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[Michael Scally MD]

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The purpose of the present study was to explore the role of personality dimensions and psychopathology on male sexual functioning as well as to examine how these variables discriminate men with and without sexual dysfunction. Regarding psychopathology, men with sexual dysfunction were expected to present higher levels of psychopathological symptoms, particularly anxiety, depressive, interpersonal sensitivity, and obsessive compulsive symptoms, when compared to sexually healthy men. Finally, men with sexual dysfunction report higher levels of neuroticism when compared to sexually healthy men.


Quinta Gomes AL, Nobre P. Personality Traits and Psychopathology on Male Sexual Dysfunction: An Empirical Study. The Journal of Sexual Medicine 2011;8(2):461-9. http://onlinelibrary.wiley.com/doi/10.1111/j.1743-6109.2010.02092.x/abstract

Introduction. The importance of the role played by personality variables in the etiology, development, and maintenance of most emotional disorders is strongly supported by empirical data. However, there is a lack of studies concerning the implication of these variables on sexual difficulties.

Aim. The purpose of the present study was to investigate the role played by personality dimensions and psychopathology on male sexual functioning as well as to clarify the way these variables discriminate men with and without sexual dysfunction.

Methods. A total of 229 men participated in the study (a community sample composed by 205 men and a clinical sample by 24 men with a DSM-IV diagnosis of sexual dysfunction). The community sample was subdivided into a control group (n = 152) and a subclinical group (n = 53), according to the cutoff scores of the International Index of Erectile Dysfunction. After giving informed consent, participants completed a set of clinical instruments. Partial correlations, regression analyses, and multivariate analyses of covariance were conducted.

Main Outcomes Measures. All participants completed a set of measures assessing personality dimensions, psychopathological symptoms, and sexual functioning.

Results. After controlling for psychopathology, men with sexual dysfunction presented significantly higher levels of neuroticism when compared to sexually healthy men. Moreover, regression analysis indicated neuroticism as the best predictor of sexual functioning (? = ?0.24,P < 0.01). Regarding psychopathology, men with sexual problems presented significantly higher levels of depressive symptoms than the controls. Additionally, depressive symptoms were a significant predictor of sexual functioning (? = ?0.41, P < 0.001).

Conclusion. Personality dimensions and psychopathology play an important role on male sexual functioning. The results may have important clinical implications.

 

[Michael Scally MD]

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It has long been known that organisms exhibit a multiplicity of physiological and behavioral rhythms that recur every 24 h. This in turn gave rise to speculation over the existence of a biological clock able to “tell the time” from the ambient day/night cycle. In the 1950s, the term “circadian” was coined to denote these daily cycles, and clock theory was consolidated. Experimental data and mathematical modeling proposed that an oscillator generates a characteristic sine-wave output with a regular cycle length, or period, responsible for repeating 24-h rhythms. Crucially, the clock is endogenous, not reactive. It does not merely passively respond to environmental changes but sustains free-running cycles that persist even when organisms are housed in constant darkness in deprivation of external time cues. Such time cues are called Zeitgebers, and by a process of phase-shifting they may reset or entrain the clock to a new environmental rhythm. The master Zeitgeber is light. The output of the clock had thus been described in sophisticated terms before its source was discovered. In 1972, it was shown that a central master clock resides in the suprachiasmatic nucleus (SCN) of the hypothalamus and receives photic inputs via the retinohypothalamic tract that enable it to synchronize to light.


Prasai MJ, Pernicova I, Grant PJ, Scott EM. An Endocrinologist's Guide to the Clock. J Clin Endocrinol Metab:jc.2010-449. http://jcem.endojournals.org/cgi/content/abstract/jc.2010-2449v1

Context: It has long been recognized that a "biological clock" residing in the suprachiasmatic nucleus controls circadian or daily variations in physiological processes. Old observations are now being revisited after the discovery of the cellular mechanism of timekeeping, the molecular clock, an autoregulatory feedback loop of transcription factors that cycles over a period of approximately 24 h. Its functioning or breakdown impinges upon the physiology and pathophysiology of numerous systems, including the endocrine system and metabolism. Here we provide an introduction to those aspects of the clock most relevant to the endocrinologist.

Evidence Acquisition: Articles were identified by searching PubMed using the search terms "circadian" and "clock" and refining results to include articles relating to endocrinology and metabolism.

Evidence Synthesis: We discuss current understanding of the mechanisms through which hormonal and metabolic axes fall under the influence of the circadian clock. Of particular interest is the complex interaction of genetic and environmental factors in determining health or disease states.

Conclusions: Research into the molecular clock provides a novel window onto endocrine and metabolic disease. These advances present new avenues for diagnostic and therapeutic strategies.

 

[Michael Scally MD]

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Researchers at NIH's Undiagnosed Diseases Program have discovered a new disease that is caused by a "mutation in a gene that prevents calcium from depositing in blood vessels." The discovery originated with a Kentucky woman Louise Benge. In her 20s, Benge now 51, "began experiencing mysterious leg pain." MRIs and X-rays of her blood vessels revealed the "calcium deposits in the artery walls." NIH scientists then scanned portions of Benge's "genome" and discovered that she, and other women who presented with similar symptoms, have a new disease. Scientists named the disease arterial calcification, or ACDC, which they say is due to CD73 deficiency, a "protein that protects arteries against calcification." To date, ACDC has been diagnosed in "exactly nine living patients from three unrelated families, among whom the disorder has been linked to a mutation in the so-called 'NT5E' gene. Five of the patients are siblings from a single family, and all five bore the NT5E mutation."


St. Hilaire C, Ziegler SG, Markello TC, et al. NT5E Mutations and Arterial Calcifications. New England Journal of Medicine 2011;364(5):432-42. MMS: Error

BACKGROUND - Arterial calcifications are associated with increased cardiovascular risk, but the genetic basis of this association is unclear.

METHODS - We performed clinical, radiographic, and genetic studies in three families with symptomatic arterial calcifications. Single-nucleotide-polymorphism analysis, targeted gene sequencing, quantitative polymerase-chain-reaction assays, Western blotting, enzyme measurements, transduction rescue experiments, and in vitro calcification assays were performed.

RESULTS - We identified nine persons with calcifications of the lower-extremity arteries and hand and foot joint capsules: all five siblings in one family, three siblings in another, and one patient in a third family. Serum calcium, phosphate, and vitamin D levels were normal. Affected members of Family 1 shared a single 22.4-Mb region of homozygosity on chromosome 6 and had a homozygous nonsense mutation (c.662C?A, p.S221X) in NT5E, encoding CD73, which converts AMP to adenosine. Affected members of Family 2 had a homozygous missense mutation (c.1073G?A, p.C358Y) in NT5E. The proband of Family 3 was a compound heterozygote for c.662C?A and c.1609dupA (p.V537fsX7). All mutations found in the three families result in nonfunctional CD73. Cultured fibroblasts from affected members of Family 1 showed markedly reduced expression of NT5E messenger RNA, CD73 protein, and enzyme activity, as well as increased alkaline phosphatase levels and accumulated calcium phosphate crystals. Genetic rescue experiments normalized the CD73 and alkaline phosphatase activity in patients' cells, and adenosine treatment reduced the levels of alkaline phosphatase and calcification.

