or secondary adrenal failure.

    “which is in keeping with observations in some short- (20,48,54) and longer-term trials (25) but differs from observations in women with primary or secondary adrenal failure (23,24).”
    Quote in the paperNot a substantial claim1 of 6 sources checked
    • cites [20] Hunt, 2000, Improvement in mood and fatigue after dehydroepiandrosterone replacement in Addison’s disease in a randomized, double blind trial., J Clin Endocrinol Metab source
    • cites [48] Libe, 2004, Effects of dehydroepiandrosterone (DHEA) supplementation on hormonal, metabolic and behavioral status in patients with hypoadrenalism., J Endocrinol Invest source
    • cites [54] van Thiel, 2005, Effects of dehydroepiandrostenedione, superimposed on growth hormone substitution, on quality of life and insulin-like growth factor I in patients with secondary adrenal insufficiency: a randomized, placebo-controlled, cross-over trial., J Clin Endocrinol Metab source
    • cites [25] Lovas, 2003, Replacement of dehydroepiandrosterone in adrenal failure: no benefit for subjective health status and sexuality in a 9-month, randomized, parallel group clinical trial., J Clin Endocrinol Metab source
    • cites [23] Arlt, 1999, Dehydroepiandrosterone replacement in women with adrenal insufficiency., N Engl J Med source
    • cites [24] Johannsson, 2002, Low dose dehydroepiandrosterone affects behavior in hypopituitary androgen-deficient women: a placebo-controlled trial., J Clin Endocrinol Metab source

  • May combine two claims.

    Findingown data

    Circulating DHEAS and androstenedione rose significantly in both sexes, with testosterone increasing to low normal levels only in females.

    “Circulating DHEAS and androstenedione rose significantly in both sexes, with testosterone increasing to low normal levels only in females.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    DHEA enhanced total body (P = 0.02) and truncal (P = 0.017) lean mass significantly with no change in fat mass.

    “DHEA enhanced total body (P ϭ 0.02) and truncal (P ϭ 0.017) lean mass significantly with no change in fat mass.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    There was no significant benefit of DHEA treatment on fatigue or cognitive or sexual function.

    “There was no significant benefit of DHEA treatment on fatigue or cognitive or sexual function.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    DHEA reversed ongoing loss of bone mineral density at the femoral neck (P < 0.05) but not at other sites.

    “DHEA reversed ongoing loss of bone mineral density at the femoral neck (P Ͻ 0.05) but not at other sites;”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Analyses by gender showed a differential effect only at the proximal radius, with significant enhancement of BMD after DHEA in men but not women (males: DHEA 0.0046 vs placebo -0.0136, P = 0.025; females: DHEA -0.0091 vs placebo -0.0062, P = 0.583).

    “Analyses by gender showed a differential effect only at the proximal radius, with significant enhancement of BMD after DHEA in men but not women [mean (SEM) BMD (grams per square centimeter) changes: males: after DHEA, 0.0046 (0.0046) and after placebo, Ϫ0.0136 (0.006) P ϭ 0.025; females: after DHEA, Ϫ0.0091 (0.0036) and after placebo, Ϫ0.0062 (0.0037), P ϭ 0.583].”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Compared with placebo, there was a reduction in scores for all dimensions of MFI-20 in the DHEA group, but the changes only bordered on statistical significance for mental fatigue at the 6-month time point (P = 0.03).

    “Compared with the placebo group, there was a reduction (improvement) in scores for all dimensions in the DHEA group, but the changes only bordered on statistical significance for mental fatigue at the 6-month time point (P ϭ 0.03).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Circulating fasting lipid profiles were unchanged as was thyroid function.

    “Circulating fasting lipid profiles were unchanged as was thyroid function (data not shown),”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Female subjects receiving DHEA reported increased occurrence of skin spots, greasy skin, and axillary hair growth.

    “Female subjects receiving DHEA reported increased occurrence of skin spots, greasy skin, and axillary hair growth (Table 7).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    DHEA increased lean mass, both total and truncal, with no effect on fat mass.

    “DHEA increased lean mass, both total and truncal, with no effect on fat mass (Table 3).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Analysis by gender showed that the effect on lean mass was more marked in females, who showed greater changes in total body lean mass than males (females: DHEA 869 vs placebo 183, P = 0.034; males: DHEA -117 vs placebo -399).

