Greetings!

The other day, a local physician objected to my giving a 64-year-old man growth hormone and anastrozole for erectile dysfunction.  I gave that physician the following explanation.  Hopefully the explanation will give you some insight into the possible strategies that can be done to help someone who has erection problems combined with diabetes and heart problems.


Mr. Smith (name changed) complained to me of erectile dysfunction.  He needed Viagra to achieve an erection; but, even with Viagra, erections were sometimes inadequate, libido was decreased, and overall energy was low.  He also suffered with hypercholesterolemia, insulin resistance, coronary artery disease, and weight gain.

 

Exam revealed an overweight male with a blood pressure of 130/70.  He had some puffiness of the fingers and face but no overt edema and otherwise exam was unremarkable.

 

Lab testing showed a fasting glucose of 108 and HgA1c of 5.9. 
Triglycerides were high at 156 and HDL low at 36.
Testosterone total was 322 with a free testosterone of 9.4 [6.6-18.1].
Prolactin was normal.  Estradiol 28.  PSA 1.2.
IGF-1 was 124 [75-212; an age-adjusted normal range].

The goal with Mr. Smith was to improve sexual function directly and indirectly.  Directly by raising levels of the hormones that directly improve sexual function out of the lower end of the normal range and back up to the upper end of normal for an age-adjusted normal range.  Indirectly by improving his overall health and cardiac function.

It is considered reasonable, in the face of ED, to raise low-normal testosterone.  "There is no universally accepted cut-off value of total testosterone that

defines the state of androgen insufficiency."[1] Mr. Smith was at the 25th percentile of normal for testosterone complaining of ED and insulin resistance (both of which are helped by testosterone replacement).

 

Though testosterone has in the past been associated with elevated lipid levels, more recent studies show no ill effects on lipids[2] and possible beneficial effects on cardiac function.  With all of the other strategies that I use simultaneous with the hormonal changes, I seldom see a worsening of lipids and most of my patients see a significant improvement.

 

Multiple studies indicate that testosterone can benefit the person with cardiac disease.  Here is a quote from Pinthus JH - Urology - 01-JUN-2006; 67(6): 1126-32:

The common belief that testosterone is a risk factor for cardiac disease derives from the simple observation that men have more CVS events than do women. However, no current data support a causal relation between greater endogenous testosterone levels and heart disease. In fact, studies have suggested that greater testosterone levels may actually have a favorable effect on the risk of CVS disease.

I wanted to use a short course of human chorionic gonadotropin (HCG) to improve ejaculate volume and libido. HCG also raises testosterone production but can sometimes raise estrogen levels too.  His estrogen level was only 28 but I wanted to keep his estrogen in the 20 to 50 range and so blocked the further elevation of estrogen by prescribing Anastrazole.  I used testosterone simultaneous with the HCG because there can be some delay with the onset of elevation of testosterone with the HCG alone. 

My plan was to drop either the HCG or the testosterone or both on a future visit and maintain erectile function with the actual improvement in health that occurs with aerobic exercise, weight loss, raising the HGH level, low dose anastrozole, and lowering blood pressure.

I asked him to start walking daily but in the beginning to keep it to mile per day and increase mileage by 1 mile per week.  Therefore, he would walk about 4 miles the first week, 5 miles the second, 6 miles the third, and progress up from there to 21 miles per week.  I think there is sufficient research to recommend 21 to 25 miles per week as the optimal amount for the best cardiac health.  I hoped this would lower his blood pressure, lower his cholesterol, and improve his sexual function (it has been proven to do all of the above).

 

I also asked him to eat at least five servings of fruits and vegetables per day and to drink two or more protein shakes per day as an appetite suppressant (using food as medicine).

I gave him a low dose of Armour thyroid (60 mg).  Hypothyroidism causes hypercholesterolemia and decreased cardiac function.  Mr. Smith was not overtly out-of-range hypothyroid by blood testing.  However, it has been shown that most healthy people have a TSH lower than 3; his was 3.9 [0.35 - 5.5].  I wanted to see his TSH around 2.  His free T3 was in the lowest 25th percentile of normal; I wanted to see his free T3 around 3.5.    This would still keep him within the normal range but is the kind of micromanagement of hormones that combined with life-style changes can cause a dramatic improvement in health.

I asked him to continue all medications as prescribed by his primary care doctor (I always encourage my patients to continue to see their primary care physician).


He reported that he does snore, so I arranged for him to have a sleep study.  He spent time with my nurse educator to learn how to give the injections and to learn more strategies about eating and exercise.  I gave him my book and several hours of recorded materials so that he might learn more of the exercise and diet strategies that would help him to better health. 

 

That is a brief summary of the general plan.  The following sections will address the specific questions about human growth hormone (HGH) and anastrozole.

