Testosterone is the primary male sex hormone, or androgen.  Circulating levels of testosterone increase at the time of puberty and peak in early adulthood for men.  Testosterone is responsible for men looking like men and feeling like men.  Following that peak is a gradual but steady decline in testosterone levels beginning in the mid-30’s. Declining testosterone levels cause a variety of symptoms including loss of muscle mass and strength, increased belly fat, impaired brain function, disrupted sleep, loss of libido, impaired sexual function and general fatigue.  But, because the loss of testosterone is gradual these symptoms typically occur little by little, and the impact on a man’s life may not be felt until his 40’s, 50’s or later.  This is sometimes referred to as andropause, or the male menopause.  This gradual decline in vitality, function and quality of life is too often attributed to “just getting old” when in reality, many of those symptoms can be reversed with proper treatment.

It is readily apparent to most that testosterone plays a crucial role in male sexual function. Sexual potency peaks along with the raging hormones of a teenager.  Similarly, testosterone is essential for building and maintaining muscle mass, youthful energy and strength.  Considering testosterone therapy to improve the way you look, feel and perform would be good enough for many.  In fact, testosterone therapy has resulted in improved libido and erectile function in middle aged men.[i]  However, recent scientific evidence has demonstrated significant adverse health implications for men with low and declining testosterone levels.  Numerous studies have now established a strong association between low testosterone and depression, metabolic syndrome, type-2 diabetes, osteoporosis and cardiovascular disease.  In one study men with low testosterone had a nearly 50% increase in mortality over a seven year period.[ii]   An unmistakable link has also been established between erectile dysfunction and the development of cardiovascular disease.

Several studies have shown that restoring testosterone to more youthful levels in middle-aged men improved insulin-sensitivity, reduced serum cholesterol, fat mass, waist circumference and inflammatory bio-markers associated with heart disease, diabetes, and metabolic syndrome.  One study concluded that “that testosterone treatment in men has potentially beneficial effects on virtually all of the coronary risk factors, as well as an independent anti-plaque forming action.”  In men with heart failure, testosterone therapy also improved functional capacity, or the ability to perform physical activity without constraint.[iii]

So why aren’t more men getting testosterone therapy?  Many physicians do not recognize the symptoms of low testosterone as a treatable condition. Traditionally, physicians have been reluctant to prescribe testosterone therapy in large part out of a misguided fear of increasing prostate cancer risk.  Recent evidence has called that conventional paradigm into question.  A large meta-analysis out of Harvard University[iv], as well as a collaborative review of 18 prospective studies[v] concluded that no significant association existed between higher testosterone levels and prostate cancer risk.  Conversely, studies have shown an increased risk of prostate cancer and aggressive prostate cancer in men with low testosterone levels.  In a group of middle-aged men treated with testosterone and followed for more than 5 years, there was no increase in the incidence of prostate cancer and PSA levels remained stable.[vi] 

 What is the bottom line?  Any man over 40 or 50 that feels off his game, run down or is experiencing any of the symptoms of low testosterone should have a thorough evaluation looking for cardiovascular disease, pre-diabetes, and osteoporosis among others.  I recommend seeking out a physician experienced in preventive health and hormone therapy for men.  At Alternity Healthcare, we utilize comprehensive evaluations and state-of-the-art diagnostics to form the basis of an individual preventive health program.  Rather than narrowly focusing on just your hormone levels, our comprehensive programs will expose your total health picture and help you to achieve renewed, long-term health and vitality.   

What are hormones anyway?  Hormones are molecular messengers that regulate your body’s energy production, temperature, growth, immune system, reproductive capabilities and brain activity. Your individual hormone balance is influenced by genetics, the environment, your lifestyle, eating habits and the function of your endocrine (hormone producing) system.  Aging is associated with declining hormones, as well as reduced quality of life and increasing risk of chronic diseases.

Over the years there have been studies both advocating hormone use and warning against it.  The Cancer Prevention Study II (a large prospective cohort of 422,373 postmenopausal women) by the American Cancer Society revealed a 16% reduction in the relative risk of death from breast cancer in women who had ever used estrogen replacement therapy.^[ii]  Later, results of the Women’s Health Initiative, a large, randomized study of 16,000 women published in 2002, suggested that the risks of HRT outweighed the benefits.  Subsequent analyses criticized its flawed design and questioned many of its conclusions.  But scores of women were frightened away from HRT and in the ensuing years, breast cancer rates dropped.  Just last month, a Canadian study[iii] attributed the drop in breast cancer rates to the decline in HRT use.  Recently, another new study stated that women were at increased risk of death from breast cancer when taking a combination of estrogen and progestin.[iv] What needs to be highlighted is the fact that these studies evaluated the effects of synthetic hormones on women’s health.

Estrogen and progesterone are the predominant sex hormones in women.  In humans, there are actually three different estrogens (estradiol, estrone and estriol).  Although typically lumped together and collectively referred to as generic “estrogen”, the differences among these related compounds are critical to understanding their individual physiologic effects in women.

Estradiol is the most abundant and powerful estrogen, produced mainly in the ovaries of pre-menopausal women. Estriol is the weakest estrogen manufactured primarily during pregnancy.  Some studies suggest it has a protective effect against breast cancer.  Estrone is the predominant estrogen in post-menopausal women.  It is made mostly in fat cells of the body by converting testosterone derivatives.  Excess body fat is a risk factor for breast cancer development, and overweight post-menopausal women have higher circulating levels of estrone. Some animal studies have linked the increase in estrone production after menopause with an increase in breast tumors.   

Progesterone supports pregnancy, and in the absence of a pregnancy initiates the menstrual cycle.  In the breast and uterus, progesterone counteracts the direct stimulation of cell growth by estrogens.  Because progesterone suppresses estrogen-driven cell proliferation, progesterone in the natural state helps keep breast cell growth in healthy balance.[v]  Progesterone improves cardiovascular function and protects against heart disease.[vi]  Progesterone reduces fluid retention and bloating, improves thyroid function, is a natural “valium” and anti-depressant and improves libido.  It is also the precursor to most other sex hormones and adrenal hormones.  Natural progesterone has recently been found to have favorable actions on the blood vessels in the brain.  It has been dubbed the “protection hormone” after it was shown to reduce death by 50% in traumatic brain injury cases and to substantially reduce disability in those that survived.  It is currently the subject of a $14 million National Institute of Health study for brain injury.[vii]

Bioidentical hormones have the exact molecular structure as those made in the human body. In other words, the two are indistinguishable from each other. Bioidentical hormones produce the same physiologic responses as those of the body’s natural hormones.  The Food and Drug Administration (FDA) considers bioidentical hormones to be natural regardless of their source, and as a result they cannot be patented.

Although HRT as conventionally practiced and studied uses synthetic hormones, the ill-effects have been indiscriminately attributed to all hormones; including natural, bioidentical versions.  This over-generalization persists despite the evidence supporting bioidentical hormones as a safer alternative; particularly with regard to breast cancer and cardiovascular risk.[viii]

Even among medical professionals, the crucial distinction between natural and synthetic hormones has been blurred so the discussion rarely involves the basic physiology of human hormones, and most evidence supporting any benefits of hormone therapy in adults is downplayed.  Most, if not all, of the research investigating the link between hormones and breast cancer doesn’t actually use natural human estrogens or progesterone.  These studies typically use pharmaceutical creations call conjugated equine estrogens (CEE) and progestins.  Most physicians don’t differentiate them but making the distinction is critical.  Why?  The physiologic effects of synthetic hormones differs substantially from that of natural or bioidentical hormones.

Conjugated equine estrogens, like that found in Premarin, are made from the urine of a pregnant horse (mare).  That is where the name was derived Pre-mar-in (pregnant mare urine).  It contains primarily estrone and equillin.  Equillin is an equine estrogen not normally found in humans.  It binds to and blocks human estrogen from attaching to its receptor and is not as easily metabolized.[ix]   The full physiologic effects in humans are not known (or perhaps not disclosed).

