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[Michael Scally MD]

Serum IGF 1 as Possible Marker for Risk and Early Diagnosis of Parkinson Disease

With a prevalence of about 2% in the population older than 60 years, Parkinson disease (PD) is one of the most common neurodegenerative disorders. Parkinson disease affects the whole brain; however, the typical symptoms (bradykinesia, rigidity, and resting tremor) are caused by a progressive loss of dopaminergic neurons in the substantia nigra (SN). In view of a steadily increasing life expectancy, new strategies are warranted to protect neurons from early degeneration. Therefore, much effort is put into determining markers to identify individuals at risk to develop PD before the first clear motor symptoms allow clinical diagnosis.

Insulinlike growth factor 1 (IGF-1) is deeply involved in many processes concerning growth and vitality. It is mainly secreted from the liver after stimulation of the somatotropic axis. Serum IGF-1 levels are reduced with increasing age. Several studies have shown that, in patients with PD, serum IGF-1 levels are higher than those in a healthy control population. In earlier studies, increased serum IGF-1 levels in PD were attributed to dopaminergic medication, which is known to induce IGF-1. However, a recent conceptional study demonstrated that serum IGF-1 levels are also elevated in patients who have never received dopaminergic medication. It may therefore be hypothesized that increased serum IGF-1 in early PD might be related to the disease process.

Based on the results of this previous study, researchers set out to (1) determine whether increased serum IGF-1 level is a potential marker for early PD in an independent cohort, (2) assess the association between serum IGF-1 level and motor function in healthy people, and (3) investigate whether serum IGF-1 level may help in the identification of individuals putatively at increased risk for PD. In addition, IGF-1 binding protein 3 (IGFBP-3) was evaluated.


Godau J, Knauel K, Weber K, et al. Serum Insulinlike Growth Factor 1 as Possible Marker for Risk and Early Diagnosis of Parkinson Disease. Arch Neurol 2011;68(7):925-31. Arch Neurol -- Abstract: Serum Insulinlike Growth Factor 1 as Possible Marker for Risk and Early Diagnosis of Parkinson Disease, July 2011, Godau et al. 68 (7): 925

Background: The level of serum insulinlike growth factor 1 (IGF-1) is increased in idiopathic Parkinson disease (PD).

Objectives: To assess whether the (1) IGF-1 level is increased in patients with PD at the time of diagnosis, (2) increased IGF-1 level is related to impaired motor function in healthy individuals, and (3) detection of increased IGF-1 level will help to identify persons at risk for PD.

Design: Cross-sectional cohort study.

Main Outcome Measures: Serum IGF-1 was measured in 15 patients with newly diagnosed untreated PD and 139 healthy elderly individuals. Participants at risk for PD (n = 11) were defined as having altered motor function according to the Unified Parkinson's Disease Rating Scale, Part III (UPDRS-III), and dopaminergic dysfunction as indicated by sonographically determined substantia nigra hyperechogenicity. Results The IGF-1 level was higher in patients with PD compared with healthy participants (P = .004) and inversely correlated with the UPDRS-III score ({rho} = -0.77). The IGF-1 level was not related to motor function in the healthy group. However, there was no significant difference between the IGF-1 level in the at-risk subgroup vs the PD patients (corrected P = .15), and the IGF-1 level was positively correlated with the UPDRS-III score ({rho} = 0.80).

Conclusion: Serum IGF-1 monitoring may be valuable in the diagnosis of PD and for the identification of individuals with a putatively increased risk for PD.

 

[zkt]

Thats downright interesting! So DA agonist increases IGF-1? Its easier to increase dopaminergic activity than IGF-1 directly. IGF-1 is VERY expensive. Dopamine agonists are cheap.

Serum IGF 1 as Possible Marker for Risk and Early Diagnosis of Parkinson Disease

With a prevalence of about 2% in the population older than 60 years, Parkinson disease (PD) is one of the most common neurodegenerative disorders. Parkinson disease affects the whole brain; however, the typical symptoms (bradykinesia, rigidity, and resting tremor) are caused by a progressive loss of dopaminergic neurons in the substantia nigra (SN). In view of a steadily increasing life expectancy, new strategies are warranted to protect neurons from early degeneration. Therefore, much effort is put into determining markers to identify individuals at risk to develop PD before the first clear motor symptoms allow clinical diagnosis.

Insulinlike growth factor 1 (IGF-1) is deeply involved in many processes concerning growth and vitality. It is mainly secreted from the liver after stimulation of the somatotropic axis. Serum IGF-1 levels are reduced with increasing age. Several studies have shown that, in patients with PD, serum IGF-1 levels are higher than those in a healthy control population. In earlier studies, increased serum IGF-1 levels in PD were attributed to dopaminergic medication, which is known to induce IGF-1. However, a recent conceptional study demonstrated that serum IGF-1 levels are also elevated in patients who have never received dopaminergic medication. It may therefore be hypothesized that increased serum IGF-1 in early PD might be related to the disease process.

Based on the results of this previous study, researchers set out to (1) determine whether increased serum IGF-1 level is a potential marker for early PD in an independent cohort, (2) assess the association between serum IGF-1 level and motor function in healthy people, and (3) investigate whether serum IGF-1 level may help in the identification of individuals putatively at increased risk for PD. In addition, IGF-1 binding protein 3 (IGFBP-3) was evaluated.


Godau J, Knauel K, Weber K, et al. Serum Insulinlike Growth Factor 1 as Possible Marker for Risk and Early Diagnosis of Parkinson Disease. Arch Neurol 2011;68(7):925-31. Arch Neurol -- Abstract: Serum Insulinlike Growth Factor 1 as Possible Marker for Risk and Early Diagnosis of Parkinson Disease, July 2011, Godau et al. 68 (7): 925

Background: The level of serum insulinlike growth factor 1 (IGF-1) is increased in idiopathic Parkinson disease (PD).

Objectives: To assess whether the (1) IGF-1 level is increased in patients with PD at the time of diagnosis, (2) increased IGF-1 level is related to impaired motor function in healthy individuals, and (3) detection of increased IGF-1 level will help to identify persons at risk for PD.

Design: Cross-sectional cohort study.

Main Outcome Measures: Serum IGF-1 was measured in 15 patients with newly diagnosed untreated PD and 139 healthy elderly individuals. Participants at risk for PD (n = 11) were defined as having altered motor function according to the Unified Parkinson's Disease Rating Scale, Part III (UPDRS-III), and dopaminergic dysfunction as indicated by sonographically determined substantia nigra hyperechogenicity. Results The IGF-1 level was higher in patients with PD compared with healthy participants (P = .004) and inversely correlated with the UPDRS-III score ({rho} = -0.77). The IGF-1 level was not related to motor function in the healthy group. However, there was no significant difference between the IGF-1 level in the at-risk subgroup vs the PD patients (corrected P = .15), and the IGF-1 level was positively correlated with the UPDRS-III score ({rho} = 0.80).

Conclusion: Serum IGF-1 monitoring may be valuable in the diagnosis of PD and for the identification of individuals with a putatively increased risk for PD.

 

[Michael Scally MD]

A Novel Case Of A Raised Testosterone And LH

[And, of course, the obvious question is why the supplement FAILED to work despite the elevated T!!!]

Researchers present the case of a 19-year-old male student who attended his General Practitioner with a history of “fluid retention”, lack of libido and erectile dysfunction. There was no further history available at this point. Routine blood tests along with serum thyroid stimulating hormone (TSH), prolactin and testosterone were requested. On the basis of the raised testosterone the laboratory added luteinizing hormone (LH) and follicular stimulating hormone (FSH) to investigate the suspicion of exogenous testosterone administration. Inhibition of the pituitary axis would be expected with use of testosterone supplements. However, an abnormally high LH level was found. This raised suspicion of a possible LH-secreting pituitary lesion (LH-oma), analytical interference (such as heterophilic antibodies) or exogenous sources of LH or human chorionic gonadotrophin (hCG) analogues.

Further investigations included serum hCG, alpha-fetoprotein (AFP), estradiol and sex hormone binding globulin (SHBG). It is recognized that some young men, particularly those who are involved in body building, are aware of the use of exogenous hCG in conditions of lowered libido or to maintain testicular volume while using exogenous testosterone. In this case, the normal hCG level confirmed that the raised LH was not caused by cross reactivity of exogenous hCG (Roche report cross reactivity of b0.1% with hCG, FSH, Thyroid stimulating Hormone and Growth Hormone) and the raised estradiol was assumed to be originating from the aromatization of the high levels of testosterone. This substantiated suspicion of an LH-oma.

Before the patient was referred to the endocrine team, they asked the GP to consult the patient regarding possible causes of the unusual gonadotrophin profile and to enquire about self-medication. The patient subsequently admitted to taking ActivaTe Xtreme™ obtained from an internet source. He explained that he had “researched” this product on the internet as he had low libido and wanted to address this problem. The patient reported that he had stopped taking the compound several weeks prior to the phlebotomy, although this statement could not be confirmed or refuted.


McDonald TJ, Perry MH, Jones AG, Donohoe M, Salzmann MB, O'Connor J. A novel case of a raised testosterone and LH in a young man. Clin Chim Acta. A novel case of a raised testosterone and LH in a ... [Clin Chim Acta. 2011] - PubMed result / ScienceDirect - Clinica Chimica Acta : A novel case of a raised testosterone and LH in a young man

A 19 year old male attended his GP with a history of "fluid retention", lack of libido and erectile dysfunction. He was found to have a high serum testosterone, and a raised luteinising hormone. After further investigations, the patient admitted to taking a supplement called ActivaTe Xtreme, obtained from an internet source, to address his low libido. ActivaTe Xtreme contains active ingredients which increase serum testosterone levels by several independent mechanisms that are not associated with luteinising hormone suppression. Urine analyses for synthetic anabolic steroids were negative, and urinary testosterone, epitestosterone and other androgens were normal. This biochemical pattern is not the same as that seen with anabolic steroids (i.e. raised testosterone, suppressed luteinising hormone and abnormal urine steroid profile). The issue of self medication with performance enhancing compounds needs to be carefully considered in order to avoid expensive and invasive investigations, missing an underlying pathology or misdiagnosing a patient. This case also raises the spectre of yet another "performance enhancing" product that may cause difficulty for those trying to ensure that sport remains on a "hormonally" equal basis.

