| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Departments of Endocrinology (S.W.v.T., J.A.R., A.M.P., N.R.B., F.R., J.W.A.S.) and Clinical Chemistry (B.B.), Leiden University Medical Center, 2300 RC Leiden, The Netherlands; and Parnassia Center for Psychiatry (A.v.H.), 2552 HS The Hague, The Netherlands
Address all correspondence and requests for reprints to: Dr. Jan W. A. Smit, Department of Endocrinology, C4-R, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands. E-mail: jwasmit{at}lumc.nl.
 |
Abstract |
|---|
 Top Abstract IntroductionPatients and MethodsResultsDiscussionReferences |
|---|
18%; P < 0.001), but not in male patients. In neither group did DHEA affect IGF-binding protein-3 levels. We conclude that DHEA, superimposed on GH substitution, does not substantially improve quality of life in patients with secondary adrenal insufficiency regardless of gender. In addition, DHEA increases IGF-I levels only in estrogen-depleted females, but not in testosterone-treated males, with secondary adrenal insufficiency. |
Introduction |
|---|
|
TopAbstractIntroductionPatients and MethodsResultsDiscussionReferences |
|---|
Many patients with GHD will also have secondary adrenal insufficiency and, therefore, decreased levels of dehydroepiandrostenedione (DHEA) (9, 10). DHEA has long been considered an inactive precursor of sex steroids. However, deficiency of DHEA due to adrenal insufficiency is associated with impaired quality of life, and treatment with DHEA in subjects with DHEA deficiency significantly improves quality of life (11, 12, 13) (see Table 1
). In addition, beneficial effects of DHEA substitution have been reported on other parameters, such as insulin resistance and bone mineral density (14, 15, 16, 17, 18, 19, 20). These beneficial effects are attributed to the conversion of DHEA into androgens and estrogens. Previously, only one study focused on the effects of DHEA in female patients with secondary adrenal failure, and it showed that quality of life parameters improved (12). Remarkably, in that study quality of life parameters were assessed predominantly by the partners of the patients, rather than by the patients themselves.
|
), we chose to include only postmenopausal women without estrogen replacement therapy. Men were all receiving stable testosterone replacement.
There are indications that DHEA substitution may increase serum levels of IGF-I (Table 1). Because our study was well controlled for GH availability, and DHEA might affect IGF-I independently of GH secretion (21), we also evaluated the effects of DHEA on IGF-I levels in our study.
|
Patients and Methods |
|---|
|
TopAbstractIntroductionPatients and MethodsResultsDiscussionReferences |
|---|
Patients with pituitary diseases and both ACTH and GH deficiencies were recruited from the Outpatients Clinic of the Department of Endocrinology and Metabolism of Leiden University Medical Center (LUMC). Recruitment of patients took place between October 2001 and April 2002. The LUMC is a large tertiary referral center for pituitary disorders. Inclusion criteria were GHD, proven by insufficient stimulation of GH secretion (GH, <7 mU/liter) during insulin-induced hypoglycemia (minimal glucose concentration after insulin administration, 2.2 mmol/liter) with stable replacement therapy with rhGH for at least 3 months before the start of the study, and ACTH deficiency, proven by insufficient cortisol secretion (cortisol, <0.55 µmol/liter) during insulin-induced hypoglycemia, with stable hydrocortisone replacement therapy for at least 3 months before the start of the study. In all subjects, IGF-I levels during treatment with rhGH were in the mean range of sex- and age-matched values. Deficiencies of other hormones of the anterior pituitary as well as antidiuretic hormone (ADH) were allowed, as long as stable substitution with T4 and ADH were realized for at least 3 months before the study. T4 was administered to obtain plasma free T4 values in the upper 50% range of the normal reference values. The dose of T4 was stable for at least 3 months before starting the study. For all male participants, stable testosterone replacement by transdermal testosterone application (50 mg/d) was required (Testoderm, Ferring Pharmaceuticals, Hoofddorp, The Netherlands). For female participants, estrogen replacement therapy was not allowed. Exclusion criteria were liver disease, malignant disease, or other severe system disease as well as the use of drugs that could potentially interfere with the assessment of study parameters, such as psychotropic drugs.