    “Analysis by gender showed that this effect was more marked in females, who showed greater changes in total body lean mass than their male counterparts [mean (SEM) lean mass (grams) changes: females, after DHEA, 869 (211) and after placebo, 183 (269), P ϭ 0.034; males, after DHEA, Ϫ117(247) and after placebo, Ϫ399(258)].”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In those receiving DHEA, there was a marked and significant reversal of this trend in the femoral neck (mean BMD changes: DHEA 0.0039 vs placebo -0.0068 g/cm2, P < 0.046) but not at any other site.

    “In those receiving DHEA, there was a marked and significant reversal of this trend in the femoral neck [mean (SEM) BMD (grams per square centimeter) changes: after DHEA, 0.0039 (0.004) vs. after placebo, Ϫ0.0068(0.003)g/cm 2 , P Ͻ 0.046] but not at any other site (Fig. 2).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Using WHO T-score criteria, in the lumbar spine, 39% of males and females were osteopenic and 7% of males and 5% of females osteoporotic; in the femoral neck, 39% of males and females were osteopenic and 2% of females were osteoporotic.

    “Using World Health Organization T-score criteria, in the lumbar spine, 39% of males and females were osteopenic and 7% of males and 5% of females osteoporotic; in the femoral neck, 39% of males and females were osteopenic and 2% of females were osteoporotic.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Changes in serum IGF-I in females reached borderline significance (P = 0.01).

    “changes in serum IGF-I in females reached borderline significance (P ϭ 0.01) (Table 2).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In females taking DHEA, serum total testosterone increased from subnormal to low normal levels (after placebo 0.13 vs after DHEA 0.41 nmol/liter, P < 0.001), but there was no associated change in circulating SHBG.

    “In females taking DHEA, serum total testosterone increased from subnormal to low normal levels (after placebo 0.13 vs. after DHEA 0.41 nmol/liter, P Ͻ 0.001), but there was no associated change in circulating SHBG.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingcitation

    They exhibited an identical profile of deficits in particular dimensions of health (role physical, general health, vitality, role emotional) as a Norwegian population of Addison's disease patients studied independently by another group.

    “Interestingly, they exhibited an identical profile of deficits in particular dimensions of health (role physical, general health, vitality, role emotional) as a Norwegian population of Addison's disease patients studied independently by another group (21) (Table 6).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [21] Lovas, 2002, Subjective health status in Norwegian patients with Addison’s disease., Clin Endocrinol (Oxf) source

  • May combine two claims.

    Findingcitation

    The hormone profile of DHEA-treated subjects was similar to that observed in our previous study, with significant increases in androstenedione in both sexes and testosterone in women but not in men.

    “The hormone profile of DHEA-treated subjects was similar to that observed in our previous study (20) with significant increases in androstenedione in both sexes and testosterone in women but not in men.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [20] Hunt, 2000, Improvement in mood and fatigue after dehydroepiandrosterone replacement in Addison’s disease in a randomized, double blind trial., J Clin Endocrinol Metab source

  • May combine two claims.

    Findingown data

    In males there was no significant change in SHBG, total testosterone, or estradiol during DHEA treatment.

    “In males there was no significant change in SHBG, total testosterone, or estradiol during DHEA treatment.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    After treatment washout, scores for both role physical and role emotional dimensions fell more markedly in the DHEA group, but the changes did not achieve statistical significance.

    “Interestingly, after treatment washout, scores for both role physical and role emotional dimensions fell more markedly (denoting deterioration of health status) in the DHEA group, but the changes did not achieve statistical significance.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    There was no difference in Sebutape scores between the placebo and DHEA groups, despite the reported subjective symptoms.

    “We measured sebum production using white adherent tapes (Sebutape; CuDerm Corp., Dallas, TX) applied to forehead skin at each assessment as described previously (41), but there was no difference in Sebutape scores between the placebo and DHEA groups (data not shown), despite the reported subjective symptoms.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [41] Kligman, 1986, Sebutape: a device for visualizing and measuring human sebaceous secretion., J Soc Cosmet Chem

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Findingown data

    During DHEA treatment, total GHQ-30 scores or self-esteem subscale declined (signifying improvement), with a rise after washout, but comparison with placebo showed these changes were not statistically significant (P values).