(b)  Rationale for HGH


HGH deficiency has been associated with hypercholesterolemia,[3] insulin resistance,[4] increased coronary artery disease, obesity, and erectile dysfunction. In multiple studies, HGH replacement has been shown to help with weight loss,[5] erectile dysfunction,[6] hypercholesterolemia,[7] and diabetes[8][9] (all of which were needed with Mr. Smith).

Replacement of HGH to the upper limits of normal for an age-adjusted normal range seems to give the best results.  Mr. Smith presented with an IGF-1 of 124.  My goal was to replace him to a level of 200 (which would still be well within the normal range for his age).

 

Please make note of the following quote from The Journal of Clinical Endocrinology & Metabolism Vol. 83, No. 2 382-395:

 

The importance of GH throughout adult life is now unequivocally accepted.GH deficiency is recognized to result in alterations in body composition,physical performance, psychological well-being, and substratemetabolism. Many of these alterations can be improved or correctedwith GH replacement. It is likely that GH replacement will in the near future become as routine as steroid, thyroid hormone, and sex hormone replacement in management of the hypopituitary adult.

 

I base the diagnosis of HGH deficiency upon a low or low normal IGF-1 on an age-adjusted normal range combined with symptoms of  HGH deficiency.  Stim testing is controversial, dangerous, and unreliable.  Badaru and Wilson  state, "In our opinion, today's GHSTs lack reproducibility and accuracy, are expensive, and can be dangerous."[10]  IGF-1 predicts the results of provocative testing and may be used in place of stim testing in adults.[11]

 

The Journal of Clinical Endocrinology & Metabolism Vol. 82, No. 2 352-356 states the following: 

The problem of diagnosing GHD now extends to adulthood, becauseGHD in adults with childhood or late-onset deficiency has beenshown to significantly increase mortality and morbidity. In the absence of GH, body mass index (BMI) increased,body composition was modified with an elevated waist/hip ratio,metabolic disorders such as syndrome X were reported, and musclestrength, myocardial efficiency, and bone mineral density werealtered. All the abnormal parameters are corrected by GH aftereither short- or long-term treatment.

Follin also reported in J Clin Endocrinol Metab (01-MAY-2006; 91(5): 1872-5) that HGH replacement improved cardiac function and insulin sensitivity.  There are many other similar studies.

HGH does not cause cancer.  Here's a quote from Endocrinology (Fifth Edition) by DeGroot and Jameson:  "No evidence indicates that GH or IGF-1 induces tumor formation." On the contrary, "the best study to date, involving over 1,000 acromegalic patients, found overall cancer incidence rates to be lower than those in the general population."

(c)  Rationale for Anastrazole

Elevated estrogen sometimes results from testosterone replacement.[12] Blocking estrogen formation with Anastrazole can accentuate the effects of testosterone on libido.[13]

  

The following is taken from Endocrinol Metab Clin N Am

36 (2007) 435-452 :

 

Because androgens are the precursors of estrogens, the administration of

exogenous testosterone results in a suspicion of an increase in estradiol

values by virtue of aromatization. Anastrozole is a potent and highly selective

aromatase inhibitor, with no intrinsic estrogenic, antiestrogenic, androgenic,

antiandrogenic, progestogenic, glucocorticoid, antiglucocorticoid, or

mineralocorticoid activities. Leder and colleagues investigated anastrozole's

ability to increase endogenous testosterone production in men who

had hypogonadism. Aromatase inhibition increased serum bioavailable

and total testosterone levels in older men who had mild hypogonadism. Serum estradiol levels decreased modestly but remained within the normal

male range. The sexual benefits of aromatase inhibitor therapy were

reported in a case report. The use of an aromatase inhibitor normalized

the testosterone level and improved sexual functioning. Greco and colleagues

showed that sustained improvement in sexual function after 12

months of PDE5 inhibitor administration is associated with increased

testosterone to estradiol ratio mainly related to reduction of estradiol levels.

These investigators hypothesized that androgen-estrogen cross-talk and

possible inhibition of aromatase activity during chronic exposure to PDE5

inhibitor use might play a role in the regulation of erectile function.

 

These authors even recommend that Anastrazole be used as first line therapy and testosterone saved for reserve.  My strategy with Mr. Smith was to start both testosterone and Anastrazole and hopefully taper him down off the testosterone later.

 

Elevated estrogen levels are also associated with prostate cancer and estrogen receptor blockers have been recommended as a way to prevent prostate cancer.  The following is taken from Timothy C. Brand, MD, et al. Chemoprevention of Prostate Cancer. Hematology/oncology Clinics of North America Volume 20 Number 4 August 2006

 

Estrogens have been shown to promote prostatic growth. Toremifene has been shown to prevent prostate cancer in a mouse model through nonandrogen pathways. This agent is currently being tested in a large clinical trial for patients who have prostatic intraepithelial neoplasia. 