CONCLUSIONS - We identified mutations in NT5E in members of three families with symptomatic arterial and joint calcifications. This gene encodes CD73, which converts AMP to adenosine, supporting a role for this metabolic pathway in inhibiting ectopic tissue calcification.

(Funded by the National Human Genome Research Institute and the National Heart, Lung, and Blood Institute of the National Institutes of Health.)

 

[Michael Scally MD]

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The purposes of this 1-yr, randomized, double-blind, placebo-controlled prospective trial in adults age 65 and over were to evaluate the effect of vitamin D2 or D3, 1,600 IU daily vs. 50,000 IU monthly, on the serum 25(OH)D concentration and serum and urinary calcium concentration, while concurrently investigating the potential importance of measuring trough 25(OH)D values.


Binkley N, Gemar D, Engelke J, et al. Evaluation of Ergocalciferol or Cholecalciferol Dosing, 1,600 IU Daily or 50,000 IU Monthly in Older Adults. J Clin Endocrinol Metab:jc.2010-0015. http://jcem.endojournals.org/cgi/content/abstract/jc.2010-0015v1 (Evaluation of Ergocalciferol or Cholecalciferol Dosing, 1,600 IU Daily or 50,000 IU Monthly in Older Adults -- Binkley et al., 10.1210/jc.2010-0015 -- Journal of Clinical Endocrinology &amp; Metabolism)

Context: Whether ergocalciferol (D2) and cholecalciferol (D3) are equally effective to increase and maintain serum 25-hydroxyvitamin D [25(OH)D] concentration is controversial.

Objective: The aim of the study was to evaluate the effect of daily and once monthly dosing of D2 or D3 on circulating 25(OH)D and serum and urinary calcium.

Design, Setting and Participants: In a university clinical research setting, 64 community dwelling adults age 65+ were randomly assigned to receive daily (1,600 IU) or once-monthly (50,000 IU) D2 or D3 for 1 yr.

Main Outcome Measures: Serum 25(OH)D, serum calcium, and 24-h urinary calcium were measured at months 0, 1, 2, 3, 6, 9, and 12. Serum PTH, bone-specific alkaline phosphatase, and N-telopeptide were measured at months 0, 3, 6, and 12.

Results: Serum 25(OH)D was less than 30 ng/ml in 40% of subjects at baseline; after 12 months of vitamin D dosing, levels in 19% of subjects (n = 12, seven receiving daily doses and five monthly doses) remained low, despite compliance of more than 91%. D2 dosing increased 25(OH)D2 but produced a decline (P < 0.0001) in 25(OH)D3. Substantial between-individual variation in 25(OH)D response was observed for both D2 and D3. The highest 25(OH)D observed was 72.5 ng/ml. Vitamin D administration did not alter serum calcium, PTH, bone-specific alkaline phosphatase, N-telopeptide, or 24-h urine calcium.

Conclusions: Overall, D3 is slightly, but significantly, more effective than D2 to increase serum 25(OH)D. One year of D2 or D3 dosing (1,600 IU daily or 50,000 IU monthly) does not produce toxicity, and 25(OH)D levels of less than 30 ng/ml persist in approximately 20% of individuals. Substantial between-individual response to administered vitamin D2 or D3 is observed.

 

[Michael Scally MD]

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This study used testicular aspiration to determine the IT concentration of the two main T precursors IT ADD and IT DHEA in the human testes of a large group of normal healthy men. In addition, they used gonadotropin suppression with a GnRH antagonist to examine the concentrations of serum and IT ADD and DHEA in a gonadotropin deprived state and after re-stimulation with various low doses of hCG. This is the first study to measure IT ADD and IT DHEA in a large number of healthy, fertile men using testicular aspiration. The results describe the range of IT ADD and IT DHEA concentrations in normal men and demonstrate that the IT concentrations of these hormones are significantly higher than their serum concentrations, yet are only about 25% the concentration of IT T.

IT ADD was only 23% of IT T, implying that ADD is rapidly converted to T in the IT environment. This relative preservation of IT T over IT ADD appears to be particularly true in the setting of gonadotropin suppression where the IT ADD is reduced to 10% of the concentration of IT T. These results suggest that it is unlikely that IT ADD or IT DHEA play a major role in supporting spermatogenesis in a low IT T setting because these compounds are rapidly converted to IT T. In contrast to IT ADD, IT DHEA, although present in a similar concentration to IT ADD at baseline, is less affected by gonadotropin suppression, suggesting that conversion of IT ADD to IT T by 17-beta-hydroxysteroid dehydrogenase is more robust than the conversion of IT DHEA to IT ADD by 3-beta-hydroxysteroid dehydrogenase. Although IT DHEA was reduced dramatically with gonadotropin suppression, serum DHEA was not significantly lower compared with baseline. These data are consistent with the conclusion that a significant fraction of circulating DHEA is adrenal in origin. Lastly, in contrast to serum DHEA, serum ADD decreased by more than 50% after treatment with acyline, implying that the testis is the major source of serum ADD.


Roth MY, Page ST, Lin K, et al. The Effect of Gonadotropin Withdrawal and Stimulation with Human Chorionic Gonadotropin on Intratesticular Androstenedione and DHEA in Normal Men. J Clin Endocrinol Metab:jc.2010-518. http://jcem.endojournals.org/cgi/content/abstract/jc.2010-2518v1

Introduction: Concentrations of intratesticular (IT) testosterone (T) are known to be 100–200 times those of serum T; however, the IT concentrations of T's precursors, their testicular to serum gradients, gonadotropin dependence, and response to stimulation with human chorionic gonadotropin (hCG) have not been studied in detail. We hypothesized that serum and IT androstenedione(ADD) and IT dehydroepiandrosterone (DHEA) would be significantly suppressed by the administration of a GnRH antagonist and increased when stimulated by hCG, without a similar suppression of serum DHEA.

Methods: We suppressed gonadotropins in 23 normal men with the GnRH antagonist acyline and randomly assigned them to one of four doses of hCG, 0, 15, 60, or 125 IU sc every other day for 10 d. Blood and IT fluid for the measurement of serum and IT hormones were obtained at baseline and after 10 d of treatment.

Results: Baseline IT ADD [median (25th, 75th percentile)] was 629 (308, 860) nmol/liter, and IT DHEA was 564 (411, 879) nmol/liter, which were 175 and 27 times higher than their respective serum concentrations. IT ADD and IT DHEA were suppressed by 98 and 82%, respectively, by acyline and significantly increased with hCG administration. Likewise, serum ADD was suppressed by 50%, but serum DHEA was unchanged.