    “During DHEA treatment, either total GHQ-30 scores (Fig 3A) or for the self-esteem subscale (Fig 3B) declined (signifying improvement), with a rise in scores after washout, but comparison with the placebo group showed that these changes were not statistically significant (DHEA vs. placebo scores: total GHQ 6 months, P ϭ 0.55, 12 months, P ϭ 0.32, after washout, P ϭ 0.23; self esteem 6 months, P ϭ 0”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    DHEA therapy increased both truncal and total body lean mass measured by DEXA.

    “DHEA therapy increased both truncal and total body lean mass measured by DEXA.”
    Quote in the paperSubstantial claim

  • The quote only partly states this claim.

    Findingown data

    Daily oral administration of DHEA in physiological dosage for 12 months has positive psychological effects.

    “and does have positive psychological effects.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The observed improvements in GHQ-30 and SF-36 during DHEA treatment and worsening after washout reflect a true drug effect rather than nonspecific fluctuation.

  • May combine two claims.

    Findingown data

    Physical and mental fatigue dimensions of the MFI-20 showed statistically nonsignificant improvement at 6 and 12 months during DHEA treatment, followed by deterioration of scores after washout.

    “with statistically nonsignificant improvement at 6 and 12 months during DHEA treatment, followed by deterioration of scores after washout.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductown data

    The trial was a double-blind, placebo-controlled, parallel group design.

    “The trial was a double-blind, placebo-controlled, parallel group design.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Serum DHEA(S) levels decline progressively with age.

    “serum DHEA(S) levels then follow a progressive age-related decline (1,2).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [1] Orentreich, 1984, Age changes and sex differences in serum dehydroepiandrosterone sulfate concentrations throughout adulthood., J Clin Endocrinol Metab source
    • cites [2] Orentreich, 1992, Long-term longitudinal measurements of plasma dehydroepiandrosterone sulfate in normal men., J Clin Endocrinol Metab source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Young et al. validated the efficacy of oral DHEA treatment in restoring physiological circulating levels of DHEA(S) in 10 adults with panhypopituitarism and showed some biotransformation of DHEA into sex steroids.

    “Young et al. (22) validated the efficacy of oral DHEA treatment in restoring physiological circulating levels of DHEA(S) in 10 adults with panhypopituitarism and showed some biotransformation of DHEA into sex steroids.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [22] Young, 1997, Panhypopituitarism as a model to study the metabolism of dehydroepiandrosterone (DHEA) in humans., J Clin Endocrinol Metab

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Johannsson et al. demonstrated behavioral changes, reported by partners, in 38 panhypopituitary females after 6 months of DHEA(S) replacement.

    “Johannsson et al. (24) demonstrated behavioral changes, reported by their partners, in 38 panhypopituitary females after 6 months of DHEA(S) replacement.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] Johannsson, 2002, Low dose dehydroepiandrosterone affects behavior in hypopituitary androgen-deficient women: a placebo-controlled trial., J Clin Endocrinol Metab source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    A large body of epidemiological data from cross-sectional correlational studies has documented an association between the decline in DHEAS levels and various age-related disorders, including increased risk of cardiovascular events, malignancy, and osteoporosis.

    “A large body of epidemiological data from crosssectional correlational studies has documented an association between the decline in DHEAS levels and various age-related disorders, including increased risk of cardiovascular events (3), malignancy (4), and osteoporosis (5).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [3] Barrett-Connor, 1986, A prospective study of dehydroepiandrosterone sulfate, mortality and cardiovascular disease., N Engl J Med source
    • cites [4] Ebeling, 1994, Physiological importance of dehydroepiandrosterone., Lancet source
    • cites [5] Sambrook, 1992, Postmenopausal bone loss in rheumatoid arthritis: effect of estrogens and androgens., J Rheumatol

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Treatment allocation details were coded and kept confidential until the trial was completed.

    “Treatment allocation details were coded and kept confidential until the trial was completed.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Our previous placebo-controlled 3-month crossover trial of 39 patients with primary adrenal insufficiency showed similar biochemical changes and enhanced psychological well-being, independent of gender.

