Although some men believe that taking testosterone medications may help them feel younger and more vigorous as they age, few rigorous studies have examined testosterone therapy in men who have healthy testosterone levels. And some small studies have revealed mixed results. For example, in one study healthy men who took testosterone medications increased muscle mass but didn't gain strength.
Cardiovascular disease, and its underlying pathological process atherosclerosis, is an important cause of morbidity and mortality in the developed and developing world. Coronary heart disease in particular is the commonest cause of death worldwide (AHA 2002; MacKay and Mensah 2004). As well as increasing with age, this disease is more common in the male versus female population internationally, which has led to interest in the potential role of sex hormones in modulating risk of development of atherosclerosis. Concerns about the potential adverse effects of testosterone treatment on cardiovascular disease have previously contributed to caution in prescribing testosterone to those who have, or who are at risk of, cardiovascular disease. Contrary to fears of the potential adverse effects of testosterone on cardiovascular disease, there are over forty epidemiological studies which have examined the relationship of testosterone levels to the presence or development of coronary heart disease, and none have shown a positive correlation. Many of these studies have found the presence of coronary heart disease to be associated with low testosterone levels (Reviews: Jones, Jones et al 2003; Jones et al 2005).
At the present time, it is suggested that androgen replacement should take the form of natural testosterone. Some of the effects of testosterone are mediated after conversion to estrogen or dihydrotestosterone by the enzymes aromatase and 5a-reductase enzymes respectively. Other effects occur independently of the traditional action of testosterone via the classical androgen receptor- for example, its action as a vasodilator via a cell membrane action as described previously. It is therefore important that the androgen used to treat hypogonadism is amenable to the action of these metabolizing enzymes and can also mediate the non-androgen receptor actions of testosterone. Use of natural testosterone ensures this and reduces the chance of non-testosterone mediated adverse effects. There are now a number of testosterone preparations which can meet these recommendations and the main factor in deciding between them is patient choice.
An international consensus document was recently published and provides guidance on the diagnosis, treatment and monitoring of late-onset hypogonadism (LOH) in men. The diagnosis of LOH requires biochemical and clinical components. Controversy in defining the clinical syndrome continues due to the high prevalence of hypogonadal symptoms in the aging male population and the non-specific nature of these symptoms. Further controversy surrounds setting a lower limit of normal testosterone, the limitations of the commonly available total testosterone result in assessing some patients and the unavailability of reliable measures of bioavailable or free testosterone for general clinical use. As with any clinical intervention testosterone treatment should be judged on a balance of risk versus benefit. The traditional benefits of testosterone on sexual function, mood, strength and quality of life remain the primary goals of treatment but possible beneficial effects on other parameters such as bone density, obesity, insulin resistance and angina are emerging and will be reviewed. Potential concerns regarding the effects of testosterone on prostate disease, aggression and polycythaemia will also be addressed. The options available for treatment have increased in recent years with the availability of a number of testosterone preparations which can reliably produce physiological serum concentrations.
Falling in love decreases men's testosterone levels while increasing women's testosterone levels. There has been speculation that these changes in testosterone result in the temporary reduction of differences in behavior between the sexes. However, it is suggested that after the "honeymoon phase" ends—about four years into a relationship—this change in testosterone levels is no longer apparent. Men who produce less testosterone are more likely to be in a relationship or married, and men who produce more testosterone are more likely to divorce; however, causality cannot be determined in this correlation. Marriage or commitment could cause a decrease in testosterone levels. Single men who have not had relationship experience have lower testosterone levels than single men with experience. It is suggested that these single men with prior experience are in a more competitive state than their non-experienced counterparts. Married men who engage in bond-maintenance activities such as spending the day with their spouse/and or child have no different testosterone levels compared to times when they do not engage in such activities. Collectively, these results suggest that the presence of competitive activities rather than bond-maintenance activities are more relevant to changes in testosterone levels.
Many studies demonstrate an improvement in mood of hypogonadal men treated with testosterone (Wang et al 1996; Azad et al 2003). The relationship between testosterone status and mood, particularly depression, remains unresolved. Using Beck’s Depression Inventory, Barrett-Connor and colleagues found that the depression score worsened as men aged, exactly at a time when testosterone levels are decreasing (Barrett-Connor et al 1999). Pope and colleagues found that testosterone treatment in men with refractory depression lowered the Hamilton Depression rating scale and the Clinical Global Impression severity rating (Pope et al 2003). The Beck Depression Inventory remained unchanged in Pope’s study.
Smith and colleagues (2005) undertook a prospective study on the contribution of stress to coronary heart disease. Their study, which involved 2512 men aged 45 to 59 years, looked at a number of metabolic parameters. They found that an increased cortisol to testosterone ratio was associated with a high risk of coronary artery disease and that this risk was mediated by components of the insulin resistance syndrome. They reported that high cortisol and low testosterone levels are associated with a worsening of insulin resistance and that there is evidence to support the possibility of improving this pattern by treatment with testosterone.
There are valid concerns about the safety of long-term treatment with testosterone particularly with respect to the cardiovascular system and the potential for stimulating prostate cancer development. There are no convincing hard data, however, to support these concerns. If anything, the data strongly suggest that adequate testosterone availability is cardioprotective and coronary risk factors such as diabetes, obesity and the metabolic syndrome are associated with reduced testosterone levels. It is certainly appropriate to avoid giving testosterone to men with prostate or breast cancer but it is not appropriate to accuse testosterone of inducing the development of de novo prostate cancers since evidence for this accusation is lacking (Wang et al 2004; Feneley and Carruthers 2006).
Testosterone is only one of many factors that influence aggression and the effects of previous experience and environmental stimuli have been found to correlate more strongly. A few studies indicate that the testosterone derivative estradiol (one form of estrogen) might play an important role in male aggression. Studies have also found that testosterone facilitates aggression by modulating vasopressin receptors in the hypothalamus.
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Hypogonadism is a disease in which the body is unable to produce normal amounts of testosterone due to a problem with the testicles or with the pituitary gland that controls the testicles. Testosterone replacement therapy can improve the signs and symptoms of low testosterone in these men. Doctors may prescribe testosterone as injections, pellets, patches or gels.