Discussion: ADD and DHEA are highly concentrated within the human testes compared with serum. Serum and IT ADD and IT DHEA are markedly suppressed with GnRH administration and stimulated by hCG, but serum DHEA is not, suggesting that most circulating DHEA is not of testicular origin.

 

[Michael Scally MD]

Prolactin synthesis and secretion by pituitary lactotroph cells is tonically suppressed by hypothalamic dopamine traversing the portal venous system to impinge on lactotroph D2 receptors. Factors inducing prolactin synthesis and secretion include estrogen, thyrotropin-releasing hormone, epidermal growth factor, and dopamine receptor antagonists.

The isolation of human prolactin in 1970 permitted development of RIAs, which enabled identification of hyperprolactinemia as a distinct clinical entity and resulted in distinguishing prolactin-secreting tumors from nonfunctioning adenomas. Testing for hyperprolactinemia is straightforward, owing to the ease of ordering a serum prolactin measurement. Accordingly, an evidence-based, cost-effective approach to management of this relatively common endocrine disorder is required.

The Clinical Guidelines Subcommittee of The Endocrine Society deemed the diagnosis and treatment of hyperprolactinemia a priority area in need of practice guidelines and appointed a Task Force to formulate evidence-based recommendations. The Task Force followed the approach recommended by the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) group, an international group with expertise in development and implementation of evidence-based guidelines.


Melmed S, Casanueva FF, Hoffman AR, et al. Diagnosis and Treatment of Hyperprolactinemia: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2011;96(2):273-88. http://jcem.endojournals.org/cgi/content/abstract/96/2/273 (Diagnosis and Treatment of Hyperprolactinemia: An Endocrine Society Clinical Practice Guideline -- Melmed et al. 96 (2): 273 -- Journal of Clinical Endocrinology &amp; Metabolism)

Objective - The aim was to formulate practice guidelines for the diagnosis and treatment of hyperprolactinemia.

Participants - The Task Force consisted of Endocrine Society-appointed experts, a methodologist, and a medical writer.

Evidence - This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence.

Consensus Process - One group meeting, several conference calls, and e-mail communications enabled consensus. Committees and members of The Endocrine Society, The European Society of Endocrinology, and The Pituitary Society reviewed and commented on preliminary drafts of these guidelines.

Conclusions - Practice guidelines are presented for diagnosis and treatment of patients with elevated prolactin levels. These include evidence-based approaches to assessing the cause of hyperprolactinemia, treating drug-induced hyperprolactinemia, and managing prolactinomas in nonpregnant and pregnant subjects. Indications and side effects of therapeutic agents for treating prolactinomas are also presented.

 

[Michael Scally MD]

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This is written in response to the article, “Cunningham GR, Toma SM. Clinical review: Why is androgen replacement in males controversial? J Clin Endocrinol Metab 2011;96(1):38-52.” [See: https://thinksteroids.com/community/threads/134297405 ]

EDITORIAL: Swerdloff R, Wang C. Testosterone Treatment of Older Men--Why Are Controversies Created? J Clin Endocrinol Metab 2011;96(1):62-5. http://www.ncbi.nlm.nih.gov/pubmed/21209046

 

[Michael Scally MD]

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Stanley TL, Chen CY, Branch KL, Makimura H, Grinspoon SK. Effects of a growth hormone-releasing hormone analog on endogenous GH pulsatility and insulin sensitivity in healthy men. J Clin Endocrinol Metab 2011;96(1):150-8. Effects of a growth hormone-releasing hormone anal... [J Clin Endocrinol Metab. 2011] - PubMed result

CONTEXT AND OBJECTIVE: Strategies to augment pulsatile GH may be beneficial in patients with excess visceral adiposity, in whom GH secretion is reduced. The objective of this study was to determine the effects of a novel GHRH (GHRH(1-44)) analog, tesamorelin, on endogenous GH pulsatility and insulin sensitivity in healthy men.

DESIGN, PARTICIPANTS, AND INTERVENTION: Thirteen males (mean age 45 +/- 3 yr and body mass index 27.3 +/- 1.2 kg/m(2)) received tesamorelin 2 mg sc once daily for 2 wk, with assessment made at baseline, after 2 wk of treatment, and after 2 wk of withdrawal.

OUTCOME MEASURES: The primary end point was change in mean overnight GH as determined by overnight frequent sampling. Secondary end points included insulin-stimulated glucose uptake as measured by euglycemic hyperinsulinemic clamp; IGF-I; and GH secretion parameters, including pulse area, pulse frequency, and basal secretion. RESULTS: Tesamorelin treatment increased mean overnight GH (change +0.5 +/- 0.1 mug/liter, P = 0.004), average log(10) GH peak area (change +0.4 +/- 0.1 log(10) mug/liter, P = 0.001), and basal GH secretion (change +0.008 +/- 0.003 mug/liter . min, P = 0.008). IGF-I increased by 181 +/- 22 mug/liter (P < 0.0001). Neither fasting glucose (P = 0.93) nor insulin-stimulated glucose uptake (P = 0.61) was significantly affected by tesamorelin.

CONCLUSIONS: Once-daily short-term treatment with a GHRH(1-44) analog, tesamorelin, augments basal and pulsatile GH secretion. Moreover, although tesamorelin significantly increases IGF-I, peripheral insulin-stimulated glucose uptake appears to be preserved.


Veldhuis JD, Roelfsema F, Keenan DM, Pincus S. Gender, Age, Body Mass Index, and IGF-I Individually and Jointly Determine Distinct GH Dynamics: Analyses in One Hundred Healthy Adults. J Clin Endocrinol Metab 2011;96(1):115-21. Gender, age, body mass index, and IGF-I individual... [J Clin Endocrinol Metab. 2011] - PubMed result

Background: GH secretion is quantifiable as mean, peak, and nadir GH concentrations; degree of irregularity (approximate entropy); and spikiness (brief staccato-like fluctuations).

Hypothesis: Distinct GH dynamics reflect relatively distinct (combinations of) subject variables, such as gender, age, body mass index (BMI), and IGF-I concentrations.

Location: The study took place at a clinical translational research unit.

Subjects: Subjects included 100 healthy adults ages 20-77 yr (59 women and 41 men), BMI 18-42 kg/m2, and IGF-I 9.2-38 nmol/liter.

Measures: Immunofluorometric GH assay was done on 10-min samples collected for 24 h.

Results: Stepwise forward-selection multivariate regression analysis revealed that mean GH concentrations were simultaneously determined (overall r = 0.36; P < 0.001) by gender (higher in women, P < 0.001), BMI (negatively, P < 0.001), and IGF-I (positively, P < 0.001). Peak GH levels were influenced (r = 0.28) by both BMI (P < 0.001) and IGF-I (P = 0.001). Nadir GH values were jointly affected by gender (higher in women, P = 0.005) and BMI (negatively, P = 0.001). GH approximate entropy was triply defined (r = 0.29) by gender (greater irregularity in women, P < 0.001), age (P = 0.022), and BMI (P = 0.008) and dually (r = 0.25) by gender (P = 0.0001) and BMI (P = 0.017) if sex steroids were included. GH spikiness was determined (r = 0.29) by gender (higher in women, P = 0.0016) and BMI (positively, P = 0.0002).