    “Our previous placebo-controlled 3-month crossover trial of 39 patients (including 15 males) with primary adrenal insufficiency showed similar biochemical changes and enhanced psychological well-being, independent of gender (20).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [20] Hunt, 2000, Improvement in mood and fatigue after dehydroepiandrosterone replacement in Addison’s disease in a randomized, double blind trial., J Clin Endocrinol Metab source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    Randomization was stratified by age and gender and undertaken by an independent statistician.

    “The randomization was stratified by age (18 -34, 35-49, 50 -65 yr) and gender and undertaken by an independent statistician.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    These changes are in accordance with DHEA being a sex steroid precursor.

    “These changes are in accordance with DHEA being a sex steroid precursor.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Five and 1% levels of significance were used for primary and secondary end points, respectively.

    “Five and 1% levels of signifi- cance were used for primary and secondary end points, respectively.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationcitation

    The magnitude of DHEA conversion to estradiol is insufficient to cornify the vaginal epithelium in rats, and by analogy, the observed lack of change in circulating estradiol levels in men receiving DHEA is not unexpected.

    “Although DHEA is converted to estradiol, the magnitude of this effect is insufficient to cornify the vaginal epithelium in rats (a sensitive assay) (42), and by analogy, we suggest that our observed lack of change in circulating estradiol levels in men receiving DHEA is not unexpected.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [42] Sourla, 1998, Effect of dehydroepiandrosterone on vaginal and uterine histomorphology in the rat., J Steroid Biochem Mol Biol source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    Twenty-three subjects had taken part in previous short-term trial but were distributed comparably across DHEA and placebo groups.

    “Twenty-three subjects had taken part in our previous, short-term trial of DHEA (20) but were distributed comparably across DHEA (n ϭ 9) and placebo (n ϭ 14) groups.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [20] Hunt, 2000, Improvement in mood and fatigue after dehydroepiandrosterone replacement in Addison’s disease in a randomized, double blind trial., J Clin Endocrinol Metab source

  • May combine two claims.

    Interpretationown data

    We report novel effects of DHEA on body composition (lean mass), femoral neck BMD, and particular psychological parameters (fatigue and self-esteem).

    “We report novel effects of DHEA on body composition (lean mass), femoral neck BMD, and particular psychological parameters (fatigue and self-esteem).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Biochemical assays had intra- and interassay coefficients of variation less than 10% throughout.

    “The intra-and interassay coefficients of variation were less than 10% throughout.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductown data

    One month after discontinuing treatment, DHEAS levels fell back to baseline low levels, confirming satisfactory washout.

    “One month after discontinuing treatment, DHEAS levels fell back to baseline low levels, confirming satisfactory washout of the active study treatment (Fig. 1).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    Because circulating DHEA levels decline with age and all subjects received the same dose of DHEA, there was a tendency for DHEAS levels to be above age-matched controls in those aged 50 yr or older.

    “Because circulating DHEA levels decline with age (1, 2) and all subjects received the same dose of DHEA, there was a tendency for DHEAS levels to be above age-matched controls in those aged 50 yr or older.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [1] Orentreich, 1984, Age changes and sex differences in serum dehydroepiandrosterone sulfate concentrations throughout adulthood., J Clin Endocrinol Metab source
    • cites [2] Orentreich, 1992, Long-term longitudinal measurements of plasma dehydroepiandrosterone sulfate in normal men., J Clin Endocrinol Metab source

  • May combine two claims.

    Study design and conductown data

    DHEAS levels were maintained throughout the 12-month period, signifying compliance with treatment.

    “These levels were maintained throughout the 12-month period, signifying compliance with treatment.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    This 12-month study of DHEA replacement in patients with Addison's disease supports the improved well-being documented in our previous short-term study and adds new information on longer-term effects of DHEA.

    “This 12-month study of DHEA replacement in patients with Addison's disease both supports the improved well-being documented in our previous short-term study and adds new information on longer-term effects of DHEA.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [20] Hunt, 2000, Improvement in mood and fatigue after dehydroepiandrosterone replacement in Addison’s disease in a randomized, double blind trial., J Clin Endocrinol Metab source

  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    For body composition and cognitive function, values at 12 months in placebo vs DHEA groups were compared, adjusting for values at baseline.