Study protocol
The study was a randomized, placebo-controlled, double-blind, crossover study, with two treatment periods of 16 wk separated by an 8-wk washout period. A block randomization scheme was used (n = 2), with stratification for gender. The randomization schedule was prepared by the Department of Pharmacy. Patients received in random order 50 mg DHEA (Vito Fit Corp., Helmond, The Netherlands) or placebo capsules (containing cellulose). The purity and quantity of DHEA were verified by HPLC analysis at the Department of Pharmacy of LUMC. DHEA or placebo capsules were taken orally each morning. rhGH was injected before bedtime. Compliance for study medication and regular medication was verified at each visit. The treatment allocation was deblinded after all study data were authorized and introduced in a database, which was closed before deblinding.
The medical ethic committee of LUMC approved the study protocol, and all patients gave written informed consent.
Measurements
All visits took place at the outpatient clinic between 0800 and 1000 h.
Quality of life questionnaires
Quality of life investigation was performed with five validated questionnaires at baseline and at the end of each treatment period. The questionnaires are described in detail below. Questionnaires were completed in a quiet room in the morning. The baseline measurements were compared with those of an age- and sex-matched control group; for each participant in the DHEA study, two age- and sex-matched controls were selected from a group of 114 healthy relatives of GH-deficient patients from the Department of Endocrinology and Metabolism of LUMC (Table 4). The socioeconomic status (level of education, profession, marital state, and living area) of controls and participants was comparable.
|
The SF-36 comprises 36 items that record general well-being during the previous 30 d (22). The items are formulated as statements or questions and were scored as numbers. Eight parameters were calculated with a range of 0–100: physical problems, bodily pain, general health, vitality, social functioning, emotional role, and mental health. The first three parameters measure physical health, the last three parameters measure mental health, and the general health and vitality scales are sensitive to both physical and mental health outcomes. Higher scores represent better quality of life (23).
Quality of life assessment of GHD in adults
The quality of life assessment of GHD in adults is developed specifically to assess the impact of GHD and GH replacement in adults (24). The items are formulated as statements and were scored as numbers. Low scores represent better quality of life (24).
Multidimensional Fatigue Inventory-20 (MFI-20)
The MFI-20 records fatigue using 20 statements (25). Five parameters are calculated from the statements (general fatigue, physical fatigue, reduced activity, reduced motivation, and mental fatigue), with a maximum score of 20/parameter. A high score indicates a higher level of fatigue or impairment (26).
Hospital Anxiety and Depression Scale
The HADS consists of 14 items pertaining to anxiety and depression (27). Each item is scored as a number, with a maximal score for each subscale (anxiety or depression) of 21. Higher scores indicate more severe anxiety or depression. A score of 6 or higher on the depression scale or 7 or higher on the anxiety scale is considered abnormal (28, 29).
Eleven Questions on Sexual Function
The Eleven Questions on Sexual Function questionnaire is developed by the National Institute for Social Sexual Research (Rutgers Nisso Group, Utrecht, The Netherlands) with the Department of Sexuology of LUMC. It measures sexual experience during the previous 30 d using 11 questions. For all patients, three parameters were calculated from eight questions: sexual fantasies, libido, and general sexual satisfaction. For patients with partners, three additional parameters were calculated related to physical sexual functioning: problems with erection or lubrication, problems with orgasm, and pain or discomfort during sexual activities. The questions were scored from 1–7; a higher number indicated a higher degree of satisfaction.
Endocrine parameters
All blood samples were taken between 0800 and 1000 h, before regular medication and study drugs were administered, with the exception of cortisol replacement therapy.
Study parameters were serum measurements of IGF-I, IGF-binding protein-3 (IGFBP-3), DHEA, DHEA sulfate (DHEAS), testosterone, estradiol, estrone, SHBG, serum lipids, hemoglobin A1C, and insulin. These measurements were performed at baseline and at the end of each study period. All blood samples were stored immediately at –80 C until measurement. Other study parameters were anthropomorphic measurements (weight, body mass index, and waist/hip ratio).
Safety parameters
A general health questionnaire was administered before the study. Laboratory safety parameters were serum levels of sodium, potassium, alanine aminotransferase, aspartate aminotransferase, 
-glucose transferase, alkaline phosphatase, and creatinine. Weight, heart rate, and blood pressure were recorded at every visit.
