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At least 19 recordsLinked to original sources

Prevention of postpartum methamphetamine use with micronized progesterone trial (PROMPT): A pilot randomized controlled trial.

OBJECTIVES: Methamphetamine use disorder (MUD) contributes to postpartum morbidity and mortality. Postpartum progesterone decline may destabilize γ-aminobutyric acid pathways, increasing craving and return to use. We assessed the feasibility and safety of micronized progesterone, generating efficacy estimates for preventing postpartum methamphetamine use. METHODS: We conducted a double-blind, randomized, placebo-controlled feasibility trial (November 2021-January 2024) at an academic center with a perinatal addiction clinic. Participants ≤ 12 weeks postpartum with ≥ 4 weeks of abstinence were randomized 1:1, stratified by opioid use disorder (OUD), to micronized progesterone 400mg (200mg twice daily) or identical placebo for 12 weeks. The primary outcome was feasibility, defined as achieving ≥ 80% of planned enrollment. Safety outcomes included adverse events (AEs) and serious adverse events (SAEs). Efficacy outcomes were return to methamphetamine use (weekly self-report and every two weeks urine toxicology) and methamphetamine craving. Analyses included intent-to-treat and per-protocol approaches, with loss to follow-up imputed as return to use. Craving trajectories were modeled using adjusted regression with interaction terms for medication for OUD (MOUD). RESULTS: Of 253 screened individuals, 43 were eligible and 34 were enrolled (91.8%; 18 progesterone, 16 placebo). Retention at 12 weeks was 88%. AE frequency was similar between groups (78% vs 81%; p > 0.05), and no maternal SAEs occurred. Four infant SAEs were deemed unrelated to treatment. Return to methamphetamine use did not differ between groups. Craving trajectories differed by MOUD type. CONCLUSIONS: Micronized progesterone was feasible and safe for postpartum individuals with MUD. MOUD-specific craving effects support evaluation in larger, multicenter efficacy trials. GOV REGISTRATION NUMBER: NCT05128071 NCT REGISTRATION: Prevention of postpartum methamphetamine use with micronized progesterone trial https://clinicaltrials.gov/study/NCT05128071.

Humans↗

Linking women leaving jail to medications for opioid use disorder: Costs to implement pre-release telehealth and peer navigation services.

AIMS: Telehealth and peer navigation are feasible strategies for connecting women in the criminal-legal system with medications for opioid use disorder (MOUD), yet implementation costs are not well understood. This study conducted a microcosting analysis of two interventions for women leaving jail in Kentucky: pre-release, PreTreatment Telehealth with a MOUD provider (TH-Only) and PreTreatment Telehealth combined with peer navigation (TH+PN) through the Justice Community Opioid Innovation Network (JCOIN). METHODS: From the provider perspective, we estimated total start-up costs, total intervention costs, and average cost per participant. Women participating in the clinical trial were randomly assigned to TH-Only (n=299) or TH+PN (n=301). Start-up costs were incurred primarily in 2019 - 2020; intervention costs represent expenses in 2021 - 2023. Cost data were collected from study and agency financial records and interviews with research staff and analyzed using Microsoft Excel (version 16.90.2). RESULTS: Start-up costs were $36,320, comprising planning, meetings, travel, and supplies. The total cost of TH-Only was $60,767, representing 259 telehealth sessions with an average duration of 47 minutes. Total cost of TH+PN was $472,148 based on 270 telehealth sessions (48 minutes), 268 peer navigation (PN) sessions (30 minutes), and 12 weeks of PN support post-release per participant. Average cost per TH-Only participant was $235 and per TH+PN participant was $1,760. CONCLUSIONS: Telehealth may be a relatively low-cost approach for jails lacking on-site MOUD services. Although more costly, combining telehealth with PN may add value by supporting service continuity and facilitating linkage to treatment during the jail to community transition.

Humans↗

Yoga MAT: A factorial randomized study using the Multiphase Optimization Strategy to develop a multicomponent yoga intervention for people with chronic pain taking medications for opioid use disorder.