Progestins are not progesterone and do not occur in nature.  They are fully synthetic compounds that lack many of the essential beneficial physiologic properties of progesterone.   The synthetic progestin found in Provera is medroxyprogesterone acetate (MPA).  Unlike progesterone, MPA has been associated with adverse cardiovascular effects, increased breast cancer risk, hair loss, increased water retention, and increased risk for depression.  Progestins do not support gestation, are specifically contraindicated for pregnant women and do not provide the anti-proliferative balance of natural progeterone.  Interestingly, progestins are not being used in the brain injury study mention above, but are routinely prescribed for post menopausal women and as birth control for younger women.

Factors other than just hormones likely contribute to overall breast cancer risk in post-menopausal women.  A study of Japanese women found no increase in breast cancer among women receiving HRT.[x]  American women have much higher overall estrogen levels compared to women in Asian countries.  The breast cancer rate in the US is four to seven times higher than China and Japan; that is, until Asian women migrate to the US and adopt our lifestyle.  So, is a woman’s lifetime exposure to estrogen a factor?  Probably.  Early menarche and late menopause are both known to increase the risk and support the lifetime exposure hypothesis.  Birth control pills, contraceptive implants, excess body fat, estrogen-mimicking environmental chemicals and synthetic hormone replacement therapy all add to that lifetime exposure. 

What should you do?  Have a frank discussion with your physician about the pros and cons of hormone replacement therapy and the physiological differences between bioidentical hormones and synthetic HRT.  If your doctor is unable or unwilling to have that discussion, find a physician familiar with the subject who will.  As critics like to point out, there are no large scale trials unequivocally demonstrating the safety of bioidentical hormones, but there is no evidence of their harm.  On the other hand, there is considerable evidence that synthetic HRT (Premarin, Provera and PremPro) raises the risk for breast cancer, heart disease, blood clots, and Alzheimer’s disease.  For the vast majority of women, bioidentical hormone therapy is a safe, effective and beneficial alternative to suffering through menopause.

[ii] Eden JA, Wren BG. Hormone replacement therapy after breast cancer: a review.  Cancer Treat Rev. 1996 Sep;22(5):335-43.

[iii] Giorgi A. Breast cancer incidence in Canada declines as hormone therapy drops. JNCI J Natl Cancer Inst (2010) 102 (19): NP. doi: 10.1093/jnci/djq408. first published online Septemebr 2010

[iv] Chlebowski R, et al. Estrogen Plus Progestin and Breast Cancer Incidence and Mortality in Postmenopausal Women. JAMA. 2010;304(15):1684-1692. doi:10.1001/jama.2010.1500

[v] Ziel H, Finkle W. Increased risk of endometrial carcinoma among users of conjugated

estrogens. N Engl J Med 1975;293(23):1167–70

[vi] Hermsmeyer RK, Thompson TL, et al. Cardiovascular effects of medroxyprogesterone acetate and progesterone: a case of mistaken identity?  Nat Clin Pract Cardiovasc Med. 2008 Jul;5(7):387-95. Epub 2008 Jun 3.

[vii] Emory University. “Progesterone for Traumatic Brain Injury Tested in Phase III Clinical Trial.” ScienceDaily 22 February 2010.

[viii] L’hermite S, Simoncini T, et al. Could transdermal estradiol + progesterone be a safer post-menopausal HRT? A review. Maturitas. 2008 Jul-Aug;60(3-4):185-201. Epub 2008 Sep 5.

[ix] Sawicki, MW; Erman, M; Puranen, T; Vihko, P; Ghosh, D (1999). “Structure of the ternary complex of human 17beta-hydroxysteroid dehydrogenase type 1 with 3-hydroxyestra-1,3,5,7-tetraen-17-one (equilin) and NADP+”. Proceedings of the National Academy of Sciences of the United States of America 96 (3): 840–5. PMID 9927655. PMC 15312

[x] Saeki T, Muneo S, et al. No increase of breast cancer incidence in Japanese women who received hormone replacement therapy: overview of a case control study of breast cancer risk in Japan.  Intl J Clin Oncol, vol 13, no. 1, 8-11, DOI: 10.1007/s10147-0728-0

 Ever since the term “male menopause” was first coined in 1949, there have been debates about whether men go though a psychological and physiological change that is similar to menopause in women.  The problem is that menopause literally means “the end of menses,” so it describes the loss of something that men never have.  Despite that, men do experience physical changes as they age that, like menopause, are caused by a decrease in hormone production.  Unlike menopause, this decrease in hormone production is drawn out over most of a man’s adult life.  This has lead to a series of attempts to find a better term to describe what is happening.  Many doctor use the term “andropause” to describe the age-related hormone changes in men.  Irritability, fatigue, depression, reduced libido and erection problems are hallmark signs of andropause.

 Andropause can be taken to mean “the end of male-ness.”  More accurately, it should be thought of as a reduction in the production of hormones called “androgens” that produce male sexual characteristics.  The chief androgen in humans is testosterone.  Testosterone is the hormone that makes men, men. 

 Testosterone production varies throughout a man’s life.  Before birth, testosterone and other androgens drive the differentiation of the embryo into a male baby.  In early infancy, testosterone levels rise and then retreat for reasons that are not well-understood.  Through childhood, testosterone is very low, but then it increases greatly in puberty.  Starting at about age 30, testosterone production drops approximately 1% to 3% a year and this decrease continues until the end of life.

 What principally distinguishes menopause from andropause, therefore, is the time scale and rate at which sex hormone production changes.  In women, menopause is a distinct life stage lasting 1-10 years.  Once menopause is complete, production of sex hormones remains at a steady lower level until the end of life.  By contrast, men normally experience no such abrupt change in sex hormone production and the decline of production continues throughout old age.

 Another way menopause is different from andropause is in how it changes fertility.  Although there are many women who mistake the appearance of menopause symptoms for the end of fertility, earlier at some point in the peri-menopause transition the ovaries will stop producing new eggs and she will no longer be able to become pregnant.  In men, however, the production of sperm can continue until very late in life at levels high enough to cause pregnancy. 

 Despite these differences in timing and fertility, however, there is a real biological change happening in men as they age.  While there is not yet any officially recognized diagnosis of andropause, researchers have been defining a wide range of ways the reduction in testosterone affects men, using terms like Symptomatic Late-Onset Hypogonadism (SLOH) and Androgen Deficiency in the Aging Male (ADAM).  These terms may be more accurate ways of describing testosterone deficiency that has dropped enough to produce recognizable symptoms. 

 Testosterone production varies not only with age but also daily and in response to stress.  Peak production occurs in the morning decreasing through the day to a valley in the evening.  Testosterone is produced by the testicles and adrenal glands and released into the blood stream where most is bound to proteins called sex-hormone binding globulin (SHBG) other proteins such as albumin.  The SHBG-bound portion is very tightly bound making it unavailable for use by the body, leaving approximately 2% “free” testosterone and 23% loosely-bound “bioavailable” testosterone[1].  When it reaches its target, a small portion of testosterone is converted into a more potent metabolite called dihydrotestosterone (DHT).

 Like menopause, testosterone deficiency is an endocrine condition that causes changes in a man’s metabolism with short and long-term effects in many different organs and systems.  The musculoskeletal system shows lower density in the bones and weaker muscles.  In the cardiovascular system, testosterone deficiency is associated with atherosclerosis, coronary artery disease, and other cardiovascular diseases[2].  In the nervous system, low testosterone shows up as decreased libido, increased rates of depression and cognitive difficulties.  It is also linked to erectile dysfunction, alterations of body hair and skin thickness, increased visceral fat, and infertility.

