Men, Testosterone, and Estrogen

     There was an article published recently in the New England Journal of Medicine ( Vol 369, pp1011-1022, Sept. 12 2012) about the effect on men of testosterone and estrogen suppression. It was only a 12 week study, but the results are interesting. I will summarize the study here.

     Firstly, I should mention that the male production of testosterone decreases slowly with age. This actually means that even an "normal" level of testosterone at age 60 is abnormal in the sense that it is diminished from the level at age 20. All men have an enzyme that converts some testosterone to estradiol, an estrogen, and this conversion provides 80% of the circulating estradiol. (I should also mention here that in addition to estrogen and progesterone, all women secrete testosterone.) There are also studies showing that one of the causes of diminished sexual drive in menopausal women is a reduction in their testosterone level, so that estrogen replacement alone may not be enough to restore their sex drive. This was shown initially by a female OB-GYN in Canada.

     The experiment reported in the NEJM showed the effects of chemical castration which eliminated testosterone production. Some of the men also received a drug to inhibit the production of estrogen when the testosterone level was allowed to rise. The results of this climical study can be summarized as follows:

     Testosterone directly regulates lean mass,  muscular strength and sexual function. Testosterone deficiency decreases lean mass, muscle strength, muscle size and sexual function. Low estradiol also contributes to loss of libido and sexual function. Interestingly enough, low estradiol also contributes to increased abdominal fat, and possibly to osteoporosis as well.

     The increase in abdominal fat is medically worrisome, because this increase is associated with resistance to insulin (i.e. to pre-diabetes) as well as the metabolic syndrome. But the solution to low estradiol should not be estrogen replacement, because that was tried with men with prostate cancer and they developed severe cardiovascular problems. 

     The message I take from this study is that after replacing testosterone when necessary, then the estradiol level should be measured. If that level is still low, then the testosterone dose should be increased to normalize the estradiol level and thereby decrease the risk of the patient's developing the metabolic syndrome. It is also trivial to add that menopausal women should have their testosterone level measured.