Recommendations for the registration of drugs intended for use in the treatment of male osteoporosis.
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Animals↗
Biomedical subjects
J M Kaufman
Publications and source records attributed to J M Kaufman.
Limited clinical utility of a self-evaluating risk assessment scale for postmenopausal osteoporosis: lack of predictive value of lifestyle-related factors.
The aim of this study was to assess the efficiency of a self-administered questionnaire to identify subjects with postmenopausal osteoporosis in the setting of first line medical care. A sample of 300 postmenopausal women completed the questionnaire based on 18 items. Bone mineral density at the lumbar spine (BMD-L), total hip (BMD-H), and femoral neck (BMD-N) was used as objective criterion for evaluation. The mean risk score was 8.2 +/- 3.21. BMD was correlated with total risk score: r = -0.32 for BMD-L, -0.36 for BMD-N, and -0.43 for BMD-H. Cutoff points for the risk score (equal likelihood points) according to a T-score threshold of -2.5 were 8.6 for BMD-L and BMD-N and 9.3 for BMD-H; specificity and sensitivity was 62% and 62%, respectively, for BMD-L, 65% and 62% for BMD-N, and 75% and 63% for BMD-H. Stepwise multiple regression analysis of the questionnaire items in relation to BMD showed higher correlation coefficients for models including individual items rather than the overall risk score. Items concerning low weight, older age, and wrist fracture after 50 years of age were always selected as significant determinants of BMD (R = 0.43-0.55). Hormonal replacement therapy was also an important determinant. Lifestyle-related items did not contribute significantly. In conclusion, the diagnostic performance of the 18-item self-administered questionnaire was poorer than a shortened questionnaire omitting lifestyle factors. The clinical utility of a questionnaire should ultimately be evaluated in the specific optic of a chosen global strategy for prevention of osteoporotic fractures.
Absorptiometry, Photon↗
Serum leptin levels in healthy ageing men: are decreased serum testosterone and increased adiposity in elderly men the consequence of leptin deficiency?
OBJECTIVE: The limited information on serum leptin levels in elderly men suggests the occurrence of an age-related decrease, with disruption of the relationship between fat mass and leptin levels. A relative leptin deficiency might thus be implicated in the increase of fat mass and decrease of serum testosterone levels in elderly men. Therefore, we have reevaluated the age-related changes in serum leptin levels and their relationship with adiposity and androgen levels in a large group of community dwelling men. SUBJECTS AND MEASUREMENTS: Serum leptin and androgen levels were measured in 271 healthy, ambulatory elderly men (median age 74 years), as well as in 61 middle-aged (median 43 years) and 40 young (median 25.5 years) controls. Adiposity was assessed by anthropometrical measurements (body mass index; BMI) and by estimation of fat mass by the bio-impedance method. RESULTS: Serum leptin levels, whether or not adjusted for BMI, were found to increase with age, the values tending to level off after the age of 45 years, and were strongly correlated to BMI (r = 0.77) and fat mass assessed by the bio-impedance method (r = 0.81). Linear regression analysis showed a similar slope for the relationship between BMI and serum leptin in the three age groups. Multiple linear regression analysis indicated BMI, age and serum insulin, but not serum testosterone, as significant independent correlates of serum leptin. Serum (free) testosterone levels were negatively correlated with age and serum leptin, also after partialization for BMI: rank correlation coefficients vs. age and serum leptin, respectively, were - 0.20 (P < 0.001) and - 0.16 (P < 0.01) for total testosterone and - 0.60 (P < 0.001) and - 0.23 (P < 0.001) for free testosterone. Dehydroepiandrosterone sulphate (DHEAS) and leptin levels emerged as significant independent correlates in a multiple linear regression model for total serum testosterone; BMI and serum insulin became highly significant correlates in the same model when leptin was omitted from the independent variables. CONCLUSION: Ageing in men is accompanied by a rise of serum leptin levels with a maintained strong association between serum leptin and adiposity in elderly men. Testosterone does not appear to be a major determinant of serum leptin in healthy men, while leptin does emerge as a negative correlate of serum testosterone. Increased fat mass and decreased testosterone production in elderly men cannot be attributed to a relative leptin deficiency.
Adult↗
Estimation of risk based on biological dosimetry for patients treated with radioiodine.
