Susan Merenstein, Pharmacist/Owner

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Testosterone for Men


Andropause: Real Men Go for Balance

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The first thing a man entering andropause generally notices is a subtle downward shift in strength and energy as hormone levels taper off. Muscle tone and stamina are the first to go and he starts to gain weight and that "spare tire." He may also develop a voracious appetite and food cravings he never had before. As symptoms kick in at mid-life, hormone testing can identify hidden imbalances that complicate symptoms of andropause and contribute to rapid aging.

The 2006 HIM Study found that nearly 40% of US males over 45 years old had low testosterone levels (an estimated 13 million US males), however the majority of men in the study did not recognize that the weight gain, sore muscles, lack of libido, insomnia, and burnout they were experiencing could have something to do with andropause and hormone imbalance – instead they put their symptoms down to "just getting old."

Getting old was the recurrent theme at a recent 50th birthday party I attended where non-stop over the hill jokes and "low-T" lamentations were heaped upon the birthday boy. All that talk of testosterone reminded me of an article in Atlantic magazine a few years ago that slammed the drug industry’s promotion of supplemental testosterone as "god's gift to men," and questioned whether every modern man really needs testosterone?

One way to begin to answer that question is to start with physiology and understand that the androgens (primarily testosterone and DHEA) in their natural state bestow the heavier bone and muscle mass, deeper voice, drive and virility we associate with the male of the species. And that when they start to decline around the age of 45, the average Joe will experience some of the following symptoms:

  • Decreased strength/stamina/endurance
  • Decreased muscle mass/sore muscles
  • Weight gain in the hips, thighs, waist, and/or breasts
  • Increased body fat
  • Poor recovery from exercise
  • Burnout and fatigue
  • Lack of mental clarity
  • Decreased sex drive and/or competitive drive
  • Prostate problems

The natural decline of hormone levels in aging men also poses an increased cardiovascular risk which is where the controversy over replacement therapy comes in: whether it can hurt or help healthy men, and those who already have heart disease. It's an important question, particularly in light of the skyrocketing numbers of men using testosterone products to feel better and to increase muscle mass and energy. According to the FDA, the use of testosterone therapies increased from 1.3 million patients in 2009 to 2.3 million patients in 2013, a doubling of prescriptions in less than five years. In light of these numbers and that the risks vs. benefits of androgen supplementation in men have not been clearly identified, the Atlantic article raised some important questions, for which recent research has some good answers.

Replacement has its place

In a 2015 study of 1472 generally healthy men between the ages of 52 and 63 with no history of heart disease, researchers found that those who received testosterone supplementation to achieve normal levels did not increase their risk of heart attack stroke or death but actually showed a reduction of risk compared to patients not on testosterone therapy. Even more good news came in a follow-up study this year (2016) of 755 male patients between the ages of 58 and 78, all with severe coronary artery disease. Researchers found that the men who received testosterone therapy as part of their follow-up treatment fared much better than those who didn't. In fact, the non-testosterone therapy patients were 80 percent more likely to suffer an adverse event.

It’s always about balance

Aging is inevitable and dropping hormone levels go with the territory, but what is not inevitable, is how rapid or steep the decline in hormones needs to be. Whether men age well, or rapidly, depends a great deal on their stress levels, diet, exercise, alcohol intake, weight gain etc. For example, the more overweight the man, the more estrogen he will churn out in his fat cells, creating a surplus in relation to waning testosterone, and a raft of estrogen related symptoms, like moodiness, depression, and female pattern of weight distribution in the hips, thighs, and breast tissue. (A fact that should not be lost on those concerned about prostate health is that estrogen is a growth hormone linked with the development of prostate cancer.)

Experts in the field of hormone testing and balance, like Dr. David Zava, owner of ZRT Laboratory will tell you that where the need is clearly established and monitored through testing, supplementing with testosterone can be beneficial, particularly, when used in tandem with a healthy lifestyle. We have worked with ZRT Labs for over 20 years and they are simply the best!