 

[Michael Scally MD]

Excess energy intake contributes to weight gain. Although energy output can help balance energy intake for weight control over time, weight loss for most sedentary people can be achieved only by reducing energy intake.

Despite long-held assumptions that diet composition might influence the rate and overall capacity for weight loss, randomized controlled trials have recently documented that regardless of shifts in total protein, carbohydrate, or fat intake, the bottom line in achieving successful weight loss is adherence to a diet that is reduced in total energy intake.

Van Horn L. Calories Count. JAMA: The Journal of the American Medical Association 2011;306(3):315-6. Calories Count, July 20, 2011, Van Horn 306 (3): 315 — JAMA


Accuracy of Stated Energy Contents of Restaurant Foods

The prevalence of obesity in the United States increased from 14% of the population in 1976 to 34% in 2008, during which time both self-reported and per-capita energy intake increased. Reducing energy intake by self-monitoring or selecting foods with lower energy contents is widely recommended for the prevention and treatment of obesity. However, the feasibility of reducing energy intake using these approaches depends in part on the availability of accurate information on the energy contents of different foods. The accuracy of the energy contents of foods prepared in restaurants is of particular concern because the frequency of eating out has increased over time in parallel with the national prevalence of obesity. Several studies have observed a positive association between the frequency of eating out and body fatness.

From 2005 through 2006, 49% of US residents ate out at least 3 meals per week and 12% ate out more than 7 meals per week, making foods consumed away from home a major contributor to dietary energy. One small study in 2004 suggested that information on the energy contents of healthy menu choices was largely reliable; however, a recent pilot study reported that a convenience sample of 29 foods with low-energy contents contained a mean of 18% more energy than stated by restaurants.

Therefore, researchers conducted a multisite study purchasing randomly selected food items with high-energy and low-energy contents from quick-serve and sit-down restaurants in 3 states to evaluate the overall accuracy of restaurant-stated energy contents and examine factors associated with the accuracy of stated energy contents of individual food items.

In this regionally representative study of randomly selected food items, there was no significant mean difference between the measured and stated energy contents in all foods considered together, and the stated energy contents averaged only 10 kcal/portion higher than the measured energy contents. However, the stated information of individual foods was variable and 19% of individually tested foods contained energy contents of at least 100 kcal/portion more than the stated energy contents, an amount that has been projected to cause 5 to 15 kg of weight gain per year if consumed daily. Although not typical, 1 side dish in our study contained an excess of 1000 kcal/portion more than the stated energy amount of 450 kcal/portion, which is an amount that is nearly half the total daily energy requirement for most individuals.

Thus, the overall results suggest that stated information on food energy content in restaurants is broadly accurate, a finding that supports increased reporting of nutrition information in restaurants. However, among entrees obtained in sit-down restaurants, those with a lower stated energy content (ie, the most appropriate choices for individuals trying to lose weight or prevent weight gain) systematically contained more energy than stated, whereas foods with higher stated energy contents had lower energy contents than stated. This finding is broadly consistent with the previous preliminary observation of high measured food energy contents relative to stated energy contents in foods with lower stated energy contents and has the potential to impede individual efforts to reduce energy intake to prevent or treat obesity.


Urban LE, McCrory MA, Dallal GE, et al. Accuracy of Stated Energy Contents of Restaurant Foods. JAMA: The Journal of the American Medical Association 2011;306(3):287-93. Accuracy of Stated Energy Contents of Restaurant Foods, July 20, 2011, Urban et al. 306 (3): 287 — JAMA

Context National recommendations for the prevention and treatment of obesity emphasize reducing energy intake. Foods purchased in restaurants provide approximately 35% of the daily energy intake in US individuals but the accuracy of the energy contents listed for these foods is unknown.

Objective To examine the accuracy of stated energy contents of foods purchased in restaurants.

Design and Setting A validated bomb calorimetry technique was used to measure dietary energy in food from 42 restaurants, comprising 269 total food items and 242 unique foods. The restaurants and foods were randomly selected from quick-serve and sit-down restaurants in Massachusetts, Arkansas, and Indiana between January and June 2010.

Main Outcome Measure The difference between restaurant-stated and laboratory-measured energy contents, which were corrected for standard metabolizable energy conversion factors.

Results The absolute stated energy contents were not significantly different from the absolute measured energy contents overall (difference of 10 kcal/portion; 95% confidence interval [CI], 15 to 34 kcal/portion; P=.52); however, the stated energy contents of individual foods were variable relative to the measured energy contents. Of the 269 food items, 50 (19%) contained measured energy contents of at least 100 kcal/portion more than the stated energy contents. Of the 10% of foods with the highest excess energy in the initial sampling, 13 of 17 were available for a second sampling. In the first analysis, these foods contained average measured energy contents of 289 kcal/portion (95% CI, 186 to 392 kcal/portion) more than the stated energy contents; in the second analysis, these foods contained average measured energy contents of 258 kcal/portion (95% CI, 154 to 361 kcal/portion) more than the stated energy contents (P <.001 for each vs 0 kcal/portion difference). In addition, foods with lower stated energy contents contained higher measured energy contents than stated, while foods with higher stated energy contents contained lower measured energy contents (P <.001).

Conclusions Stated energy contents of restaurant foods were accurate overall. However, there was substantial inaccuracy for some individual foods, with understated energy contents for those with lower energy contents.

 

[Michael Scally MD]

Modest Effect Of Isolated Aerobic Exercise On Weight Loss

Although many trials assess aerobic exercise in combination with diet or pharmacotherapy, only a handful of studies examine the isolated effect of exercise (without caloric restriction) in overweight populations. Consequently, there is a need to systematically assess the efficacy of isolated aerobic exercise as a weight loss therapy. If isolated aerobic exercise is shown to be effective, its application will be encouraged in combination therapies. On the other hand, if isolated aerobic exercise is shown to have a minimal impact on weight loss, although this would not rule out synergistic effects of combination therapies, the focus of treatment could shift to other weight loss strategies.

Researchers undertook a systematic review and meta-analysis of randomized controlled trials (RCTs) that evaluated the efficacy of isolated aerobic exercise on weight loss. The specific objective of this review was to determine the effect of isolated aerobic exercise on abdominal obesity, blood pressure, total cholesterol, triglyceride levels, and weight in overweight and obese populations.

The study was designed to determine the efficacy of isolated aerobic exercise programs at reducing weight and cardiovascular risk in overweight and obese populations. They found that aerobic exercise programs of moderate intensity, with durations ranging from 12 weeks to 12 months, resulted in modest weight and waist circumference reduction. This result suggests that a program of isolated aerobic exercise is not an efficacious weight loss therapy for overweight and obese populations. Isolated aerobic exercise does provide modest improvements in systolic blood pressure, diastolic blood pressure, total cholesterol, and triglyceride levels, and it may still work synergistically, in conjunction with diet, as a weight loss therapy.


Thorogood A, Mottillo S, Shimony A, et al. Isolated Aerobic Exercise and Weight Loss: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. The American Journal of Medicine 2011;124(8):747-55. ScienceDirect - The American Journal of Medicine : Isolated Aerobic Exercise and Weight Loss: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background Aerobic exercise is a common nonpharmacological intervention for the management of obesity. However, the efficacy of isolated aerobic exercise at promoting weight loss is unclear. We conducted a systematic review and meta-analysis to evaluate the efficacy of isolated aerobic exercise programs in overweight and obese populations.

Methods We searched for published randomized controlled trial reports of aerobic exercise through January 20, 2010. Trials with an isolated aerobic exercise intervention were included. A random-effect model was used to synthesize the results of each intervention.

Results We identified 14 trials involving 1847 patients. The duration of aerobic exercise programs ranged from 12 weeks to 12 months. Results were pooled for programs with 6-month duration and programs with 12-month duration. Six-month programs were associated with a modest reduction in weight (weighted mean difference [WMD] = -1.6 kg; 95% confidence interval [CI], -1.64 to -1.56) and waist circumference (WMD = -2.12 cm; 95% CI, -2.81 to -1.44). Twelve-month programs also were associated with modest reductions in weight (WMD = -1.7 kg; 95% CI, -2.29 to -1.11) and waist circumference (WMD = -1.95 cm; 95% CI, -3.62 to -0.29).

Conclusion Moderate-intensity aerobic exercise programs of 6-12 months induce a modest reduction in weight and waist circumference in overweight and obese populations. Our results show that isolated aerobic exercise is not an effective weight loss therapy in these patients. Isolated aerobic exercise provides modest benefits to blood pressure and lipid levels and may still be an effective weight loss therapy in conjunction with diets.

 

[Michael Scally MD]

High Prevalence - 33% - of Body Dysmorphic Disorder Symptoms in Patients Seeking Rhinoplasty

Rhinoplasty takes a unique position in the field of facial aesthetic surgery. The morphology of the nose and its central position in the face seem to be crucial not only for facial harmony, but also for normal psychological function. The nasal shape is frequently one of the factors that disturb, consciously or unconsciously, our personality development and body image. The latter is believed to motivate the pursuit of cosmetic surgery. The only diagnostic category in the current list of psychiatric disorders, the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition), that directly addresses body image concerns is body dysmorphic disorder.