A multicentre study was undertaken to assess the cytogenetic damage to peripheral blood lymphocytes in 31 patients treated with 131I for thyrotoxicosis using the cytokinesis-blocked micronucleus assay. The results were compared to those for eight thyroid carcinoma patients using the same method. For each patient, blood samples were taken immediately before and 1 week after iodine administration. The first blood sample was divided into three fractions and each fraction was subsequently irradiated in vitro with 0, 0.5 and 1 Gy 60Co gamma rays, respectively. After blood culture for 70 h, cells were harvested, stained with Romanowsky-Giemsa and the micronuclei scored in 1000 binucleated cells. For both patient groups, a linear-quadratic dose-response curve was fitted through the data set of the first blood sample by a least squares analysis. The mean increase in micronuclei after 131I therapy (second blood sample) was fitted to this curve and the mean equivalent total body dose (ETBD) calculated. Surprisingly, in view of the large difference in administered activity between thyroid carcinoma patients and thyrotoxicosis patients, the increase in micronuclei after therapy (mean +/- S.D.: 32 +/- 30 and 32 +/- 23, respectively) and the equivalent total body dose (0.34 and 0.32 Gy, respectively) were not significantly different (P > 0.1). The small number of micronuclei induced by 131I therapy (32 +/- 29), compared with external beam radiotherapy for Hodgkin's disease (640 +/- 381) or cervix carcinoma (298 +/- 76) [1], gave a cancer mortality estimate of less than 1%. This also explains why late detrimental effects in patients after 131I treatment have not been reported in the literature.
Adult↗
A critical evaluation of simple methods for the estimation of free testosterone in serum.
The free and nonspecifically bound plasma hormone levels generally reflect the clinical situation more accurately than total plasma hormone levels. Hence, it is important to have reliable indexes of these fractions. The apparent free testosterone (T) concentration obtained by equilibrium dialysis (AFTC) as well as the fraction of serum T not precipitated by 50% ammonium sulfate concentration (non-SHBG-T; SHBG, sex hormone-binding globulin), often referred to as bioavailable T, appear to represent reliable indexes of biologically readily available T, but are not well suited for clinical routine, being too time consuming. Several other parameters have been used without complete validation, however: direct immunoassay of free T with a labeled T analog (aFT), calculation of free T (FT) from total T and immunoassayed SHBG concentrations (iSHBG), and the free androgen index (FAI = the ratio 100T/iSHBG). In the view of substantial discrepancies in the literature concerning the free or bioavailable T levels, we compared AFTC, FT, aFT, FAI, and non-SHBG-T levels in a large number of sera with SHBG capacities varying from low, as in hirsute women, to extremely high as in hyperthyroidism. All these indexes of bioavailable T correlated significantly with the AFTC concentration; AFTC and FT values were almost identical under all conditions studied, except during pregnancy. Values for aFT, however, were only a fraction of either AFTC or FT, the fraction varying as a function of SHBG levels. Also, the FAI/AFTC ratio varied as a function of the SHBG levels, and hence, neither aFT nor FAI is a reliable index of bioavailable T. The FT value, obtained by calculation from T and SHBG as determined by immunoassay, appears to be a rapid, simple, and reliable index ofbioavailable T, comparable to AFTC and suitable for clinical routine, except in pregnancy. During pregnancy, estradiol occupies a substantial part of SHBG-binding sites, so that SHBG as determined by immunoassay overestimates the actual binding capacity, which in pregnancy sera results in calculated FT values that are lower than AFTC. The nonspecifically bound T, calculated from FT, correlated highly significantly with and was almost identical to the values of non-SHBG-T obtained by ammonium sulfate precipitation, testifying to the clinical value of FT calculated from iSHBG.
Adult↗
[How to evaluate osteoporosis: bone densitometry and biochemical tests].
The use of bone densitometry, by dual energy x-ray absorptiometry, allows the identification, at an early stage, of subjects who will, 15-20 years later, present a fracture event. Furthermore, this technique is the most appropriate to confirm the efficacy of preventive or curative therapeutic approaches of osteoporosis. A balanced utilisation of biochemical tests is mandatory to exclude a secondary cause of osteoporosis, to help in the choice of the most appropriate therapeutic strategy and to evaluate the early response of patients to the administered drugs.
Absorptiometry, Photon↗
[Postmenopausal osteoporosis in women].