    “For the other primary end points (body composition and cognitive function), values at 12 months in placebo vs. DHEA-treated groups were compared, adjusting for values at baseline.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    BMD measurements had precision less than 1% in lumbar spine and hip.

    “The precision of BMD measurements was less than 1 or 1% in lumbar spine and hip, respectively.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S1 (asserted). May combine two claims.

    Study design and conductreasoning

    The study had 95% power to detect a 2.5% change in hip BMD and 80% power to detect a 1% change in spine BMD.

    “We aimed to recruit at least 100 patients to have 95% power to detect a 2.5% change in hip BMD and 80% power to detect a 1% change in spine BMD.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    One hundred patients were required to power the study to detect changes in BMD.

    “One hundred patients were required to power the study to detect changes in BMD, and we aimed to recruit at least this number of subjects who fulfilled the entry criteria, within a 3-month time interval.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationown data

    Our data represent the most comprehensive evaluation of the effects of DHEA on cognition in Addison's disease.

    “Nevertheless, our data represent the most comprehensive evaluation of the effects of DHEA on cognition in Addison's disease.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Study design and conductnone given

    The GHQ-30 and SF-36 tests have been validated and used on large populations of normal individuals.

    “Because both the GHQ-30 and SF-36 tests have been validated and used on large populations of normal individuals”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationnone given

    This trial describes the longest duration of DHEA replacement therapy in a comparatively large number of patients with Addison's disease.

    “This trial describes the longest duration of DHEA replacement therapy in a comparatively large number of patients with Addison's disease”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    Both our earlier short-term trial and the present study showed no statistically significant change in circulating IGF-I levels, in agreement with another recent replacement study, arguing against a primary role of this hormone in mediating increases in lean muscle mass.

    “Despite earlier reports suggesting changes in IGF-I with DHEA replacement, both our earlier short-term trial (20) and the present study showed no statistically significant change in circulating IGF-I levels, in agreement with another recent replacement study (50), arguing against a primary role of this hormone in mediating increases in lean muscle mass.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [20] Hunt, 2000, Improvement in mood and fatigue after dehydroepiandrosterone replacement in Addison’s disease in a randomized, double blind trial., J Clin Endocrinol Metab source
    • cites [50] Christiansen, 2004, Dehydroepiandrosterone supplementation in women with adrenal failure: impact on twenty-four hour GH secretion and IGF-related parameters., Clin Endocrinol (Oxf) source

  • Classified as probably not a substantial claim. May combine two claims.

    Interpretationreasoning

    Although the improvement in BMD is modest, compared with conventional therapies, this change may become significant if compounded, as would be the case with long-term DHEA treatment of patients.

    “Although the improvement in BMD is modest, compared with conventional therapies, this change may become sig-nificant if compounded, as would be the case with long-term DHEA treatment of patients.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationcitation

    The absence of significant changes in cognitive functions during DHEA therapy agrees with previous studies of DHEA supplementation in subjects with normal adrenal function.

    “This agrees with previous studies of DHEA supplementation in subjects with normal adrenal function (51,52).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [51] van Niekerk, 2001, Salivary cortisol and DHEA: association with measures of cognition and well-being in normal older men, and effects of three months of DHEA supplementation., Psychoneuroendocrinology source
    • cites [52] Huppert, 2000, Dehydroepiandrosterone (DHEA) supplementation for cognition and well-being, Cochrane Database Syst Rev CD000304 source
56 of 56

  • The authors state this as an assumption.

    Practice effects on the cognitive tests would be equal in both study groups.

    “Analysis assumes that practice effects would be equal in both study groups.”

  • The paper relies on this without support.

    The normative comparison populations are sufficiently comparable to the Addison's disease patients for baseline score comparisons.

    “We recognize that these control subjects were not contemporaneous, making such comparison tentative.”

  • The paper relies on this without support.

    The normal laboratory reference range for DHEAS is appropriate for judging normalization in this study population, despite not being adjusted for age or gender.

    “The bold horizontal lines denote the normal laboratory reference range for DHEAS (not adjusted for age or gender).”

  • The paper relies on this without support.