Men in balance do these things during andropause

  • *Test their hormone levels to detect and correct imbalances linked to symptoms.
  • Follow up with a natural hormone friendly physician
  • Lose weight as needed. Fat cells contain aromatase, an enzyme that robs the male body of available testosterone by converting it into estrogen.
  • Stick with a program! A low glycemic Mediterranean style diet that's high in protein and fiber and low in fat and carbs can help rebalance hormones and assist weight loss
  • Throw out testosterone robbers like caffeine, alcohol, cigarettes, and unnecessary stressors like burning the candle at both ends day in and day out etc.
  • Take up strength training or weight bearing exercise to boost testosterone and DHEA levels naturally by building up lean muscle mass
  • Counteract stress (the higher the stress levels, the lower the testosterone) with regular exercise – 45 minutes is optimal but even 10 mins. 3x a day adds up to 30 minutes and that is GOOD
  • St-r-e-t-c-h and breathe deep to release tension held in the muscles and lower stress hormones that deplete T levels
  • Hit the sack earlier – less than 7 hours of sleep disrupts appetite hormones to increase cravings and feelings of hunger
  • Take time to do the things you enjoy! Stress reduction is the key to normalizing cortisol and T levels

*Topical supplements rubbed into the skin (gels, creams) do not always show up in a serum test and can lead to possible OVER supplementation. This is why so many physicians test hormone levels in saliva or dried blood spot sampling to track and adjust dosage as needed.

The Good Andropause

I encourage you to read the Atlantic article with the awareness that hormone balance never boils down to just one hormone! Getting to the land of optimal health and aging is about getting ALL key players – estrogen, progesterone, testosterone, DHEA, cortisol, thyroid – working together in sync! Just like the symphony orchestra, if one instrument is out of tune, so goes the melody…hormones are your internal symphony. Replacement has its place as long as it is in tune with your body’s natural rhythms and need for proper care, feeding and rest during andropause!

Candace Burch

Be aware of your symptoms, get educated and take a proactive role in your health!

Don’t guess….test your hormones in Saliva or Blood Spot today!

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The changes men experience with aging sometimes mirror those experienced by women. Energy often ebbs, and that's no surprise, but what's with the night sweats, the belly fat that won't go away and (gasp) those breasts that are looking too much like a woman's? And then there's increased irritability, memory trouble, decreased libido and erection problems, indecision, and, sometimes, depression. Understandably, men attribute these and other symptoms to getting older, but many doctors believe, and studies are confirming, that the cause is often more than age alone. Found in men under age 45, these changes can be symptoms of "hypogonadism" (lower than functional levels of various hormones, including testosterone). When they develop as part of the normal aging process in many men, the more accurate term for an older population would be "hypogonadic syndrome" or "andropause." Estimates of its prevalence vary widely, ranging from a low of three million to as many as 19 or 20 million men age 45 or older.


Research Findings

Research has shown men between the ages of 18-25 only make 4-7 mg of testosterone per day!

Researchers were surprised by the finding of a recent study based on blood tests taken of 2,162 male patients age 45 or older who were making a standard visit to their primary care physician -- 38.7% had suboptimal levels of serum testosterone. (Though it should be noted that as men get older, this becomes a less reliable measure, due to natural changes that occur with aging.) Interestingly these men also had a higher incidence of history of hypertension, high cholesterol, diabetes and obesity. Given that the study specifically focused on average men, making a routine visit to their doctor, these findings are surprising. It is important to note that Solvay Pharmaceuticals, makers of a testosterone gel, provided funding for this multi-center study.

The reason men usually don't realize the extent of these changes is that they typically evolve slowly over time, and there is no clear marker for them (as there is for women whose periods become erratic and eventually came to a halt). Both genders experience hormone changes with age, but not in the same way. The gradual lowering of testosterone in men may eventually cause a shift toward estrogen, as body fat starts producing increasing amounts of it. When this occurs, it may cause enlarging breasts, night sweats, and, to some degree, excess abdominal fat.

But the imbalance is not just testosterone -- it's also related to other hormones, including estradiol, progesterone, DHEA, cortisol, thyroid, and adrenals. Men over 45 or so who show these symptoms should consider being evaluated for low functional testosterone and hormonal imbalance. Since hormones function in concert, not as disparate elements, it is important to check hormone levels before treatment. We look at as many hormones as we can to see how they are interacting and if they are balanced as a group.

What Will It Do?