Postmenopausal osteoporosis is now considered a major public health problem in aging women, due to the burden related to the consequent fractures. Over recent years, several pharmacological approaches were developed for the prevention and treatment of osteoporosis. Besides regular physical exercise and calcium rich diet, calcium supplementation can be suggested to both genders, after seventy years as well as systematic vitamin D supplementation in order to cope with the frequent lack observed in our country. Hormone replacement therapy is the first choice in prevention of postmenopausal osteoporosis. Based on a careful evaluation of the needs of a postmenopausal woman as well as on the risk/benefit ratio derived from her individual risk factors, selective estrogen receptor modulators (raloxifene) or second generation bisphosphonates (alendronate) can be considered as alternative to estrogens. Due to its prohibitive cost, nasal calcitonin should be only considered for very specific cases. In osteoporosis confirmed by bone densitometry or by occurrence of fractures, bisphosphonate (alendronate) reduces subsequent fracture rate. Fluoride salts can, in some cases, improve spinal symptomatic osteoporosis. The use of etidronate, a molecule from the past, should be avoided as much as possible and, at any rate, strictly restricted to its legal indication including women with several vertebral crush fractures and severely decreased bone mineral density.
Aged↗
Testosterone, body composition and aging.
In addition to growth hormone (GH), sex hormones are important determinants of body composition. Aging is accompanied by a decrease in free testosterone levels and, as BMI as well as fat mass increase with age (with a redistribution of body fat), whereas muscle mass decreases, it is tempting to attribute a causal role to the decrease in androgen levels. In our study involving 372 males aged >20-85, age was found to be positively correlated with BMI and fat mass as measured by impedance, and negatively correlated with levels of free testosterone and free insulin-like growth factor-I. Multiple regression analysis revealed that BMI and age were independent determinants of testosterone levels. The latter decreased from 598+/-188 (SD) ng/dl in the young controls to 453+/-161 ng/dl in the elderly group, free testosterone decreasing from 15.35+/-4.10 to 8.38+/-2.51 ng/dl. Fat-free mass decreased by 18.9%. In a subgroup of 57 men aged 70-80 years, testosterone levels correlated negatively with percentage body fat (r=-0.57), abdominal fat (r=-0.56) and plasma insulin levels (r=-0.40). As GH levels and pulsatility also decrease with age and as, moreover, androgens amplify endogenous secretion of GH, it is not easy to determine the relative role of androgen deficiency in the age-associated changes in body composition. Moreover, increase in fat mass (obesity), as occurs in aging males, is in itself associated with low levels of free testosterone and GH which both normalize after weight reduction. The role of testosterone in the age-associated changes in body composition is, however, further suggested by the increase in lean body mass and in mid-arm circumference and the decrease in waist-to-hip ratio observed after testosterone treatment of elderly men with decreased testosterone levels. Also in healthy eugonadal men, testosterone treatment, at least in supraphysiological doses, causes an important increase in fat-free mass (+/-10%) and in muscle size. The changes in muscle volume are associated with an increase in muscle fibre diameter, suggesting that testosterone induces muscle cell hypertrophy. In conclusion, aging in males is accompanied by an important increase in fat mass and a decrease in lean body mass. Several indices of body composition are significantly correlated with plasma testosterone levels before and after correction for BMI and age. It is evident, however, that in addition to testosterone levels, the age-associated somatopause is also a determinant of the changes in body composition.
Adult↗
The Multi Unit Activity analyzer: a Windows based hardware-software system for low cost, high speed analog to digital data conversion, data acquisition and window discrimination.
The Multi Unit Activity analyzer is a hardware-software package for multi-purpose, two-channel data acquisition, with a computer dependent maximal digitizing frequency selectable from 1 to 27,000 s(-1) on both channels simultaneously. The hardware is connected to an IBM compatible PC through one of the serial ports (standard RS 232 interface). Software was developed to view digitized signals and record or read them on or from the harddisk. The program can also perform amplitude based window discrimination on the raw signal, on-line or during replay. The system is used for recording and analyzing multi unit activity from neuronal tissue in our electrophysiology lab but it can be applied in a variety of other settings. Basic programming routines are available that allow customized data acquisition.
Analog-Digital Conversion↗
Immediate salvage procedure for infected penile prosthesis.