Conclusion: In healthy adults, combinations of gender, age, BMI, and IGF-I specify distinct GH dynamics, thus requiring balanced representation of these variables in comparative GH studies.


Newman CB, Frisch KA, Rosenzweig B, et al. Moderate doses of hGH (0.64 mg/d) improve lipids but not cardiovascular function in GH-deficient adults with normal baseline cardiac function. J Clin Endocrinol Metab 2011;96(1):122-32. Moderate doses of hGH (0.64 mg/d) improve lipids b... [J Clin Endocrinol Metab. 2011] - PubMed result

CONTEXT: Data regarding effects of lower-dose GH on cardiopulmonary function in GH-deficient (GHD) adults are limited.

OBJECTIVES: The objective was to assess effects of lower-dose GH on exercise capacity and echocardiographic parameters in GHD adults.

DESIGN: The study was a 6-month double-blind, placebo-controlled randomized trial.

SETTING: The study was conducted at the General Clinical Research Center.

PARTICIPANTS: Thirty hypopituitary adults with GHD were studied.

INTERVENTION: Subjects were randomized to recombinant human GH or placebo for 6 months, followed by open-label recombinant human GH for 12 months.

MAIN OUTCOME MEASURES: Primary endpoints were exercise duration, maximal oxygen consumption, and left ventricular ejection fraction. Secondary endpoints were echocardiographic indices of systolic and diastolic function, left ventricular mass, lipids, and body composition.

RESULTS: In the 6-month double-blind phase, mean GH dose was 0.64 mg/d. Mean IGF-I sd score increased from -4.5 to -1.0. Exercise duration, maximal oxygen consumption, left ventricular ejection fraction, and other echocardiographic parameters were normal at baseline and did not change. GH decreased total and low-density lipoprotein cholesterol by 7.5% (P = 0.016) and 14.7% (P = 0.002) (P = 0.04 vs. placebo). Mean lean body mass increased by 2.2 kg (P = 0.004), fat mass decreased by 1.7 kg (P = 0.21), and percent body fat decreased by 2.5% (P = 0.018), although between-group changes were not significant.

CONCLUSIONS: Human GH did not improve exercise performance or echocardiographic parameters or decrease fat mass but significantly decreased total and low-density lipoprotein cholesterol, increased IGF-I, and increased lean body mass. These results indicate that responses to human GH are variable and should be assessed at baseline and during treatment.


Verrua E, Filopanti M, Ronchi CL, et al. GH response to oral glucose tolerance test: a comparison between patients with acromegaly and other pituitary disorders. J Clin Endocrinol Metab 2011;96(1):E83-8. http://www.ncbi.nlm.nih.gov/pubmed/20962023

CONTEXT: The cutoff value of nadir GH after an oral glucose tolerance test (OGTT) used to define disease remission in acromegaly is higher than that observed in healthy subjects. However, it is uncertain whether the impaired GH inhibition might be related to subtle abnormalities of GH secretion or to functional and/or anatomical hypothalamic-pituitary disconnection due to tumor per se or treatments.

OBJECTIVE: The objective of the study was to evaluate the impact of pituitary disorders other than acromegaly on GH response to OGTT.

DESIGN, SUBJECTS, AND METHODS: Thirty-three patients (24 females and nine males, aged 50.1 +/- 12.3 yr, 13 operated and two irradiated) with various hypothalamic-pituitary disorders (HPDs), 45 healthy subjects (controls), and 42 cured acromegalic patients matched for sex, age. and body mass index were investigated. All subjects were studied for IGF-I levels and GH levels before and during the OGTT.

RESULTS: In HPD patients mean postglucose nadir GH levels were 0.11 +/- 0.08 mug/liter without any difference between patients treated with neurosurgery and/or radiotherapy and untreated and between patients with and without pituitary stalk alterations and/or hyperprolactinemia. Mean nadir GH values were similar in HPD patients and controls (0.11 +/- 0.08 vs. 0.08 +/- 0.08 mug/liter, P = 0.23) and lower than those found in cured acromegalic patients (0.18 +/- 0.13 mug/liter, P = 0.02), although there was an overlapping in about half of patients.

CONCLUSIONS: Hypothalamic control of glucose-mediated GH suppression is not perturbed in patients with HPD. These data indicate that defective GH suppression to glucose that is found in acromegaly is unlikely to reflect a lack of integrity of hypothalamic function.

 

[Michael Scally MD]

A change of pace! Keep focused.

 

[GirlyMan]

A change of pace! Keep focused.

Very cool. I especially liked the sirens over Watts. Thanks!

 

[Michael Scally MD]

Regular physical activity leads to remarkable benefits determining a better quality of life related to a higher psychophysical well-being. To reach an ideal weight, to shape the body, to prevent physical pathologies, to fight stress, or to avoid a sedentary life, an exponential increase of people who regularly go to the gymnasium has been observed in the last 2 decades. Nevertheless, active individuals are not free from risks. In fact, it is not uncommon to observe pathological behaviors among gym clients, both men and women, which can endanger health. Similarly to patients with eating disorders (EDs), active individuals usually worry about their body shape, put special attention on their eating patterns, show exercise dependence, and have a perfectionism personality trait. Furthermore, considering themselves too frail and flaccid, male gym clients often spend many hours a day at the gymnasium engaging in strength training programs, undergo hyperproteic diets, assume food integrators and anabolic drugs, and continuously monitor their muscle development and their body mass.

Despite these attitudes that have not yet been defined and coded in psychiatric nosography, this body image disorder has been addressed as bigorexia, reverse anorexia, or muscle dysmorphia (MD). In particular, this disorder shares many characteristics with ED (i.e., persistent and rigid eating patterns for weight control), Obsessive-compulsive disorder (i.e., compulsory body monitoring and exercise dependence) and body dysmorphic disorder (i.e., body image disorder), with the individuals, nonchalant of positive and negative comments, completely concentrating on themselves, fearing of being imperfect, feeling ashamed of showing themselves. Muscle dysmorphia is often masked by the demands of the sport, being elite bodybuilders at higher risk. Furthermore, this disorder is more often observed in men aged 18–35 years, although women are not exempt from this problem. The aim of this study was to identify whether body weight control is a relevant aspect for exercise among gym clients and to evaluate whether their body concerns, eating concerns, and exercise dependence resemble ED or MD.