BACKGROUND: People taking medications for opioid use disorder (MOUD) commonly experience chronic pain. Yoga interventions show promise for decreasing pain-related disability in other populations. More time spent in yoga practice may improve pain-related outcomes. METHODS: The Multiphase Optimization Strategy (MOST) provided the framework for developing an optimized yoga intervention package. In a 2x2x2x2 factorial experiment, we evaluated four candidate intervention components which, when added to a weekly yoga class, might increase yoga engagement. The primary outcome was minutes per week of yoga practice (classes and other yoga practice) over the 12-week intervention period. We sought to determine which combination of intervention components was associated with the most yoga practice for people with chronic pain taking buprenorphine or methadone as MOUD. RESULTS: We enrolled 192 adults. There was a significant main effect for Component "B" (having two private sessions with a yoga teachers; IRR = 1.10, 90%CI 1.02; 1.18), and a synergistic interaction between Components "B" and "D" (D was financial incentives for attending class; IRR = 1.11, 90%CI 1.02; 1.19). This combination of these two components (without other potential components) was associated with the second highest model-predicted mean minutes of yoga per week (157.1min; 90% CI = 120.1-194.0) which was only 4min less than the combination including all four components. CONCLUSIONS: We identified a combination of intervention components as the optimized intervention. A next step will be to test the effect of this optimized intervention on pain and substance use outcomes in a randomized controlled clinical trial.

Humans↗

Perioperative care for patients with opioid exposure and opioid use disorder: screening and treatment strategies.

PURPOSE OF REVIEW: The prevalence of opioid tolerance, dependence, and use disorder is increasing among patients presenting for surgical care, yet perioperative management strategies for these patients remain inconsistent. This review examines the impact of preoperative opioid exposure on surgical outcomes, the scope of untreated opioid use disorder (OUD) among surgical patients, and advances in clinical and systems-level approaches to perioperative care. RECENT FINDINGS: Preoperative opioid exposure independently predicts worse surgical outcomes, including higher opioid consumption, readmissions, complications, and mortality, in a dose-dependent manner. Perioperative opioid exposure predicts persistent opioid use after surgery, with the duration of exposure a stronger predictor of subsequent OUD than daily dose. Data-driven prescribing guidelines and structured opioid tapering reduce overprescribing without compromising pain control. Among surgical patients with diagnosed OUD, approximately two-thirds do not receive medications for opioid use disorder (MOUD), though treatment engagement and maintenance substantially improve outcomes. Evidence now clearly supports perioperative buprenorphine continuation over interruption. SUMMARY: Effective perioperative management of opioid-complex surgical patients requires systematic screening, evidence-based prescribing, MOUD continuation, and institutional infrastructure. The primary barrier is shifting from evidence generation to implementation.

Humans↗

The contribution of moulds and yeasts to the fermentation of 'agbelima' cassava dough.

Agbelima, a fermented cassava meal widely consumed in Ghana, Togo and Benin, is produced by fermenting grated cassava with one of several types of traditional cassava dough inoculum. During fermentation a smooth textured sour dough is produced, the toxicity of cassava is reduced and there is a build up of volatile aroma compounds. Four types of inocula were included in the present investigation. In one type moulds were found to form a dominant part of the microbiota, the species present being Penicillium sclerotiorum, P. citrinum, P. nodulum, Geotrichum candidum and a basidiomycete. All these moulds were found to possess cellulase activity which was responsible for the hydrolysis of cassava tuber cellulose during fermentation leading to a breakdown of the coarse texture of cassava dough. The yeasts Candida krusei, C. tropicalis and Zygosaccharomyces spp. were present in high numbers in the four types of inocula including the moudly inoculum. The yeasts C. tropicalis and some strains of Zygosaccharomyces, all of which possessed cellulase activity, were also found to contribute to the modification of cassava texture during fermentation. All yeasts and moulds exhibited linamarase activity and were therefore capable of breaking down the cyanogenic glucosides present in cassava.

Basidiomycota↗

Specific autoantibodies precede the symptoms of rheumatoid arthritis: a study of serial measurements in blood donors.

OBJECTIVE: Autoantibodies have been demonstrated in single serum samples from healthy subjects up to 10 years before they developed rheumatoid arthritis (RA). However, the time course for the development of antibodies before onset of clinical RA is unknown, nor is it known which antibody, or combinations of antibodies, might be most sensitive or specific for predicting future development of the disease. The present study was undertaken to investigate this. METHODS: Patients with RA who had been blood donors before the onset of disease symptoms were enrolled. Frozen serum samples from each donor were retrieved, together with 2 serum samples from controls matched for age, sex, and date of donation. All samples were tested for IgM rheumatoid factor (IgM-RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies. RESULTS: Seventy-nine patients with RA (62% female; mean age at onset of symptoms 51 years) were included. A median of 13 samples (range 1-51) per patient were available; the earliest samples had been collected a median of 7.5 years (range 0.1-14.5) before the onset of symptoms. Thirty-nine patients (49%) were positive for IgM-RF and/or anti-CCP on at least one occasion before the development of RA symptoms, a median of 4.5 years (range 0.1-13.8) before symptom onset. Of the 2,138 control samples, 1.1% were positive for IgM-RF, and 0.6% were positive for anti-CCP. CONCLUSION: Approximately half of patients with RA have specific serologic abnormalities several years before the onset of symptoms. A finding of an elevated serum level of IgM-RF or anti-CCP in a healthy individual implies a high risk for the development of RA. We conclude that IgM-RF and anti-CCP testing with appropriately high specificity may assist in the early detection of RA in high-risk populations.