 

The estrogen receptor blockers can have an effect on lipids.  "Toremifene is an oral nonsteroidal antiestrogen for treatment of metastatic breast cancer in post-menopausal women. It is a derivative of tamoxifen, which is also an antiestrogen. Toremifene is as effective as tamoxifen in treating metastatic breast cancer; however, cross-resistance has been suggested. Further, toremifene appears to have a more favorable effect on lipid levels than tamoxifen. In one study, toremifene increased high-density lipoprotein (HDL) cholesterol serum concentrations whereas tamoxifen decreased HDL cholesterol serum concentrations."[14]

 

Anastrazole offers a safer way to both improve sexual function and help prevent prostate cancer.  Anastrozole is a nonsteroidal aromatase inhibitor (unlike Tamoxifen and Toremifene which are estrogen receptor blockers). Anastrozole is highly potent and specific for aromatase, and represents the fourth generation of aromatase inhibitors. Anastrozole significantly suppresses serum estradiol levels, and it offers an alternative to tamoxifen in postmenopausal women with breast cancer and in the treatment of men. Unlike aminoglutethimide, an early aromatase inhibitor, anastrozole does not inhibit adrenal steroid synthesis. There are no absolute contraindications to Anastrazole other than pregnancy. 

 

In a review article in American Heart Journal, Sandra Lewis, MD says the following:[15]

 

Until recently, the standard endocrine treatment for breast cancer was tamoxifen, which appears to have a generally favorable effect on lipid parameters, although this does not translate into cardioprotective effects. The third-generation aromatase inhibitors (AIs), including anastrozole, have recently emerged as alternatives for the treatment of postmenopausal women with hormone-sensitive breast cancer. Anastrozole, currently the only AI with established long-term safety data in the adjuvant setting, results in significantly fewer thromboembolic and cerebrovascular events compared with tamoxifen, and a similar incidence of ischemic cardiovascular events.

 

So, Tamoxifen seems to have a generally favorable effect on lipids and anastrozole even more so demonstrating "significantly fewer thromboembolic and cerebrovascular events" even without the lifestyle changes that I helped Mr. Smith begin.

 

Anastrazole can sometimes result in elevated LFT's and a rise in blood pressure.   The incidence of elevated LFT's is not frequent enough that routine testing is recommended (unlike Crestor which Mr. Smith was taking for high cholesterol). 

 

Also, in combination with the diet that I recommended, the walking, and the growth hormone replacement, I expected Mr. Smith's weight to go down and his blood pressure with it -that proved to be the case. 

Discussion


On Mr. Smith's second visit to see me (four weeks after I started treatment), he had lost exactly 10 pounds (down from 221.6 to 211.6) and his sitting blood pressure had dropped from 130/70 to 120/68.  He felt more energy and reported improved erection firmness (with less need for Viagra).  He had been walking almost daily (after listening to my recorded materials about walking) and had worked up to one mile per day.  He also started some of my diet recommendations including increasing fruits and vegetables.  Recall, I did not prescribe any appetite suppressant.

 

I stopped the HCG, continued the testosterone, Anastrazole, and Armour Thyroid.  I asked him to continue to increase his walking by one mile per week.  

 

In short, Mr. Smith self referred and presented with a blood pressure that was not optimally controlled, his weight was out of control, and he felt too tired to exercise.  In addition, he suffered with erectile dysfunction.  In four weeks, he become regular with his exercise, lost 10 pounds, dropped his systolic blood pressure 10mmHg, improved his energy, and enjoyed improved erections.

I had asked Dr. Lung Doctor (name changed) to evaluate Mr. Smith in the sleep lab.  This week, Mr. Smith did test positive for sleep apnea and is scheduled for another trip to the sleep lab next week to be fitted with CPAP.  With treatment of his sleep apnea, Mr. Smith can look forward to possibly finding it easier to lose weight, a further drop in his blood pressure, and an improvement in sexual function (as well as less risk of sudden death).

I have several hundred patients (some of them physicians) who have been helped in a dramatic way that would agree with my strategy.  Many of them have been able to achieve normal blood sugars without their diabetes medication.  Some have been able to decrease or stop pain medication after many years (osteoblast activity is also improved by both growth hormone and testosterone and those with low levels sometimes present with pain and osteopenia advanced far beyond what their age would suggest and with poor healing after back surgery).  Some have seen great improvement in sexual function and so have saved their failing marriage.  Some have normalized cholesterol levels that were out of control even on their other medications.  Some have been able to fight off depression and feel well without their anti-depressants.  HGH deficiency can cause all of the above problems and replacement has been shown to have all of the above results.  Many experience significant weight loss without weight loss drugs or surgery.  I hope the board will take into consideration the welfare of the many people who have been helped by me and who continue to enjoy the benefits of my therapy.