 Men with low testosterone levels have higher risks of osteoporosis and fractures.  As testosterone decreases, deposition of new bone also decreases, reducing bone strength and density.  Osteoporotic men given testosterone supplementation reduce the rate of bone degradation and increase bone density.  Fractures, especially hip fractures, in the elderly are very dangerous to both men and women.  Men are more likely to die following hip fracture than women.  The one year mortality rate following hip fracture for men is double that of women.[3] 

 As both men and women age, they lose muscle strength.  Testosterone is an anabolic steroid, which builds muscle, so it makes sense that reduced levels would reduce muscle mass and strength.  The loss of independence and increased overall frailness we associate with old age are partly a consequence of this decline of the anabolic effects of testosterone.  Older me with relatively low testosterone levels are at increased risk of frailty than those with higher levels.[4]   Elderly men that have higher testosterone levels have better physical capacity as measured by physical fitness tests.  They also are better able to carry out normal daily activities, like writing, eating, walking, and dressing. Men given testosterone supplementation have reduced body fat, increased lean muscle mass, and increased grip strength.  They also gain upper and lower body strength and aerobic endurance.

 It has been a long-standing belief in the medical community that higher levels of testosterone put men at increased risk for heart disease.  The exact opposite is in fact true – lowered amounts of testosterone increase the risk of heart disease over normal men.  Men that have coronary artery disease have lower levels of testosterone than men without blocked arteries.  No study so far, in fact, shows a relation between higher testosterone and coronary artery disease.  Neither does an increased testosterone level from supplementation lead to increased heart disease.  This overturns years of dogma and leads to the question whether testosterone supplementation can help men with cardiovascular disease?

Fortunately, men with decreased testosterone and coronary artery disease do show improvement when given testosterone supplementation.  Angina frequency and intensity are reduced, they tolerate exercise longer before experiencing chest pain, and have improved mood.

Mood and other emotional and cognitive disturbances are another group of symptoms that men and women share and may be related to hormonal changes.  The brain produces testosterone and receptors for testosterone are common in the brain.  We are just beginning to understand the effects on the brain of late-life testosterone deficiency. 

Elderly men in one study that had higher levels of bioavailabile testosterone did better on tests that are designed to find brain damage or dementia.  Declining testosterone also appears to reduce the type of thinking called “spatial cognition” – tasks that require attention to objects in three-dimensional space like visual perception, object perception, and visual memory.   Men with lower levels of testosterone also report greater levels of memory problems and other dementia symptoms as they age. Testosterone also appears to both help protect and heal nerve cells in the brain.  In laboratory studies, testosterone protects neurons from attack by a variety of possible toxins.  It also helps heal severed nerves and produces other chemicals that help nerves re-grow after injury.

 With all these effects on the brain, it is no surprise it is being looked at as a way to treat one of the worst diseases of aging, Alzheimer’s disease (AD).  AD is characterized by progressive loss of higher brain functions and the deposition of plaque in the brain.    Testosterone and other hormones appear to possibly impact this process and are being considered as therapies for AD.  In some laboratory studies, testosterone significantly reduced the impact of AD on memory loss and the production of these plaques.

Another effect of menopause is that declining sex hormone production reduces interest in sex.  Men also experience a decline in sexual desire with reduced testosterone levels.  In fact, decreased libido with no other cause is a standard symptom for clinically-significant decreased testosterone.  Men with decreased testosterone also have more trouble producing or maintaining an erection.  Several small studies have shown that testosterone supplementation in older men results in both increases in libido and in a higher sense of well-being and satisfaction.

Weight gain in elderly women is frequently blamed on the hormonal and metabolic changes caused by menopause.  Similarly, decreased testosterone is linked to increased body fat, especially “visceral” fat.  Visceral fat is also called abdominal fat or organ fat.  It is the fat that is located inside the abdomen instead of just under the skin where most fat deposits are located.  Packed in among and around the abdominal organs, visceral fat is associated with a much greater risk of cardiovascular disease, diabetes, hypertension, atherosclerosis and premature death. 

 Any doctor that sees middle-aged men is asked: “Do men have male menopause?” or: “Does male menopause exist?”  Because of the very different ways that men and women’s bodies change the production and availability of sex hormones, these are really the wrong questions.  The question that we should ask is: “Should men be evaluated for sex-hormone changes in later life?”  This answer to this question is a very firm and unequivocal: “Yes.”

 Without proper evaluation of androgen levels, many treatable symptoms will go unaddressed.  With proper evaluation, men can be treated in ways that will improve general health, longevity, and quality of life. 

 Unfortunately, most clinicians either do not recognize the symptoms of testosterone deficiency or believe that these symptoms are “normal aging.”  When doctors miss addressing testosterone deficiency, they cheat their patients of powerful treatment options.

 Complicating evaluation and treatment of androgen deficiency, however, is the difficulty in measuring or defining what is an abnormally low level.  Men’s testosterone levels in later life are variable and poorly-defined.  Among the issues: there are multiple protocols for testing androgens, each with different reference values, there are different androgen fractions (free testosterone vs. bioavailabile testosterone, etc.) that can mask the amount actually available for use by the body, and the reference standards for the “normal” range are incredibly broad. 

 The biggest issue in simply using blood tests to determine if a man is testosterone deficient is that the blood levels will vary greatly form one day to the next.  Even if the test is drawn the same time of day on successive days, the blood levels of testosterone can be very different.  This is why a full evaluation that considers the combination of clinical symptoms and blood tests is so important.

 Just as with estrogen replacement therapy in women, however, there has been a great deal of controversy about possible hormone replacement therapy in men.  The chief concern has been worries that testosterone replacement could stimulate heart disease or prostate cancer.  Fortunately, the concerns for both negative side-effects appear to be overblown.  As said, there is growing evidence that testosterone can help protect the heart from cardiovascular disease. 

 The case of prostate cancer is a bit more complicated.  Many treatments for prostate cancer attempts to reduce testosterone to suppress tumor growth.  Obviously, giving testosterone to a man with a prostate tumor is therefore not an option.  The question has been: will testosterone supplements provoke prostate cancer?  Fortunately, the answer appears to be, “No.”[5]  Increased testosterone levels are not linked to higher rates of prostate cancer or more deaths from prostate cancer.  In fact, it is quite the opposite.  Men with higher amounts of testosterone show lower incidence and mortality for prostate cancer, as well as for cardiovascular disease and for all causes of death[6].

 The decline in late-life androgen production is a very real and very treatable phenomenon.  Unfortunately, 50 years of debate about whether there is such a thing as “male menopause” has obscured these hormonal changes.  There is a growing realization that proper evaluation and treatment of testosterone deficiency is both appropriate and beneficial for many men.  For optimal results, I recommend seeking out a physician experienced in bioidentical hormone replacement therapy within a broader program addressing overall lifestyle modification and enhancement.

[2] Liu PY, Death AK, Handelsman DJ. Androgens and cardiovascular disease. Endocrine Review. 2003 Jun;24(3):313-40.

[3] Haentjens P, Magaziner J, et al. Meta-analysis: Excess Mortality After Hip Fracture Among Older Women and Men. Annals Intern Med 2010; 152:380-390

[4] Hyde Z, Flicker L, Almeida OP, et al. Low Testosterone Tied to Frailty in Older Men.  J Clin Endocrinol Metab. Pub Online April 24, 2010; doi:10.1210/jc.2009-2754

[5] Eaton NE, Reeves GK, Appleby PN, Key TJ. Endogenous sex hormones and prostate cancer: a quantitative review of prospective studies. British Journal of Cancer. 1999 Jun;80(7):930-4

[6] Khaw, KT, Dowsett, M, Folkerd E, et al. Endogenous testosterone and mortality due to all causes, cardiovascular disease, and cancer in men: European Prospective Investigation into Cancer in Norfolk (EPIC-Norfolk) prospective patient study. Circulation. 2007 Dec 4;116(23):2694-701.