Therefore, this well-established psychiatric disorder seems to be of particular relevance in appearance-enhancing medical treatments. According to its current definition, body dysmorphic disorder is defined as an excessive concern with an imagined or slight defect in physical appearance, leading to significant distress and/or impairment in one or more important areas of functioning. Despite the suspected high prevalence, the increased availability of literature and the increased awareness of aesthetic surgeons regarding this disorder, there is still no standardized approach or guideline for proper identification of these patients in a cosmetic surgery setting.

Body dysmorphic disorder is often present in a hidden state. Patients are often too ashamed to seek help from their general practitioner or mental health practitioner. Moreover, they frequently show impaired judgment regarding the psychiatric origin of their problems and often seek cosmetic treatment because they are convinced they warrant medical rather than psychiatric attention.

The wide variety in prevalence rates of body dysmorphic disorder in a cosmetic setting is attributable to difference in interpretation and application of the diagnostic criteria for the disorder. This raises questions regarding the utility of the present criteria for body dysmorphic disorder in a cosmetic surgery setting.

The vast majority of clinical reports and retrospective studies reveal that patients with body dysmorphic disorder show a low degree of satisfaction and a deterioration of disorder symptoms and even become violent toward themselves and their surgeon. Therefore, there is a growing consensus that body dysmorphic disorder should be considered a contraindication for aesthetic surgery.

Any part of the body may be the focus of concern in body dysmorphic disorder, but the most common areas involved are the skin, hair, and nose. Cosmetic rhinoplasty is one of the most requested aesthetic procedures by patients with the disorder. In addition, the clinical profile of patients with symptoms of the disorder seeking rhinoplasty is unclear.

The aims of the present study were to determine the prevalence of body dysmorphic disorder, according to its definition in the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition), and its symptoms in patients seeking rhinoplasty in a tertiary university center using validated questionnaires for the disorder and to determine the clinical profile (demographic characteristics, nasal deformity, and quality of life) of patients according to the severity of their symptoms.

The central role of the nose in the face and the psychological impact of any deformity make the nose one of most prevalent areas of concern in patients with body dysmorphic disorder. In addition, Veale et al. showed in their study of 25 patients with the disorder who underwent aesthetic surgery that rhinoplasty had the worst outcome after cosmetic surgery. Despite the estimated high prevalence and potential impact of the disorder on the outcome after rhinoplasty, large-scale studies investigating its prevalence and symptoms in this particular population are missing. Moreover, the clinical profile of patients with symptoms of the disorder seeking rhinoplasty is unclear.


Picavet VA, Prokopakis EP, Gabriels L, Jorissen M, Hellings PW. High Prevalence of Body Dysmorphic Disorder Symptoms in Patients Seeking Rhinoplasty. Plastic and Reconstructive Surgery;128(2):509-17. High Prevalence of Body Dysmorphic Disorder Symptoms in Pati... : Plastic and Reconstructive Surgery

Background: Nasal aesthetic deformities may be associated with significant body image dissatisfaction. The only diagnostic category in the current list of psychiatric disorders that directly addresses these concerns is body dysmorphic disorder. This large-scale study determined the prevalence of body dysmorphic disorder and its symptoms in patients seeking rhinoplasty and evaluated the clinical profile of these patients.

Methods: Two hundred twenty-six patients were given questionnaires including demographic characteristics, visual analogue scales for nasal shape, the Yale-Brown Obsessive Compulsive Scale modified for body dysmorphic disorder to assess severity of symptoms, a generic quality-of-life questionnaire, and the Derriford Appearance Scale 59, to assess appearance-related disruption of everyday living. Independent observers scored the nasal shape.

Results: Thirty-three percent of patients showed at least moderate symptoms of body dysmorphic disorder. Aesthetic goals (p < 0.001), revision rhinoplasty (p = 0.003), and psychiatric history (p = 0.031) were associated with more severe symptoms. There was no correlation between the objective and subjective scoring of the nasal shape. Yale-Brown scale modified for body dysmorphic disorder scores correlated inversely with the subjective nasal scoring (n = 210, p < 0.001), without relation to the objective deformity of the nose. Body dysmorphic disorder symptoms significantly reduced the generic quality of life (n = 160, p < 0.001) and led to significant appearance-related disruption of everyday living (n = 161, p < 0.001).

Conclusions: The prevalence of moderate to severe body dysmorphic disorder symptoms in an aesthetic rhinoplasty population is high. Patients undergoing revision rhinoplasty and with psychiatric history are particularly at risk. Body dysmorphic disorder symptoms significantly reduce the quality of life and cause significant appearance-related disruption of everyday living.

 

[Michael Scally MD]

Re: The big 4 (now 5) for preventing hair loss.

Curcuma Aeruginosa In The Treatment Of Male-Pattern Baldness

Curcuma aeruginosa Roxb., a member of the Zingiberaceae family, is an indigenous plant of Southeast Asia and the Indian subcontinent. Previous in vitro studies have shown that an extract of C. aeruginosa Roxb. exhibited superior inhibitory activities on testosterone conversion compared with extracts from other plants in the Zingiberaceae family. Animal studies also indicated that the C. aeruginosa hexane extract suppressed flank gland growth primarily by inhibiting 5a-reductase activity, in turn impairing the conversion of testosterone to DHT (unpublished data).

The present multicenter, double-blind, placebo controlled study was conducted to assess the efficacy and safety of 5% extract of C. aeruginosa, compared with 5% minoxidil solution, as well as the synergism of the two actives in promoting hair growths in men with AGA. Minoxidil is an established therapy for AGA in both men and women although the specific mechanism of action is unknown. It is arguably the most widely used medication for AGA, both as OTC and prescription agents.

In men with hair loss in the vertex area of the scalp, the combination of 5% hexane extract of C. aeruginosa and 5% minoxidil slowed hair loss and increased hair growth.


Pumthong G, Asawanonda P, Varothai S, et al. Curcuma aeruginosa, a novel botanically derived 5alpha-reductase inhibitor in the treatment of male-pattern baldness: a multicenter, randomized, double-blind, placebo-controlled study. J Dermatolog Treat. Curcuma aeruginosa, a novel botanically derived 5?... [J Dermatolog Treat. 2011] - PubMed result

Background: Several botanically derived agents are available for the treatment of male-pattern baldness.

Objective: The aim of this study was to evaluate the efficacy of 5% hexane extract of Curcuma aeruginosa, a botanically derived inhibitor of 5alpha-reductase and 5% minoxidil in the treatment of androgenetic alopecia.

Methods: Eighty-seven men with androgenetic alopecia (AGA) were randomized to receive 5% Curcuma aeruginosa, 5% minoxidil, combination formulation (5% hexane extract of Curcuma aeruginosa + 5% minoxidil) or placebo, twice daily for 6 months. Efficacy was assessed by target area hair count, global photographic review as well as patients' subjective assessments of hair regrowth and hair shedding.

Results: There were statistically significant improvements in global photographic review (p < 0.001), subjects' overall assessments of hair regrowth (p = 0.008), and hair shedding (p = 0.004) when the combination formulation was compared with placebo. Similarly, treatment with 5% minoxidil and 5% C. aeruginosa extract also led to some degrees of hair regrowth. There were no serious adverse events during and after the study.

Conclusion: In men with hair loss in the vertex area of the scalp, the combination of 5% hexane extract of C. aeruginosa and 5% minoxidil slowed hair loss and increased hair growth.

 

[Michael Scally MD]

Effect Of Sodium Oxybate [GHB: 4-hydroxybutyrate] On Growth Hormone Secretion

Classically, narcolepsy is defined as a sleep disorder with excessive daytime sleepiness and cataplexy as the main symptom. However, in recent years, there has been increasing attention paid to other core features of the syndrome. For example, fragmented nighttime sleep is a prominent symptom in many narcoleptic patients and often warrants treatment. In addition, patients are frequently overweight, storing excess fat in abdominal depots. The increasing interest for the broad symptomatology of narcolepsy was further fueled by new insights in the pathophysiology of the disease.

In the last decade, it has been shown that deficiencies in hypothalamic hypocretin (orexin) neurotransmission are the primary cause of narcolepsy both in humans and in several animal models of the disease. The hypocretin system is involved in a broad range of functions, including autonomic and hormonal regulation. Therefore, recent research has focused on consequences of the hypocretin deficiency in narcolepsy beyond disordered sleep regulation, such as metabolic and endocrine changes.

Given the relation between sleep and the somatotropic axis, changes in growth hormone (GH) dynamics have received particular attention in narcolepsy. In healthy subjects, there is a clear association between GH secretion and sleep. This is especially clear in young males, in which the majority of 24-h GH is secreted during the first period of slow-wave sleep (SWS) at night. In a previous study, researchers showed that GH secretion was less strictly confined to the night in hypocretin-deficient narcolepsy. As the relation between SWS and GH secretion was preserved, it was suggested that a shift of SWS episodes to the day was paralleled by a daytime shift of GH secretion.

Sodium oxybate (SXB) has evolved into a first-line treatment for narcolepsy. SXB is a short-acting hypnotic that is dosed twice at night, at bedtime, and 2.5–4 h later. It significantly consolidates nighttime sleep and ameliorates cataplexy, and in higher doses it may decrease excessive daytime sleepiness. In contrast to other hypnotics, SXB is one of the few compounds that increases rather than decreases SWS. This led to the hypothesis that it may also act as a GH secretagogue. Indeed, it has been shown that single-dose SXB administration leads to an increase in GH secretion in healthy young men, paralleled by an increase in SWS.

In the present study, researchers assessed the effect of repeated, twice-a-night administration of SXB on 24-h GH secretion patterns in both patients with hypocretin-deficient narcolepsy and matched healthy controls. GH secretion was assessed during a 24-h sample occasion with concomitant sleep registrations at baseline and after 5 nights of SXB.