The study mentioned above found a higher than expected incidence of high cholesterol, diabetes, and obesity with low testosterone. Supplementing testosterone when clinically indicated has been shown to improve blood sugar regulation and reverse heart disease. Supplementation will also increase bone growth, increase lean muscle mass, improve mood and memory, improve energy, reduce cholesterol and improve libido.

Proper diet and a healthful lifestyle help all body systems to function better, giving men "the biggest bang for their buck in hormone treatment." Plenty of protein and avoidance of dairy products, alcohol and caffeine because even two cups of coffee can adversely affect DHEA production and two drinks a day can adversely affect testosterone levels. Regular exercise is also a must, but we recommend moderate exercise such as walking, hiking, yoga, swimming and biking, which is less taxing on the body, rather than intense forms of it.



Andropause and Treatment Options

Andropause is also referred to as male menopause and has been the subject of increasing attention in the past few years in the medical community and media. Through several proposed mechanisms, aging men suffer from the dual effects of having too little testosterone and excess estrogen (estradiol). Aging men sometimes convert testosterone to estrogen. Testosterone receptor sites in cells throughout the body then take up the estrogen. When an estrogen molecule occupies a testosterone receptor site on a cell membrane, it blocks the ability of serum testosterone to induce a healthy hormonal signal. It does not matter how much serum free testosterone is available if excess estrogen is competing for the same site.

Testosterone is much more than a sex hormone. Other receptor sites of testosterone are the brain and heart. Testosterone improves oxygen uptake throughout the body, helps control blood sugar, regulate cholesterol and maintain immune function. The body requires testosterone to maintain youthful cardiac output and neurological function. Men suffering from depression often have lower levels of testosterone than control subjects.

Testosterone levels decline gradually in men, starting from approximately age 30, and this decline continues throughout life. On the average, a man’s testosterone levels begin to decline at a rate of about 1% per year after age 40.

SYMPTOMS OF HYPOGONADISM (DECREASED TESTOSTERONE):

  1. Decreased or absent libido
  2. Decreased or absent morning erection
  3. Erectile dysfunction
  4. Depression
  5. Poor concentration
  6. Decreased beard growth
  7. Loss of musculature
  8. Decreased energy level
  9. Hot flashes
  10. Decreased muscle mass, body hair, facial hair
  11. Gynecomastia

ADAM (Androgen Deficiency in the Aging Male) Questionnaire:

  1. Do you have a decrease in libido or sex drive?
  2. Do you have a lack of energy?
  3. Do you have a decrease in strength or endurance?
  4. Have you lost weight?
  5. Have you noticed a decreased enjoyment of life?
  6. Are you sad or grumpy?
  7. Are your erections less strong?
  8. Have you noted a recent deterioration in your ability to play sports?
  9. Are you falling asleep after dinner?
  10. Has there been any recent deterioration in your work performance?

Men answering YES to questions 1,7, or a combination of any 3 or more might be candidates for testosterone replacement therapy. Please consult a qualified healthcare practitioner for further testing via blood or saliva (see saliva testing) or urine.


A Therapeutic Protocol for Andropause:

Male hormone therapy has been shown to be dramatically effective in relieving symptoms of andropause and restoring drive, health, potency, and a renewed sense of renewed vitality. The treatment includes careful monitoring of testosterone and estrogens (estradiol), and supplemental therapy so that a healthy balance can be achieved. Remember, an imbalance can occur either because of decreases in testosterone levels, increases in estrogen levels, or a combination of both.

  • Reduce estradiol levels and increase testosterone levels through dieting, exercise, and nutritional supplements such as Zinc and Vitamin C. We know that testosterone is converted to estradiol via the aromatase enzyme. Estrogen stores in fatty tissue and speeds up aromatase activity; therefore, diet and exercise in a weight-loss plan can cut down the estradiol buildup. Zinc supplementation of 100mg per day is believed to decrease testosterone conversion to estradiol, possibly by affecting the number of androgen receptor sites. Vitamin C has been used also to decrease aromatase activity in doses of 1-3 grams daily. This is a conservative approach that may be helpful in a man with borderline numbers and symptoms, or someone who wants to delay the onset of andropause. For further help please refer to the end of this section for complete supplement information.

