Thursday, September 20, 2012

Maybe Testosterone Replacement Is Not the Answer

I have advocated for testosterone replacement for men with low or even low-normal testosterone levels for many years. More and more doctors have gotten on board with that approach despite a very vocal minority of doctors who consider it dangerous or non-effective.

Some of the symptoms of low testosterone include muscle loss and strength decline, cognitive decline, cardiovascular disease, decreased libido, erectile dysfunction, depression, decreased masculinity, fat gain, metabolic disorders, decreased energy and work performance, and even height loss due to loss of bone density.

Unless the man is concerned about fertility, the usual method of replacement is a transdermal gel or cream, and some of the better known products are AndroGel, Axiron, Testim, and Fortesta. In younger men concerned about fertility, testosterone injections are given every two weeks or up to every three months, depending on the form.

Some of the risks of testosterone therapy include growth of prostate cancer and breast cancer, worsened symptoms of benign prostatic hypertrophy, liver toxicity and liver tumor (only with oral administration), gynecomastia (breast tissue growth), erythrocytosis (thickening of blood due to increased red blood cell production), testicular atrophy and infertility, skin diseases (usually only with the patch), and new or exacerbated sleep apnea.

Most or all of these can be managed with an aromatase inhibitor to prevent the conversion of testosterone to estrogen and with maintaining moderate T levels as opposed to high-normal.

For a good overview of the benefits and risks, The benefits and risks of testosterone replacement therapy: A review by Nazem Bassil, Saad Alkaade, and John E Morley (2009) is a an excellent open access paper (Ther Clin Risk Manag.; 5: 427–448).

All of this brings me to the point of this post - there might be another way to get the benefits while reducing the risks.

Dr. William Llewellyn often researches and writes about hormone manipulation in athletes (body builders mostly) and the general public - his team offers testosterone therapy for aging men. He recently posted an article that summarizes some new research on using aromatase inhibitors to reduce estrogen and increase testosterone, without the risks of t-replacement therapy. Better yet, these can be taken as a daily pill with no liver risks, and no injections to worry about.

Arimidex vs. Femara for increasing testosterone in men (HRT)

Testosterone medications like AndroGel, Axiron, Testim, and Fortesta are the products most widely prescribed to treat age related hormone decline in men, a condition know as andropause or adult hypogonadism. However, direct hormone replacement is not ideal for all patients. This often includes men looking to maintain fertility, or those with low testosterone caused by excess estrogen. To better treat such cases, a number of alternate therapies are being investigated. Several of these involve anti-estrogenic or aromatase-inhibiting drugs, which can raise testosterone levels by lowering the activity of estrogen. This works because estrogen is a strong inhibiting signal towards testosterone synthesis in men. When estrogen levels go up, testosterone drops.

Researchers at the Aretaieion Hospital in Athens Greece recently completed a study comparing the use of Femara (letrozole) and Arimidex (anastrozole) in men with low testosterone, which are two of the more potent and modern aromatase inhibitors. The study involved infertile men (n=29), all having testosterone concentrations below 300 ng/dL and a T/E ratio under 10. The men were divided into two groups, each given either 1 mg of anastrozole or 2.5 mg of letrozole per day. The medications were continued for six months. At the end of therapy, basic health markers were compared to baseline, including hormone levels and sperm density. The data is presented in the tables below.

The results in this study appeared to be promising for both drugs. Sperm density was improved in 73.4% of the men taking letrozole, and 78.6% for those using anastrozole. Testosterone was substantially improved for both groups as well. With men taking letrozole, testosterone increased from 275 ng/dL to 495 ng/dL on average, an 80% bump. With anastrozole, the average testosterone level went from 265 ng/dL to 513 ng/dL, or a 94% increase. Side effects were mild and transient, including GI upset, lethargy, headache, and liver enzyme elevations in a small number of patients. Both drugs were deemed “well tolerated”, and none of the participants were forced to discontinue treatment.

No comparative conclusions could be drawn in this study. Letrozole and anastrozole appeared equally effective at treating men with low testosterone, infertility, and low T/E ratio. There are still questions that need to be answered, especially when it comes to the long-term safety of this type of therapy. In particular, there are some concerns with a potential loss of bone mineral density, or elevations in serum cholesterol and cardiovascular disease risk. Still, the results here were promising, and add to a series of other positive studies with men taking AI drugs for low testosterone. The present researchers have furthered this discussion by recommending the use of T/E ratio as an additional diagnostic tool. A ratio below 10:1 would identify those hypogonadal men that might benefit from aromatase inhibitor therapy.

Source: Fertil Steril. 2012 May 11. [Epub ahead of print]


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