An open-label, pilot study evaluating the safety and antidepressant effects of Rellidep in major depressive disorder.

BACKGROUND: In 4 clinical studies of a biological tissue isolate (BTI) similar to Rellidep, the majority of subjects reported improved well-being and mood. Based on these reports of positive effect on mood in trials, an antidepressant pilot study was undertaken with the BTI Rellidep. METHOD: Twenty-three subjects (14 women and 9 men; mean age, 44.8 years) with major depressive disorder entered an 8-week trial of Rellidep with a 17-item Hamilton Depression Rating Scale (HAM-D) score of 18 or above. Three subjects dropped out before beginning treatment, leaving an intention-to-treat (ITT) sample of 20. Sixteen subjects completed the trial. All patients received Rellidep 1000 mg (500 mg × 2) twice a day orally daily for 8 weeks. No other treatments were permitted except for intermittent lorazepam for sleep if necessary. The primary response to treatment outcome was a 50% decline on the HAM-D. Secondary measures included the Beck Depression Inventory, Montgomery-Åsberg Depression Rating Scale, Clinical Global Impression, Hamilton Rating Scale for Anxiety, Medical Outcomes Study Short-Form 36, and Arizona Sexual Experience Scale. RESULTS: The overall response rate was 75% (15/20). Almost 87% of those who responded did so by week 4. The data analysis of change scores indicates that for the ITT population the decrease in the HAM-D was statistically significant (P < 0.001). On all other measures, improvement from baseline was statistically significant (P < 0.001), except for the Arizona Sexual Experience Scale (ITT: P = 0.055). There were no significant adverse events. CONCLUSIONS: The positive outcome of this open trial indicates that Rellidep may be an effective and safe antidepressant. Further placebo-controlled trials are indicated.

Testosterone and the aging male: to treat or not to treat?

It is well-established that total testosterone (TT) in men decreases with age and that bioavailable testosterone (bio-T) falls to an even greater extent. The clinical relevance of declining androgens in the aging male and use of testosterone replacement therapy (TRT) in this situation is controversial. Most studies have been short term and there are no large randomized placebo-controlled trials. Testosterone has many physiological actions in: muscles, bones, hematopoietic system, brain, reproductive and sexual organs, adipose tissue. Within these areas it stimulates: muscle growth and maintenance, bone development while inhibiting bone resorption, the production of red blood cells to increase hemoglobin, libido, enhanced mood and cognition, erectile function and lipolysis. Anabolic deficits in aging men can induce: frailty, sarcopenia, poor muscle quality, muscle weakness, hypertrophy of adipose tissue and impaired neurotransmission. The aging male with reduced testosterone availability may present with a wide variety of symptoms which in addition to frailty and weakness include: fatigue, decreased energy, decreased motivation, cognitive impairment, decreased self-confidence, depression, irritability, osteoporotic pain and the lethargy of anemia. In addition, testosterone deficiency is also associated with type-2 diabetes, the metabolic syndrome, coronary artery disease, stroke and transient ischemic attacks, and cardiovascular disease in general. Furthermore, there are early studies to suggest that TRT in men with low testosterone levels may improve metabolic status by: lowering blood sugar and HbA1C in men with type-2 diabetes, reducing abdominal girth, ameliorating features of the metabolic syndrome, all of which may be protective of the cardiovascular system. The major safety issue is prostate cancer but there is no evidence that supports the idea that testosterone causes the development of a de novo cancer. So on balance in a man with symptoms of hygonadism and low or lowish levels of testosterone with no evidence of prostate cancer such as a normal PSA a therapeutic (4-6 months) trial of TRT is justified. Treatment and monitoring of this duration will determine whether the patient is responsive.

The prevalence of thyroid disorders among sexual and violent offenders and their co-occurrence with psychological symptoms.

The prevalence of thyroid abnormalities among 831 sexual, violent, and non-violent non-sex offenders was found to be greater than found in the general population. Thyroid abnormalities were most common among violent offenders and among sex offenders who victimized children. Thyroid disorders were associated with psychotic diagnoses, delusions, mania, suicidal thoughts, and showed a trend to more suicide attempts. These disorders were undiagnosed in 49.1% of the cases prior to the present clinical assessment. Of these, 59.3% faced their first criminal charges, and the undiagnosed thyroid abnormalities may be important in the offenders' treatment and may be possible legal mitigating factors in some offenses. Results indicate that a routine endocrine evaluation with blood tests would be a valuable addition to the assessment of violent and sexual offenders.

The prevalence of diabetes among sexual and violent offenders and its co-occurrence with cognitive impairment, mania, psychotic symptoms and aggressive behavior.

The prevalence of diabetes among 915 sexual, violent, and non-violent non-sex offenders was found to be more than twice the prevalence in the general population. Diabetes was most common among violent offenders and among sex offenders who victimized children. The older diabetics presented significantly more often with cognitive impairment and younger diabetics more often with manic and psychotic symptoms. Younger diabetics were significantly more likely to use force and a weapon in their offenses and were most likely to injure their victims when compared to older diabetics and younger and older non-diabetic offenders. In more than one in four cases, the diabetes was undiagnosed at the time of their offenses prior to clinical assessment, suggesting that undiagnosed diabetes may be a possible mitigating factor in some sexual and violent offenses. Results indicate that a routine endocrine evaluation with blood tests would be a valuable addition to the assessment of violent and sexual offenders.