They have shown that twice-a-night administration of SXB for 5 consecutive days consistently increases nocturnal GH secretion in both healthy controls and hypocretin-deficient narcolepsy patients. This was paralleled by a concomitant increase in SWS. The increases in both in GH and SWS were most prominent after the first dose of SXB at sleep onset. SXB reinforced the relation between GH and SWS, as evidenced by an almost doubled cross-correlation between the two.


Donjacour CEHM, Aziz NA, Roelfsema F, et al. Effect of sodium oxybate on growth hormone secretion in narcolepsy patients and healthy controls. American Journal of Physiology - Endocrinology And Metabolism 2011;300(6):E1069-E75. Effect of sodium oxybate on growth hormone secretion in narcolepsy patients and healthy controls

Hypocretin deficiency causes narcolepsy and may affect neuroendocrine systems and body composition. Additionally, growth hormone (GH) alterations my influence weight in narcolepsy. Symptoms can be treated effectively with sodium oxybate (SXB/GHB; ?-hydroxybutyrate) in many patients. This study compared growth hormone secretion in patients and matched controls and established the effect of SXB administration on GH and sleep in both groups.

Eight male hypocretin-deficient patients with narcolepsy and cataplexy and eight controls matched for sex, age, BMI, waist-to-hip ratio, and fat percentage were enrolled. Blood was sampled before and on the 5th day of SXB administration. SXB was taken two times 3 g/night for 5 consecutive nights. Both groups underwent 24-h blood sampling at 10-min intervals for measurement of GH concentrations. The GH concentration time series were analyzed with AutoDecon and approximate entropy (ApEn).

Basal and pulsatile GH secretion, pulse regularity, and frequency, as well as ApEn values, were similar in patients and controls. Administration of SXB caused a significant increase in total 24-h GH secretion rate in narcolepsy patients, but not in controls. After SXB, slow-wave sleep (SWS) and, importantly, the cross-correlation between GH levels and SWS more than doubled in both groups.

In conclusion, SXB leads to a consistent increase in nocturnal GH secretion and strengthens the temporal relation between GH secretion and SWS. These data suggest that SXB may alter somatotropic tone in addition to its consolidating effect on nighttime sleep in narcolepsy. This could explain the suggested nonsleep effects of SXB, including body weight reduction.

 

[Michael Scally MD]

Olive Oil Consumption, Plasma Oleic Acid, And Stroke Incidence

Cerebrovascular events are responsible for a substantial clinical burden, with their incidence currently exceeding that of coronary heart disease, in particular in older age groups. Risk of stroke could be reduced by improvement of lifestyle factors, including diet, notably by increasing fruits and vegetables consumption and decreasing sodium intake, which is strongly correlated with hypertension.

Adherence to the Mediterranean diet (MeDi) was related to a lower risk of mortality from cardiovascular diseases and to a reduction in major cardiovascular risk factors. High olive oil consumption is one of the most constant features of the MeDi, and may account for most of its cardioprotective properties.

Olive oil contains 80% monounsaturated fats (MUFA) in the form of oleic acid, 20% polyunsaturated fats, and several antioxidant components, including phenolic compounds found in virgin olive oil. A higher consumption of olive oil has been associated with a decreased risk for myocardial infarction (MI), a lower risk of all-cause mortality after MI, and a lower carotid intima-media thickness. Olive oil was the only component of the MeDi specifically associated with lower blood pressure in a large European cohort.

The assumption that high olive oil consumption may be associated with a reduced incidence of stroke independently of other dietary habits and stroke risk factors has never been explored. Researchers investigated the relationship between olive oil consumption, plasma oleic acid as a biological marker of oleic acid intake, and 6-year stroke incidence in older participants in the Three-City (3C) Study.

In the present population-based study, intensive olive oil use was prospectively associated with a lower stroke risk after controlling for numerous confounding factors, including lifestyle and nutritional factors, main stroke risk factors, and blood lipids.


Samieri C, Feart C, Proust-Lima C, et al. Olive oil consumption, plasma oleic acid, and stroke incidence. Neurology 2011;77(5):418-25. Olive oil consumption, plasma oleic acid, and stroke incidence

Objective: To determine whether high olive oil consumption, and high plasma oleic acid as an indirect biological marker of olive oil intake, are associated with lower incidence of stroke in older subjects.

Methods: Among participants from the Three-City Study with no history of stroke at baseline, we examined the association between olive oil consumption (main sample, n = 7,625) or plasma oleic acid (secondary sample, n = 1,245) and incidence of stroke (median follow-up 5.25 years), ascertained according to a diagnosis validated by an expert committee.

Results: In the main sample, 148 incident strokes occurred. After adjustment for sociodemographic and dietary variables, physical activity, body mass index, and risk factors for stroke, a lower incidence for stroke with higher olive oil use was observed (p for trend = 0.02). Compared to those who never used olive oil, those with intensive use had a 41% (95% confidence interval 6-63%, p = 0.03) lower risk of stroke. In the secondary sample, 27 incident strokes occurred. After full adjustment, higher plasma oleic acid was associated with lower stroke incidence (p for trend = 0.03). Compared to those in the first tertile, participants in the third tertile of plasma oleic acid had a 73% (95% confidence interval 10-92%, p = 0.03) reduction of stroke risk.

Conclusions: These results suggest a protective role for high olive oil consumption on the risk of stroke in older subjects.

 

[Michael Scally MD]

Low Endogenous Testosterone Levels Are Associated With Increased Risk Of All-Cause And Cardiovascular Disease Death

Serum testosterone levels exhibit a gradual decline as men age, with longitudinal studies showing declines between 0.4 and 2.6% per year. At the same time, SHBG rises, resulting in a greater decline (>/=2% per year) in free testosterone. The prevalence of late-onset hypogonadism (defined according to recent clinical guidelines as presence of clinical symptoms and low testosterone levels) is less than 10%.

In observational studies, low serum testosterone and late-onset hypogonadism have been associated with abdominal obesity, cardiovascular risk factors and the metabolic syndrome, type 2 diabetes mellitus, increased inflammatory biomarkers, and dyslipidemia among other outcomes that may increase risk of premature death. In recent years, several observational studies have examined the association between endogenous testosterone levels and mortality. Many, but not all, of these studies have shown that low testosterone levels are associated with increased overall and cardiovascular disease (CVD) mortality. Pooling of data from these studies in a systematic review and meta-analysis may provide clarity to the conflicting data or identify study or subject characteristics associated with variation in results among studies.

The primary objective of this research is to assess the association between endogenous testosterone levels and all-cause and CVD mortality from observational studies conducted in men. Secondarily, it will assess whether important clinical [e.g. baseline testosterone level, smoking status, and body mass index (BMI)], demographic (e.g. age), or study-related (e.g. length of follow-up and type of testosterone assay) factors influence or modify study results.

In this systematic review and meta-analysis, researchers identified 21 studies that met protocol-defined inclusion criteria, 12 of which were eligible for meta-analysis. Although meta-analysis of these community-based studies showed that a decrease of 2.18 SD in total testosterone was associated with a 35 and 25% increased risk of all-cause and CVD mortality, respectively, the observation of considerable between-study heterogeneity (significant for all-cause mortality and borderline significant for CVD mortality) limits the validity of these summary estimates. Factors implicated in study heterogeneity were age, baseline total testosterone, length of the follow-up period, and whether blood samples were collected in the morning.


Araujo AB, Dixon JM, Suarez EA, Murad MH, Guey LT, Wittert GA. Clinical Review: Endogenous Testosterone and Mortality in Men: A Systematic Review and Meta-Analysis. Journal of Clinical Endocrinology & Metabolism. Clinical Review: Endogenous Testosterone and Mortality in Men: A Systematic Review and Meta-Analysis

Context: Low testosterone levels have been associated with outcomes that reduce survival in men.

Objective: Our objective was to perform a systematic review and meta-analysis of published studies to evaluate the association between endogenous testosterone and mortality.

Data Sources: Data sources included MEDLINE (1966 to December 2010), EMBASE (1988 to December 2010), and reference lists.

Study Selection: Eligible studies were published English-language observational studies of men that reported the association between endogenous testosterone and all-cause or cardiovascular disease (CVD) mortality. A two-stage process was used for study selection. 1) Working independently and in duplicate, reviewers screened a subset (10%) of abstracts. Results indicated 96% agreement, and thereafter, abstract screening was conducted in singlicate. 2) All full-text publications were reviewed independently and in duplicate for eligibility.

Data Extraction: Reviewers working independently and in duplicate determined methodological quality of studies and extracted descriptive, quality, and outcome data.

Data Synthesis: Of 820 studies identified, 21 were included in the systematic review, and 12 were eligible for meta-analysis [n = 11 studies of all-cause mortality (16,184 subjects); n = 7 studies of CVD mortality (11,831 subjects)]. Subject mean age and testosterone level were 61 yr and 487 ng/dl, respectively, and mean follow-up time was 9.7 yr. Between-study heterogeneity was observed among studies of all-cause (P < .001) and CVD mortality (P = 0.06), limiting the ability to provide valid summary estimates. Heterogeneity in all-cause mortality (higher relative risks) was observed in studies that included older subjects (P = 0.020), reported lower testosterone levels (P = 0.018), followed subjects for a shorter time period (P = 0.010), and sampled blood throughout the day (P = 0.030).

Conclusion: Low endogenous testosterone levels are associated with increased risk of all-cause and CVD death in community-based studies of men, but considerable between-study heterogeneity, which was related to study and subject characteristics, suggests that effects are driven by differences between cohorts (e.g. in underlying health status).

