Estrogen is Important for Men to Keep Healthy Neurological System

This study discussed the role on estrogen on preventing neurodegeneration.  This important function of estrogen is one of the reasons I warn men not to lower estradiol too much: we need it for healthy brain function and to protect against neurological degeneration. Yes, excess estradiol may increase breast tissue size, cause water retention, moodiness and erectile dysfunction and some men need to lower it while on testosterone replacement therapy with aromatase inhibitors. But overdosing these agents can wipe one's estradiol. Bone density loss, worse hair and skin health, and cognitive issues may appear the. So, be conservative and retest a month after starting anastrazole or tamoxifen (two of the several aromatase inhibitors available). Adjust dose so that estradiol is not under 15-20 pg/dL or over 35 pg/dL.  Some men only require 0.5 mg of anastrazole 2-3 times a week after induction therapy of 1 mg per day for 3 days.  However, no optimum dosing protocol has been studied in men on testosterone who experience large estradiol increases on therapy.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3135156/

TESTOSTERONE STUDY IN OLDER MEN STOPPED EARLY DUE WITH GREATER HEART RISK

A placebo controlled study using a 1 percent testosterone gel (Testim) in  700 older men  (aged 65 and older) was stopped early due  a higher incidence of cardiovascular events in the testosterone arm.

These findings contradict those from a previously published study performed in 2,416  men  that reported  that a 30% reduction in cardiovascular events occurred in men with higher blood levels of testosterone.

The halted study associated the higher incidence of events with higher total and free testosterone and higher estradiol blood levels. The study does not provide relative risk differences between testosterone and estradiol levels, so it is not known which factor has the highest impact on cardiovascular risks.  

Testosterone converts into estradiol, a female hormone, via aromatization in the liver and other tissues. Previous studies have shown that men with even slightly elevated estrogen levels doubled their risk of stroke and had far higher incidences of coronary artery disease. High estradiol can also cause enlargement of breast tissue, water retention and possibly erectile dysfunction in men.  However, men with low estradiol are more prone to osteoporosis and cognitive loss, so a good balance of this hormone is important for a man’s health.

Nelson Vergel, author of the best-selling book Testosterone: A Man’s Guide, said “ I am glad that the  study authors suggest that a similar study needs to be performed by providing not only testosterone supplementation but also an aromatase inhibitor to assess if any decrease in cardiovascular events is seen by decreasing testosterone conversion into estradiol. Reducing aromatase conversion of testosterone into estradiol also frees up more testosterone to do its job”.

The most popular aromatase inhibitor used in men is anastrazole (brand name: Arimidex), which is dosed in small oral doses 3 times a week. But a mixture of testosterone plus anastrazole cream has recently entered the market.

“We  are the only pharmacy that provides by prescription a testosterone cream that has been formulated with anastrazole for both  products to be absorbed through the skin”, said Jaime Rios, co-owner of APS Pharmacy , a specialty pharmacy that ships economical hormone products nationwide. "This cream makes it easy for men to control their estradiol without having to remember to take an oral medication", added Rios.

More men’s clinics are taking notice of balancing estradiol in men using testosterone. One of them is Defy Medical  .  “We monitor estradiol closely in men served by our clinic and provide treatment solutions that are affordable to any man”, said Jasen Bruce, clinic manager for Defy." We also provide the most economical testosterone and estradiol blood test to any man who wishes to have these hormones tested", added Bruce.

How to Stop Testosterone Safely and Possibly Reset Your Hormonal Axis

From the book: Testosterone: A Man's Guide (click here)

Some men need to stop using testosterone or other androgens because side effects are a problem (e.g. low sperm count interferes with their goal to have children). Most physicians advise the patient to just stop testosterone without thinking about the possible consequences of the hypogonadal state after treatment cessation.  Will the patient be worse off than when he started? 

Testosterone  replacement therapy and anabolic steroids can lead to  HPTA (Hypothalamic-Pituitary-Testicular Axis- shown in figure below) dysfunction.  Supplemental testosterone can inhibit the release of the body’s own testosterone production through negative feedback inhibition on LH levels. This feedback inhibition also results in suppression of FSH levels, leading to suppression of sperm production (spermatogenesis).