 Do our hormones decline because we get old?  Or do we feel old because our hormones decline?  One of the most pronounced health issues facing boomer men is plummeting testosterone levels.  Beginning in their mid to late 30’s or early 40’s, men lose 1% – 3% of their testosterone per year.  There is no abrupt drop off like women in menopause, but the decline for men continues throughout the remainder of their lives.  Insufficient testosterone levels can lead to a number of debilitating conditions with signs and symptoms including erectile dysfunction, low libido, impaired physical performance and frailty, decreased vitality, reduced bone mass, decreased muscle mass and strength, unfavorable lipid profiles, increased fatigue, sleep disturbances, depression, anemia and impaired cognitive function.

 With studies like the recent Massachusetts Male Aging Study[1] demonstrating an overall reduction in average testosterone levels for American men over the last 30 years, and studies linking lower testosterone to increased risk for cardiovascular disease, obesity, type-2 diabetes, metabolic syndrome, osteoporosis and premature death, there is renewed interest in testosterone therapy for men to improve quality of life.  The Health in Men Study published this April found that older men with relatively low testosterone levels were more likely to be frail or to become frail over the next several years than men with normal testosterone levels.[2]

 The National Institutes of Health and the National Institute on Aging have undertaken a new study called the Testosterone Trial.[3]  This study began in 2009 and seeks to determine if testosterone treatment for one year compared to placebo will be associated with improved walking speed, improvement in sexual activity, improvement on the vitality scale and verbal memory test, and anemia correction.  It will include 800 men aged 65 or older with low testosterone and one or more of these symptoms: impaired walking or physical function, low vitality, cognitive dysfunction, low sexual function, or anemia.

 It is estimated that more than 4 million men over age 45 in the United States have low testosterone, and only a small percentage are receiving treatment.  Many physicians hesitate to offer testosterone replacement to men with the misguided belief that testosterone causes or fuels prostate cancer.  Unfortunately this misconception has been perpetuated in medicine for so long that it had come to be accepted as true.  It certainly seems counterintuitive to link the two when the incidence of prostate cancer increases with age, while testosterone levels decrease.  Several extensive reviews of the medical literature, including an analysis out of Harvard University have revealed no such association.   Lack of consensus about the diagnostic criteria also causes confusion.  Many doctors will not treat men with all of the symptoms of low testosterone, even if they are near the rock bottom of the normal range, because it is still within that range. Another factor causing apprehension is the abuse of steroid hormones at unnaturally high levels by professional athletes for performance enhancement.

 What is the bottom line?  Any man over 40 or 50 that feels off his game, run down or is experiencing any of the symptoms of low testosterone should have a thorough evaluation.  I recommend seeking out a physician experienced in preventive health and hormone therapy for men.  Rather than narrowly focusing on just your hormone levels, a comprehensive program will expose your total health picture and help you move toward achieving optimal health. 

[1] O’Donnell AB, Araujo AB, McKinlay JB. The health of normally aging men: The Massachusetts Male Aging Study.  Exp Gerontol. 2004 Jul;39(7):975-84.

[2] Hyde Z, Flicker L, et al. Low Testosterone Predicts Frailty in Older Men: The Health in Men Study.  J Clin Endocrinol Metab, April 2010

[3] http://clinicaltrials.gov/ct2/show/NCT00799617

Testosterone is produced by the ovaries and adrenals in young women in low doses (free testosterone levels range between 2–8 pg/mL). The bulk of the present research on the use of testosterone has been conducted on women with surgical menopause, hypopituitarianism, anorexia nervosa, and primary adrenal insufficiency; patients with HIV and low body weight;[1] and patients with steroid- and oral contraceptive–induced suppression of endogenous androgens. Although there has been little if any formal study on testosterone use in normal aging in women, we know that adequate levels of testosterone play an important role in helping women maintain a healthy body composition.

Women begin to gain body fat 10 years before they experience menopause, and many women gain weight when taking birth control pills, but doctors frequently overlook the role that testosterone can play in helping to ameliorate this weight gain. Testosterone therapy results in an increase in fat-free body mass and mitigates central fat deposition associated with estrogen use.[2] In a double-blind placebo-controlled small study of androgen-deficient women, testosterone replacement demonstrably increased thigh muscle mass as measured by CT scanning.[3]

Loss of libido in the aging female is the most common complaint that leads physicians to consider testosterone deficiency as a possible cause and the main consideration for treatment with testosterone. Multiple factors directly affect sexual inclination. Poor relationship status, self-image issues, multiple medications and their side effects, other stress factors, aging, and concurrent chronic or acute illnesses are some of the most frequently encountered deterrents of sex drive. Many of these factors cannot be altered, and all factors should be taken into account.  While circulating testosterone levels do not definitively diagnose low testosterone as the cause for loss of libido, it may be helpful to keep in mind that premenopausal women have a range of 20 to 75 ng/dL total testosterone while postmenopausal women can present with values as low as 5 to 10 ng/dL.  The seminal study on impaired sexual function improvement with supplemental testosterone comes from a double-blind, placebo-controlled study in the New England Journal of Medicine. Seventy-five women 31 to 56 years old after undergoing oophorectomy (removal of ovaries) and hysterectomy were randomly assigned to receive placebo, conjugated estrogen and either 150 mcg or 300 mcg doses of transdermal testosterone. The women who received the higher dose of testosterone reported a two- to threefold increase in sexual desire, masturbation, sexual intercourse, and sense of positive well-being as compared with placebo or conjugated estrogen alone.[4]

Besides helping women maintain lean muscle mass and an enjoyable sex life well into their forties, fifties, sixties and beyond, there is some evidence pointing to additional positive effects of testosterone on a woman’s health as she ages.  A report in the Journal of Women’s Health examined the hypothesis that testosterone deficiency is a key predictive factor for heart disease in aging women or women who have had hysterectomies.[5] Cardiovascular disease is the leading cause of death in postmenopausal women. Women who have hysterectomies are three times more likely to develop cardiovascular disease compared to women who have not had one. Women who have hysterectomies often receive estrogen replacement therapy but not testosterone replacement.  Although this seems to make sense in context of the numerous reports linking low testosterone to an increased risk of cardiovascular disease and premature death in men, a recent observational study may suggest the opposite.

In this study, researchers measured levels of testosterone in 344 women, aged 65-98 years. They found that women with the highest testosterone levels — in the top 25 percent of this study group— were three times as likely to have coronary heart disease compared to women with lower testosterone levels. These women were also three times as likely to have a group of metabolic risk factors called the metabolic syndrome compared to women with lower testosterone levels.   A greater degree of insulin resistance is the proposed mechanism.  Testosterone therapy reduces insulin resistance, metabolic syndrome and cardiovascular risk in men.  Curious.  This is a pre-publication report, so seeing the full study in next month’s Journal of Clinical Endocrinology and Metabolism should be interesting.

Breast cancer is the most common cancer in women.  Acting through androgen receptors, testosterone opposes estradiol induced proliferation of human breast cell lines[6]. Cases where endogenous testosterone levels are elevated, such as with polycystic ovary syndrome, are associated with breast tissue atrophy and a decreased risk of breast cancer.[7] There are, however, conflicting data on the potential role of supplemental testosterone in the development of breast cancer.

Though treatment with testosterone in the aging woman is gaining popularity, there is a definitive need for studies specific to this population to evaluate the safety and efficacy of testosterone as a therapeutic modality for postmenopausal women, as well as for younger women with loss of libido, to define its best use in prevention and wellness.   It is thought by some to be the missing link in hormone replacement therapy.  As more studies show the benefits of improved quality of life, preserved sexual function, restored libido, and healthy body composition from testosterone therapy, the more routine it will become for women seeking to optimize their health.