 

[Michael Scally MD]

Latisse For Androgenetic Alopecia (Male/Female Pattern Baldness)—AGN is running two large phase-2 trials, one for men and one for women:

Safety and Efficacy Study of Bimatoprost in the Treatment of Men With Androgenic Alopecia: Safety and Efficacy Study of Bimatoprost in the Treatment of Men With Androgenic Alopecia - Full Text View - ClinicalTrials.gov (men)

Safety and Efficacy Study of Bimatoprost in the Treatment of Women With Female Pattern Hair Loss: Safety and Efficacy Study of Bimatoprost in the Treatment of Women With Female Pattern Hair Loss - Full Text View - ClinicalTrials.gov (women)

Both trials have 300 patients and will report data in late 2012.


[Latisse - DailyMed: About DailyMed – (bimatoprost ophthalmic solution) 0.03% is indicated to treat hypotrichosis of the eyelashes by increasing their growth including length, thickness and darkness. Bimatoprost is a structural prostaglandin analog. Although the precise mechanism of action is unknown the growth of eyelashes is believed to occur by increasing the percent of hairs in, and the duration of the anagen or growth phase.]

 

[Michael Scally MD]

Beneficial Effect of Niacin on Erectile Function in Men Suffering Erectile Dysfunction and Dyslipidemia


Erectile dysfunction (ED) is a common condition affecting more than 50% of men aged between 40 and 70. Currently, phosphodiesterase type-5 inhibitor (PDE5i) is the first-line treatment for ED, with satisfactory results. Nevertheless, a significant proportion of ED patients are either contraindicated for PDE5i or have an inadequate response to PDE5i. Therefore, development of alternative treatments is necessary.

ED is closely related to coronary artery disease and other cardiovascular diseases. Endothelial dysfunction and atherosclerosis are believed to be the common underlying pathophysiology for these conditions. There is evidence suggesting that the improvement of vascular condition and endothelial function by 3-hydroxy-3- methylglutaryl-coenzyme A reductase inhibitors (“statins”) may lead to an improvement in ED. Niacin is another class of lipid-lowering agent, with characteristics of increasing serum high-density lipoprotein (HDL) cholesterol level and subsequent improvement in lipid profile. Studies have suggested that niacin could also improve endothelial function and atherosclerosis.

Researchers postulated that niacin may have a similar effect to statins in improving erectile function in patients with ED. Therefore, they aimed to assess the effect of niacin on erectile function in male patients suffering from both ED and dyslipidemia.

The data from this study suggest for the first time in the literature that niacin alone could improve the erectile function of patients with dyslipidemia suffering from ED. The effect is clinically significant in patients with moderate to severe ED. Because of the close relationship between ED and dyslipidemia, niacin might be an important therapy for managing both conditions. Further studies would be beneficial to refine further the indications and benefits of niacin in patients with ED.


Ng C-F, Lee C-P, Ho AL, Lee VWY. Effect of Niacin on Erectile Function in Men Suffering Erectile Dysfunction and Dyslipidemia. The Journal of Sexual Medicine. Effect of Niacin on Erectile Function in Men Suffering Erectile Dysfunction and Dyslipidemia - Ng - 2011 - The Journal of Sexual Medicine - Wiley Online Library

Introduction. Dyslipidemia is closely related to erectile dysfunction (ED). Evidence has shown that the lipid-lowering agent, 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor (statins), can improve erectile function. However, information about the potential role of another class of lipid-lowering agent, niacin, is unknown.

Aim. To assess the effect of niacin alone on erectile function in patients suffering from both ED and dyslipidemia.

Methods. A single center prospective randomized placebo-controlled parallel-group trial was conducted. One hundred sixty male patients with ED and dyslipidemia were randomized in a one-to-one ratio to receive up to 1,500 mg oral niacin daily or placebo for 12 weeks.

Main Outcome Measures. The primary outcome measure was the improvement in erectile function as assessed by question 3 and question 4 of the International Index of Erectile Function (IIEF Q3 and Q4). Secondary outcome measurements included the total IIEF score, IIEF-erectile function domain, and Sexual Health Inventory for Men (SHIM) score.

Results. From the overall analysis, the niacin group showed a significant increase in both IIEF-Q3 scores (0.53 ± 1.18, P < 0.001) and IIEF-Q4 scores (0.35 ± 1.17, P = 0.013) compared with baseline values. The placebo group also showed a significant increase in IIEF-Q3 scores (0.30 ± 1.16, P = 0.040) but not IIEF-Q4 scores (0.24 ± 1.13, P = 0.084). However, when patients were stratified according to the baseline severity of ED, the patients with moderate and severe ED who received niacin showed a significant improvement in IIEF-Q3 scores (0.56 ± 0.96 [P = 0.037] and 1.03 ± 1.20 [P < 0.001], respectively) and IIEF-Q4 scores (0.56 ± 1.03 [P = 0.048] and 0.84 ± 1.05 [P < 0.001], respectively] compared with baseline values, but not for the placebo group. The improvement in IIEF-EF domain score for severe and moderate ED patients in the niacin group were 5.28 ± 5.94 (P < 0.001) and 3.31 ± 4.54 (P = 0.014) and in the placebo group were 2.65 ± 5.63 (P < 0.041) and 2.74 ± 5.59 (P = 0.027), respectively. There was no significant improvement in erectile function for patients with mild and mild-to-moderate ED for both groups. For patients not receiving statins treatment, there was a significant improvement in IIEF-Q3 scores (0.47 ± 1.16 [P = 0.004]) for the niacin group, but not for the placebo group.

Conclusions. Niacin alone can improve the erectile function in patients suffering from moderate to severe ED and dyslipidemia.

 

[Michael Scally MD]

Inducible Nitric Oxide Synthase (iNOS) In Muscle Wasting Syndrome, Sarcopenia, And Cachexia

Muscle atrophy-also known as muscle wasting-is a debilitating syndrome that slowly develops with age (sarcopenia) or rapidly appears at the late stages of deadly diseases such as cancer, AIDS, and sepsis (cachexia). Despite the prevalence and the drastic detrimental effects of these two syndromes, there are currently no widely used, effective treatment options for those suffering from muscle wasting.

In an attempt to identify potential therapeutic targets, the molecular mechanisms of sarcopenia and cachexia have begun to be elucidated. Growing evidence suggests that inflammatory cytokines may play an important role in the pathology of both syndromes. As one of the key cytokines involved in both sarcopenic and cachectic muscle wasting, tumor necrosis factor alpha (TNFalpha) and its downstream effectors provide an enticing target for pharmacological intervention. However, to date, no drugs targeting the TNFalpha signaling pathway have been successful as a remedial option for the treatment of muscle wasting. Thus, there is a need to identify new effectors in this important pathway that might prove to be more efficacious targets.

Inducible nitric oxide synthase (iNOS) has recently been shown to be an important mediator of TNFalpha-induced cachectic muscle loss, and studies suggest that it may also play a role in sarcopenia. In addition, investigations into the mechanism of iNOS-mediated muscle loss have begun to reveal potential therapeutic strategies. In this review, researchers will highlight the potential for targeting the iNOS/NO pathway in the treatment of muscle loss and discuss its functional relevance in sarcopenia and cachexia.

Hall DT, Ma JF, Marco SD, Gallouzi IE. Inducible nitric oxide synthase (iNOS) in muscle wasting syndrome, sarcopenia, and cachexia. Aging (Albany NY). http://www.impactaging.com/papers/v3/n8/pdf/100358.pdf

 

[Michael Scally MD]

Recreational Use Of Erectile Dysfunction Medications

There are currently three oral medications approved by the Food and Drug Administration (FDA) for the treatment of erectile dysfunction (ED): sildenafil (Viagra), tadalafil (Cialis), and vardenafil (Levitra). These erectile dysfunction medications (EDMs) are well tolerated and effective for treating ED of various etiologies and it is estimated that over 25 million men worldwide have been prescribed sildenafil alone (Pfizer Inc.).

Although these EDMs have been FDA approved to treat ED, mounting evidence indicates that these drugs have become increasingly used as a sexual enhancement aid among men without a medical indication. This phenomenon has raised concern particularly with respect to its association with increased sexual risk behavior. Studies indicate that in samples of men who have sex with men (MSM), those who recreationally use sildenafil are between two and six times as likely as nonusers to engage in unprotected anal intercourse with a partner of unknown or serodiscordant HIV status. Recreational EDM users also report a higher number of sex partners during the past 1–2 months, and about a twofold rate in sexually transmitted infections (STIs), including HIV infection.

The current study examined patterns of and associated risk factors for recreational EDM use in a large geographically diverse sample of undergraduate men in the United States. The present investigation was designed to provide the first national study conducted in the Unites States examining EDM use in heterosexual, bisexual, and gay undergraduate men. Our first aim was to assess the rates of recreational use of sildenafil, tadalafil, and vardenafil and explore descriptive characteristics related to their use, such as frequency and length of use, motivations for use, source(s) of acquisition, and concomitant illicit drug use. Second, we aimed to investigate associated risk factors for recreational EDM use, including demographic characteristics, as well as sexual behavior and substance abuse characteristics.

Results indicated that 4% of participants had recreationally used an EDM at some point in their lives, with 1.4% reporting current use. The lifetime rate of use reported here in was similar to that of a young population-based sample in Finland (3%), as well as a small sample of undergraduate men in the United States (6%). These rates of recreational EDM use were in contrast to much higher rates reported in South American undergraduate and graduate samples (9–15%), most likely owing to the fact that prescriptions for EDMs in these countries are not required.