    The observed improvements in GHQ-30 and SF-36 during DHEA treatment and worsening after washout reflect a true drug effect rather than nonspecific fluctuation.

    “During DHEA treatment, scores for the subscales of GHQ-30 and SF-36 improved and worsened more markedly (albeit nonsignificantly) after washout of DHEA.”
4 of 4

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Two different works are numbered reference 53

    Minor

    The reference list assigns number 53 to both a study of cognition in aging men and a trial in patients with secondary adrenal insufficiency, making citations to that number ambiguous.

  • SF-36 table cites a reading-test manual as its normative source

    Minor

    The table identifies reference 34 as the source of its SF-36 normative data, but reference 34 is a manual for the National Adult Reading Test.

2 of 2

Cited works that were retracted

Works this paper cites that were later retracted, from the retraction notices publishers deposit. Major when the notice came out before this paper was published.

  • Cites a retracted work: 10.1002/14651858.cd000304

    Major

    The cited work was retracted on 2006-04-19 (notice 10.1002/14651858.cd000304.pub2), before this paper was published (2008-02-01). Its authors could have known.

    Cited work 10.1002/14651858.cd000304 · retracted 2006-04-19 · notice 10.1002/14651858.cd000304.pub2 · this paper published 2008-02-01

1 of 1

Cites

1 retracted

Flagged first, then by citations

1 of the 62 references couldn’t be matched to a known paper.

Research works printed but not linked: 3

  1. Baker, 1997, Assessing the potential for finetuning the management of Addison’s disease/steroid replacement therapy 188th Society for Endocrinology (UK) meeting, London, J Endocrinol Abstract Suppl, 155, P2
  2. Kligman, 1986, Sebutape: a device for visualizing and measuring human sebaceous secretion., J Soc Cosmet Chem, 37, 369
  3. Huppert, 2000, Dehydroepiandrosterone (DHEA) supplementation for cognition and well-being, Cochrane Database Syst Rev CD000304

Cited by

Sorted by citations

Related

Authors
Gurnell, E. M., Hunt, P. J., Curran, S. E., Conway, C. L., Pullenayegum, E. M., Huppert, F. A., Compston, J. E., Herbert, J., & Chatterjee, V. K. K.
Affiliations
  • University of Cambridge (GB)
  • Christchurch Hospital (NZ)
  • Departments of Medicine (E.M.G., S.E.C., J.E.C., V.K.K.C.), University of Cambridge, Addenbrooke’s Hospital, Cambridge CB2 0QQ, United Kingdom
ORCID
Venue
The Journal of Clinical Endocrinology & Metabolism
Publisher
The Endocrine Society
Published
2008-02-01
Volume
93
Issue
2
Pages
400-409
ISSN
  • 0021-972X (ISSN-L)
  • 1945-7197
DOI
10.1210/jc.2007-1134
PMC
PMC2729149
OpenAlex
W1976527790
Cited by
189
References
62
Citations by year
2026: 4 · 2025: 5 · 2024: 8 · 2023: 5 · 2022: 13 · 2021: 9 · 2020: 10 · 2019: 3 · 2018: 8 · 2017: 4 · 2016: 9 · 2015: 11 · 2014: 16 · 2013: 9 · 2012: 15
FWCI
11.45
Type
journal article
Language
en
Open access
Locations
  • The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Research Bank (Australian Catholic University) (submittedVersion)
Funders
  • Wellcome Trust
  • National Institute for Health and Care Research
  • National Osteoporosis Society
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
Keywords
DHEA replacement therapy, Addison's disease, DHEA sulfate, bone mineral density, lean body mass, body composition, psychological well-being, fatigue, cognitive function, androgen production, androstenedione, testosterone, glucocorticoid deficiency, mineralocorticoid deficiency
MeSH terms
Addison Disease, Adult, Aged, Body Composition, Cognition, Dehydroepiandrosterone, Double-Blind Method, Female, Humans, Male, Middle Aged, Prospective Studies, Quality of Life, Surveys and Questionnaires, Absorptiometry, Photon, Bone Density, Statistics, Nonparametric, Dehydroepiandrosterone Sulfate, Hormone Replacement Therapy

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-11.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-11.

Cited sources are checked by gpt-6-sol.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review