Laboratory assays
All analyses for each subject were analyzed in the same run. The total serum IGF-I concentration was measured by immunoluminometric assay (ILMA) after dissociation and blocking of the IGFBPs with IGF-II (Nichols Advantage, Nichols Institute Diagnostics, San Clemente, CA). The detection limit was 0.12 ng/ml (0.9 nmol/liter). The intraassay coefficient of variation (CV) ranged from 4.4–5.2%, and the interassay CV ranged from 5.7–7.4%. The plasma IGFBP-3 concentration was measured by RIA (Nichols Institute Diagnostics). The interassay CV was less than 6.8% at the concentrations measured in the present study. The limit of detection was 0.0625 mg/liter (2.8 nmol/liter). Normal values range from 46–122 nmol/liter in subjects aged 30–50 yr and from 49–112 nmol/liter in subjects aged 50–70 yr. GH concentrations were measured with a sensitive, time-resolved fluoroimmunoassay (Wallac, Turku, Finland) that was specific for 22-kDa GH. The standard was recombinant human GH (Genotropin, KabiVitrium, Uppsala, Sweden), which was calibrated against World Health Organization First International Reference Preparation 80/505. To convert milliunits per liter to micrograms per liter, divide by 2.6. The limit of detection (defined as the value 2 SD above the mean value of the zero standard) was 0.03 mU/liter. The intraassay CV ranged from 1.6–8.4% in the assay range from 0.26–47 mU/liter, with a corresponding interassay CV of 2.0–9.9%. DHEA was measured by RIA after extraction (DHEA-kit, Diagnostics Products Corp., Bad-Nauheim, Germany). The detection limit was 0.012 µg/liter (0.04 nmol/liter), the intraassay CV was 5.2–10.8%, and the interassay CV was 5.9–11.7%. DHEAS was measured by ILMA (Immulite, Diagnostics Products Corp., Los Angeles, CA). The detection limit was 148 µg/liter (0.4 µmol/liter), the intraassay CV was 7.0–9.5%, and the interassay variation was 8–15%. Androstenedione was measured by RIA (Diagnostic Systems Laboratories, Sinsheim, Germany), with a detection limit of 0.02 ng/ml (0.07 nmol/liter), an intraassay CV of 2.7–6.3%, and an interassay CV of 9.3–11.7%. Total testosterone was measured by RIA (Diagnostics Products Corp.), with a detection limit of 0.08 ng/ml (0.2 nmol/liter), and intra- and interassay CVs of 10–19%. Estrone was measured using RIA (Diagnostic Systems Laboratories, Veghel, The Netherlands), with a detection limit of 1.1 pg/ml (40 pmol/liter), an intraassay CV of 4.4–9.4%, and an interassay CV of 5–17%. SHBG was measured by ILMA (Immulite, Diagnostics Products Corp., Bad-Nauheim, Germany), with a detection limit of 0.34 mg/liter (4.0 nmol/liter), an intraassay CV of 4.1–7.7%, and an interassay CV of 4–20%. Estradiol was determined with the Elecsys E170 (Roche, Basel, Switzerland), with a detection limit of 1.36 pg/ml (5 pmol/liter), an intraassay CV of 1.6–2.0%, and an interassay CV of 1.6–2.7%. Hemoglobin A1C was measured using the Bio-Rad Variant method (Bio-Rad Laboratories, Veenendaal, The Netherlands), with a detection limit of 3.6%, an intraassay CV of 1%, and an interassay CV of 1–2%. Serum insulin was measured by immunoradiometric assay (BioSource, Etten-Leur, The Netherlands), with a detection limit of 0.1 mU/liter (0.6 pmol/liter), an intraassay CV of 2.1–4.5%, and an interassay CV of 3.1–4.3%. A Hitachi 747 autoanalyzer (Roche, Mannheim, Germany) was used to quantify serum concentrations of total cholesterol and triglycerides with enzymatic tests (all from Roche). High density lipoprotein cholesterol was measured with a homogenous enzymatic assay (Hitachi 911, Roche). Low density lipoprotein cholesterol concentrations were calculated with the Friedewald formula.
Statistics
The sample size was determined by a formal power analysis based on the rise in IGF-I in the study by Arlt et al. (11). In this study, a pooled SD of changes in IGF-I of 11% was found. It was calculated that with two groups of 15 patients each, a rise in IGF-I of 12% could be detected with 80% power and an 
of 0.05. When no carryover effect was present, a minimal IGF-I rise of even 8% could be detected.
