Myocardial Infarction and Stroke Risk in Young Healthy Men Treated with Injectable Testosterone.

This study was conducted to examine the association between testosterone therapy and new myocardial infarction (MI) and stroke events in a series of patients treated at Low T Centers across the United States, consisting of mainly young (mean age = 46), otherwise, healthy men. Electronic medical records were queried between the years 2009 and 2014 to identify patients diagnosed with hypogonadism, MI, and stroke, as indicated by ICD-9 codes. The incidence of MI and stroke events was compared to community-based registries. 39,936 patients recruited from 40 Low T Centers across the United States were treated and 19,968 met eligibility criteria for receiving testosterone treatment. The incidence rate ratio (IRR) for MI in testosterone- (T-) treated versus nontreated patients was 0.14 (C.I. = 0.08 to 0.18, P < 0.0001) whereas the IRR for stroke for T-treated versus nontreated patients was 0.11 (C.I. = 0.02 to 0.13, P < 0.0001). There was no evidence of worsening preexisting MI or stroke in patients treated with testosterone. The experience in Low T Centers shows that, in an injectable testosterone patient registry, testosterone is generally safe for younger men who do not have significant risk factors. Of patients that developed MI with testosterone, there was no association with testosterone or hematocrit levels.

High estrogen in men after injectable testosterone therapy: the low T experience.

Testosterone replacement improves quality of life and is aromatized in men in adipose tissues to estrogen. Hyperestrogenism is believed to be harmful to male sexuality. This is a description of our experience of screening 34,016 men in the Low T Centers, of which approximately 50% were converted to treatment. Men were treated with injectable testosterone, and we have available data from 2009 to 2014. The data were extracted from our electronic health record (AdvancedMD) of 35 Low T Centers across the United States. In all, 7,215 (20.2%) out of the 34,016 patients had high estradiol levels defined as ≥42.6 pg/ml. Estradiol was measured using electro-chemiluminescence immunoassay. Of the patients who had high estradiol levels, the age distribution was as follows: 132/989 (13.3%) were older than 65 years, 3,753/16,955 (22.1%) were between 45 and 65 years; 2,968/15,857 (18.7%) were between 25 and 44 years, 7/215 (3.3%) were younger than 25 years. The difference between extreme age groups (<25 and ≥65) was statistically significant using a chi-square test (p = .013). The correlation coefficient of serum estradiol to age was .53, SD = 8.21. It was observed that practitioners used aromatase inhibitor and selective estrogen receptor modulator to treat symptoms of hyperestrogenism, irrespective of blood estradiol levels. Gynecomastia was rarely documented as a reason for the prescription. Our finding was that high estradiol levels were not associated with higher rates of low libido but established higher rates of documented low libido with those with normal or lower estradiol levels. The difference was statistically significant (p < .05).

Testosterone use in women: how safe is it?

Treatment of sex hormones deficiencies in men and women is a subject of considerable discussion due in no small measure to safety concerns. In order to appreciate the appropriate balance between potential risk and benefit, it is important to understand the issues at hand. This is particularly true in the case of the use of testosterone in women. To understand the effect of testosterone supplementation in deficient patients, it is useful to review the normal physiology of testosterone in women. An understanding of the impact of testosterone deficiency will further elucidate perspectives on the topic. This paper aims to present a rational consideration of the known and potential adverse effects of testosterone supplementation in women. Areas of concern regarding the use of androgens in women generally fall into three categories: masculinization, cardiovascular effects and cancer risks, but there are a variety of other issues to be borne in mind. Full understanding of these risks in the context of treating females experiencing testosterone deficiency is limited in some cases, and inferences have to be drawn from other areas.

The implications of increasing age on erectile dysfunction.

Erectile dysfunction (ED) has long been correlated with psychological well-being. More recently, an understanding has developed of ED being, in some cases, a vascular condition of the penile artery. Given the narrowness of the penile artery, a small amount of atherosclerosis may result in ED before any other manifestations are evident, making ED a useful marker for other vascular conditions with potentially greater clinical implications. In light of this, possible underreporting of ED takes on added significance. A questionnaire regarding ED prevalence and management was distributed for self-administration to men in the waiting room of primary care clinics; the data were analyzed with a focus on the relationship between ED and age. The study had a remarkable response rate of >95%. The prevalence of ED in the ≥70-year age-group was 77%, compared with 61% in the 40- to 69-year age-group (p = .0001). ED correlated linearly with age (R(2) = .80, p < .0001). Among those who had ED, more than half had not discussed it with any provider; the likelihood of discussing ED did increase with the reported severity of symptoms (p < .0001). Older men had more severe ED than younger men (p < .0001). Furthermore, 72% of men with a history of ED were never treated. Younger men were more likely to be treated than older men (p = .004). Given the potential implications of underreporting ED, and the willingness of the men in this study to complete the questionnaire, further work may be merited on new models for ED assessment and follow-up.

Androgens in the etiology of Alzheimer's disease in aging men and possible therapeutic interventions.

