Ask the doctor: Are testosterone and cholesterol levels related? - Harvard Health
WebMD explains researchers' efforts to find out if testosterone supplements can head off heart trouble. Testosterone has been linked to cardiac risk factors like peripheral artery effect on cardiac risk factors, including HDL ("good") cholesterol levels. . about the relationship between testosterone and other cardiac risk factors. Testosterone therapy may be used for a variety of medical conditions. It may also have side effects, such as acne or other skin problems.Why Does Testosterone Decrease - The Truth About How to Boost Testosterone- Thomas DeLauer
While meta-analyses of such trials [ 2 ] suggest that TRT does not increase CVD risk, a recent randomized trial suggested that TRT might increase risk in certain clinical populations [ 3 ]. In this article, we review newly published studies evaluating TRT in older men and explore alterations in circulating lipids as one possible mechanism whereby T might influence CVD risk.
Multiple cross-sectional studies have examined the association between endogenous T levels and the presence of coronary artery disease. Wu and von Eckardstein [ 4 ] performed an extensive review of these cross-sectional analyses and concluded that despite inconsistencies among the studies, overall, coronary disease appeared to be associated with low endogenous T concentrations in men.
More recently, Malkin et al. The authors also found higher vascular and all-cause mortality among men with low plasma T levels when compared with men without androgen deficiency.
However, while these types of analyses attempt to control for covariates, they do not allow clear discernment as to whether T levels are directly related to CVD risk or, alternatively, serve as a marker of ill health overall. Similar to these cross-sectional analyses, longitudinal data have shown mixed findings, although most studies have not demonstrated a relationship between circulating T levels and incident CVD.
This type of study design generally entails measurement of a single, or possibly two, serum T levels in participants, whose health trajectories are then followed over the ensuing years. These longitudinal analyses, therefore, relate endogenous T levels to the development of disease over time.
Multiple longitudinal studies [ 6 — 9 ] and a meta-analysis of these [ 10 ] have found that low T levels are associated with higher all-cause mortality but whether or not these results were attributable to increased CVD remains unclear. Additional studies have focused specifically on cardiovascular events and mortality. The Rancho Bernardo study followed men aged 40—79 years over a year period and found no association between plasma T levels and either extant CVD or subsequent cardiovascular morbidity and mortality [ 11 ].
In contrast, men in the highest quartile of serum T in the MrOS study had the lowest incidence of CVD events over 5 years of follow-up [ 12 ]. Additional longitudinal studies have similarly found that neither high nor low T levels predict incident myocardial infarction [ 14 — 16 ]. An alternative approach, employed to examine the association between T levels over time and CVD, was a nested case—control study within the Baltimore Longitudinal Study of Aging [ 17 ] and the Multiple Risk Factors Intervention Trial [ 18 ].
Subjects enrolled in these studies were followed over a long period of time and then divided into cases or controls, based on development of coronary events.
Testosterone and the heart - Harvard Health
T levels were then measured in stored blood samples from initial study visits and analyzed for differences between the two groups. Investigators found no differences in baseline circulating T levels, between the controls and those men who developed incident coronary events, over a decade of follow-up.
In aggregate, though there have been mixed results regarding the relationship between low endogenous T levels and incident CVD, these studies suggest that, if anything, higher T levels may be protective.
The inconsistency among the longitudinal data may in part be due to the design of such studies and the reliance on single, or even duplicate measures of serum T. Since day-to-day variation of T concentrations in a given individual can be large [ 19 ], these single low measurements may not be as meaningful as multiple measurements over time.
An alternative interpretation of these longitudinal data, like those from cross-sectional studies, is that low T levels are a marker of ill health.
Studies of very healthy older men do not show significant declines in serum T over time [ 21 ]. Overall, these types of longitudinal analyses also fail to provide evidence of a direct, causal relationship between androgen exposure and CVD. Given the absence of a clear, causal relationship, clinical use of TRT is predicated on the presence of hypogonadal symptoms rather than cardiometabolic disease.
Accordingly, clinical intervention studies have been performed to investigate whether TRT can mitigate CVD risk factors among men with low endogenous T concentrations; however, none of these have been powered to examine CVD event rates. Three meta-analyses of randomized controlled trials to date did not indicate an association between TRT and CVD [ 222 — 23 ], but a more recent meta-analysis [ 24 ] came to the opposite conclusion.
However, these authors did not restrict their data to randomized controlled trials that limited enrollment to older men with low baseline T, making their conclusions more difficult to interpret regarding TRT and CVD in men treated according to clinical guidelines [ 1 ].
In contrast, another recent meta-analysis [ 25 ] that included the largest number of studies so far did not find any association between TRT and CVD risk. The authors further suggested that the Xu meta-analysis may have noted an association because their definition of cardiovascular events was more inclusive than typical restriction to major adverse cardiovascular events.
Furthermore, another meta-analysis found that TRT appeared to confer mortality benefit specifically in hypogonadal men with Type 2 diabetes [ 26 ]. However, it is important to remember that all of these studies, regardless of findings, have methodological weaknesses that limit their interpretive value.
Nevertheless, of potential concern are results from the TOM trial [ 3 ]. This randomized controlled trial of elderly, frail men was halted early by the data safety monitoring board due to an excess of cardiovascular events noted among older men randomized to testosterone as compared with placebo. It is notable, however, that these community-dwelling participants had very significantly reduced mobility, a high prevalence of chronic disease, and that they received rather high doses of T in this study.