[2] Davis S, Walker K. Effects of estradiol with and without testosterone on body composition and relationship with lipids in postmenopausal women. Menopause 2000;7:395–401.

[3] Miller K, Biller B, Beauregard C. Effects of testosterone replacement in androgen-deficient women with hypopituitarism; a randomized, double-blind, placebo-controlled study. J Clin Endocrinol Metab 2006;91:1683–90.

[4] Shifren J, Braunstein G, Simon J. Transdermal testosterone treatment in women with impaired sexual function after oophorectomy.        NEJM 2000;343:682–8.

[5] Rako S. Testosterone deficiency: a key factor in the increased cardiovascular risk to women following hysterectomy or with natural aging?    J Womens Health. 1998 Sep;7(7):825-9

[6] Ando S, De Amicis F. Breast cancer from estrogen to androgen receptor. V Mol Molecular and Cellular Endocrinology 2002;193:121–8.

[7] Gammon M, Thompson W. Polycystic ovaries and the risk of breast cancer.

Am J Epidemiol 1991;134:818–24.

Telomeres are longer in your youth and shorter as we age.  Shortened telomeres have also been found in people with chonic or inflammatory diseases compared to their same aged peers.  It appears that inflammation and oxidative stress can cause faster or premature telomere shortening.  Shorter telomeres have been associated with metabolic abnormalities, obesity, cardiovascular diseases, demetia and cancers.

Most cancer cells have much shorter telomeres than normal cells of the same individual.  Some cancer cell have longer telomeres than normal cells, but in both cases there is a heightened actitivity of the enzyme Telemorase; responsible for producing the telomere.  It is postulated that this heightened enzyme activity is what confers near immortality to cancer cells and allows them to continue to divide uncontrollably.   A study from the International Journal of Cancer in April of this year found  ”among premenopausal women the risk of breast cancer is 60 percent or 70 percent higher with the shortest telomere lengths”.

What can you do to reduce the rate at which your telomeres shorten?

• reduce excess body fat ( especially visceral fat) and improve body composition
• get regular aerobic and resistance exercise
• Sleep 7-9 hours per night
• Reduce stress
• Stop smoking
• Follow a mediterranean-style diet: increasing fruits and vegetable, health fats, soluble fiber, more fish
• Avoid highly processed foods, fast foods, artifical sweeteners that increase oxidative stress
• Achieve hormone balance with bioidentical hormones

Telomere testing is now available at Alternity Healthcare through Spectracell Labs.

Estrogen, progesterone and testosterone are the three major sex hormones in both men and women, with the ratios and levels varying according to gender.  Estrogen and progesterone are the predominant hormones in women.  Any discussion of one must include the other, although this article will focus primarily on estrogen.

Estrogen is made in the ovaries, the corpus luteum, adrenal glands, breast and fat cells.

Estrogen is a generic term referring to a group of molecules. In humans, the three main identified estrogen molecules are estriol (E3), estradiol (E2), and estrone (E1).  A proper balance of estrogen enhances sensuality, improves the appearance of skin, moisturizes eyes, lubricates the vagina, preserves mental clarity, plumps up the breasts, and protects the bones and cardiovascular system.

When the scientific and lay communities refer to estrogen, they typically refer to its three components as one. At times, this oversimplification leads to errors in separating the individual function of the estrogens, particularly when discussing the differences between estrogen preparations used as hormone-replacement therapy available on the market. Although their actions are perceived and often recorded as one, the component molecules of estrogen have different potencies and effects.

Types of Internal Estrogens

Estradiol is the most powerful, abundant and active form of estrogen.  Prior to menopause, it is made mainly by the ovaries.  Post menopausal production occurs in individual cells throughout the body, particularly fat cells and stromal cells in the breast. Estradiol directly affects a wide range of cellular functions, as estrogen receptors are ubiquitous.

Estriol is the weakest of the estrogens. Estriol is primarily manufactured during pregnancy by the placenta. It attaches to cell receptors affecting hair, nails, and skin.  Recorded data on estriol’s function demonstrate that estriol’s effects are limited mainly to the vaginal walls with little effect on the heart and bones in non-pregnant women. In the non-pregnant, young, and premenopausal woman, estriol is made in the liver in small doses. Studies have shown it to have a protective effect against breast cancer.

Estrone is manufactured in fat cells after menopause primarily from testosterone derivatives (androstenedione). Estrone levels tend to rise after menopause and the increase in estrone has been implicated in an increased incidence of breast tumors but most data have been obtained from animal studies. Overweight older women have high circulating levels of estrone.

External Estrogens

Your hormonal health can also be affected by external estrogens and estrogen-like compounds introduced into your body.  These include bioidentical estrogens, synthetic estrogens, xenoestrogens, and phytoestrogens.  Bioidentical hormones are hormones manufactured with a molecular structure identical to that naturally found in the human body.  They are made from a plant source, frequently soy or yams, and are ideal for use in hormone replacement therapy.  “Bioidentical hormones” is not a marketing term. The term has been used for more than a decade in the inserts to all FDA-approved commercial hormone preparations that contain hormones molecularly identical to human hormones.  Bioidentical estrogen preparations include: 17-Beta estradiol (Alora, Climara, Estrace), 17-Beta estradiol patches (Vivelle-Dot, Vivelle, Estraderm), Estradiol transdermal spray (Evamist) and combinations of estradiol, estriol and estrone in compounded formulations (Biest, Triest).  In recent studies, bioidentical estrogens have demonstrated an ability to reduce degradation of telomere length.  Telomeres are protective end-caps on chromosomes, the length of which is correlated with biological age.

Synthetic estrogens are chemically manipulated and are molecularly very different from human estrogens.  These are the most common formulations used for hormone replacement therapy in the United States.  Synthetic estrogens are derived from the urine of pregnant mares, as the name Premarin implies.  The most popular preparations are conjugated equine estrogen (Premarin), esterified estrogen (Estaratab), and ethynil estradiol (Estynil).

Xenoestrogens are produced as by-products of the chemical pollution in our society and are very hazardous to your health.  They can be absorbed through your skin, inhaled when you breathe and ingested with your food.  Examples include dioxins, polychlorinated biphenyls (PCB), and dichlorodiphenal-trichoroethane (DDT), among others.  They can be stored in fat cells for long periods of time and although relatively weak, they can act in combination to increase your risk for certain cancers.

Phytoestrogens are abundant in nature and can weakly interact with estrogen receptors.  These compounds include lignans found in cereals, vegetables, green tea, legumes and flax; isoflavones in soy, beer, chickpeas, beans and lentils; and coumestrol present in grapes (resveratrol), alfalfa and clover.  In moderate doses, phytoestrogens have been shown to exert a protective effect on breast cancer by inhibiting the production of estrogen.

Estrogen Metabolism

The various metabolites of estrogen must also be considered in evaluating the overall hormonal milieu in your body.  These metabolites are 2-hydroxyestrogen (2OH), 4-hydroxyestrogen (4OH) and 16alpha-hydroxyestrogen (16OH).  The 2-hydroxyestrogen metabolite is considered a “good” estrogen because it has anti-cancer properties.  It does not exert proliferative effects on other cells and antagonizes the effects of other estrogens.  This metabolite also reaches very high levels during pregnancy, suggesting a protective effect against high hormone elevations.  Synthetic estrogens can reduce the formation of 2-hydroxyestrogens.  A competing pathway results in the production of 16alpha-hydroxyestrogen which has a high affinity for the estrogen receptor and strongly stimulates cell proliferation leading to cancerous changes in estrogen sensitive tissues.  Studies have shown this 16 alpha metabolite to be important for preservation of bone tissue.  It is, therefore, important to maintain an optimal ratio of 2-hydroxy:16alpha-hydroxy metabolites. The ratio can be measured by a urine or blood test.  A low ratio may put you at increased risk for breast, uterine and ovarian cancer.  A minor pathway leads to the production of the 4-hydroxyestrogen metabolite.  This metabolite also promotes cancerous changes but doesn’t bind to an estrogen receptor, rather it works by directly damaging cellar DNA.  Synthetic estrogens are metabolized to 4-hydroxy products; another compelling reason to avoid them.