Segura-Garcia C, Ammendolia A, Procopio L, et al. Body uneasiness, eating disorders, and muscle dysmorphia in individuals who overexercise. J Strength Cond Res 2010;24(11):3098-104. Body uneasiness, eating disorders, and muscle dysm... [J Strength Cond Res. 2010] - PubMed result

This study aimed to investigate exercise dependence, body and eating concerns of active individuals in relation to muscle dysmorphia (MD) and eating disorders (EDs). One hundred and thirty-four active individuals (86 men, 48 women) and 20 ED women were divided into 4 groups according to their sex and the difference between their actual and desired body weight (group A: men who wanted to gain weight; group B: men who wanted to lose weight; group C: women who wanted to lose weight; group D: ED women). The Eating Disorder Inventory 2, Body Uneasiness Test, and Muscle Dysmorphia Inventory questionnaires were administered. All women desired to reduce their body weight, whereas 55% of men wanted to increase their muscle mass, also using anabolic steroids and food integrators. All groups showed a similar use of diuretics and laxatives (range 10-21%). The findings highlighted the presence of minor body image disorders in groups B and C. Conversely, body image was remarkably altered in groups D and A. Recognizing main MD traits, physical trainers should recommend further psychological counseling. Information should also be provided to gym clients regarding the health risks associated with purgative behaviors, use of steroids, and abuse of food supplements.

 

[Michael Scally MD]

Androgen receptor as a therapeutic target

Androgens such as testosterone and dihydrotestosterone mediate their biological effects through the androgen receptor (AR). The testes produce the majority of androgen with some contribution from the adrenal glands. Androgens play a role in a wide range of developmental and physiologic responses and are involved in male sexual differentiation, maintenance of spermatogenesis, and male gonadotropin regulation. The growth and survival of the prostate is dependent on androgen. When androgens increase in males during puberty, there is an increase in growth of the prostate gland, and in adult males when androgens are reduced by castration, there is involution of the prostate and apoptosis of prostate epithelial cells. Thus, the prostate gland is an androgen- dependent organ in which androgens are the predominant mitogenic stimulus. This dependency of the prostate epithelium on androgens provides the underlying rationale for treating advanced prostate cancer with androgen ablation.

The AR has distinct functional domains that include the C terminal LBD, a DNA-binding domain (DBD), and an NTD. The AR DBD has been crystallized, which would allow for rational drug design, but the high degree of homology of this domain with other steroid hormone receptors may predict poor specificity and toxic side effects. The transcriptional activity of most steroid hormone receptors is predominantly through the activation function (AF)-2 region in the LBD, the exception being the AR in which it is the AF-1 region in the NTD that contributes most of the transcriptional activity. AR LBD functions independently of the NTD and can still bind ligand even if the AF-1 region is deleted or mutated; however, no transcriptional activity can be achieved without the AF-1 region in the NTD.


Sadar MD. Small Molecule Inhibitors Targeting the "Achilles' Heel" of Androgen Receptor Activity. Cancer Res. Small Molecule Inhibitors Targeting the "Achilles'... [Cancer Res. 2011] - PubMed result

Androgen ablation therapy remains the gold standard for the treatment of advanced prostate cancer, but unfortunately, it is not curative, and eventually the disease will return as lethal castration-resistant prostate cancer (CRPC). Mounting evidence supports the concept that development of CRPC is causally related to continued transactivation of androgen receptor (AR). All current therapies that target the AR are dependent on the presence of its C-terminal ligand-binding domain (LBD). However, it is the N-terminal domain (NTD) of the AR that is the "Achilles' heel" of AR activity, with AF-1 being essential for AR activity regardless of androgen. Recent efforts to develop drugs to the AR NTD have yielded EPI-001, a small molecule, sintokamide peptides, and decoys to the AR NTD with EPI-001, the best characterized and most promising for clinical development based upon specificity, low toxicity, and cytoreductive antitumor activity. Cancer Res; 71(4); 1-6. (c)2011 AACR.

 

[Michael Scally MD]

[Email me for the full-text article.]

Carlsohn A, Cassel M, Linne K, Mayer F. How much is too much? A case report of nutritional supplement use of a high-performance athlete. Br J Nutr 2011:1-5. How much is too much? A case report of nutritional... [Br J Nutr. 2011] - PubMed result

Although dietary nutrient intake is often adequate, nutritional supplement use is common among elite athletes. However, high-dose supplements or the use of multiple supplements may exceed the recommended daily allowance (RDA) of particular nutrients or even result in a daily intake above tolerable upper limits (UL). The present case report presents nutritional intake data and supplement use of a highly trained male swimmer competing at international level. Habitual energy and micronutrient intake were analysed by 3 d dietary reports. Supplement use and dosage were assessed, and total amount of nutrient supply was calculated. Micronutrient intake was evaluated based on RDA and UL as presented by the European Scientific Committee on Food, and maximum permitted levels in supplements (MPL) are given. The athlete's diet provided adequate micronutrient content well above RDA except for vitamin D. Simultaneous use of ten different supplements was reported, resulting in excess intake above tolerable UL for folate, vitamin E and Zn. Additionally, daily supplement dosage was considerably above MPL for nine micronutrients consumed as artificial products. Risks and possible side effects of exceeding UL by the athlete are discussed. Athletes with high energy intake may be at risk of exceeding UL of particular nutrients if multiple supplements are added. Therefore, dietary counselling of athletes should include assessment of habitual diet and nutritional supplement intake. Educating athletes to balance their diets instead of taking supplements might be prudent to prevent health risks that may occur with long-term excess nutrient intake.

 

[Michael Scally MD]

[Email me for the full-text article.]

The present study explored associations between sex hormones and Ischaemic Heart Disease (IHD) in a large cohort of community-dwelling men aged 70-88 years at baseline, using electronic record linkage. They hypothesised that men with lower testosterone and higher LH levels would be more likely to experience an IHD event (either a hospital admission or death) during a follow-up period of up to 7 years. The results are NOT surprising!


Hyde Z, Norman PE, Flicker L, et al. Elevated Luteinizing Hormone Predicts Ischaemic Heart Disease Events in Older Men. The Health In Men Study. Eur J Endocrinol. Elevated Luteinizing Hormone Predicts Ischaemic He... [Eur J Endocrinol. 2011] - PubMed result

Context - Hypogonadism in men is associated with insulin resistance, elevations in pro-inflammatory cytokines and fibrinogen, and an atherogenic lipid profile. However, it is uncertain whether the age-related decline in testosterone is associated with ischaemic heart disease (IHD) events.

Objective - To determine whether testosterone, and its associated hormones, sex hormone binding globulin (SHBG) and luteinizing hormone (LH), predict IHD events.

Design - Prospective cohort study.

Methods Between 2001-04, 3,637 community-dwelling men aged 70-88 years underwent a clinical assessment of cardiovascular risk factors, and biochemical assessment of testosterone, SHBG, and LH. Free testosterone was estimated. Participants were followed until December 2008 using electronic record linkage to capture IHD events (hospital admission or death).