Not all studies show a shutdown of the HPTA in patients after testosterone cessation. In a study previously mentioned in the Moodiness section, Dr. Rabkin compiled data for 42 patients who were treated with testosterone for 12 weeks and then randomized (double blind) to receive placebo injections for six weeks. At week 13 (one week after their first placebo injection and three weeks since the last active injection), mean testosterone level was 286 ng/dL. At week 15 (after 2 placebo injections), mean testosterone level was 301, and after week 17 (after 3 placebo injections), mean serum level was 324 ng/dL. None of these values was statistically different from the mean baseline testosterone level of 308 ng/dL. These data suggest that for men who were already hypogonadal there was no further decline in the body’s production of testosterone once testosterone therapy was discontinued after 12 weeks of use. It is not known if longer term testosterone use would have the same results.

When high-dose testosterone use (as in bodybuilding) is discontinued the HPTA dysfunction that occurs when it is stopped may be a lot more pronounced.  Stopping treatment may cause the patient to suffer all the symptoms of hypogonadism for weeks or months.  Many lose a lot of the muscle mass they gained through their cycle of anabolics plus testosterone. In some cases a specific medical protocol is required for HPTA normalization. If you go to bodybuilding sites, you will see Clomid and HCG mentioned a lot for this purpose.

There is no controlled data from studies using any protocols to accelerate the normalization of normal testosterone production in men who have used either supplemented physiologic (normal) or supraphysiologic (above normal) doses of testosterone for long periods.

For men who had normal testosterone before starting testosterone or anabolic steroids (athletes, bodybuilders or certain people with wasting syndrome) and who want or need to stop those compounds, some physicians have attempted to jump-start testicular testosterone production using a combination of products that have different effects on the HPTA and estrogen receptors. One such physician is Dr. Michael Scally from Houston (read the interview with him: Click here ) who presented a poster at the Lipodystrophy and Adverse Reactions in HIV conference in San Diego in 2002 that reported the use of a protocol to normalize testosterone production in HIV-positive patients after prolonged anabolic steroid and testosterone use for their wasting syndrome.

The protocol consisted of the use of HCG, clomiphene citrate, and tamoxifen (read about each of these products in their respective sections). Treatment takes place over two discrete intervals. The first treatment interval is to initiate the restoration of gonadal function. The second interval is to restore the hormonal pathways among the hypothalamus, the pituitary and the gonads. The medications are initiated simultaneously after cessation of androgens when it is expected that the body would try to start to slowly make its own testosterone. If the testosterone ester (cypionate, enanthate, undecanoate, Sustanon) that the patient used is known (the most common one in the United States is depo testosterone or testosterone cypionate), its half-life in the body can be estimated so that the date to begin the medical protocol can be predicted with some accuracy to assess a time when no pharmaceutical testosterone remains in the body.

The protocol for HPTA normalization contains: 

       First 15 days:

  HCG 2,500 IU (subcutaneous) once every other day; 

Clomiphene citrate 50 mg orally twice a day; and

Tamoxifen 20 mg orally once a day.

A satisfactory testosterone level on day 15, typically 350 ng/mL or greater, is followed by the oral medications (no HCG) for an additional

15 days.

This protocol has not been tested in many patients but has shown good results in restoring HPTA in a month. I know that this sounds like a long time but without treatment the body’s restoration process would take about the same length of time that somebody was using androgens.  In some, HPGA function and testosterone production never returns to normal. Hopefully we will see data on approaches like this one used in patients who need to stop testosterone or anabolics after long term use. However, no such studies are listed in clinicaltrials.gov.

Most doctors will refuse to prescribe the protocol above since they are not familiar with it. But remember that this protocol will likely not help most men who had low testosterone before starting TRT anyway.  It is more likely to be helpful to those who used testosterone and anabolics for muscle building purposes and who were not hypogonadal before starting their muscle building cycles.

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