  • Another approach is more appropriate when the lab values and symptoms are more definitive, and in these men, increasing testosterone levels is more clearly a major goal. The testes may be fully intact, but are not receiving proper signals to secrete testosterone. This is Secondary Hypogonadism, in which the signal hormones, LH (Leutinizing Hormone) and FSH (Follicle-Stimulating Hormone) may be below normal. Chorionic Gonadotropin is very similar in structure to LH, and an injection of HCG can often reactivate the testicular secretion of testosterone. Doses vary, as well as duration of therapy but a major advantage is that, because there is no exogenous testosterone, no supplementary testosterone given, there is no suppression of the body’s own (endogenous) production of testosterone.

  • The use of Pro-Hormones can be beneficial, and the use of agents such as adrostenedione in athletes has received much publicity. Other pro-hormones commonly used are norandrostenedione, norandrostenediol, DHEA (dehyroepiandrosterone), pregnenolone, and progesterone. Pro-hormones do not have direct action but rely on the body for conversion to more active hormones. These hormones are usually available in non-prescription formulas, and are believed to be active in topical applications. Progesterone is very interesting in that it is active in both the aromatase and 5-alpha-reductase systems to moderate or block conversion to estradiol and dihydrotestosterone, respectively. In low (5-10mg) doses, progesterone can be an important adjunct in andropause therapy.

  • Direct testosterone supplementation in physiologic doses is the most familiar to patients and physicians. For many men, this will be the treatment of choice as it is easy to understand, and when properly administered and monitored, can be effective in restoring testosterone levels. Prior to beginning testosterone therapy, the physician should perform and office exam that includes gathering usual lab values such as cholesterol, CBC, hematocrit, PSA, testosterone (total and FREE recommended), and estradiol. The baseline testosterone and estradiol numbers should be established so that, after therapy is started, it will be very clear whether or not the patient’s levels are moving in the desired direction.

Dosing Forms

ORAL—This is an inefficient way of dosing because of the high first-pass effect, in which the liver converts most of the testosterone into inactive metabolites. Most researchers and experienced clinicians do not recommend oral dosing because doses as high as 400mg per day may be required to obtain physiologic levels. Note: methyltestosterone has greater bioavailability by the oral route, but is not preferred because of its adverse side effect profile and potential harm to the liver.

INTRAMUSCULAR INJECTION—This is probably the most common form of dosing, but it has a serious drawback in its uncontrolled release. Many men will experience high testosterone levels in the first week (typically dosed at 2 or 3-week intervals), with noticeable declining effects beyond that. Also, there is more possibility of increasing conversion to Estradiol as the body cannot properly store the excess. Instead of reaching a more positive testosterone-estrogen ratio, the opposite effect sometimes occurs with gynecomastia as an occasional outcome, as well as potential testicular shrinkage and thicker blood, which can decrease blood flow to the penis.

SUBLINGUAL OR BUCCAL—Given this way, testosterone is best given in 3-4 doses daily. Effective sublingual doses can range from 10-40mg per day. This must be done in a consistent daily dosage, not as needed and most men will find the multi dosing cumbersome and difficult to be compliant.

IMPLANTABLE PELLETS—This is an office procedure that is relatively simple and offers a major compliance advantage: effectiveness can last from 3-5 months from a procedure, eliminating the compliance issue.

TOPICAL—Currently, topical application seems to be the most effective way of dosing testosterone-creams, lotions, and gels have been used with good results. There are two good reasons that sex steroid hormones may be applied topically: they are potent, and they are highly lipid soluble. Thus, if 5-10mg of testosterone (out of, for example 150mg applied) penetrates the skin, therapeutic levels are achieved. When using testosterone gel a larger surface area compared with a more concentrated, smaller volume is an important factor in restoring testosterone levels and maintaining them in a consistent manner. Studies have shown that a once-a-day application can be sufficient to elevate and maintain levels.