Arthritis, Rheumatoid↗

Increased levels of C-reactive protein in serum from blood donors before the onset of rheumatoid arthritis.

OBJECTIVE: We previously reported that approximately half of the patients with rheumatoid arthritis (RA) have specific serologic abnormalities (elevated serum concentrations of IgM rheumatoid factor and/or anti-cyclic citrullinated peptide antibodies) starting several years before the onset of symptoms. In this study, the presence of serologic signs of inflammation in patients with preclinical RA was investigated with serial measurements of C-reactive protein (CRP). METHODS: Seventy-nine patients (61% female; mean age at onset of symptoms 51 years) who had been blood donors before the onset of RA were identified. Frozen serum samples from each donor were retrieved, together with 1 sample from a control donor matched for age, sex, and date of donation. CRP was measured using a highly sensitive latex-enhanced assay. The dates of donation were categorized into 15 1-year periods preceding the onset of RA symptoms. For each period, the median CRP levels in the patient and control groups were compared using the Mann-Whitney U test. The course of CRP concentrations over time in the patient group was estimated with random coefficient analysis. RESULTS: A median of 13 samples (range 1-51) per patient were available; the earliest donation was made a median of 7.5 years (range 0.4-14.5 years) before the onset of symptoms. A total of 1,078 patient samples and 1,071 control samples were tested. For all 1-year periods, the median CRP concentration was increased in the patient group compared with the control group, but this difference was statistically significant only for the periods 0-1 year, 1-2 years, and 4-5 years before the onset of symptoms. The CRP concentration increased significantly over time in patients with preclinical RA; levels were slightly higher in the group of patients who had serologic abnormalities before the onset of symptoms than in those without such serologic abnormalities. CONCLUSION: After observing specific serologic abnormalities 5 years before the onset of RA symptoms, we now report increased levels of CRP in blood donors in whom RA later developed; these increases were most common within the 2 years before the onset of symptoms. The preclinical increase in CRP levels was observed both in donors with and in those without serologic abnormalities.

Arthritis, Rheumatoid↗

Inverse correlation of secreted frizzled-related protein 4 and beta-catenin expression in endometrial stromal sarcomas.

Endometrial stromal sarcomas are rare uterine tumours. Whereas the histology and immunohistochemistry of these tumours are well documented, almost nothing is known about the molecular mechanisms involved in their pathogenesis. To characterize the genes altered in these malignancies, a genome-wide cDNA library was generated by suppression subtractive hybridization and a set of differentially expressed clones was isolated. These were then used to produce custom-spotted cDNA arrays. Genes deregulated in endometrial stromal sarcomas were identified by cDNA array hybridization and were confirmed by quantitative real-time PCR analyses and in situ hybridization. Following cDNA array analysis, more than 300 genes deregulated in endometrial stromal sarcoma were selected and sequenced. Among the most significantly deregulated genes were those of secreted frizzled-related proteins (SFRPs), in particular secreted frizzled-related protein 4 (SFRP4). SFRPs are putative modulators of the Wnt-signalling pathway and play a role in different cellular events including cell proliferation. Compared with normal endometrium, the expression of SFRP4 was decreased in both low-grade endometrial stromal sarcoma (ESS; n = 10) and undifferentiated endometrial sarcoma (UES; n = 4), being lower in the latter more aggressive form. These results were verified on paraffin wax-embedded tissue by quantitative real-time PCR analysis and in situ hybridization. Furthermore, the expression of beta-catenin, an important component of the Wnt-signalling pathway, was regulated in an opposite manner to SFRP4, being particularly increased in undifferentiated sarcomas. The activation of the Wnt-signalling pathway was additionally supported by the immunohistochemical demonstration that beta-catenin was translocated to the nucleus in UES. SFRP4 may therefore be a putative tumour suppressor involved in deregulation of the Wnt pathway and in the pathogenesis of ESS and UES.