Harte CB, Meston CM. Recreational use of erectile dysfunction medications in undergraduate men in the United States: characteristics and associated risk factors. Arch Sex Behav 2011;40(3):597-606. Recreational Use of Erectile Dysfunction Medications in Undergraduate Men in the United States: Characteristics and Associated Risk Factors

Mounting evidence indicates that erectile dysfunction medications (EDMs) have become increasingly used as a sexual enhancement aid among men without a medical indication. Recreational EDM use has been associated with increased sexual risk behaviors, an increased risk for STIs, including incident HIV infection, and high rates of concomitant illicit drug use. The aim of the present study was to investigate the characteristics and associated risk factors for recreational EDM use among young, healthy, undergraduate men. A cross-sectional sample of 1,944 men were recruited from 497 undergraduate institutions within the Unites States between January 2006 and May 2007. The survey assessed patterns of EDM use, as well as demographic, substance use, and sexual behavior characteristics. Four percent of participants had recreationally used an EDM at some point in their lives, with 1.4% reporting current use. The majority of recreational EDM users reported mixing EDMs with illicit drugs and particularly during risky sexual behaviors. Recreational EDM use was independently associated with increased age, gay, or bisexual sexual orientation, drug abuse, lifetime number of sex partners, and lifetime number of "one-night stands." Recreational EDM users also reported a 2.5-fold rate of erectile difficulties compared to nonusers. Overall, recreational use of EDMs was associated with sexual risk behaviors and substance abuse; however, a relatively small proportion of undergraduates reported using EDMs. Results also suggest that a sizable portion of recreational EDM users are heterosexual men, and that use does not solely occur within the environments of venues that cater to men having sex with men.

 

[Michael Scally MD]

The steroid hormones testosterone and dihyrdotestosterone are small, four ringed planar molecules that exert profound affects important for the development of the male phenotype during embryogenesis and at puberty. Androgen signalling is also important for reproductive health in both male and females as well as anabolic actions in bone and muscle tissue. The actions of these potent signalling molecules are mediated by the product of a single gene that codes for a protein of 110 kDa: the androgen receptor (AR; NR3C4) is an intracellular protein that functions as a ligand-activated transcription factor. The AR is a member of the nuclear receptor superfamily, which in addition to steroid receptors includes receptors for vitamins, bile acids and fatty acid derivatives. These proteins are highly modular and contain a ligand binding domain (LBD) in the C-terminus, a flexible hinge region linking to the DNA binding domain (DBD) and then a highly variable N-terminal domain (NTD). In this review the role of intrinsic disorder in AR function is discussed along with the potential to develop new drugs that will target the structurally plastic NTD.


McEwan IJ. Intrinsic disorder in the androgen receptor: identification, characterisation and drugability. Mol Biosyst. Intrinsic disorder in the androgen receptor: ident... [Mol Biosyst. 2011] - PubMed result

The androgen receptor (AR) regulates networks of genes in response to the steroid hormones testosterone and dihydrotestosterone. The receptor protein is made up of both stably folded globular domains, involved in hormone and DNA binding, and regions of intrinsic disorder, including the N-terminal domain (NTD). The AR-NTD has a modular activation function (termed AF1) and is important for gene regulation, participating in multiple protein-protein interactions. Biophysical studies have revealed that AR-NTD/AF1 has limited stable secondary structure and conforms to a 'collapsed disordered' conformation. The AR-NTD/AF1 has the propensity to adopt an alpha-helical conformation in response to a natural osmolyte or a co-regulatory binding partner. The AR is a key drug target in the management of advanced prostate cancer and recently a small molecule inhibitor was identified that interacts with the NTD/AF1 and impairs protein-protein interactions and recruitment of the receptor to target genes.

 

[Michael Scally MD]

Anabolic And Androgenic Activities Of 19 Nortestosterone Steroids

Anabolic/androgenic steroids (AAS) exert two different effects: development and maintenance of secondary male sexual characteristics (androgenic effects) and promotion of muscle growth (anabolic effects).

These drugs are used in the fast recovery from protein-wasting disorders. In HIV patients, anabolic steroids are used to regain lean muscle mass, as well as to prevent organ failure and secondary immune dysfunction. These compounds have proved to be an effective oral therapy to promote weight gain after extensive surgery, chronic infections and severe trauma. They are indicated in the treatment of anemia caused by deficient red-cell production, osteoporosis and metastatic cancer.

Generally, testosterone is considered to be a poor AAS because, when orally taken, it is rapidly degraded, and only small amounts reach the systemic circulation. Additionally, when testosterone is injected, effective levels of the drug are not sustained because of rapid degradation.

In order to maximize the effectiveness of AAS, the basic chemical structure of testosterone is generally modified by
(I) esterification at the 17 beta-hydroxyl group,
(II) alkylation at the 17 alpha-position, or
(III)modification in any of the 1,2,9, or 11 carbon of the ring structure in the molecule.

Family of 19-nor-testosterone is produced by the removal of the 19 methyl group of testosterone. This change increases the anabolic effect. The 19-nor-testosterone is more planar than testosterone, increasing its receptor-binding affinity. However, it binds with similar affinity to androgen receptors in skeletal muscle and in prostate. The 19-nor-testosterone is not converted to dihydrotestosterone (DHT) in tissues containing 5 alpha-reductase enzyme. Instead, it is converted to dihydro-19-nor-testosterone that is a compound that binds less tightly to androgen receptor in the same way that the DHT. These factors could explain the diminished effect of 19-nor-testosterone relative to testosterone on androgen target tissues containing 5 alpha-reductase enzyme (e.g., seminal vesicles) together with greater effect than testosterone on tissues containing little or none of this enzyme, e.g., levator ani and skeletal muscle.

In an attempt to meet these goals, many AAS drugs have been created with various levels of success. However, there is no AAS developed to date that contains a pronounced anabolic potency, while having no androgenic effect. It is important to note that with the creation of new AAS, subsequent modifications result in alterations in the drug’s anabolic to androgenic ratio and modify the potential side effects that could occur in response to the drug. In integrating both measures, the anabolic index, which relates the ratio of anabolic to androgenic response for a given steroid, is used. If the anabolic index is higher than one, it indicates a higher trend towards anabolic effect and, therefore, classifies the drug as an anabolic steroid. A measure lower than one, in turn, assesses the steroid as androgenic.

Several authors have developed Quantitative Structure-Activity Relationship (QSAR) models for estrogens, progestagens, and corticosteroid steroid hormones. The steroid benchmark with the corresponding globulin affinity is the most extensively studied dataset of steroids. Recently, researchers reported multi-linear regression (MLR) QSAR models for congeneric series of AAS: 17 beta-hydroxy-5 alpha-androstane, 4,5 alpha-dihydrotestosterone, and testosterone steroid families.

They reported too a robust biosilico model of linear discriminant analysis (LDA). This model was used to analyze the anabolic–androgenic activities of structurally diverse steroids and to discover novel AAS, as well as to give a structural interpretation of their AAR. They have selected 366 steroids with a structural variability and included four different steroids families: 17 beta- hydroxy-5 alpha-androstane, 4,5 alpha-dyhidrotestosterone, testosterone and 19-nor-testosterone derivatives. The general idea of their work is to develop general models of classification for steroids with high and moderate-low Anabolic–Androgenic Ratio (AAR). Subsequently, they quantify their anabolic and/or androgenic activities in the models of MLR according to the family that each selected molecule belong to. Finally, their approach could help in the future successful identification of “real” or “virtual” AAS.

The main aim of the present report is to develop MLR QSAR models for anabolic and androgenic steroids of the 19-nor-testosterone steroids family using quantum and physicochemical MDs and a genetic algorithm (GA) as a method for the selection of the best set of variables. The QSAR models provide a structural interpretation of their anabolic–androgenic activities and design new anabolic and androgenic steroids.


Alvarez-Ginarte YM, Montero-Cabrera LA, de la Vega JM, Noheda-Marin P, Marrero-Ponce Y, Ruiz-Garcia JA. Anabolic and androgenic activities of 19-nor-testosterone steroids: QSAR study using quantum and physicochemical molecular descriptors. J Steroid Biochem Mol Biol. Anabolic and androgenic activities of 19-nor-testo... [J Steroid Biochem Mol Biol. 2011] - PubMed result

Quantitative structure-activity relationship (QSAR) study of 19-nor-testosterone steroids family was performed using quantum and physicochemical molecular descriptors. The quantum-chemical descriptors were calculated using semiempirical calculations. The descriptor values were statistically correlated using multi-linear regression analysis. The QSAR study indicated that the electronic properties of these derivatives have significant relationship with observed biological activities. The found QSAR equations explain that the energy difference between the LUMO and HOMO, the total dipole moment, the chemical potential and the value of the net charge of different carbon atoms in the steroid nucleus showed key interaction of these steroids with their anabolic-androgenic receptor binding site. The calculated values predict that the 17alpha-cyclopropyl-17beta, 3beta-hydroxy-4-estrene compound present the highest anabolic-androgenic ratio (AAR) and the 7alpha-methyl-17beta-acetoxy-estr-4-en-3-one compound the lowest AAR. This study might be helpful in the future successful identification of "real" or "virtual" anabolic-androgenic steroids.

 

[Michael Scally MD]

Longer Lives for Obese Mice, With Hope for Humans of All Sizes
http://www.nytimes.com/2011/08/19/science/19fat.html

August 18, 2011
By NICHOLAS WADE

Sustaining the flickering hope that human aging might somehow be decelerated, researchers have found they can substantially extend the average life span of obese mice with a specially designed drug.

The drug, SRT-1720, protects the mice from the usual diseases of obesity by reducing the amount of fat in the liver and increasing sensitivity to insulin. These and other positive health effects enable the obese mice to live 44 percent longer, on average, than obese mice that did not receive the drug, according to a team of researchers led by Rafael de Cabo, a gerontologist at the National Institute on Aging.

Drugs closely related to SRT-1720 are now undergoing clinical trials in humans.