Note: Since young men only make 4-7 mg/day, 50-100mg may only yield 5-10mg testosterone but the rest may turn into DHT in Estradiol and yield side effects. 14

The choice of application site is quite important. When the gel is applied to the trunk or axillary area, the resulting balance of testosterone, DHT, and estradiol (E2) will be very much in the normal physiologic range. However, if the gel is applied to the scrotum, the level of DHT becomes much higher because the prostate has a much higher level of the enzyme 5-alpha-reductase. DHT then becomes an important androgen player. This might be preferred for a man with higher levels of estradiol, because DHT cannot be converted into estradiol. Although some experts have voiced concern about excess DHT may be linked to increased prostate growth and possible prostatic hypertrophy, practical experience has not supported that theory. The incidence of prostate problems in those who wore scrotal patches was no greater than that in subjects given placebo.* Additional studies have indicated a 15% decrease in the size of the prostate in men treated with pure DHT gels, probably due to inhibition of the normal production of DHT and estradiol (E2) occurring in the prostate itself.** It does appear that DHT acts as a circulating androgen, and it is thought to be more potent than testosterone; however, it is much more tightly bound to SHBG and is therefore less bioavailable.**

*McClure D, Oses R, Ernest ML. Hypogonadal impotence treated by transdermal testosterone.Urology. 1991;37:224-228.

**DeLignieres B. Transdermal dihydrotestosterone treatment of andropause.Ann Med. 1993;25:235-241.


Supplements to Modify Testosterone, Estradiol & DHT:

ZINC: The mineral zinc is important in many ways and plays an important role in andropause. It inhibits aromatase, the enzyme that converts testosterone to estradiol. A deficiency of zinc is associated with increased activity of the aromatase system, which results in a higher level of estradiol and a lower level of testosterone. Oral daily doses of 50-100mg of zinc can reduce the estradiol level and increase the level of testosterone until physiologic levels of zinc are restored. 1

VITAMIN C: Deficiencies in vitamin C are also associated with increased aromatase activity; doses of at least 1gm a day can be helpful in treating an elevated level of estrogen.2

CHRYSIN: Chrysin is a naturally occurring bioflavinoid that acts as an aromatase inhibitor. In controlled studies 3, chrysin was found to be similar in potency and effectiveness to a pharmaceutical aromatase inhibitor used clinically to treat patients with an estrogen-dependent carcinoma. Chrysin is poorly absorbed orally, so doses range from 1-3gm/day.4 Transdermally applied chrysin is effective at a much lower dose; the recommended dosage is from 100-300mg/day. In addition, chrysin may produce anti-anxiety effects similar to diazepam but without sedation and muscle relaxation. 5

PROGESTERONE: In men, progesterone has several important roles to play in the metabolism of testosterone, estradiol and DHT. Progesterone is an aromatase inhibitor; it prevents the excess production of estradiol. 6 It also is a 5 alpha reductase competitor that governs the conversion of testosterone to potent dihyrotestosterone(DHT). 7 According to one article, 7 the development of benign prostatic hypertrophy (BPH) occurs when the progesterone level declines as the patient ages, and this causes the levels of estradiol and DHT to increase. The suggested dosage of transdermally applied progesterone ranges from 2-5mg daily for men, and this dose may be applied to the anus for better absorption.

SAW PALMETTO: Saw Palmetto is a naturally occurring nonprescription plant product derived from the berries of Serenoa repens. According to a recently published article 8, saw palmetto may be safely used for BPH, and it causes no adverse effects. In this same article the mechanism of action of saw palmetto is discussed-inhibition of 5-alpha reductase enzyme, adrenergic receptor antagonism, and intraprostatic androgen receptor blockade. A randomized, placebo-controlled trial9 showed that a saw palmetto blend seems to be a safe, highly desirable choice for men with moderately symptomatic BPH. Suggested oral dose=160mg twice a day.

DIM in Men: A principal breakdown product of 13C called DIM helps to maintain the level of free or active T. As we age, our bodies take longer to “clear” the estrogen in our bodies and higher than healthy levels of estrogen are common, especially in men who are obese or who are regular social drinkers. Long term safety has been demonstrated in DIM.

NETTLE ROOT: In Germany, nettle root has been used to treat BPH for years. It is believed to act like saw palmetto in its inhibition of 5-alpha reductase enzyme. 9 Nettle root is also considered helpful because it may displace testosterone from SHBG (sex hormone binding globulin).10 Therefore it may be useful for men who have a physiologic level of total testosterone but a low level of FREE testosterone. Suggested oral dose-240mg/day, and may be combined with saw palmetto in some formulations.