Cytoskeletal Proteins↗

Bowen's disease of shaft of penis. Successful treatment with 5-fluorouracil.

Bowen's disease is a precancerous lesion of the superficial layers of the skin. The topical application of 5-fluorouracil has been successfully used in the treatment of such lesions. An ususual case of Bowen's disease of the skin of the penile shaft treated successfully with topical 5-fluorouracil is presented along with a review of different modes of treatment.

Administration, Topical↗

Chromosomal alterations in low-grade endometrial stromal sarcoma and undifferentiated endometrial sarcoma as detected by comparative genomic hybridization.

OBJECTIVE: Endometrial stromal sarcomas (ESS) are very rare neoplasms constituting less than 0.5% of all malignant uterine tumors. The aim of the present study was to characterize the karyotypic abnormalities in these malignant mesenchymal tumors and to find specific chromosomal aberrations with eventual correlation with histologic grades. METHODS: Twelve cases of endometrial stromal sarcomas consisting of nine low-grade ESS and three undifferentiated endometrial sarcomas (UES) were investigated by comparative genomic hybridization (CGH). RESULTS: Ten of the twelve cases (83.3%) displayed chromosomal gains or losses. Deletions occurred more frequently than gains (63.4% versus 36.6%). In low-grade ESS, gains on 1, 6q, 9q, 16p, 19, 20q, 22q and losses on 2, 4q, 6, 7, 11q, 13q, 15q, 16q, 20p, X were detected. CGH with UES exhibited gains on 2q, 4q, 6q, 7p, 9q, 20q and losses on 3q, 10p, 14q. One low-grade ESS and one UES did not reveal any chromosomal aberration. CONCLUSIONS: Chromosomal aberrations in endometrial sarcomas are heterogeneous and do not clearly correlate with the histologic grades. There is no increased accumulation of aberrations from low-grade ESS to UES. Despite the karyotypic variations, chromosomal deletion on 7p was the most common finding (55.6%) in low-grade ESS and may play a role in tumor development and progression.

Chromosome Aberrations↗

Analysis of intracardiac electrograms showing monomorphic ventricular tachycardia in patients with implantable cardioverter-defibrillators.

Ventricular tachycardia (VT) initiation and its relation to various clinical factors was studied by reviewing intracardiac electrograms from patients with implantable cardioverter-defibrillators. Events were divided into (1) sudden onset without preceding ventricular premature complexes (VPCs), (2) extrasystolic onset with VPCs, or (3) paced, depending on the type and morphology of the last 5 beats before initiation of VT. Prematurity index, sinus rate, cycle length, and presence of short-long-short sequence for each episode was noted. A total of 268 episodes of VT among 52 patients were analyzed. Extrasystolic initiation was the most frequent pattern (177; 66%) followed by sudden onset (75; 28%) and paced (16; 6%). Among extrasystolic onset, 99 episodes (56%) were due to multiple VPCs and 149 episodes (84%) had different VPC morphology than the subsequent VT. Among pacing-induced VT, 13 of 16 episodes were due to inappropriate pacing due to undersensing of prior R waves. Sudden-onset episodes were slower (mean cycle length 383+/-97 ms) than extrasystolic (mean cycle length 336+/-88 ms, p = 0.002) and paced (mean cycle length 313+/-85 ms, p = 0.01) onset. Patients in the sudden-onset group had better left ventricular ejection fraction (33+/-15%) than the extrasystolic (29+/-11%, p<0.001) and paced (28+/-14%, p<0.01) groups. Extrasystolic onset with multiple, late coupled VPCs was the most common pattern of VT initiation and was associated with lower ejection fraction. Sudden-onset initiation was more common with better preserved systolic function.

Aged↗

Symptomatic renal angiomyolipoma: report of 8 cases, 2 with spontaneous rupture.

Of the 97 patients with symptomatic renal angiomyolipoma not associated with tuberous sclerosis reported in the literature 13 have presented with a clinical picture of shock because of spontaneous rupture and massive retroperitoneal hemorrhage. Eight new patients with symptomatic renal angiomyolipomas are described, 2 of whom presented with an acute abdomen. Renal angiomyolipomas are essentially benign tumors. Several angiographic and pyelographic characteristics have been described but none appears to be unequivocally diagnostic. Because of the inability to make a precise preoperative diagnosis and the possibility of massive hemorrhage, nephrectomy is indicated in patients with such unilateral solid tumors in the absence of the tuberous sclerosis complex.