The findings “demonstrate for the first time the feasibility of designing novel molecules that are safe and effective in promoting longevity and preventing multiple age-related diseases in mammals,” Dr. de Cabo and colleagues write in Thursday’s issue of the new journal Scientific Reports. Their conclusion supports claims that had been thrown in doubt by an earlier study that was critical of SRT-1720.

A drug that makes it cost-free to be obese may seem more a moral hazard than an incentive to good health. But the rationale behind the research is somewhat different: the researchers are trying to capture the benefits that allow mice on very low-calorie diets to live longer. It just so happens that such benefits are much easier to demonstrate in mice under physiological stress like obesity than in normal mice.

“The drugs could be used as a preventative to stave off diseases, but I don’t think they will ever be an excuse to abuse your body,” said David Sinclair, a biologist at Harvard Medical School and co-chairman of the scientific advisory board of Sirtris, which developed SRT-1720.

The company, a small pharmaceutical concern in Cambridge, Mass., designed SRT-1720 and a set of similar drugs to mimic resveratrol — the trace ingredient of red wine that is thought to activate protective proteins called sirtuins.

The sirtuins help bring about the 30 percent extension of life span enjoyed by mice and rats that are kept on very low-calorie diets. Since few people can keep to such an unappetizing diet, researchers hoped that doses of resveratrol might secure a painless path to significantly greater health and longevity.

But large doses of resveratrol are required to show any effect, so chemical mimics like SRT-1720 were developed to activate sirtuin at much lower doses.

Sirtuins have proved to be highly interesting proteins, but the goal of extending life span was set back last year when extensive trials of resveratrol showed it did not prolong mice’s lives, although it seemed to do them no harm. Another blow came in 2009, when biologists at Pfizer reported that SRT-1720 and other resveratrol mimics did not activate sirtuins and did not have any beneficial effects in fat mice.

The report by Dr. de Cabo and his colleagues may do much to rescue SRT-1720 from this shadow. They found that SRT-1720 offered substantial benefits to the fat mice, with no signs of toxicity. Unlike the Pfizer study, which was short term, they followed large groups of mice for over three years.

“This is good evidence that this compound has a positive effect on the physiology of the obese animal, and that is definitely promising for humans,” said Jan Vijg, an expert on aging at the Albert Einstein College of Medicine in the Bronx.

Dr. de Cabo and his team “make a reasonable case” that the compound works by activating sirtuins, although they have not proved it, Dr. Vijg said.

In one sense it does not much matter how the drug obtains its effects, as long as it works. But the credibility of SRT-1720 and its cousins also rests on their design as sirtuin activators.

Despite the positive new results with SRT-1720, Sirtris is not putting it into clinical trials because the company believes another of its resveratrol mimics, SRT-2104, is more promising. That drug “is more suitable for human consumption,” said Dr. Sinclair, a co-author of Dr. de Cabo’s report.

“Questions were raised about the molecules and if they are working the way we said they were,” Dr. Sinclair said. “But with this paper, the weight of evidence is shifting back in favor of the premise that we can tweak the aging pathway with drugs.”

Obese mice are a standard research tool, but experts differ as to how relevant they are to humans. “They’ve poisoned the mice with this high-fat diet that makes them very sick indeed, and with SRT-1720 they can reverse some portion of that illness,” said Dr. Richard A. Miller, an expert on aging mice at the University of Michigan.

Dr. Miller said the finding “looks like something people should pay a lot of attention to,” but added that the study would have been even more interesting if it had shown an effect on normal mice.

Dr. de Cabo and his team included normal, untreated lean mice in their study as a control group for the treated and untreated fat mice. The treated fat mice lived longer than the untreated ones, but died long before the normal mice. Although the treated fat mice lived significantly longer on average, there was little difference between their maximum life span and that of the untreated mice. The drug, in other words, helped the fat mice enjoy more of their available life span without increasing the span itself.

The researchers’ findings would be more significant if they had showed that SRT-1720 prolonged the lives of normal mice. Dr. Sinclair said that this leg of the study had been started at the same time, but that the treated normal mice were taking longer to die and could not be reported with the others. Dr. de Cabo said the results were “encouraging” but could not be discussed until they were published early next year. But Dr. Vijg noted that since the drug did not extend the maximum life span of fat mice, it would be surprising if it did so with lean mice.

Some researchers say that too much attention has been given to resveratrol and its sirtuin-activating mimics, and that other compounds like the antibiotic rapamycin may be even more promising. But the sirtuins “are worth a lot of attention even though some of the early claims have proved hard to reproduce,” Dr. Miller said.

Because of the uncertainty about several earlier findings, the sirtuin field has become polarized. “Some people are strongly in support, and others are convinced there’s nothing there,” said Brian Kennedy, president of the Buck Institute for Research on Aging. He described himself as standing in the middle, but hopeful that the sirtuins would turn out to be “key modulators of aging.”


Minor RK, Baur JA, Gomes AP, et al. SRT1720 improves survival and healthspan of obese mice. Sci Rep 2011;1. http://www.nature.com/srep/2011/110818/srep00070/pdf/srep00070.pdf

Sirt1 is an NAD+-dependent deacetylase that extends lifespan in lower organisms and improves metabolism and delays the onset of age-related diseases in mammals. Here we show that SRT1720, a synthetic compound that was identified for its ability to activate Sirt1 in vitro, extends both mean and maximum lifespan of adult mice fed a high-fat diet. This lifespan extension is accompanied by health benefits including reduced liver steatosis, increased insulin sensitivity, enhanced locomotor activity and normalization of gene expression profiles and markers of inflammation and apoptosis, all in the absence of any observable toxicity. Using a conditional SIRT1 knockout mouse and specific gene knockdowns we show SRT1720 affects mitochondrial respiration in a Sirt1- and PGC-1?-dependent manner. These findings indicate that SRT1720 has long-term benefits and demonstrate for the first time the feasibility of designing novel molecules that are safe and effective in promoting longevity and preventing multiple age-related diseases in mammals.

 

[Michael Scally MD]

The Accuracy of Diagnostic Tests for Growth Hormone Deficiency

Growth hormone (GH) and the insulin-like growth factor-1 (IGF-1) are involved in the regulation of somatic growth in children. In adults, this axis plays a role in maintaining normal body composition, skeletal mass, cardiovascular risk factors, and physical and physiological functioning. GH deficiency has been related to insulin insensitivity, increased body fat and decreased muscle mass; other studies have implicated that low levels of IGF-I are associated with increased risks of myocardial infarction, ischemic cardiac disease, and stroke. Thus, there has been interest in the clinical use of GH replacement in patients with GH deficiency with the expectation that this agent could normalize body composition, enhance physical function, and prevent cardiovascular disease.

Expert reviews and consensus statements consider insulin-induced hypoglycemia (insulin tolerance test; ITT) as the reference standard for the diagnosis of this condition. Alternative stimulation tests use GHRH+arginine, GHRH+growth hormone-releasing peptide (GH-RP), glucagon stimulation, and GH-RP. Until now, a summary of the available literature assessing the accuracy of the available tests for GH deficiency in adult patients suspected of having the condition has not been conducted.

The aim of this systematic review and meta-analysis is to appraise and summarize the available evidence of the diagnostic accuracy of tests of growth hormone deficiency in adults. Several GH stimulation tests with fairly good diagnostic accuracy are available for the diagnosis of growth hormone deficiency in adults. The supporting evidence however, is indirect (as is not directly informative of patient outcomes) and at high risk of bias.


Hazem A, Elamin M, Malaga G, et al. The Accuracy of Diagnostic Tests for Growth Hormone Deficiency in Adults: A Systematic Review and Meta-analysis. European Journal of Endocrinology. http://www.eje-online.org/content/early/2011/08/19/EJE-11-0476.full.pdf+html

Context: The diagnostic accuracy of tests used to diagnose growth hormone (GH) deficiency in adults is unclear.

Objective: To conduct a systematic review and meta-analysis of studies that provided data on the available diagnostic tests.

Data Sources: We searched electronic databases (MEDLINE, EMBASE, Cochrane CENTRAL, Web of Sciences and Scopus) through April 2011. Review of reference lists and contact with experts identified additional candidate studies.

Study Selection: Reviewers, working independently and in duplicate, determined study eligibility.

Data Extraction: Reviewers, working independently and in duplicate, determined the methodological quality of studies and collected descriptive, quality and outcome data.

Data Synthesis: Twenty-three studies provided diagnostic accuracy data; none provided patient outcome data. Studies had fair methodological quality, used several reference standards, and included over 1100 patients. Several tests based on direct or indirect stimulation of GH release were associated with good diagnostic accuracy although most were assessed in 1 or 2 studies decreasing the strength of inference due to small sample size; Serum levels of GH or IGF-1 had low diagnostic accuracy. Pooled sensitivity & specificity of the two most commonly used stimulation tests were found to be 95%, 89% for the ITT and 73%, 81% for the GHRH+arginine test. Meta-analytic estimates of accuracy were associated with substantial heterogeneity.

Conclusion: Several tests with reasonable diagnostic accuracy are available for the diagnosis of growth hormone deficiency in adults. The supporting evidence, however, is at high risk of bias (due to heterogeneity, methodological limitations, and imprecision).

 

[Michael Scally MD]

The Relationships between Sex Hormones and Sexual Function in Middle-Aged and Older European Men

The importance of testosterone (T) for the maintenance of normal sexual function is well established in young eugonadal and hypogonadal men. However, its role in the sexual function of aging men remains controversial. Thus, a recent meta-analysis demonstrated a sizable and significant impact of T replacement therapy on libido but a moderate, nonsignificant, and inconsistent effect on erectile function in older patients (mean age, >50 yr).