LYCOPENE: This carotenoid gives tomatoes that luscious red color. Studies have consistently shown evidence of the benefit of tomatoes was strongest for cancers of the prostate, lung, and stomach. Dr. Omer Kucuk, MD, professor of medicine and oncology at the Barbara Ann Karmanos Cancer Institute in Detroit, MI, adds clinical support to the epidemiological evidence of health benefits of tomatoes. Dr. Kucuk and colleagues followed 35 men with localized prostate cancer who were scheduled to undergo surgical removal of the prostate. For 3 weeks prior to surgery the study participants were randomly assigned to receive twice daily either 250mg of standardized tomato extract (equal to 15mg Lycopene) or no intervention. Following removal of the prostates, the glands were analyzed to determine whether there were any differences between the 2 study groups. The treated group had smaller tumors, and these were more likely to be confined to the prostate. Levels of serum PSA were found to decline in the Lycopene group but increased in the non-treated group. Also, the tumors showed signs of regression and decreased malignancy. Further research is warranted to establish a link between dietary supplements of natural whole tomato extract and prostate cancer prevention and treatment.13

NOTE: The H. Lee Moffitt Cancer Center in Tampa, Florida is using 15mg Lycopene capsules in their new study #0105 “ A Randomized Pilot Clinical Trial of the Action of Lycopene in Localized Prostate Cancer: Administration Prior to Radical Prostatectomy”. The study is funded by the NCI (National Cancer Institute).

1. Om AS,Chung KW.Dietary zinc deficiency alters 5 alpha reduction and aromatization of testosterone and androgen and estrogen in rat liver. J Nutr 1996; 126:842-848.

2. Shippen,E., Fryer W. The Testosterone Syndrome. New York: M. Evans and Company, Inc; 1998:185-186.

3. Campbell DR, Kurzer MS. Flavinoid inhibition of aromatase enzyme activity in human preadipocytes. J Steroid Biochem Mol Bio 1993; 46:381-388.

4. Walle UK, Galijatovic A, Walle T. Transport of the flavinoid chrysin and its conjugated metabolites by the human intestinal cell line Caco-2.Biochem Pharmacol 1999; 58:431-438.

5. Wolfman C, Viola H, Pladini A, et al. Possible anxiolytic effects of chrysin, a central benzodiazepine receptor ligand isolated from Passiflora coerulea. Pharmacol Biochem Behav 1994; 47:1-4.

6. Eckhart P. Invitation for a clinical trial for prostate cancer treatment. Prostate Cancer Hormone Therapy. 1997. Available at: http:// dreckhart.hypermart.net. Accessed January 14,2000.

7. Ling YZ, Li JS, Kato K, et al. Synthesis and in vitro activity of some epimeric 20 alpha-hydroxy,20-oxime and aziridine prenene derivatives as inhibitors of human 17 alpha-hydroxylase/C17,20-lyase and 5 alpha-reductase. Bioorg Med Chem 1998; 6:1683-1693.

8. Marks LS, Partin AW, Epstein JI,et al. Effects of saw palmetto herbal blend in men with symptomatic benign prostatic hyperplasia. J Urol 2000; 163:1451-1456.

9. McCaleb RS. The Encyclopedia of Popular Herbs: Your Complete Guide to the Leading Medicinal Plants. Roseville,CA; Prima Pub: 2000.

10. [No author listed] Nettle root inhibits binding of DHT. SmartBodyz Nutrition. 1996. Available at http://www.smartbodyz.com/nettle-3.htm. Accessed Oct. 3,2000.

11. Michnovicz JJ, Adlercreutz H, Bradlow HL. Changes in levels of urinary estrogen metabolites after oral indole-3-carbinol treatment in humans. J Natl Cancer Inst 1997; 89:718-723.

12. Michnovicz JJ, Bradlow HL.Altered estrogen metabolism and excretion in humans following consumption of indole-3-carbinol. Nutr Cancer 1991; 16:59-66.

13. Kucuk, O. “Phase II Randomized Clinical Trial of Lycopene Supplementation before Radical Prostatectomy,” Cancer Epidemiology Biomarkers and Prevention, August 2001.

14. Dr. David Zava, PhD. Research ZRT Labs.

Note: Article used with permission Bruce Biundo, BS Pharm, RPh- Professional Compounding Centers of America, Inc. Houston, Texas-November 2001.