Adult↗

Insulin-like growth factor-I deficiency caused by a partial deletion of the IGF-I gene: effects of rhIGF-I therapy.

Insulin-like growth factor-I (IGF-I) is one of the most important regulator of growth. IGF-I deficiency is associated with prenatal and post-natal growth failure and may arise primarily as a result of GH receptor/post-receptor abnormalities or defects in the synthesis and transport of IGF-I. We have previously reported a 17.2-year-old boy with severe growth retardation and undetectable serum levels of IGF-I caused by a partial deletion of the IGF-I gene. This short review will concentrate on results of a recent study which examined the effects of rhIGF-I therapy on the GH-IGF system of this patient. Similar to healthy individuals, this patient had normal IGFBP-3 but elevated ALS levels. IGF-I treatment has improved linear growth and insulin sensitivity in this patient by restoring IGF-I levels and by normalizing circulating GH, IGFBPs and insulin levels.

Adolescent↗

Increased levels of insulin-like growth factor binding protein-2 in sera and tumours from patients with colonic neoplasia with and without acromegaly.

OBJECTIVE: Patients with acromegaly are at increased risk of developing colorectal carcinoma and premalignant tubulovillous adenoma. The pathogenesis of these neoplasms could involve a stimulatory effect of serum growth factors on colonic epithelial cell proliferation. The aim of this study was to evaluate changes in (1) serum IGF-I, IGF-II, IGFBP-3 and IGFBP-2 and (2) changes in local expression of IGFBPs and p53 in colonic epithelium in patients with colonic neoplasia with and without acromegaly. DESIGN: A cross-sectional retrospective study was performed. Fasting serum samples were obtained at the time of colonoscopy for patients with acromegaly and at the time of surgery for patients with colonic neoplasia without acromegaly. MEASUREMENTS: Serum IGF-I, IGF-II, IGFBP-2 and IGFBP-3 were measured using specific immunoassays. Tissue expression of IGFBP-2, IGFBP-3 and p53 status were determined by immunohistochemistry. PATIENTS: Group 1: 26 age- and sex-matched control subjects (range 40-69 years); group 2: 18 patients with acromegaly without colonic neoplasia (range 39-68 years); group 3: 18 patients with acromegaly and colonic neoplasia (range 41-74 years, 11 = adenoma, seven = carcinoma); group 4: 19 patients with colonic neoplasia without endocrine disease (range 43-91 years, four = adenoma, 15 = carcinoma). Immunohistochemical staining of colonic biopsies was performed for IGFBP-2, IGFBP-3 and p53 in groups 3 and 4. RESULTS: Mean serum IGF-I and IGFBP-3 levels were significantly elevated in group 2 (371 +/- 131 microg/l and 6.5 +/- 1.8 mg/l, respectively) and group 3 (379 +/- 174 microg/l and 5.8 +/- 1.6 mg/l, respectively), and significantly reduced in group 4 (103 +/- 36 microg/l and 2.4 +/- 1 mg/l) compared to controls (165 +/- 40 microg/l and 4.7 +/- 1 mg/l; P < 0.0001, P < 0.001, respectively). However, median serum IGFBP-2 levels were significantly elevated in group 3 (P < 0.01) and group 4 (P < 0.0001). Immunostaining for IGFBP-2 showed strong areas of immunoreactivity in the cytoplasm of malignant colonic epithelium compared to benign epithelium. IGFBP-3 immunostaining showed strong areas of immunoreactivity in the cytoplasm and in the nucleus of malignant and benign colonic epithelium compared to the normal epithelium. Nuclear staining for p53 was observed in three patients from group 3 (two carcinoma, one adenoma) and four patients from group 4 (all carcinoma). CONCLUSION: Our results describe changes in IGFBP-2 expression in colonic neoplasia in patients with and without acromegaly, which suggest that this binding protein may regulate local bioavailability of IGF, which in turn could modulate colonic cell proliferation and/or differentiation.

Acromegaly↗

Standard and low-dose IGF-I generation tests and spontaneous growth hormone secretion in children with idiopathic short stature.