Data were analyzed on a per protocol base. Treatment effects were analyzed using univariate ANOVA. The model associated with the ANOVA had an intercept representing treatment effects. All data were presented separately for men and women. The effects of treatment were also measured by adjusting for carryover and time effects. The tests for carryover and time effects followed the procedures described by Hills and Armitage (30). Carryover and time effects were also tested. If no time or carryover effects were detected, data from both study periods were combined. Categorical data were analyzed with the 
2 test. Data are presented as the mean ± SEM. SPSS for Windows version 11.0 (SPSS, Inc., Chicago, IL) was used for analysis, and a P value of 0.05 was considered significant.
|
Results |
|---|
|
TopAbstractIntroductionPatients and MethodsResultsDiscussionReferences |
|---|
Thirty-four patients were recruited, 17 women and 17 men (Fig. 1). One man was excluded before initiation of treatment, because he developed allergic reactions of the skin to transdermal testosterone replacement therapy. Therefore, 16 men and 17 women started the study. One female patient had progression of a nonendocrine pituitary adenoma, documented by magnetic resonance imaging during the first study period, and decided to withdraw from the protocol. One male patient died at home during the second phase of the study, probably because of an acute myocardial infarction, but the exact cause of death could not be verified because no autopsy was performed. Data from these two patients were not included in the analyses of the data (see Fig. 1). Thirty-one patients (16 women and 15 men) completed the study. The baseline characteristics of these patients are given in Table 2. No side effects, such as acne or greasiness of the skin, were observed in any patient. All women were postmenopausal, and none received estrogen replacement therapy. All men used transdermal testosterone replacement therapy. All patients had GHD that had been treated for a mean period of 5.2 ± 0.6 yr. The causes of pituitary insufficiency are given in Table 2.
|
|
Baseline values compared with values obtained in controls.
Quality of life parameters of patients compared with controls are given in Table 3. Multiple parameters appeared to be worse in patients than in controls despite conventional hormonal replacement therapy. In general, women had more abnormal quality of life parameters than men. Women scored significantly worse than age- and sex-matched controls in seven of 15 tested parameters, whereas men scored worse in three of 15 tested parameters than age- and sex matched controls. In women, physical functioning (SF-36), role limitations due to physical and emotional problems (SF-36), and general and physical fatigue (MFI-20) were worse than in controls. In men, general health perception was worse than in controls (MFI-20). In both men and women, social functioning (SF-36) and activity level (MFI-20) were worse than in controls.
|
. There were no carryover or time effects for any of the study parameters. Remarkably, parameters that were abnormal at baseline compared with controls did not improve significantly upon treatment with DHEA. In women, a significant improvement in the depression score (HADS) was observed. In both women and men, change in health (SF-36) improved significantly. DHEA had no effect on the different dimensions of fatigue or on parameters of sexual functioning. Patients with partners showed no beneficial effect of DHEA on sexual performance, nor did the satisfaction about their sex life change. IGF-I and IGFBP-3 concentrations: effects of DHEA vs. placebo
DHEA treatment significantly increased serum IGF-I levels by approximately 18% in female patients compared with placebo treatment (P < 0.001; Table 5 and Fig. 2). In contrast, in male patients, there was no significant effect of DHEA, compared with placebo, on IGF-I levels (Table 5 and Fig. 2). DHEA did not influence IGFBP-3 levels in female or male patients.
|
|
DHEA treatment increased serum levels of DHEA, DHEAS, estrone, and androstenedione substantially in both men and women (Table 5). DHEA substitution increased estradiol only in women. Interestingly, after DHEA treatment, androstenedione and estrone levels in women reached the baseline levels in men.
Other parameters: effects of DHEA vs. placebo
BMI, waist, and waist/hip ratio were not influenced by DHEA treatment. Fasting serum lipid levels, glucose and insulin levels were not influenced by DHEA (data not shown).
Side effects of DHEA
There were no side effects reported during DHEA or placebo treatment. Some patients experienced an increase in perspiration, but this was not different between the groups. There were no differences observed between DHEA vs. placebo treatment in systolic or diastolic blood pressure, pulse rate, or safety laboratory parameters.
|
Discussion |
|---|
|
TopAbstractIntroductionPatients and MethodsResultsDiscussionReferences |
|---|
At present, four randomized trials have been published on the effect of DHEA substitution on quality of life parameters in patients with primary and/or secondary adrenal insufficiency. These studies are summarized in Table 1. Three studies documented beneficial effects on parameters of quality of life (11, 12, 13). In contrast, the study by Lovas et al. (31) found no significant effect of DHEA on these parameters. However, that study was criticized, because of it was severely underpowered (32). The researchers used a parallel group design, which requires a much larger number of patients, compared with the crossover design of the other three studies. In addition, Lovas et al. (31) used a low dose of DHEA, compared with the other studies and with our study.