Results - Mean follow-up was 5.1 years. During this period, 618 men (17.0%; 95% CI 15.8-18.3%) experienced an event, of which 160 were fatal. Men with higher baseline total or free testosterone levels experienced fewer IHD events (HR=0.89; 95% CI 0.82-0.97 and HR=0.86; 95% CI 0.79-0.94 for each one standard deviation increase in total and free testosterone, respectively). These associations were maintained after adjustment for age and waist:hip ratio, but did not persist after adjustment for prevalent IHD or other cardiovascular risk factors. SHBG was not associated with IHD events. In contrast, higher LH levels were associated with reduced event-free survival in both univariate (HR=1.15; 95% CI 1.08-1.22) and adjusted analyses (HR=1.08; 95% CI 1.01-1.15).

Conclusions - Dysregulation of the hypothalamic-pituitary-gonadal axis may be a risk factor for IHD. Further studies of men with either elevated LH or low testosterone are warranted.

 

[Michael Scally MD]

Appearance and performance enhancing drugs (APEDs) are substances used for their effects on one’s outward appearance (e.g., increased muscle, reduced fat) or for improving one’s performance and likelihood for personal achievement (e.g., weightlifting, sports, fighting, sex, job performance).Anabolic-androgenic steroids (AASs) are a family of synthetic hormones derived from natural sex hormones such as testosterone and its derivatives or precursors (e.g., dihydrotestosterone(DHT)) and are included under the umbrella of APEDs. AAS use is often discussed as a subset of APED use and the majority of scientific, clinical, and public attention has focused on this single drug class. AASs have obtained notable public interest due to scandals involving professional and Olympic athletes as well as tragedies involving suicide/homicide, cardiac events, or other severe psychiatric or medical complications.

Currently, there is no formal category of AAS or APED misuse in the Diagnostic and Statistical Manual for Mental Disorders - 4th edition (DSM-IV; American Psychiatric Association, 1994), but AASs are listed as an “other” substance in the SUD subsection. The recognition of potential health risks and the sociopolitical environment perpetuated by cheating athletes has brought about a diagnostic dilemma –developing a set of criteria that captures both the drug- based psychopathology of APED use and the defining attitudinal and behavioral psychopathology of body image disturbance, rigid dieting, and compulsive exercise. Where these diagnostic criteria would place APED use in the larger landscape of psychopathology is yet unclear.

The purpose of this review is to critically examine the existing attempts to define and diagnose pathological APED use and delineate key elements needed for revision to the diagnostic system. To accomplish this goal, they (a) briefly describe the scope and risks associated with APED use, (b) review the most recent proposal to diagnose pathological APED use as a SUD, (c) describe the unique features of APED use that are most clearly associated with risk and pathology, and(d) offer a possible solution and outline for future research.


Hildebrandt T, Lai JK, Langenbucher JW, Schneider M, Yehuda R, Pfaff DW. The diagnostic dilemma of pathological appearance and performance enhancing drug use. Drug Alcohol Depend. The diagnostic dilemma of pathological appearance ... [Drug Alcohol Depend. 2010] - PubMed result

Appearance and performance enhancing drug (APED) use includes the use of a range of pharmacologically distinct substances and concurrent investment in outward appearance or achievement, dietary control, and frequent exercise. A number of existing reviews and conceptual papers have defined pathological forms of APED use within the APED class of anabolic-androgenic steroids (AASs) and using the framework of AAS dependence. We review published data on APED use including human studies of AAS users and identified three defining phenomenological features associated with increased health risk and pathology. These features included (1) polypharmacy or the concurrent use of several pharmacologically distinct substances used to change outward appearance or increase likelihood of personal achievement; (2) significant body image disturbance; (3) rigid practices and preoccupations with diet and exercise. Investigations into the latent structure of APED use suggest these features cluster together in a homogenous group of APED users who have the highest health risk and most psychopathology. These features are discussed in the context of AAS dependence and problems with defining classic tolerance-withdrawal symptoms among APED users. Suggestions for a resolution and outline for future research needed to determine the best system for identifying and diagnosing pathological APED use are discussed.


Of note is the following passage:

3.2.3. Anabolic steroid – induced hypogonadism as a medical confound.

Anabolic steroid-induced hypogonadism (ASIH) is a medical consequence of illicit APED use and is not dependent on drug tolerance or withdrawal. Although the hedonic values and pharmacological properties of AASs are heterogeneous, they share a common ability to cause suppression of natural androgen production, which persists after the cessation of AAS use. This neuroendocrine effect involves suppression of circulating gonadotropic hormones via negative feedback at the level of the hypothalamus. The psychological effects of this hypogonadism are similar to those described for AAS withdrawal and this overlap offers the potential to equate drug withdrawal to ASIH. However, the two phenomena are distinct; drug withdrawal is believed to motivate an individual to seek greater amounts of the drug to relieve discomfort whereas ASIH can be resolved with an individual’s natural return to normal levels of androgen production without the use of exogenous androgens. This latter goal is what most APED users pursue post-cycle. Thus, the distinction between ASIH and AAS withdrawal involves a shifting focus from the classic motivation-reward system to the functioning of the HPG axis. This shift is likely to lead to more appropriate medical treatments for post-cycle psychological symptoms, such as the use of clomiphene citrate to stimulate testosterone production.

 

[Michael Scally MD]

Going through the criminal justice system -- even if the case does not lead to a guilty verdict -- appears to be an independent risk factor for suicide, researchers found.

In a study of Danish national registry data that included more than 27,000 suicides, the odds of committing suicide were greater after any contact with the criminal justice system for both men (OR 2.27, 95% CI 2.19 to 2.35) and women (OR 3.31, 95% CI 3.09 to 3.54), according to Roger Webb, PhD, of the University of Manchester in England, and colleagues.

That association applied even in cases resulting in noncustodial sentences (OR 1.82 for men and 3.03 for women) or not-guilty verdicts (OR 2.37 for men and 3.28 for women), Webb and his co-authors reported online in the Archives of General Psychiatry.

The researchers noted in their paper that the interaction with the justice system either directly caused the increased suicide risk -- or that individuals who had contact with the justice system were predisposed to suicide based on other risk factors.

"In practice, the causal mechanisms may combine elements from both of these explanations," they wrote. "Hence, these people may experience an exacerbation in their already elevated suicide risk on coming into contact with the system for the first time."

The findings indicated a need for more extensive national suicide prevention strategies, they added.

"In particular, improved mental health service provision is needed for all people in contact with the criminal justice system, including those not found guilty and those not given custodial sentences," Webb and colleagues wrote.

Using Danish national registries, the researchers examined data on suicides committed by individuals 15 and older from 1981 to 2006.

The analysis included 27,219 suicides (18,063 by men and 9,156 among women) matched with 524,899 controls by age, sex, and date (the controls were still alive when the matched case committed suicide).

Among the suicide cases, the prevalence of a criminal justice history was higher in men than in women (34.8% versus 12.8%).

However, the strength of the association between a criminal justice history and likelihood of suicide was consistently stronger for women for each specific verdict category.

Adjustment for psychiatric admissions and social risk factors attenuated the association between any contact with the justice system and the odds of suicide -- although it was still statistically significant for both men (OR 1.56) and women (OR 1.92).

Compared with individuals with no criminal history, the likelihood of suicide was elevated for each specific verdict category, especially custodial sentencing.