PURPOSE: The most devastating complication after the insertion of a penile prosthesis is the development of infection. The standard approach involves removing the entire device, treating intensively with antibiotics and attempting to reinsert a prosthesis at a later date, often with a suboptimal result. Based on the encouraging results of others, during the last 24 months we have used in 2 separate private urological practices a salvage procedure for treatment of infected inflatable penile prostheses. MATERIALS AND METHODS: The protocol used in 7 men with an infected inflatable penile prosthesis included removal of all device components, a 7-step vigorous intraoperative irrigation with 4 different solutions, including vancomycin, immediate reimplantation of a new inflatable penile prosthesis and postoperative outpatient antibiotics with oral ciprofloxacin or intravenous vancomycin or cefazolin. RESULTS: Of the 7 men 6 have experienced excellent results with no infection, minimal morbidity and preservation of penile length. The only failure occurred in a poorly controlled diabetic who required multiple revisions and may have had latent infection for months before it became apparent. CONCLUSIONS: We believe that an immediate salvage procedure for an infected inflatable penile prosthesis is an effective treatment for this difficult complication.
Adult↗
Prevention and treatment of postmenopausal osteoporosis. National Consensus of the "Belgian Bone Club", November 1996.
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Anabolic Agents↗
Declining gonadal function in elderly men.
Ageing in men is accompanied by a progressive decline of gonadal function with, in particular, a decline of total and free testosterone (T) plasma levels resulting in a significant proportion of elderly men over age 60 years presenting with subnormal T levels compared with the levels in young adults. A great interindividual variation in T levels is observed in elderly men, a variability explained in part by physiological variables and differences in life style, while associated acute or chronic diseases may accentuate the age-related decline of T levels. The progressive decrease of plasma T levels has been shown to result from both primary testicular changes and altered neuroendocrine regulation of Leydig cell function. At present, little is known about the clinical relevance of the relative hypoandrogenism of elderly men and there is an urgent need for more longitudinal studies, which may clarify a possible role of decreased T levels in the modulation of the clinical consequences of ageing in men. In view of the lack of relevant controlled clinical trials having careful assessment of the risks and benefits of androgen replacement therapy in elderly men, this treatment should be reserved for selected patients with clinically and biochemically manifest hypogonadism, after careful screening for contraindications.
Aged↗
201Tl scintigraphy does not allow visualization of the thyroid in euthyroid and hyperthyroid patients treated with amiodarone.
A retrospective study was performed to evaluate the usefulness of thallium scintigraphy for visualization of thyroid morphology and function. Moreover, applying absolute quantitation, we wished to confirm the qualitatively reduced 99Tc(m) uptake reported by Wiersinga et al. in both euthyroid and hyperthyroid patients treated with amiodarone. Over a period of 2 years (1995-96), 10 patients (group A; 2 females, 8 males, mean age 68.6 years, range 61-74 years) receiving amiodarone treatment for cardiac arrhythmias for at least 4 months were referred for exploration of either hyperthyroidism (n = 4) or for exclusion of parathyroid adenoma (n = 6). During the same period, 17 patients (group B; 10 females, 7 males, mean age 62 years, range 19-91 years) referred for Tc-Tl subtraction scintigraphy, and in whom follow-up revealed no thyroid or parathyroid pathology, were used as controls. In all patients, thyroid status was assessed by thyroid function tests. 201Tl and 99Tc(m) uptake was calculated as a percentage of the injected dose, taking account of net injected counts and background and isotope decay correction. Original images were scored using a 2-point scoring system (0 = poor, 1 = fair or good). Uptake of both 99Tc(m) and 201Tl was significantly reduced in group A (99Tc[m]: 0.16 +/- 0.21%; 201Tl: 0.30 +/- 0.21%; mean +/- S.D.) compared to group B (99Tc[m]: 1.58 +/- 1.07%; 201Tl: 0.72 +/- 0.37%) (P < 0.005). The mean relative reduction in 99Tc(m) uptake was more pronounced (90% decrease) than that of 201Tl (58% decrease). In group A, the 99Tc(m) and 201Tl image quality was poor in 10 of 10 and 8 of 10 patients respectively. In group B, the 99Tc(m) and 201Tl image quality was poor in 3 of 17 and 4 of 17 patients respectively. The decreased uptake of 201Tl may reflect the inhibitory effect of iodides on adenyl cyclase and its stimulation by TSH. In conclusion, the data presented confirm the qualitatively reduced pertechnetate uptake reported by Wiersinga et al. Furthermore, 201Tl uptake by the thyroid in euthyroid or hyperthyroid patients treated with amiodarone is also reduced. Although quantitatively less pronounced, it does not allow proper visualization of the thyroid.