With respect to the effects of DHEA in secondary adrenal failure, our study can only be compared with that by Johannsson et al. (13). Although three other studies also contained patients with secondary adrenal failure, their analyses did not include or did not permit separate evaluation of patients with primary vs. secondary adrenal failure (11, 12, 31). In contrast with the beneficial effects of DHEA on quality of life predominantly assessed by the partners of the patients reported by Johannsson et al. (13), we observed only subtle beneficial effects of DHEA on quality of life reported by the patients themselves.
In the present study we confirmed the impaired quality of life in female and male patients with pituitary diseases despite conventional hormonal substitution therapy. DHEA substitution had only limited effects on these parameters. It can be proposed that the study is underpowered to detect significant changes in quality of life. However, the absolute changes in quality of life scores that were abnormal at baseline were hardly influenced by DHEA. The most severely affected parameter, role limitations due to physical problems (SF-36), changed only from 66.2 (baseline) to 68.8 (DHEA), whereas the control value was 93.4. Therefore, our data argue against a major effect of DHEA on quality of life parameters in such patients.
It is presently unclear by which mechanisms DHEA improves quality of life. The mechanism of action of DHEA is attributed to the conversion of DHEA into estrogens and androgens. Although this is also reflected in the changes in plasma concentrations of the respective hormones in the present study, these hormonal changes were not accompanied by apparent major changes in quality of life.
Another mechanism could be that DHEA increases quality of life by increasing IGF-I levels. Remarkably, in the presence of fixed GH availability, DHEA increased IGF-I levels in estrogen-depleted females, but not in testosterone-treated males, with secondary adrenal insufficiency. However, the increase in IGF-I was again not accompanied by an important improvement in quality of life in women.
The study by Arlt et al. (11, 33) indicated that treatment with 50 mg DHEA increased IGF-I slightly only in patients with primary adrenal failure, but not in patients with secondary adrenal failure. These researchers suggested that this differential effect of DHEA on IGF-I in primary vs. secondary adrenal failure may be due to a GH-mediated effect. In the present study we controlled for an effect of GH by including only patients with GHD taking a fixed dose of rhGH during the entire study. Therefore, an effect of DHEA cannot be caused by any changes in GH availability. In accordance, other studies did not find any effect of DHEA substitution in healthy volunteers on GH secretion (15, 21). These observations point to an effect of DHEA, independent of GH, on IGF-I production and/or clearance. Remarkably, this effect of DHEA was only present in estrogen-depleted women. In a study by Span et al. (34), it was demonstrated that estrogen replacement blunts the IGF-I response to rhGH in women. This could explain why in our study, effects of DHEA were found on IGF-I in estrogen-deplete women, whereas this effect was not found in the study by Johannsson et al. (13). We did not find an effect of DHEA on IGF-I in testosterone-substituted men. It is known that testosterone in healthy subjects and GHD patients enhances IGF-I levels (35, 36, 37), which may preclude an additional effect of DHEA. Apparently, the effect of DHEA on IGF-I levels is sex- and/or sex hormone dependent.
The absence of relevant effects of DHEA on quality of life points to a fundamental problem in the concept of conventional hormonal substitution. Hormonal substitution therapy has been extremely successful in the treatment of the major syndromes of endocrine insufficiency, with respect to reduction of morbidity and mortality. However, in general, many patients treated for endocrine insufficiencies still suffer from more or less vague complaints and a decreased quality of life. It is likely that these complaints are at least in part caused by intrinsic imperfections of hormone replacement strategies in mimicking normal hormone secretion (38). Accordingly, the patients with pituitary diseases evaluated in the present study showed decreased quality of life for several parameters, compared with age- and sex-matched controls, despite optimal endocrine replacement therapy according to current standards. The fact that DHEA superimposed on conventional endocrine therapy causes only subtle improvements points to our limited understanding of the mechanisms by which quality of life in these patients is affected.
DHEA did not affect sexual satisfaction in our study, in contrast with a positive effect of DHEA in other studies. In healthy subjects and in patients with primary and secondary adrenal failure, positive effects of DHEA were described on sexual function (11, 13, 15, 16, 31). However, these studies were carried out in younger patients. In our study, the women were postmenopausal, almost half of the patients had no partner, and the men were substituted with testosterone replacement. We cannot exclude the possibility that these factors may have obscured a potential positive effect of DHEA on sexual function.