However, the strongest associations with increased odds of suicide were for sentencing to psychiatric treatment (OR 11.37 for men and 13.15 for women), and in cases where charges were conditionally withdrawn (OR 2.26 for men and 5.00 for women), similar to a suspended sentence in the U.S.

Suicide was particularly likely for individuals with recent or frequent contact with the justice system, or for violent offenders.

"We believe that our findings of rising suicide risk with increasing recency and frequency of contact point toward a strong independent effect of criminal justice history," Webb and his colleagues wrote.

"Whether offending and criminal justice system contact play a causal role in exacerbating risk among already vulnerable individuals requires further examination using more detailed datasets and complex study designs."

The authors acknowledged some limitations of the study, including the possibility of residual confounding from unmeasured factors, the lack of information on current status in the criminal justice system, and the fact that many offenders had multiple verdicts, making it difficult to isolate the risk relative to each specific category.

Other limitations cited included the inability to assess the timing of mental illness in relation to criminal activity, and the possibility that the findings would not apply to larger countries with higher crime rates.

Medical News: Suicide More Likely After Even Minor Crimes - in Psychiatry, General Psychiatry from MedPage Today


Webb RT, Qin P, Stevens H, Mortensen PB, Appleby L, Shaw J. National Study of Suicide in All People With a Criminal Justice History. Arch Gen Psychiatry:archgenpsychiatry.2011.7. Arch Gen Psychiatry -- Abstract: National Study of Suicide in All People With a Criminal Justice History, February 7, 2011, Webb et al. 0 (2011): archgenpsychiatry.2011.7v1

Context Previous research has focused on suicide among male prisoners and ex-prisoners, but little is known about risk in the wider offender population.

Objective To examine suicide risk over 3 decades among all people processed by a national criminal justice system.

Design Nested case-control study.

Setting The whole Danish population.

Participants Interlinked national registers identified all adult suicides during 1981 to 2006 according to any criminal justice system contact since 1980. Exposure was defined according to history of criminal justice adjudication, up to and including each subject's last judicial verdict before suicide (or date of matching for controls). There were 27 219 suicides and 524 899 controls matched on age, sex, and time, ie, controls were alive when their matched case died.

Main Outcome Measure Suicide.

Results More than a third of all male cases had a criminal justice history, but relative risk against the general population was higher for women than men. Independent effects linked with criminal justice exposure persisted with confounder adjustment. Suicide risk was markedly elevated with custodial sentencing, but the strongest effects were with sentencing to psychiatric treatment and with charges conditionally withdrawn. Risk was raised even in people with a criminal justice history but without custodial sentences or guilty verdicts. It was especially high with recent or frequent contact and in people charged with violent offenses.

Conclusions We examined a section of society in which major health and social problems frequently coexist including offending, psychopathology, and suicidal behavior. The need for developing more far-reaching national suicide prevention strategies is indicated. In particular, improved mental health service provision is needed for all people in contact with the criminal justice system, including those not found guilty and those not given custodial sentences. Our findings also suggest that public services should be better coordinated to tackle co-occurring health and social problems more effectively.

 

[Michael Scally MD]

Large M, Sharma S, Compton MT, Slade T, Nielssen O. Cannabis Use and Earlier Onset of Psychosis: A Systematic Meta-analysis. Arch Gen Psychiatry:archgenpsychiatry.2011.5. Arch Gen Psychiatry -- Abstract: Cannabis Use and Earlier Onset of Psychosis: A Systematic Meta-analysis, February 7, 2011, Large et al. 0 (2011): archgenpsychiatry.2011.5v1

Context A number of studies have found that the use of cannabis and other psychoactive substances is associated with an earlier onset of psychotic illness.

Objective To establish the extent to which use of cannabis, alcohol, and other psychoactive substances affects the age at onset of psychosis by meta-analysis.

Data Sources Peer-reviewed publications in English reporting age at onset of psychotic illness in substance-using and non-substance-using groups were located using searches of CINAHL, EMBASE, MEDLINE, PsycINFO, and ISI Web of Science.

Study Selection Studies in English comparing the age at onset of psychosis in cohorts of patients who use substances with age at onset of psychosis in non-substance-using patients. The searches yielded 443 articles, from which 83 studies met the inclusion criteria.

Data Extraction Information on study design, study population, and effect size were extracted independently by 2 of us.

Data Synthesis Meta-analysis found that the age at onset of psychosis for cannabis users was 2.70 years younger (standardized mean difference = -0.414) than for nonusers; for those with broadly defined substance use, the age at onset of psychosis was 2.00 years younger (standardized mean difference = -0.315) than for nonusers. Alcohol use was not associated with a significantly earlier age at onset of psychosis. Differences in the proportion of cannabis users in the substance-using group made a significant contribution to the heterogeneity in the effect sizes between studies, confirming an association between cannabis use and earlier mean age at onset of psychotic illness.

Conclusions The results of meta-analysis provide evidence for a relationship between cannabis use and earlier onset of psychotic illness, and they support the hypothesis that cannabis use plays a causal role in the development of psychosis in some patients. The results suggest the need for renewed warnings about the potentially harmful effects of cannabis.

 

[Michael Scally MD]

Re: Vitamin D Deficiency

Lucas RM, Ponsonby AL, Dear K, et al. Sun exposure and vitamin D are independent risk factors for CNS demyelination. Neurology 2011;76(6):540-8. http://www.neurology.org/content/76/6/540.abstract

Objectives: To examine whether past and recent sun exposure and vitamin D status (serum 25-hydroxyvitamin D [25(OH)D] levels) are associated with risk of first demyelinating events (FDEs) and to evaluate the contribution of these factors to the latitudinal gradient in FDE incidence in Australia.

Methods: This was a multicenter incident case-control study. Cases (n = 216) were aged 18–59 years with a FDE and resident within one of 4 Australian centers (from latitudes 27°S to 43°S), from November 1, 2003, to December 31, 2006. Controls (n = 395) were matched to cases on age, sex, and study region, without CNS demyelination. Exposures measured included self-reported sun exposure by life stage, objective measures of skin phenotype and actinic damage, and vitamin D status.

Results: Higher levels of past, recent, and accumulated leisure-time sun exposure were each associated with reduced risk of FDE, e.g., accumulated leisure-time sun exposure (age 6 years to current), adjusted odds ratio (AOR) = 0.70 (95% confidence interval [CI] 0.53–0.94) for each ultraviolet (UV) dose increment of 1,000 kJ/m2 (range 508–6,397 kJ/m2). Higher actinic skin damage (AOR = 0.39 [95% CI 0.17–0.92], highest grade vs the lowest) and higher serum vitamin D status (AOR = 0.93 [95% CI 0.86–1.00] per 10 nmol/L increase in 25(OH)D) were independently associated with decreased FDE risk. Differences in leisure-time sun exposure, serum 25(OH)D level, and skin type additively accounted for a 32.4% increase in FDE incidence from the low to high latitude regions.