Thus, broad extension of these findings to less frail and less chronically ill populations of hypogonadal men may not be appropriate. In fact, a similar study of comparable size and design did not observe such an increase in CVD events among men randomized to the T arm [ 27 ].
An additional noteworthy difference between these two studies was the baseline mean T concentration among study subjects; while baseline T concentrations in the TOM trial were in the hypogonadal range, those in the European study were in the low-normal range, perhaps reflecting differences in overall health status between the participants. Therefore, the higher rate of cardiovascular events noted in the TOM trial might be attributable to a poorer baseline cardiometabolic profile among the participants.
Importantly, the interpretive value of these randomized controlled trials remains limited, as these studies were not powered to look at CVD events as an outcome. Nonetheless, the results of the TOM trial provide important cautionary information regarding the potential for TRT to be harmful in at least some populations of older men and points to the need for larger studies.
Recently, larger cross-sectional studies have been undertaken to better define the cardiovascular effects of TRT. In contrast to the cross-sectional studies mentioned above, these studies have attempted to analyze large populations of men who received exogenous T, presumably as TRT.
Two of these large analyses have concluded that TRT is associated with an increase in cardiovascular events and these studies have received significant attention in the media [ 2829 ]. However, interpretation of these data is complicated by nature of their retrospective design and complexities in determining subject behavior within a population, and hence, do not allow for conclusions regarding causality.
All patients included in this retrospective analysis had low serum T concentrations and had undergone coronary angiography. After adjustment for over 50 variables, those individuals who had received a prescription for T following coronary angiography had a higher incidence of CVD events compared with the group who had not received a T prescription over an average of Furthermore, the actual exposure to T among the subjects is not clear, as the treatment group was categorized on the basis of a single-filled prescription, and post-treatment T levels were not measured nor was long-term use confirmed.
Notably, this study generated substantial controversy on the basis of these and other criticisms [ 31 ]. In a second study, Finkle et al.
However, data on prescription fulfillment were lacking, and whether the men prescribed TRT truly were hypogonadal, by both symptoms and T concentrations prior to receiving the prescription for T, was not determined. Contrary to the results of the population-based studies reviewed above, Shores et al. Overall, these types of retrospective analyses do not substantiate conclusions assigning a causal role for TRT in the development of cardiovascular morbidity but they clearly underscore the need for larger, randomized trials of TRT and CVD.
A randomized clinical trial powered to assess disease risk associated with TRT, including prostate cancer and cardiovascular events, has been estimated to require — subjects followed for approximately 7 years. Overview Testosterone therapy may be used for a variety of medical conditions. It may come with side effects, such as acne or other skin problems, prostate growth, and reduced sperm production.
Testosterone therapy may also affect your cholesterol levels. Research on testosterone and cholesterol has produced mixed results, however. Some researchers have found that testosterone lowers both high-density lipoprotein HDL and low-density lipoprotein LDL levels. Studies on the effect of testosterone on total cholesterol are also contradictory. On the other hand, several studies have found testosterone has no effect on triglyceride levels.
Read on to learn more about testosterone and cholesterol. Testosterone therapy is usually given for one of two reasons. First, some males have a condition known as hypogonadism.
An update on testosterone, HDL and cardiovascular risk in men
Testosterone is an important hormone. It plays a key role in the development and maintenance of male physical traits. The second reason is to treat the natural decline of testosterone.
American surgeons achieved success in this area inwhen they transplanted a testicle from a healthy man to his identical twin who was born without testicles. More recently, surgeons in Russia and China have experimented with transplants between unrelated men. They have reported some success, but only in recipients who were treated with powerful immunosuppressive medications. Testicular transplantation is technically possible, but the operation should not be considered except in extremely rare circumstances.
There must be an easier way to treat testosterone deficiency. Cardiac events and mortality Four small, brief trials of testosterone's effect on treadmill performance in men with heart disease hint that the hormone may be helpful.
Clearly, though, it's much more important to see if testosterone therapy can change the risk of actual clinical cardiovascular events. The Mayo Clinic scientists who reviewed 30 placebo-controlled trials of testosterone therapy identified only six that reported clinical events. Together, these studies evaluated men who received placebo and who received testosterone for up to three years; testosterone did not appear to change the incidence or severity of cardiovascular events, though there was a trend toward more heart problems in the men who got the hormone.
The most important cardiovascular event is death from heart disease. The Massachusetts Male Aging Study linked high free testosterone levels with a modest increase in risk of death from coronary artery disease, but other studies report the opposite, finding that low testosterone levels are associated with an increased risk of cardiac death.
None of these observational studies establish causality, and none can tell us if testosterone therapy is heart-healthy or -harmful; more research is needed. Are we the men we were? Testosterone levels decline slowly as men age. But a study suggests that sincethe hormone's levels have fallen in American men independent of age. Researchers measured testosterone levels in 1, randomly selected men during three time periods, —89, —97, and — There was a slow but steady decline in average testosterone levels over the study period.
Since smoking boosts testosterone levels, and obesity has the opposite effect, the scientists checked to see if the change could be explained by a decline in smoking or an increase in obesity, but neither possibility held up. More research is needed to find out why testosterone levels have declined. Testosterone-replacement controversy Heart disease is the number one killer of American men, but most men who receive testosterone therapy are taking the drug to treat other organs.
Testosterone therapy may be safe for the heart, but how about the rest of the body? Although the problem is relatively common, it is underdiagnosed. Experts do not recommend routine testing for testosterone deficiency.
But you should request a test if you have symptoms such as those listed above. If you have your testosterone levels measured, try to have the blood drawn between 7 a.