Adult↗
Recommendations for the registration of agents used in the prevention and treatment of glucocorticoid-induced osteoporosis.
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Animals↗
Oral alendronate induces progressive increases in bone mass of the spine, hip, and total body over 3 years in postmenopausal women with osteoporosis.
To determine the effects of long-term daily oral alendronate sodium (ALN) on bone mass in postmenopausal women with osteoporosis, 19 centers enrolled 516 postmenopausal women aged 45-80 years with spine bone mineral density (BMD) at least 2.5 SD below the mean for young premenopausal women in a 3-year, double-blind, placebo-controlled study. Subjects were randomly allocated to one of four treatment groups: placebo; alendronate, 5 or 10 mg/day for 3 years; or alendronate, 20 mg/day for 2 years followed by 5 mg/day for the 3rd year. All patients received 500 mg/day of supplemental calcium to ensure adequate calcium intake. BMD was measured by dual-energy X-ray absorptiometry at several skeletal sites. Nonsignificant mean decreases in BMD of the spine, femoral neck, and trochanter of 0.6, 0.7, and 0.4%, respectively, occurred in the placebo group at 3 years. Relative to placebo-treated patients, spine BMD increased by 5.4%, 7.4%, and 8.4% in the 5, 10, and 20/5 mg ALN groups, respectively. Increases at the femoral neck were 3.5%, 5.5%, and 4.3%, and those at the trochanter were 5.1%, 7.2%, and 7.2%, respectively. Thus, efficacy of 10 and 20/5 mg ALN was similar, whereas the 5 mg dose was less effective. BMD continued to increase over the entire 3-year study duration in the ALN-treated groups and, compared with the other dosage groups, 10 mg ALN produced the largest gains in BMD during the 3rd year. Changes in biochemical markers of bone turnover and mineral homeostasis confirmed the effect of ALN to decrease bone turnover to a new steady-state level. The safety and tolerability of ALN were comparable with those of placebo. In summary, 10 mg daily oral ALN given for 3 years significantly and progressively increases bone mass and is a generally well-tolerated treatment for osteoporosis in postmenopausal women.
Administration, Oral↗
Whole-body bone scan findings in X-linked hypophosphatemia.
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Adult↗
The N-methyl-D-aspartate-mediated inhibitory control of gonadotropin-releasing hormone release in the hypothalamus of the adult male guinea pig is expressed through opioidergic systems.
Previously, we reported on a dual role of N-methyl-D-aspartate (NMDA) receptor-mediated neurotransmission in the control of GnRH secretion from the medial basal hypothalamus (MBH) of the adult male guinea pig, with a predominantly inhibitory action in the intact animal, which is reversed to a facilitatory role by orchidectomy. In the present study we examined the hypothesis that endogenous opioids are involved in the NMDA receptor-mediated inhibition of GnRH release. A static incubation system was used to test the effects of excitatory amino acid agonists and an excitatory amino acid antagonist, alone or in the presence of either the opiate agonist morphine or the mu-receptor antagonist naloxone, on in vitro GnRH release from the isolated MBH of intact, orchidectomized, or sham-operated guinea pigs. GnRH output from the MBH of intact guinea pigs was markedly suppressed in the presence of the NMDA-specific receptor agonist, N-methyl-D,L-aspartic acid (NMA; 50 mM), whereas NMDA-specific receptor blockade with D,L-amino-5-phosphonovaleric acid (AP-5; 1 mM) resulted in a pronounced facilitation of GnRH release, as did exposure to the non-NMDA-specific receptor agonist, kainic acid (50 mM). Opioidergic blockade with naloxone (1 mM) caused a reversal of the responses to NMA and AP-5, with exposure to these compounds this time resulting in clear facilitation and inhibition, respectively. The stimulatory action of kainic acid, on the other hand, remained unaffected by the presence of naloxone. Morphine inhibited basal GnRH output and also annulled the stimulatory effect of AP-5 on GnRH secretion. The results obtained from MBHs of sham-operated guinea pigs were identical to those seen for the intact animals, with naloxone effectively increasing baseline GnRH release and reversing the inhibitory effect of NMA and stimulatory action of AP-5 on GnRH secretion to a facilitation and inhibition, respectively. On the other hand, NMA caused a marked stimulation, whereas AP-5 produced a significant inhibition of GnRH release from the MBHs of orchidectomized guinea pigs; neither of these effects was altered by the presence of naloxone, which, moreover, had only a marginal effect on basal GnRH output in this group of animals. In conclusion, our present data provide evidence to support the view that the primary inhibitory action of NMDA receptor-mediated neurotransmission on GnRH release in the MBH of the intact male guinea pig is the result of activation of opioidergic systems and that a marked reduction of opioid tone after orchidectomy brings a facilitatory NMDA receptor-mediated system to the fore. On the other hand, non-NMDA-specific kainate receptor-mediated facilitation of GnRH, previously shown to be unaffected by gonadal status, appears to be also independent from opioidergic modulation.