Animal experiments and cell biology studies have provided evidence that both estrogens and androgens can play a protective role against Alzheimer's disease (AD) related neurodegeneration. Males who become hypogonadal in later life often report problems with their memory. Lower than normal testosterone levels have also been detected in patients prior to the onset of AD, as well as in younger late-onset male AD patients, when compared to appropriate controls. The results of some small clinical trials suggest that testosterone can improve cognitive function in andropause. Although such improvement in cognitive function is subtle, patients on testosterone replacement therapy have reported memory improvements in both declarative and procedural domains. In contrast, there is no clinical evidence to date which suggest that the hormone dihydroepiandrosterone (DHEA) can improve cognitive function. Rises in the levels of the gonadotropins, follicle stimulating hormone (FSH) and luteinizing hormone (LH), have been associated with AD, but the clinical effects of reducing their levels remain to be determined. We hypothesize that androgens, gonadotropin modulators, or perhaps selective androgen receptor modulators may be useful components of therapy aimed at preventing the onset or delaying the progression of AD in male patients.

Is it andropause? Recognizing androgen deficiency in aging men.

In primary care practice, it is not unusual to encounter male patients in their 50s or older who report having loss of libido, erectile dysfunction, fatigue, and depression. Such signs and symptoms may signal an age-related decline in androgen levels, which commonly begins after age 40. However, psychologic problems and medical illness often confound the diagnosis. Drs Tan and Pu, who are currently conducting research on androgen deficiency, discuss the diagnostic difficulties of the physiologic phenomenon of andropause and offer a comprehensive approach to clinical assessment and laboratory evaluation.

Novel treatment options for overlapping yet distinct erectile dysfunction and andropause syndromes.

The Food & Drug Administration has recently approved, or is in the process of approving newer drugs such as the phosphodiesterase inhibitors and apomorphine to treat men's health issues including erectile dysfunction. Increasing age results in a gradual hypogonadal state in men, for which different novel delivery systems of androgens are currently offered for the symptomatic patient. As such, many men are presenting to healthcare practitioners for the first time. The age of presentation for erectile dysfunction and andropause often overlaps, typically in the fifties and beyond, therefore, it makes sense to screen for erectile dysfunction in andropause patients and vice versa. Erectile dysfunction is usually a harbinger for other illnesses, such as coronary heart disease and depression. The hypogonadal state, likewise, could be a harbinger for other ill health states in men, including obesity, depression, osteoporosis and possibly memory loss. While the newer treatments for erectile dysfunction and andropause are distinctly different and targeted at symptom relief, the presentation of the patient with erectile dysfunction or andropause offers an excellent opportunity for screening for other health states and health education strategies.

An integrative review on current evidence of testosterone replacement therapy for the andropause.

OBJECTIVES: This paper examines the evidence supporting testosterone replacement in aging males. Confounding factors contributing to low testosterone levels and challenges to diagnosis of the andropause will also be considered. METHODS: A thorough review using an integrative approach citing published literature and the ongoing work of the authors. A search was performed using National Library of Medicine PubMed. Electronic and print journals available at the Texas Medical Center library were also considered. RESULTS: Information based on collective trials in older men has added to evidence for benefits and side effects of testosterone replacement inferred from studies in younger hypogonadal patients and animal models. In general, most investigators agree with short-term safety but long-term safety is unknown. Testosterone therapy in aging males improves body composition, certain domains of brain function and may also decrease cardiovascular risk in biological models. Measurable clinical effects are less apparent. Potential risks include erythrocytosis, edema, gynecomastia, and prostate stimulation. The possibility of increased risk of clinically significant prostate cancer and cardiovascular disease has been considered. CONCLUSION: The search continues for an ideal replacement androgen and larger long-term studies are needed. At this time, androgen replacement is on a case-by-case basis and prostate cancer screening should be completed prior to instituting therapy. Routine androgen replacement therapy for aging males will have significant economic implications, and is not currently recommended.

The interlinked depression, erectile dysfunction, and coronary heart disease syndrome in older men: a triad often underdiagnosed.

The prevalence of depression, erectile dysfunction (ED), and coronary heart disease (CHD) increases with age, and the symptoms related to these three illnesses are closely interlinked. The term "DEC syndrome" is introduced to refer to this triad of comorbid conditions. When a patient presents with one component of the DEC syndrome, physicians should also screen for the other two components. Studies have shown that depression may predispose an individual to an increased risk of developing CHD, and older men with CHD are more likely to be depressed. Likewise, patients with ED are more likely to be clinically depressed, and patients with clinical depression often have ED. Furthermore, patients presenting with ED are often hypertensive, and thus have a significantly higher prevalence of cardiovascular complications. Multifactorial problems require multifactorial approaches, and the care of older men can improve if physicians are aware of this interlinked syndrome.

Use of clomiphene citrate to reverse premature andropause secondary to steroid abuse.

OBJECTIVE: To report a case of symptomatic hypogonadism induced by the abuse of multiple steroid preparations that was subsequently reversed by clomiphene. DESIGN: Case report. SETTING: University-affiliated andrology practice within family practice clinic. PATIENT(S): A 30-year-old male. INTERVENTION(S): Clomiphene citrate, 100-mg challenge for 5 days, followed by treatment at same dose for 2 months. MAIN OUTCOME MEASURE(S): Clinical symptoms, androgen decline in aging male questionnaire, total T, FSH, LH. RESULT(S): Reversal of symptoms, normalization of T levels with LH surge, restoration of pituitary-gonadal axis. CONCLUSION(S): Clomiphene citrate is used typically in helping to restore fertility in females. This represents the first case report of the successful use of clomiphene to restore T levels and the pituitary-gonadal axis in a male patient. The axis was previously shut off with multiple anabolic steroid abuse.