OBJECTIVE: Abnormalities in the GH-IGF-I axis, consistent with GH insensitivity (GHI), have been reported in some patients with idiopathic short stature (ISS). The standard IGF-I generation test (IGFGT) has not demonstrated mild GHI in subjects with ISS. The aim of this study was to investigate the GH-IGF-I axis in ISS by performing standard and novel low-dose IGFGTs together with determination of spontaneous GH secretion. PATIENTS AND METHODS: Twenty-one (17 male) prepubertal children with ISS, mean age 8.3 years (4.5-12.2), mean height -3.48 SD (-5.40 to -1.79), mean peak GH to provocation with glucagon/clonidine 32.3 mU/l (14.1-66.0) were studied. Serum IGF-I and IGFBP-3 levels were measured during standard (GH 0.033 mg/kg/day x 4) and low (GH 0.011 mg/kg/day x 4) dose IGFGTs at 0, 12, 36 and 84 h. The low-dose IGFGT was performed in seven naive GH-deficient patients (4 male), mean age 8.5 years (range 4.1-11.1). Determination of spontaneous 24-h GH secretion was performed in the 21 ISS patients. RESULTS: Basal IGF-I and IGFBP-3 standard deviation scores (SDS) in ISS patients were -1.39 (-2.4-1.16) and -0.45 (-1.13-0.38), respectively, IGF-I being lower than IGFBP-3 (P < 0.0001). IGF-I increased in the standard IGFGT at 12 h (P < 0.005), 36 h (P < 0.001) and 84 h (P < 0.001); maximal increment 1.54 (-0.32-3.48), and in the low-dose test at 12 h (P < 0.005), 36 h (P < 0.001) and 84 h (P < 0.005); maximal increment 0.53 (0.08 to -1.23). IGFBP-3 SDS increased in the standard IGFGT at 36 h (P < 0.01) and 84 h (P < 0.001); maximal increment 0.72 (-0.44-1.96), and in the low-dose test at 84 h (P < 0.005); maximal increment 0.33 (-0.08-0.87). Five/19 patients with an IGF-I response > 2 x coefficient of variation (CV) of assay in the standard test failed to respond in the low-dose test, suggestive of mild GHI. In GH-deficient patients, IGF-I increased at each time point (P < 0.05) and IGFBP-3 at 36 h (P < 0.05). Mean GH secretion, expressed in SDS, compared with 66 normal stature controls was: basal GH -0.48 (-0.84-0.93), height of GH peaks compared with zero -0.36 (-1.26-1.51) (both P < 0.05), total GH secretion -0.76 (-1.22-0.42), total GH secretion above baseline -0.67 (-1.21-0.94) (both P < 0.01). CONCLUSIONS: In children with ISS, basal IGF-I and IGFBP-3 SDS values were below the mean, IGF-I showing a greater response in both IGFGTs. In the standard IGFGT, the IGF-I increase at 36 h was equal to that at 84 h. The low-dose IGFGT, in combination with the standard test, may identify patients with mild GHI.

Case-Control Studies↗

Dehydroepiandrosterone (DHEA) replacement reduces growth hormone (GH) dose requirement in female hypopituitary patients on GH replacement.

OBJECTIVE: GH dose requirement is lower in ACTH replete compared with ACTH deficient hypopituitary patients suggesting that adrenal androgens may augment IGF-I generation for a given GH dose. This study aimed to determine the effect of dehydroepiandrosterone (DHEA) administration on GH dose requirements in hypopituitary adults. DESIGN: A double blind placebo controlled trial was conducted adding 50 mg DHEA to the standard replacement of hypopituitary patients, including GH, over an initial 6 months, followed by an open phase study of 6 months DHEA replacement and a final 2 month washout phase after DHEA withdrawal. The dose of GH was adjusted to achieve a constant serum IGF-I. PATIENTS: Thirty female and 21 male hypopituitary patients were enrolled. Data from 26 women and 18 men were analysed after patient withdrawal. MEASUREMENTS: The primary outcome objective was the GH dose required to achieve a stable serum IGF-I. Secondary outcome measures were lipoprotein profiles, insulin, insulin sensitivity, IGFBP-3, waist/hip ratio and indices of bone remodelling. RESULTS: DHEA replacement in female patients lead to a 14.6 +/- 20% reduction in the dose of GH for a constant serum IGF-I (P < 0.05, 95% CI: 1.8, 32.7). This was maintained for 12 months and there was a significant fall in serum IGF-I two months after withdrawal of DHEA. There was no change in the male group. CONCLUSIONS: DHEA replacement may reduce GH dose requirements in female hypopituitary patients.

Adult↗