The bulk of previous research has been conducted in the United States and focused on patients with erectile dysfunction (ED) using either the International Index of Erectile Dysfunction (IIED) or the single item measure from the Massachusetts Male Aging Study. Moreover, few of the existing instruments have been specifically developed for administration in large, population-based studies of nonpatient samples, and none of these measures assessed all aspects of sexual functioning [e.g. the IIED, Brief Sexual Function Inventory, and the Male Sexual Health Questionnaire do not assess frequency of sexual intercourse or masturbation]. In addition, many of the items included in the existing instruments are not appropriate for use in elderly men from the general population, as opposed to patients seeking medical attention for sexual or genitourinary complaints.

Recent work has explored the association between a number of sex hormones, broader aspects of sexual function, and psychological symptoms of male aging. This has been prompted by the worldwide increase in the number of men over 65 yr of age, which is predicted to double between 1980 and 2025, and the appreciation that sexual function remains a significant part of life in the elderly population. Furthermore, ED has become a more prevalent disorder, possibly related to the rise in obesity and vascular diseases.

Because circulating T declines with aging, androgen deficiency may affect a number of men at the lower extreme end of the physiological distribution. Although T deficiency is found in patients presenting with ED alone, it is commonly not the principal cause. Nevertheless, there is an increasing tendency to consider T treatment, especially in those patients unresponsive to phosphodiesterase type 5 inhibitors. Moreover, the practice of using T in the management of ED is currently not supported by an adequate evidence base. The causal relationship between low T and ED, unlike loss of sexual interest and spontaneous erection, has not been firmly established, although there is some preliminary animal experimental evidence that T may regulate nitric oxide-mediated vasodilation in ex vivo penile vasculature. It is, therefore, important to further investigate the relationships between T (and other sex hormones) and various domains of sexual function in a general population sample of men without the substantial biases inherent in patient samples.

Little research has explored the associations between sex hormones other than T and broader domains of sexual function such as sexual function-related distress (SF Distress). Recent work has been mixed, but some evidence has suggested that T metabolites such as estradiol (E2) and dihydrotestosterone (DHT) may be implicated in the agerelated decline of sexual function. For example, in a randomized, double-blind, placebo-controlled trial, researchers demonstrated that suppression of circulating serum DHT (by 5alpha-reductase inhibitors) resulted in modest, but reversible, reduction in sexual function in men. In addition, no previous studies have used mass spectrometry-based methods [e.g. gas chromatography-mass spectrometry (GC-MS)] with improved accuracy and precision in serum T, DHT, and E2 measurements, as recommended by The Endocrine Society, in studies of male sexual function.

Using baseline data from the European Male Ageing Study (EMAS), an ongoing epidemiological study of aging in middle-aged and older men, research recently showed that low T was associated with three sexual symptoms (e.g. decreased morning erection, ED, and decreased frequency of sexual thoughts). However, this work was focused on developing evidence-based criteria for identifying late-onset hypogonadism in the general population.

In contrast, the current study aimed to examine the relationships between multiple sex hormones (T, E2, and DHT) measured by GC-MS and all the principal domains of sexual function [i.e. overall sexual functioning (Overall SF), SF Distress, masturbation, and ED] in men with a current sexual partner. A secondary aim was to investigate whether any observed associations could be explained by lifestyle, health, and psychological factors.

Three main findings emerged from the current study.

First, T, and not E2 or DHT, was found to be related to Overall SF in middle-aged and older European men.

Second, there was a T threshold for the relationship between total T, Overall SF, and ED.

Third, E2 was the only hormone associated with SF Distress.

Moreover, this is the first study to simultaneously explore, in community-dwelling men, all aspects of sexual function including frequency of sexual behavior activities (pertinent to the wide age range under study) including libido, masturbation, ED, and distress while controlling for lifestyle factors (e.g. smoking, alcohol consumption), the presence of morbidities (e.g. heart disease, diabetes), and the availability of a sexual partner.


O'Connor DB, Lee DM, Corona G, et al. The Relationships between Sex Hormones and Sexual Function in Middle-Aged and Older European Men. Journal of Clinical Endocrinology & Metabolism. The Relationships between Sex Hormones and Sexual Function in Middle-Aged and Older European Men

Context: Limited data are available exploring the associations between sex hormones, multiple domains of sexual functioning, and sexual function-related distress in nonpatient samples in Europe.

Objectives: The aim of the study was to investigate the relationships between serum testosterone (T), estradiol (E2), and dihydrotestosterone (DHT) and sexual function in a multicenter population-based study of aging in men.

Design: Using stratified random sampling, 2838 men aged 40-79 yr completed the European Male Ageing Study-Sexual Function Questionnaire and provided a blood sample for hormone measurements. T, E2, and DHT were measured using gas chromatography-mass spectrometry.

Setting: We conducted a community-based population survey in eight European centers.

Main Outcome Measures: Self-reported sexual function (overall sexual function, sexual function-related distress, erectile dysfunction, masturbation) was measured.

Results: Total and free T, but not E2 or DHT, was associated with overall sexual function in middle-aged and older men. E2 was the only hormone associated with sexual function-related distress such that higher levels were related to greater distress. Free T levels were associated with masturbation frequency and erectile dysfunction in the fully adjusted models, such that higher T was associated with less dysfunction and greater frequency. Moreover, there was a T threshold for the relationship between total T, sexual function, and erectile dysfunction. At T concentrations of 8 nmol/liter or less, T was associated with worse sexual functioning, whereas at T levels over 8 nmol/liter, the relationship came to a plateau.

Conclusions: These findings suggest that different hormonal mechanisms may regulate sexual functioning (T) vs. the psychological aspects (E2) of male sexual behavior. Moreover, there was a T threshold for overall sexual function such that at levels greater than 8 nmol/liter the relationship between T and sexual function did not become stronger.

 

[Michael Scally MD]

Does Weight Loss Improve Semen Quality And Reproductive Hormones - YES

The prevalence of overweight and obese individuals is increasing globally and concern is rising over the reproductive consequences of male obesity. Male obesity has been linked to subfecundity and a dose-response relationship between increasing BMI and subfecundity has been proposed. Furthermore, male obesity has been associated with abnormal semen characteristics, although results are conflicting. The hormonal abnormality associated with obesity is likely to play a major role, and although controversial, previous studies have shown that the endocrine abnormalities may be reversed by weight reduction.

Several studies have focused on inhibin B (Inh-B), and more recently anti-Müllerian hormone (AMH), both produced almost exclusively by the Sertoli cells, as markers of spermatogenesis. Studies have shown Inh-B to be positively associated with fecundability, and obesity has been shown to be associated with a decreased level of Inh-B. However, results are conflicting and studies on the association between obesity and AMH are lacking.

It is unclear to what extent obesity affects a man’s reproductive potential. The existing studies on this subject are all cross-sectional, a limited design for deriving causal inferences. There may be a causal link between male obesity and poor semen quality, however, they may also share a common etiological factor. Longitudinal studies investigating how weight loss affects semen quality are needed to disentangle these two hypotheses, but no such studies have yet been published. In this paper, researchers present results from a pilot cohort study with prospectively collected data, investigating how obesity and weight loss affect reproductive hormones including AMH and Inh-B, conventional semen characteristics as well as sperm DNA integrity.

They observed that the altered androgen profile tended to improve following weight loss and that weight loss may potentially lead to improvement in semen quality, although they can not conclude this to be a result of the reduction in body weight per se. The observation has biologic plausibility, but the findings should be replicated in a larger cohort with longer follow-up time including a wider range of BMI levels.


Hakonsen LB, Thulstrup AM, Skaerbech Aggerholm A, et al. Does weight loss improve semen quality and reproductive hormones? Results from a cohort of severely obese men. Reprod Health 2011;8(1):24. Reproductive Health | Abstract | Does weight loss improve semen quality and reproductive hormones? Results from a cohort of severely obese men.

Background - A high body mass index (BMI) has been associated with reduced semen quality and male subfecundity in some studies, but no studies following obese men losing weight have been published. We examined semen quality and reproductive hormones among morbidly obese men and studied if weight loss improved the reproductive indicators.

Methods - In this pilot cohort study, 43 men with BMI > 33 kg/m2 were followed through a 14 week residential weight loss program. The participants provided semen samples and had blood samples drawn, filled in questionnaires, and had clinical examinations before and after the intervention. Conventional semen characteristics as well as sperm DNA integrity, analysed by the sperm chromatin structure assay (SCSA) were obtained. Serum levels of testosterone, estradiol, sex hormone-binding globulin (SHBG), luteinizing hormone (LH), follicle-stimulating hormone (FSH), anti-Mullerian hormone (AMH) and inhibin B (Inh-B) were measured.

Results - Participants were from 20 to 59 years of age (median = 32) with BMI ranging from 33 to 61 kg/m2. At baseline, after adjustment for potential confounders, BMI was inversely associated with sperm concentration (p = 0.02), total sperm count (p = 0.02), sperm morphology (p = 0.04), and motile sperm (p = 0.005) as well as testosterone (p = 0.04) and Inh-B (p = 0.04) and positively associated to estradiol (p < 0.005). The median (range) percentage weight loss after the intervention was 15 (4 - 25) %. Weight loss was associated with an increase in total sperm count (p = 0.02), semen volume (p = 0.04), testosterone (p = 0.02), SHBG (p = 0.03) and AMH (p = 0.02). The group with the largest weight loss had a statistically significant increase in total sperm count [193 millions (95% CI: 45; 341)] and normal sperm morphology [4% (95% CI: 1; 7)].

Conclusion - This study found obesity to be associated with poor semen quality and altered reproductive hormonal profile. Weight loss may potentially lead to improvement in semen quality. Whether the improvement is a result of the reduction in body weight per se or improved lifestyles remains unknown.