Estrogen and progesterone are antagonists. Their actions are designed to balance each other and keep each other in check. We cannot live in a healthy state without hormonal balance.  Hormones do not act independently, under normal circumstances, in healthy bodies.

Progesterone

Progesterone is manufactured primarily by the corpus luteum (the follicle transformed after ovulation) and also to a small degree by the  arenals. In the ovary, progesterone production is activated at ovulation (15 days before the next menstruation), stimulated by the release of luteinizing hormone from the pituitary gland and is crucial to the survival of the ovum once fertilized. When pregnancy occurs, progesterone production increases rapidly and its manufacture is taken over by the placenta. If a woman does not get pregnant, the corpus luteum involutes and progesterone production diminishes and eventually disappears in parallel with estrogen production, heralding menstruation.

Progesterone is a precursor to most sex hormones, including estrogen in the ovaries, testosterone, all androgens, and other adrenal hormones, making it an extremely important hormone for reasons far beyond its role as a sex hormone.  Progesterone in the breast and uterus counteracts the stimulation of cell growth, which is a direct action of estrogen. It accomplishes this action by activating the progesterone receptor, which in turn, down-regulates the estrogen receptor. Because progesterone suppresses estrogen-driven cell proliferation, progesterone in the natural state helps keep breast cell growth in healthy balance.

Commercially and compounded bioidentical hormone preparations containing progesterone include:  Progesterone in peanut oil capsule (Prometrium), progesterone vaginal gel (Crinone), micronized progesterone in various compounded forms (capsules, troches, transdermal creams, vaginal suppositories), combinations of estradiol and progesterone in compounded formulations.

Beyond the commercial bioidentical hormone formulations, individually compounded preparations of bioidentical estrogens, progesterone and testosterone are prepared in compounding pharmacies or laboratories (some are FDA approved; all are regulated by the state they operate in) on an individualized basis as prescribed by a physician. These products contain the same active estrogens, progesterone, and testosterone as those found in the commercial preparations listed above. The difference is that they are individually mixed in tablet, capsule, troches, gels, or creams to the specifications of the prescribing physician for the individual patient.

The synthetic, non-human progestin found in Provera is medroxyprogesterone (MPA).  It has very different biologic effects than natural human progesterone.  Provera reduces the beneficial effects of estrogen on plasma lipoproteins, can lead to vascular spasms, opposes the beneficial effects of estrogen on the brain and has been shown to enhance the estrogen-induced proliferation of pre-existing breast cancer cells;  the opposite effects of bioidentical or natural progesterone.

Among the lay public as well as within the scientific and medical communities, there remains considerable confusion surrounding estrogen and progesterone formulations.  The confusion comes from the lack of clear distinction between their molecular formulas, the lack of focus on their different effects in the human body, and the use of nonspecific nomenclature when referring to estrogen and progesterone regardless of their actual differences in chemical structure or activity.

Hormone Replacement Therapy

Scientific studies on the effects of hormone replacement therapy after menopause have had conflicting results and conclusions.  As early as 1976, scientific data demonstrating the safety of bioidentical hormones appeared in the conventional medical literature from the American College of Obstetrics and Gynecology. Reports of increased risk of endometrial and breast carcinoma among users of synthetic conjugated estrogens also appeared in the scientific literature around the same time  As early as 1980 and continuing into the recent literature, untoward side effects of synthetic progestins, such as thrombotic phenomena; breast tissue cell hyperplastic changes;  cardiovascular symptoms, headaches, elevated blood pressure, and changes in cholesterol, carbohydrate, and lipid metabolism prompted more research into bioidentical (micronized) progesterone as a safer option.  A double-blind study comparing transdermal estradiol and Premarin reported in the American Journal of Obstetrics and Gynecology as early as 1985 suggested that  bioidentical hormones were superior in relieving postmenopausal symptoms without side effects.

Womens Health Initiative

Most recently, the Women’s Health Initiative (WHI) has been the source of confusing and sensationalized reports indicting all hormone replacement for causing breast cancer and heart disease.  The goal of the study was to evaluate the long-term effect of hormone-replacement therapy (HRT) versus placebo in the prevention of heart disease, osteoporosis, cancer, and strokes in postmenopausal women. The only form of hormone-replacement therapy used in the study was synthetic conjugated equine estrogens (Premarin) and synthetic progestins (Provera). Unfortunately, the WHI did not include a bioidentical arm even though bioidentical hormone usage and statistically significant studies consistently demonstrated positive results and sustainable safety and efficacy records.  The WHI was supposed to definitively answer questions about the efficacy and benefits of HRT but only created confusion and concern.  There were three treatment arms in WHI:  the first used a combination of synthetic hormones, Premarin plus Provera, called PremPro; a second arm used only a conjugated equine estrogen (CEE), Premarin and a third arm evaluated the effects of calcium and vitamin D on fracture risk. Subjects in the PrePro combined synthetic hormone arm were reported to have an increased risk of breast cancer, stroke and coronary artery disease.  The results from the Premarin only group were less publicized but demonstrated a reduced relative risk for both breast cancer and heart disease; the risk of thrombophlebitis was increased.  Initial news reports on the calcium and vitamin D arm suggested no benefit from taking those supplements.  Subsequent analysis has determined that the study was poorly designed and the initial analysis faulty.

Concerns with the WHI study design include the type of hormone used, dosing pattern, route of administration, timing of hormone usage, mean age of the participants, and prior health status of the participants.  The WHI used only synthetic hormones taken orally and at a relatively high, fixed dose.  The participants were, on average, 63 years old and more than ten years beyond menopause; the crucial time to mitigate the pro-inflammatory effects of the postmenopause transition.  Studies have demonstrated estrogen’s ability to block chronic inflammatory mediators, including interleukin-6, tumor necrosis factor alpha and prostaglandin E2.  Estrogen has also been found to have significant antioxidant effects.

Participants in the WHI were not adequately prescreened for breast cancer or subclinical atherosclerotic heart disease, and it was reported in JAMA, the Journal of the American Medical Association in 2002 that a substantial portion of the participants had prior health histories which included obesity, hyperlipidemia, angina, strokes and smoking.  The adverse outcomes WHI attributed to hormone therapy, especially cardiovascular, could very well be linked to age and pre-existing risk factors.  A reanalysis by Rossouw et al  published in JAMA in 2007 separated WHI participants by age and found a reduced risk for coronary heart disease in all women taking hormone therapy 10 or fewer years from menopause.  The only statistically significant increase in cardiac events occurred in women 20 plus years postmenopause.  Furthermore, the results of the WHI Coronary-Artery Calcium Score Study performed after the conclusion of the WHI, demonstrated a 61% reduction in coronary artery calcification in women taking estrogen.  This translates into a reduced incidence of subclinical coronary artery disease in women receiving estrogen.  Although breast cancer may be the greater fear for women, 10 times more women die from cardiovascular disease every year than breast cancer.

As mentioned above, the WHI used only synthetic hormones.  Synthetic estrogens are metabolized to 4OH estrogen, which has been found to be thirty-times more toxic to cellular DNA than bioidentical estrogens.  Synthetic progestins appear to attenuate most beneficial effects of estrogens and enhance estrogen’s proliferative effects.  That may explain any increased risk of breast cancer noted after 10 or more years of synthetic hormone replacement therapy.

