Got testosterone – page 101 cancer blood transfusion

This is one of the more important studies looking at this topic. Why? Vast majority of studies are epi/correlational/observational studies that find an association between T and X disease, pos or neg. Page 1 of any good epi book correlation does not = causation and so there’s a limited amount of conclusive info from such studies, no matter how compelling they appear. This was a direct intervention study where they actively manipulated the variables (in this case T and estradiol) with meds to raise/lower T and estradiol to see what impact it had on risk factors for CVD. What did they find? Levels of T nor E independently impacted known risk factors, but the ratio of T/E did. That’s something that more cutting edge scientists/docs have understood for a while, and why men should never go on an AI unless absolutely needed, which is most cases, they don’t need.

Why men have more heart disease than premenopausal women has been unclear, but a new study shows that the sex hormones testosterone and estrogen alter cardiovascular risk factors in a way that raises a man’s risk of heart disease. Results of the study will be presented Saturday at the Endocrine Society’s 97th annual meeting in San Diego.

Men have higher testosterone and lower estrogen levels than premenopausal women. Therefore, doctors have suspected that testosterone may promote cardiovascular disease or that estrogen may protect against it, or both, according to Elaine Yu, MD, MSc, the study’s lead investigator and an assistant professor at Harvard Medical School, Boston.

Their study, conducted in 400 healthy men ages 20 to 50, found that higher levels of testosterone led to lower levels of HDL cholesterol, or good cholesterol, but estrogen appeared to have no effect on HDL cholesterol. In contrast, the investigators reported that low levels of estrogen led to higher fasting blood glucose (sugar) levels, worsening insulin resistance and more fat in muscle, markers for developing diabetes, which is itself a risk factor for heart disease.

At the start of the study, all men received the drug goserelin (Zoladex, AstraZeneca) to suppress their own production of testosterone and estrogen. Then the 198 men in the first group received daily treatment for four months with either a placebo (dummy) gel or one of four doses of testosterone gel (AndroGel, AbbVie), ranging from low to high (1.25 to 10 grams). This treatment set the men’s testosterone levels from very low (as in before puberty) to high-normal, Yu said.

The other group, made up of 202 men, received the same treatment as in group 1 but also received anastrozole (Arimidex, AstraZeneca) to block conversion of testosterone to estrogen. Men naturally convert some testosterone to estrogen. Blocking this process resulted in very low levels of estrogen in the second group, according to Yu.

The researchers found that neither testosterone nor estrogen regulated changes in LDL, or bad, cholesterol; blood pressure; and body weight. It appears that these common risk factors for cardiovascular disease are not regulated by sex hormones, Yu said.

We know being obese suppresses T levels, and losing some BF one of most effective ways to increase T levels. One reason we are seeing men with lower T levels is in part due to increased rates of obesity, and automatically putting an obese man on TRT due low T is not always the right approach. The first thing I ask men with low T on the net is what’s their BMI, or bodyfat % of they know it, as that’s often the answer to their problem and they’re looking a magic shot (literally) vs dropping some fat. This review covers that topic well:

Obesity, increasing in prevalence globally, is the clinical condition most strongly associated with lowered testosterone concentrations in men, and presents as one of the strongest predictors of receiving testosterone treatment. While low circulating total testosterone concentrations in modest obesity primarily reflect reduced concentrations of sex hormone binding globulin, more marked obesity can lead to genuine hypothalamic-pituitary-testicular axis (HPT) suppression.

HPT axis suppression is likely mediated via pro-inflammatory cytokine and dysregulated leptin signalling and aggravated by associated comorbidities. Whether estradiol-mediated negative hypothalamic-pituitary feedback plays a pathogenic role requires further study. Although the obesity-hypogonadism relationship is bi-directional, the effects of obesity on testosterone concentrations are more substantial than the effects of testosterone on adiposity. In markedly obese men submitted to bariatric surgery, substantial weight loss is very effective in reactivating the HPT axis.

In contrast, lifestyle measures are less effective in reducing weight and generally only associated with modest increases in circulating testosterone. In randomised controlled clinical trials (RCTs), testosterone treatment does not reduce body weight, but modestly reduces fat mass and increases muscle mass. Short-term studies have shown that testosterone treatment in carefully selected obese men may have modest benefits on symptoms of androgen deficiency and body composition even additive to diet alone. However, longer-term, larger RCTs designed for patient-important outcomes and potential risks are required.

Until such trials are available, testosterone treatment cannot be routinely recommended for men with obesity-associated non-classical hypogonadism. Lifestyle measures or where indicated bariatric surgery to achieve weight loss, and optimisation of comorbidities remain first line.