Conclusions: Sun exposure and vitamin D status may have independent roles in the risk of CNS demyelination. Both will need to be evaluated in clinical trials for multiple sclerosis prevention.

 

[Michael Scally MD]

Low cholesterol and statin drugs, a class of cholesterol-lowering drugs, are hypothesized to protect against prostate cancer. Several biologic mechanisms have been proposed by which they might reduce prostate cancer risk, although the mechanism remains unknown. Given the role of testosterone and its metabolite estradiol in prostate carcinogenesis, it has been hypothesized that reductions in circulating testosterone or estradiol via inhibition of cholesterol synthesis, their precursor, might inhibit prostate cancer development and growth.

Most clinical studies that compared hormone concentrations in men before and after statin therapy reported no change in testosterone concentration, although a few studies reported a small, non-significant decrease in testosterone concentration, and one found an increase in testosterone concentration. While these studies do not support an important effect of statins on testosterone synthesis, most were small; only four included more than 25 men and all had fewer than 200 men.

Most of the observational studies reported no difference in testosterone concentration between statin users and nonusers and no association between circulating cholesterol and testosterone concentrations. Three other studies found a positive association between cholesterol and testosterone, and two found an inverse association. Many of the observational studies did not adjust for important potential confounders such as age. Additionally, most of the observational studies only reported correlation coefficients or regression coefficients for a single continuous term in linear regression models. These methods assume a linear association between cholesterol and sex steroid hormone concentrations and might not detect non-linear associations.

This study analyzed data from the Third National Health and Nutrition Examination Survey (NHANES III), a large, nationally representative study of the US population to investigate whether having a lower cholesterol concentration or use of a cholesterol-lowering drug is associated with lower testosterone and estradiol concentrations in men. Because Phase I of NHANES III was conducted when statin drugs were new to the market, too few men were using this class of drug to evaluate separately whether testosterone concentration differed between statin users and nonusers and between users and nonusers of other cholesterol-lowering drugs. Other cholesterol-lowering drugs are less effective at lowering cholesterol than statin drugs.


Mondul AM, Selvin E, Rohrmann S, et al. Association of serum cholesterol and cholesterol-lowering drug use with serum sex steroid hormones in men in NHANES III. Cancer Causes Control 2010;21(10):1575-83. Association of Serum Cholesterol and Cholesterol-Lowering Drug Use with Serum Sex Steroid Hormones in Men in NHANES III

PURPOSE: Low cholesterol levels and statin drugs may protect against prostate cancer with a worse prognosis. Their protective mechanism is unknown, but has been hypothesized to be related to cholesterol's role as a sex steroid hormone precursor. We evaluated whether serum testosterone and estradiol differ by cholesterol or cholesterol-lowering drug use.

MATERIALS AND METHODS: Testosterone and estradiol were measured for 1,457 male participants in the Third National Health and Nutrition Examination Survey. We estimated multivariable-adjusted geometric mean hormone concentration by quintiles of cholesterol concentration and by cholesterol-lowering drugs use.

RESULTS: Across quintiles of cholesterol, testosterone level did not differ (mean, 95% confidence interval (CI); Q1: 5.25, 5.02-5.49, Q5: 5.05, 4.76-5.37 ng/ml; p-trend = 0.32), whereas estradiol levels were lower (Q1: 38.7, 36.9-40.5; Q5: 33.1, 31.8-34.5 pg/ml; p-trend < 0.0001). Neither testosterone (no: 5.12, 4.94-5.30, yes: 4.91, 4.33-5.57 ng/ml, p = 0.57) nor estradiol (no: 35.9, 34.8-37.1; yes: 33.9, 29.4-39.2 pg/ml; p = 0.39) differed by cholesterol-lowering drugs use.

CONCLUSION: Testosterone did not differ by cholesterol or cholesterol-lowering drug use. Estradiol was lower in men with higher cholesterol, but did not differ by cholesterol-lowering drug use. Our results suggest that the lower risk of advanced prostate cancer among statin users is not readily explained by a cholesterol-mediated effect of statins on sex hormone levels.

 

[Michael Scally MD]

According to a new study, over one quarter of the people in the United States who regularly use antidepressants were never actually diagnosed with any of the symptoms the drugs are used to treat. [IMO, these is probably very conservative with the numbers easily around 50%. Antidepressants are handed out like water oils!] The stunning revelation notes that millions of people could be victims of the unfortunate side-effects of these drugs without actually garnering any of the proven health benefits. Essentially, people are getting all of the bad that comes with these medicines, with none of the intended goods.

In order to come to their findings, the researchers utilized the data in the Collaborative Psychiatric Epidemiologic Surveys. That information contains nationally representative samples of over 20,000 American adults that were interviewed between the years of 2001 and 2003. As per the report, nearly one in ten people told interviewers that they took antidepressants in the previous year without having any of the necessary conditions to qualify for the drugs.

The National Institute of Mental Heath cites nearly 15 million Americans as sufferers of major depression, and 40 million more as suffers of various anxiety disorders. In 2009, sales of antidepressants ranked fourth among prescription U.S. drugs with a $9.9 billion intake.


Pagura J, Katz LY, Mojtabai R, Druss BG, Cox B, Sareen J. Antidepressant use in the absence of common mental disorders in the general population. J Clin Psychiatry. Antidepressant use in the absence of common mental... [J Clin Psychiatry. 2011] - PubMed result

OBJECTIVE: To examine the prevalence of antidepressant use in the absence of lifetime mental disorders and to examine sociodemographic correlates, indicators of need (hospitalization, suicidal behavior, perceived need, subthreshold disorders, disability, traumatic events), and antidepressant characteristics of such use.

METHOD: Data came from the Collaborative Psychiatric Epidemiologic Surveys (N = 20,013), a nationally representative cross-sectional sample of community-dwelling adults in the United States. Sociodemographic correlates and indicators of need were examined as predictors of past-year use of antidepressants in the absence of a lifetime DSM-IV diagnosis as assessed by the World Mental Health Composite Diagnostic Interview. The surveys were conducted between 2001 and 2003.

RESULTS: Among individuals who took an antidepressant in the past year (n = 1,441), 396 (26.3%) did not meet criteria for any lifetime diagnosis assessed. Respondents taking antidepressants in the absence of a lifetime diagnosis tended to be older, white, and female. All indicators of need except past-year suicidal behavior were significant predictors (adjusted odds ratios ranging from 2.12 to 14.22, P < .001), with 89% of individuals taking antidepressants in the absence of a lifetime diagnosis endorsing at least 1 indicator of need. Individuals taking antidepressants in the absence of a DSM-IV disorder were more likely to have been prescribed these medications by family physicians or other doctors compared to psychiatrists.

CONCLUSIONS: These results suggest that antidepressant use among individuals without psychiatric diagnoses is common in the United States and is typically motivated by other indicators of need. These findings have important implications for the delivery of medical and psychiatric care and psychiatric nosology.