The synthetic hormones used in WHI, Premarin and PremPro are administered orally.  They are subjected to first pass through the liver resulting in increased production of clotting proteins and inflammatory markers, C-reactive protein.  Orally administered estrogen preparations have long been associated with an increased risk of venous thromboembolism (VTE), or blood clots.  In each of the two hormone therapy arms of the WHI, an increase in VTE was reported.   Transdermal estrogen has been shown to eliminate the thromboembolic effects noted by orally administered estrogens.   Two studies published in Circulation, the Journal of the American Heart Association, in 2005 and 2007 showed that transdermal estrogens did not increase the risk for blood clots, even when combined with micronized progesterone.

Breast Cancer

Public perception that all hormone preparations cause breast cancer was fueled by the notoriety gained in the media from the results of the combined estrogen-progestin arm of the WHI that ostensibly revealed an increased risk of invasive breast cancer among hormone users.  Those erroneous conclusions of so-called experts have been refuted by subsequent analyses. When corrected for multiple breast cancer risk factors, the results were no longer considered statistically significant.  Additionally, the combined WHI arm was discontinued after 5 years, and most cancer researchers agree it takes 7-10 years of dividing for a breast cancer cell to become a detectable lesion.  This further suggests that hormone replacement was not the cause of breast cancer.  A large review of studies prior to WHI published in the New England Journal of Medicine, 1997 demonstrated a 24% reduction of breast cancer deaths among women during the first ten years of hormone replacement.

Beginning hormone replacement therapy at the onset of menopause and continuing for  10 years significantly reduced the incidence of Alzheimer’s disease in the Cache Cohort Study published in 2002.  Women who began HRT ten years or later had an increased incidence of Alzheimer’s.  Similar results were reported in the journal, Menopause, in 2005:  replacing hormones early in menopause and continuing them for several years protected against cognitive decline and that benefit persisted for up to 15 years later.

Although the controversy surrounding the use of hormone replacement therapy is far from resolved, there is mounting evidence of its benefits for most women.  A recent study in Menopause reported that a “significant proportion of obstetrician-gynecologists continue to express skepticism regarding the WHI results”. The medical and scientific community will probably not reach any consensus until a definitive randomized trial directly comparing synthetic hormones with bioidentical hormones, while taking into account age, risk factors, timing and route of administration, and differing biologic activity during the crucial first ten years of menopause.

That being said, there is ample evidence to recommend hormone replacement for most women.  Bioidentical hormone therapy should be initiated at menopause or during perimenopause to provide protection for the cardiovascular system, maintain adequate bone mass and body composition, enhance sexual desire and responsiveness, preserve cognitive function, and minimize the unpleasant symptoms associated with the menopausal transition.  Women would be best served to seek out a physician specializing in bioidentical hormone therapy.  The most effective hormone balancing is achieved within a broader program addressing lifestyle modificatons, proper nutrition and nutritional modulation of hormone metabolites, high quality nutritional supplements, liver-gut detoxification, regular exercise, stress management and adequate sleep.   Remember, aging is inevitable, but how you age is up to you.

Osteoporosis is defined by a reduction in bone mass, bone quality or the presence of a fragility fracture. It contributes to nearly 1.5 million fractures per year in the US.

One out of every two women will experience an osteoporotic fracture in her lifetime. For men, the number is one in four. Common fracture sites include the hip, spine, wrist and rib. For anyone with an osteoporotic fracture, the one year mortality approaches 20%

Bone is a living tissue balanced by the actions of osteoblasts that lay down new bone and osteoclasts responsible for bone resorption. Bone mineral density is a measure of the adequacy of mineralization of bone. Peak bone mass occurs before age 30. The gold standard test is a DEXA bone densitomitry scan.

Recent scientific information implicates chronic inflammation, oxidative cell damage and advanced glycosalated end products (AGE’s) as contributors to the development of osteoporosis. Bone loss is also correlated with vasclar calcifications and the development of cardiovascular disease.

Risk factors for the development of osteoporosis include:

• low estrogen in women and low testosterone in men
• low body weight (<127 lbs)
• smoking
• lack of exercise
• excessive alcohol
• deficiency in calcium and/or vitamin D
• excess phosporous intake (soda)
• high protein diet (acidic)
• diabetes, thyroid disease, celiac disease, inflammatory bowel disease, arthritis

To reduce your risk of osteoporosis be sure to eat a healthy diet that includes colorful fruits and vegetables, regularly engage in aerobic and resistance exercise, take adequate calcium, vitamin D and omega-3 fatty acid supplements.

Every woman over 40 and man over 50 should consider having their bone mineral density checked. Preventing osteoporosis is better than treating it; especially after an osteoporotic fracture.

As men grow older, testosterone levels fall, with a steeper decline in unbound or free testosterone; the biologically active portion. The decline in testosterone levels associated with aging is attributable to a number of factors. There is a decline in the absolute number of Leydig cells, which produce testosterone in the testes, and each remaining cell shows a reduced testosterone production. Furthermore, those aging cells respond less robustly to their signal to produce testosterone. Another factor affecting the functional availability of testosterone is the age-related increase in sex hormone binding globulin (SHBG). Up to 50% of circulating testosterone is bound to SHBG, so increased SHBG reduces the available amount of free testosterone. The net result is gradually declining testosterone levels and less available free testosterone. The condition of testosterone, or androgen, deficiency in aging is known as andropause. Its prevalence in healthy males over the age of 40 has been demonstrated in observational studies, but there is no agreed upon blood level that defines andropause. The risk of having low testosterone levels is significantly higher in men with hypertension, hyperlipidemia, diabetes, obesity and asthma or chronic obstructive pulmonary disease than in men without these conditions, and has been noted to be as high as 40% in some studies.

Lower testosterone levels have been associated with poorer cognitive function, higher body mass index, increased body fat, declining muscle mass and strength and impaired general and sexual health in aging men. Recently, lower testosterone levels have also been linked to a number of chronic diseases including, metabolic syndrome, type II diabetes, cardiovascular disease, and prostate cancer, and has been shown to predict higher overall mortality.

EARLY SIGNS

The first signs of declining testosterone levels are generally vague: diminished subjective perception of energy levels, feeling like you’ve lost your edge, increased irritability, decline in mood, decline in memory and concentration, and loss of early morning erections. Interestingly, the decline in sex drive and frequency of sexual thoughts usually precedes the decline in actual performance. More often than not, these symptoms are dismissed as “just getting older”. If not addressed, testosterone levels continue to fall and patients notice difficulty with maintaining muscle mass and strength, difficulty controlling body fat, reduced stamina and poorer athletic performance; despite a maintained activity level or exercise regime. Increased erectile dysfunction, decreased sense of well being and decreased bone mass are other identifiable signs or symptoms of andropause.

Whenever testosterone is discussed, most people think first of male sexual potency and the reproductive organs. The heart, in fact, is one of the organs with the greatest number of testosterone receptors. Testosterone is associated with several effects on cardiac health. It has been linked with reducing coronary artery disease and hypertension risks as well as improving cardiac function in patients with preexisting heart disease. In Circulation, the journal of the American Heart Association, a study in 2000 demonstrated that low-dose testosterone reduced angina symptoms in men with stable angina. Reported in the same Journal in 2007, low testosterone concentrations were associated with increased mortality due to cardiovascular disease, cancer and all causes. Several other studies in the Journal of the American College of Cardiology and Circulation documented the association of low testosterone with increased intima medial thickness; a surrogate marker for heart disease. A 2009 review article in the International Journal of Impotence Research noted that “erectile dysfunction is a marker for underlying vascular disease and its presence predicts increased incidence of subsequent cardiovascular disease.”