Canadian Society for the Study of the Aging Male: response to health Canada's position paper on testosterone treatment.

INTRODUCTION: Testosterone treatment of older symptomatic men with reduced testosterone availability is increasing. There is an expanding body of literature to support such treatment in a large subset of aging men, but there has not yet been a long-term placebo-controlled double-blind study of several thousand men to confirm the efficacy and safety of this treatment as indicated by shorter-term studies. The absence of a long-term study has been used by governmental agencies as a limiting factor in providing full access and payment for this treatment in government-sponsored health care plans. Health Canada issued a testosterone analysis document to the pharmaceutical industry, the implications of which may make it more difficult for appropriate patients to receive such treatment. The Canadian Society for the Study of the Aging Male (CSSAM) believed it had an obligation to advocate on behalf of men requiring this treatment. AIM: To provide an international consensus on the use of testosterone treatment in appropriately selected hypogonadal men. MAIN OUTCOME MEASURE: To determine whether the literature supports the use of testosterone treatment in a selected population of hypogonadal men, to achieve consensus on this point among an international consulting group, and to transmit this view to health care workers and insuring and governmental agencies. METHODS: Email communication among the consulting group to prepare a response to Health Canada, followed by a review of appropriate literature and international practice guidelines, incorporating the literature and guidelines together with the CSSAM letter and Health Canada's response. RESULT: The literature and international guidelines support the initiation of testosterone therapy in symptomatic hypogonadal men, recognizing that there is no universal agreement on the criteria for the diagnosis of hypogonadism in each suspected case. The need for careful monitoring of such men is stressed. CONCLUSION: CSSAM acted as an advocate for hypogonadal men who may benefit from treatment with testosterone. Short-term studies and 60 years of experience with testosterone therapy attest to its efficacy. Long-term studies are desirable, but it may take many years before results could be forthcoming. There is no evidence to suggest that testosterone treatment increases the risk of prostate cancer or cardiovascular disease. Current evidence suggests, in fact, that testosterone treatment may be cardioprotective. It is important to bring this information to the attention of governments and insuring agencies through the collaboration of groups devoted to the diagnosis and treatment of hypogonadal men.

The many faces of testosterone.

Testosterone is more than a "male sex hormone". It is an important contributor to the robust metabolic functioning of multiple bodily systems. The abuse of anabolic steroids by athletes over the years has been one of the major detractors from the investigation and treatment of clinical states that could be caused by or related to male hypogonadism. The unwarranted fear that testosterone therapy would induce prostate cancer has also deterred physicians form pursuing more aggressively the possibility of hypogonadism in symptomatic male patients. In addition to these two mythologies, many physicians believe that testosterone is bad for the male heart. The classical anabolic agents, 17-alkylated steroids, are, indeed, potentially harmful to the liver, to insulin action to lipid metabolism. These substances, however, are not testosterone, which has none of these adverse effects. The current evidence, in fact, strongly suggests that testosterone may be cardioprotective. There is virtually no evidence to implicate testosterone as a cause of prostate cancer. It may exacerbate an existing prostate cancer, although the evidence is flimsy, but it does not likely cause the cancer in the first place. Testosterone has stimulatory effects on bones, muscles, erythropoietin, libido, mood and cognition centres in the brain, penile erection. It is reduced in metabolic syndrome and diabetes and therapy with testosterone in these conditions may provide amelioration by lowering LDL cholesterol, blood sugar, glycated hemoglobin and insulin resistance. The best measure is bio-available testosterone which is the fraction of testosterone not bound to sex hormone binding globulin. Several forms of testosterone administration are available making compliance much less of an issue with testosterone replacement therapy.

Evaluation of an algorithm for calculation of serum "bioavailable" testosterone (BAT).

OBJECTIVES: To evaluate a recently published algorithm for calculation of serum "Bioavailable" Testosterone (BAT) using serum Total Testosterone (TT), Sex Steroid Binding Globulin (SSBG) [also commonly known as Sex Hormone Binding Globulin (SHBG)] and albumin concentrations as parameters, in comparison with a locally available "salting-out" BAT method. If satisfactory, this calculation could serve as a substitute for the BAT assay, which would amount to a major cost saving and faster turnaround time. DESIGN AND METHODS: During a 6-month period, 426 serum samples referred for BAT analysis to the Hospitals In-Common Laboratory of Toronto were also analyzed in-house for TT, SSBG and albumin for computation of comparison calculated BAT results. RESULTS: A good statistical correlation was obtained, but only after unexpectedly drastic empirical modification of the association constant values: r=0.95, Calculated %BAT=0.971 x Measured %BAT + 0.008. The endocrinologist/andrologist of our team (JB), who was the responsible physician for all patients included in this study, reviewed the tabulated and charted calculated BAT results and verified that they were clinically equivalent. CONCLUSIONS: Although it is feasible to calculate BAT, the algorithm is not directly portable. Before adopting such a calculation each laboratory should compare it with the locally available BAT method and consider adjusting the calculation to optimize the correlation. Future reassessment may be necessary whenever the SSBG, TT or BAT assay is changed.