2-Amino-5-phosphonovalerate↗
Influence of some biological indexes on sex hormone-binding globulin and androgen levels in aging or obese males.
Several aspects of the regulation of androgen secretion and plasma levels in males remain controversial. Among these, we cite the problem of whether the age-related decrease in testosterone (T) levels is an intrinsic aging phenomenon or is a sequel of previous illness, the mechanisms underlying the increase in sex hormone-binding globulin (SHBG)-binding capacity in aging men and the supranormal capacity observed immediately after a weight-reducing diet, and the role of insulin in the age-associated decrease in dehydroepiandrosterone (sulfate) [DHEA (DHEAS)] levels. To gain further insight into these issues, we investigated the influence of age, smoking, body mass index (BMI), serum albumin, insulin, GH, and insulin-like growth factor I (IGF-I) levels, respectively, on androgen levels and SHBG-binding capacity in a nonobese healthy population (n = 250) as well as in an obese population (n = 50) before and after weight loss. The influence of GH supplementation on SHBG, DHEAS, DHEA, and insulin levels was studied in a small group of men (n = 8) with isolated GH deficiency. In nonobese healthy men, age was inversely correlated with serum levels of all androgens studied (although total T levels stayed relatively stable until age 55 yr) as well as with albumin, GH, and IGF-I levels and positively correlated with BMI, insulin levels, and SHBG-binding capacity. Nevertheless, SHBG levels were significantly negatively correlated with insulin levels (P < 0.001) as well as with mean 24-h GH and IGF-I levels. Among possible confounding factors affecting (free) T [(FT)] levels in healthy men, smoking appeared to be accompanied by higher (F)T levels than those in nonsmokers. BMI increased with age, but although BMI was negatively correlated with T, FT, and SHBG, respectively, the age-dependent decrease in T levels persisted after correction for BMI. Data not corrected for BMI may, nevertheless, overestimate the age-associated decrease in T levels. The albumin concentration decreased with age, and if FT is the feedback regulator of plasma T levels, albumin concentration might be a codeterminant (although, evidently, less important than SHBG) of T levels and contribute to the age-associated decrease in T levels. In any case, albumin concentration is a codeterminant of DHEAS concentration. T, DHEA, and DHEAS levels were significantly correlated, but this correlation disappeared after controlling for age; hence, there is no evidence for an adrenal-gonadal interaction in men. In obese men, T, FT, and SHBG levels were significantly lower than those in the nonobese men and inversely correlated with BMI; DHEAS levels were slightly lower than those in the nonobese controls, but no significant correlation between DHEA or DHEAS, and insulin levels was observed. After a weight-reducing, protein-rich diet, resulting in a mean weight loss of +/- 15 kg, SHBG-binding capacity increased to normal values notwithstanding the fact that the subjects were still obese and that the insulin levels remained higher than those in the nonobese controls. Considering that after weight loss, GH and IGF-I levels remained lower than those in the nonobese controls, that adult men with isolated GH deficiency presented with higher SHBG levels than normal controls, which decreased to normal levels during GH substitution, and that elderly men have elevated SHBG levels notwithstanding high insulin levels, we suggest that the low GH and/or IGF-I levels might play a role in the elevated SHBG levels observed in both elderly males and obese men after a weight-reducing diet. As weight loss did not influence DHEAS levels notwithstanding an important decrease in insulin levels, our data do not support a role of insulin in the regulation of plasma DHEAS levels.
Adult↗