In conclusion, DHEA substitution, superimposed on replacement with rhGH, has only subtle aspects of quality of life in patients with pituitary diseases with GH and ACTH deficiencies. Remarkably, DHEA increases IGF-I levels only in estrogen-depleted females, not in testosterone-treated males, with secondary adrenal insufficiency.
|
Footnotes |
|---|
Abbreviations: CV, Coefficient of variation; DHEA, dehydroepiandrostenedione; DHEAS, DHEA sulfate; GHD, GH deficiency; HADS, hospital anxiety and depression scale; IGFBP-3, IGF-binding protein-3; ILMA, immunoluminometric assay; MFI-20, Multidimensional Fatigue Inventory-20; rhGH, recombinant human GH; SF-36, Short Form-36.
Received September 16, 2004.
Accepted March 17, 2005.
|
References |
|---|
|
TopAbstractIntroductionPatients and MethodsResultsDiscussionReferences |
|---|
This article has been cited by other articles:
 |
|
 |
|
  A. A. Alkatib, M. Cosma, M. B. Elamin, D. Erickson, B. A. Swiglo, P. J. Erwin, and V. M. Montori A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials of DHEA Treatment Effects on Quality of Life in Women with Adrenal Insufficiency J. Clin. Endocrinol. Metab., October 1, 2009; 94(10): 3676 - 3681. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Binder, S. Weber, M. Ehrismann, N. Zaiser, C. Meisner, M. B. Ranke, L. Maier, S. A. Wudy, M. F. Hartmann, U. Heinrich, et al. Effects of Dehydroepiandrosterone Therapy on Pubic Hair Growth and Psychological Well-Being in Adolescent Girls and Young Women with Central Adrenal Insufficiency: A Double-Blind, Randomized, Placebo-Controlled Phase III Trial J. Clin. Endocrinol. Metab., April 1, 2009; 94(4): 1182 - 1190. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. M. Gurnell, P. J. Hunt, S. E. Curran, C. L. Conway, E. M. Pullenayegum, F. A. Huppert, J. E. Compston, J. Herbert, and V. K. K. Chatterjee Long-Term DHEA Replacement in Primary Adrenal Insufficiency: A Randomized, Controlled Trial J. Clin. Endocrinol. Metab., February 1, 2008; 93(2): 400 - 409. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Hahner, M. Loeffler, M. Fassnacht, D. Weismann, A.-C. Koschker, M. Quinkler, O. Decker, W. Arlt, and B. Allolio Impaired Subjective Health Status in 256 Patients with Adrenal Insufficiency on Standard Therapy Based on Cross-Sectional Analysis J. Clin. Endocrinol. Metab., October 1, 2007; 92(10): 3912 - 3922. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Panjari and S. R. Davis DHEA therapy for women: effect on sexual function and wellbeing Hum. Reprod. Update, May 1, 2007; 13(3): 239 - 248. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Brooke, L. A. Kalingag, F. Miraki-Moud, C. Camacho-Hubner, K. T. Maher, D. M. Walker, J. P. Hinson, and J. P. Monson Dehydroepiandrosterone Improves Psychological Well-Being in Male and Female Hypopituitary Patients on Maintenance Growth Hormone Replacement J. Clin. Endocrinol. Metab., October 1, 2006; 91(10): 3773 - 3779. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. Wierman, R. Basson, S. R. Davis, S. Khosla, K. K. Miller, W. Rosner, and N. Santoro Androgen Therapy in Women: An Endocrine Society Clinical Practice Guideline J. Clin. Endocrinol. Metab., October 1, 2006; 91(10): 3697 - 3710. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. M. Dekkers, A. A. van der Klaauw, A. M. Pereira, N. R. Biermasz, P. J. Honkoop, F. Roelfsema, J. W. A. Smit, and J. A. Romijn Quality of Life Is Decreased after Treatment for Nonfunctioning Pituitary Macroadenoma J. Clin. Endocrinol. Metab., September 1, 2006; 91(9): 3364 - 3369. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. K. Miller, B. M. K. Biller, C. Beauregard, J. G. Lipman, J. Jones, D. Schoenfeld, J. C. Sherman, B. Swearingen, J. Loeffler, and A. Klibanski Effects of Testosterone Replacement in Androgen-Deficient Women with Hypopituitarism: A Randomized, Double-Blind, Placebo-Controlled Study J. Clin. Endocrinol. Metab., May 1, 2006; 91(5): 1683 - 1690. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Basson Sexual Desire and Arousal Disorders in Women N. Engl. J. Med., April 6, 2006; 354(14): 1497 - 1506. [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