None of my patients are professional athletes or even amateur athletes who come to me simply to be strong or look pretty.  There is a colossal difference between jacking someone up on hormones to levels that are higher than normal (as do professional ball players) so that they can be strong compared with adjusting levels to healthy normal ranges on age-adjusted levels to combat disease (as with Mr. Smith).

Current accepted mortality is 1% for gastric bypass surgery, which has never been compared with aggressive medical therapy (in the last good study of gastric bypass, the control group was obese people who got a driver's license).
[16]  I do aggressive medical therapy but assure you that 1 in 100 people who walk into my office do not die before they leave (as do the 1% who die in the hospital when having gastric bypass surgery)-and all my strategies are supported by the medical literature. 

 

It is the aggressive application of multiple proven strategies (like going for a walk) that makes my practice unique.  My patients succeed not because of any one thing but because of the orchestration of many beneficial things at the same time.  I try to micromanage metabolism by simultaneously micromanaging multiple hormones, diet, and exercise in an effort to combat significant diseases-nothing more or less. 

 

I have developed some ways of combining common proven therapies (like simply eating five or more fruits or vegetables per day) that are being used separately into one program.  I am always searching for a better way to combine all that is known about life-style changes and endocrinology into a program that offers a detailed systematic path out of the mire of chronic disease and back to better health.  I personally spend at least 1.5 to 2 hours with every patient on the first appointment and give him or her all access to my cell phone number.  Type 2 diabetics are asked to call my cell phone every morning for the first two weeks at least as I micromanage medications, diet, exercise, and hormones to help them to better blood sugar control.  The usual result is very impressive improvements in health.


I still offer an open invitation for any board member to come any day unannounced and just spend the day watching what goes on in my office.  I feel like this formal process at best offers only the tail of the elephant and so is open to misinterpretation.

Donal Bergman, MD (while President of American Assn. of Clinical Endocrinologists) said,  "Treating an illness before it happens or at least before it progresses is not how American medicine works.  It's not the way insurance works.  It's not the way Medicare works."
[17]   This letter describes how I am using research-based medicine to make this statement not true for Mr. Smith.


LifeStream Medical, Inc.

Charles Runels, MD

750 Downtowner Loop W., Suite A, Mobile, AL  36609

http://TempleRepair.com

251-342-6466


[1] Erwin Goldstein, MD.  A Clinical Paradigm for the Combined Management of Androgen Insufficiency and Erectile Dysfunction. Endocrinol Metab Clin N Am

36 (2007) 435-452

 

[2] American Family Physician, Volume 73, Number 9 May 1, 2006.

[3] Miller KK - J Clin Endocrinol Metab - 01-FEB-2005; 90(2): 768-74.  GH deficiency increases cytokines, and worsens lipid metabolism, insulin sensitivity, and blood pressure.

[4] Barreto-Filho JA - J Clin Endocrinol Metab - 01-MAY-2002; 87(5): 2018-23.  Describes the cardiac disease and insulin resistance associated with growth hormone deficiency.

 

[5]J Clin Endocrinol Metab - 01-MAR-2005; 90(3): 1466-74.

[6] Christian G. Stief, Stefan U ckert and Udo Jonas. JMHG Volume 2 No. 3 pp 325-332. September 2005

[7]J Clin Endocrinol Metab - 01-MAR-2005; 90(3): 1466-74.

[8]J Clin Endocrinol Metab - 01-MAR-2005; 90(3): 1466-74

[9] The Journal of Clinical Endocrinology & Metabolism Vol. 82, No. 2 352-356. 

[10] Badaru A., Wilson D.M.:  Alternatives to growth hormone stimulation testing in children.  Trends Endocrinol Metab 15. 252-258.2004

[11] The Journal of Clinical Endocrinology & Metabolism Vol. 82, No. 4 1195-1201.

[12] Erwin Goldstein, MD.  A Clinical Paradigm for the Combined Management of Androgen Insufficiency and Erectile Dysfunction. Endocrinol Metab Clin N Am

36 (2007) 435-452

[13] Endocrinol Metab Clin N Am.  36 (2007) 435-452

[14]Timothy C. Brand, MD, et al. Chemoprevention of Prostate Cancer. Hematology/oncology Clinics of North America Volume 20 Number 4 August 2006

 

[15]Sandra Lewis, MD.  Do endocrine treatments for breast cancer have a negative impact on lipid profiles and cardiovascular risk in postmenopausal women?

.American Heart Journal - Volume 153, Issue 2 (February 2007)

[16]Journal Watch Gastroenterology August 22, 2007

[17] American Medical News March 1, 2004