ERECTILE DYSFUNCTION MAY PREDICT HEART DISEASE

Erectile dysfunction affects up to 10% of men in their 40′s and more than half of all men by age 70. Reported in JAMA, the Journal of the American Medical Association in 2005, nearly 9500 men aged 55 and older were evaluated every three months over a nine year period for cardiovascular disease and erectile dysfunction (ED). At the start of the study, 85% had no cardiovascular (CV) disease and 47% had ED. The authors found over the course of the study that the risk of incident cardiovascular events was nearly double for men with ED; an association in a similar range to that for current smokers or individuals with family history of CV disease.

More evidence of this frightening association comes from a ten-year Mayo Clinic study. In that study, the strong association between ED and coronary artery disease (CAD) suggested they could be “differing manifestations of a common underlying vascular pathology.” Study participants were divided by ten-year intervals and the youngest men (age 40-49) had the lowest incidence of ED. In each age group, the incidence of CAD increased dramatically in those with ED. Surprisingly, “the risk was highest in the youngest men with ED”. That is, those 40-49 year olds with ED were found to have the highest incidence density of CAD per 1000 person-years. This data suggests all men with ED, and particularly young men with ED, are ideal candidates for cardiovascular risk factor screening. Other factors that can contribute to ED include: diabetes, hypertension, high cholesterol, obesity, cigarette smoking, anxiety, depression and certain pharmaceutical medications. (See the April newsletter: http://alternityhealthcare.com/newsletters/vol2_iss4.html)

Interestingly, average male testosterone levels have dropped over the last 15 years, according to a 2007 population study published in the Journal of Endocrinology and Metabolism. During this same time period, in an effort to reduce the incidence of atherosclerotic heart disease, there has been a push to reduce cholesterol to ever lower and lower levels. Despite that effort, cardiovascular disease incidence has exploded: it is the leading cause of death in the United States. And, the idea that cholesterol is the main cause of atherosclerotic cardiovascular disease is becoming increasingly tenuous; since more than 60% of those having a heart attack have a normal cholesterol profile. Cholesterol, though vilified as the cause of cardiovascular disease, is the precursor molecule for testosterone and all other steroid hormones. Reducing cholesterol too much can interfere with adequate testosterone production. Has the zeal to reduce cholesterol inadvertently affected testosterone levels, ED incidence and, by extension actually increased the risk for cardiovascular disease?

The brain is another organ with an abundance of testosterone receptors. Testosterone was found to be associated with maintained cognitive function in the aging brain, lowered dementia risk and improvements in the neurophysiology of patients with preexisting dementia. A study published in the journal Neurology in 2004 demonstrated an association between low testosterone levels and subsequent development of Alzheimer’s disease. Another small study in the Archives of Neurology, 2006, evaluated the effects of testosterone therapy on cognition, neuropsychiatric symptoms, and quality of life in male patients with Alzheimer’s disease and healthy elderly men. It found that patients receiving testosterone had significant improvement in quality-of-life scores, improved numerical scores and less decline in visuospatial functions. The Health in Men Study published in the Clinical Endocrinology Journal 2008 concluded that “higher serum free testosterone is associated with better cognitive function in aging men.” In this same journal, an observational study of 3453 men aged 65-83 years suggested that healthy lifestyle choices may slow the decline in testosterone. These interventions included:

• no smoking
• moderate physical activity
• avoiding excessive alcohol
• eating fish > 3 times per week
• eating red meat a < 6 times per week
• maintaining a BMI < 25
• using reduced fat milk
• avoiding added salt in food

Numerous population studies have demonstrated the inverse relationship between both retention of lean mass and gain in fat mass associated with declining testosterone levels. In addition to correlating testosterone decline with loss of lean mass, studies have been done looking at the relationship between testosterone replacement and a return to a more favorable body composition. The consensus in the literature is that testosterone supplementation is accompanied by gains in lean mass across all age groups, reduced body fat with some preferential fat loss on the trunk (central or visceral fat). Visceral fat accumulation and waist circumference have been shown to be independent risk factors for the development of coronary artery disease (CAD). Like the relationship between lean mass, there is a similar correlation between testosterone levels and bone mineral density (BMD) noted in multiple studies over the last 20 years. Retained lean mass is associated with increased strength and coordination, maintained physical function and less injury from falls. Body fat reduction is associated with reduced risk for the development of CAD, type II diabetes and metabolic syndrome. Maintained BMD reduces the risk for the development of osteoporosis and subsequent fractures.

CONTROVERSY

Many physicians hesitate to offer testosterone replacement to aging men with the misguided belief that testosterone causes or fuels prostate cancer. A review of the medical literature, however, reveals no such causal association. A retrospective analysis published in the New England Journal of Medicine in 2004 found no causal relationship between testosterone replacement and prostate cancer or heart disease. A 2007 review out of Harvard concluded that: “Although there is yet to be a large, long term, controlled study on the effect of [testosterone replacement therapy] on [prostate cancer] risk, it should be abundantly clear that raising [testosterone] in hypogonadal men has little, if any, impact on prostate cancer risk or growth in the short to medium term. The withholding of testosterone replacement therapy in men because of fear of prostate cancer risk or progression is no longer tenable in an age of evidence-based medicine, because neither evidence nor theory supports this position.” Perceived risks associated with testosterone treatments and its abuse in the areas of athletic enhancement has caused much apprehension and confusion without scientific basis.

TESTING

Before making the decision to supplement with testosterone, appropriate lab testing should be undertaken. Two tests, total testosterone and free testosterone are essential.

Additional information can be gained from measuring dihydrotestosterone (DHT) and estrogen; two substances to which testosterone can be metabolized. These can affect the amount of testosterone available and can cause unwanted side effects, such as breast enlargement, hair loss and prostate enlargement. A baseline PSA must be obtained to screen for preexisting prostate disease. Monitoring growth hormone, thyroid hormone, leutinizing hormone (LH), DHEA, lipid profile and blood count are also clinically prudent in a comprehensive hormone optimization program.

TESTOSTERONE SUPPLEMENTATION

There are a variety of formulations and routes of administration of testosterone available. The best method and formulation should be determined individually between patient and physician. Optimally, the delivery method and formulation should be clinically effective in alleviating the signs and symptoms of testosterone decline and produce predictable, reproducible physiologic levels of testosterone. Currently, there are no recommended oral testosterone formulations. Topical placement with creams or patches – the route of choice for testosterone replacement in women – has limited application in men. Although convenient, there are several distinct disadvantages: low obtainable maximum serum testosterone levels, a large percentage converted to DHT, troublesome local skin reactions and a very large skin area needed to achieve therapeutic levels. The current standard bearer for direct testosterone supplementation is weekly intramuscular injections of a depot formulation (suspended in oil). This route gives predictable results, adequate therapeutic levels and avoids excess conversion to DHT. Subcutaneous testosterone pellets or implants are available but require a small surgical procedure to insert them. They also produce predictable therapeutic levels.

Another alternative is to stimulate your own testicular function to produce more testosterone, using human chorionic gonadotropin (HCG). This method mimics your natural pituitary physiology but responsiveness declines with advancing age; greater than 90% response rate at age 40 to under 50% at age 65. A simple blood test can help predict the likelihood of success.

If you, or someone you love, is experiencing symptoms of andropause, or have concerns about your hormone balance, I recommend seeking out a physician that specializes in bioidentical hormone replacement therapy. It is equally important to address other lifestyle issues such as: (1) eating a balanced diet that includes colorful fruits and vegetables, quality proteins and fish, healthy fats and a moderate amount of whole grains, (2) engaging in regular physical activity or exercise, (3) avoid smoking or excessive alcohol consumption, (4) getting 7-9 restful hours of sleep per night. Rather than narrowly focusing on just your hormone levels, a comprehensive program will expose your total health picture and help you move toward achieving optimal health.