Testosterone and Prostate Cancer
Cancer of the reproductive system is frequent in both men and women. In females, it’s commonly breast or uterine cancer, while we males have to worry about the dreaded “Big C” in the form of prostate cancer. This disease occurs in men with such alarming frequency that one in five will be affected by it in their lifetime. The chance for developing it also increases significantly with age, making it most common in men over the age of 50. The risks for benign prostate hypertrophy (BPH) also go up as we get older, a disease characterized by the non-cancerous enlargement of the prostate gland. BPH is an early warning sign that prostate cancer may be looming and it occurs so often in men over the age of 60 that it’s almost considered normal. With these diseases affecting many millions of men in this country, scientists have long sought to understand the root causes, the first step to establishing effective treatments and preventative measures. Although their triggers have not yet been fully made clear, as is the case with women and breast cancer, sex hormones have long been understood to play a role in their etiology.
Sex steroids can be potent growth mediating hormones. This holds true not only for skeletal muscle, but also for reproductive tissues. These hormones are responsible for stimulating the development of our sex organs in early life, and are vital to maintaining their proper functioning throughout the rest of it. It seems reasonable that they would be linked to the growth of cancer when it strikes these bodily tissues. But what role exactly do these hormones play in the development of these diseases? Are androgens inherently dangerous to the human body? With androgen replacement therapy in older men strongly on the rise, it begs the obvious and important question: Are we taking unnecessary risks by artificially maintaining youthful levels of testosterone into late adulthood? According to a major press release on the Reuters Newswire, the answer to that question is a resounding yes.
Free Testosterone
The headline reads, “High Hormone Levels Linked to Prostate Risk.”[1] It goes on to briefly discuss a recently conducted study at Johns Hopkins University in Baltimore, Maryland, which focused on discerning the relationship between androgen levels, various markers of body composition and prostate cancer. The study involved a relatively large group of men, more than 750 in total. Although the exact details have not yet been made public, the news brief notes that the key risk factor uncovered for prostate cancer during this study was one’s level of free testosterone. According to Dr. Kellogg Parsons, the urologist who led the study, “The association between free testosterone and prostate cancer risk in older men was not affected by height, weight, percent of body fat or muscle mass.” He also warned, “Since testosterone replacement therapy increases the amount of free testosterone in the blood, older men considering or receiving testosterone replacement should be counseled as to the association until data from long-term clinical trials becomes available.”
Misplacing the Blame?
So, case closed, right? Androgens cause prostate cancer. Or is it that simple? It may not be, and it may not even be the androgens that are of primary blame here. We will not know what other hormones were examined during the study until it’s officially published, but I, for one, would really like to know what was happening to estrogen. Several other studies seem to strongly contradict the notion that testosterone is the primary culprit. Their determinations support the idea that estrogens and androgens are both important to the progress of prostate cancer and BPH, and estrogen suppression may be a more effective preventative or treatment option. For instance, one study published in early 2003 discusses various instances in which anti-estrogenic drugs have been shown to be very effective treatment options for prostate hyperplasia.[2] It goes on to report that toremifene, an estrogen receptor antagonist that could only be described as “Super Nolvadex,” is entering phase III human clinical trials in the U.S. for the treatment of prostate cancer. Such therapy would only serve to increase testosterone levels, due to the antagonism of estrogen’s action. Despite this, disease progression can be effectively retarded with a pure anti-estrogenic drug like this. Another study makes note of the prostate tissue growth-promoting effects of testosterone in monkeys, but also reports that these effects are reversed when an aromatase inhibitor is concurrently taken.[3] Again, this provides strong support for primarily targeting estrogen, not testosterone. Yet another study notes that testosterone suppression needs to be profound in order to significantly affect prostate size. Here, levels needed to be suppressed to .3 nanomoles per liter, a figure 50 times below normal serum levels, just to get an 18 percent reduction in prostate size.[4]
DHT: The Better Alternative
If we want to believe it’s the estrogen conversion from testosterone that is of key importance, we need to not only look at what happens when we supplement this hormone, but also what happens with a steroid that cannot convert to estrogen. Two studies illustrate the variance in affect between testosterone and its non-aromatizable relative dihydrotestosterone, when it comes to the prostate. The first study involved 13 men, ages 57-70.[5] They were given a standard replacement dose of testosterone enanthate, 100 milligrams per week, for three months. During the course of this study, the men noticed a significant increase in PSA (prostate specific antigen, a marker for prostate growth stimulation and cancer risk). This increase remained for three months after stopping treatment, suggesting clearly that testosterone administration may create side effects at the prostate level in older men. The second looked at 37 men ages 55-70 who supplemented transdermal DHT for anywhere from six months to five years.[6] Twenty-seven subjects noted very significant and lasting elevations in serum DHT, which coincided with a drop in serum testosterone (to a point well below normal), and a drop in estrogen of approximately 50 percent. Ultrasound and PSA evaluations showed a significant decrease, not increase, in prostate size. The remaining 10 subjects did not respond as well to transdermal hormone therapy, and as a result did not note the same strong elevations in DHT. They also noticed only a slight reduction in testosterone levels and no changes in serum estrogen. This group reported a 14 percent increase in prostate size.
In Closing
Prostate cancer and benign prostatic hypertrophy have long been understood to be partially dependent on sex steroid hormones. The exact relationship that these hormones play in triggering these diseases remains to be fully discovered. Studies using dihydrotestosterone seem to make an excellent reference for the role androgens specifically play in diseases like BPH and prostate cancer, as this hormone is understood to be the most potent androgen in the human body. Were androgen action the sole specific trigger, one would expect DHT to present even greater risks for prostate enlargement than testosterone. That does not seem to be the case and actually, the opposite seems to be holding true. With the data provided, it would be extremely premature to abandon the notion that androgen replacement therapy is a high-risk undertaking. Instead, it suggests that estrogen is of most importance. This understanding might lead to new ways of supplementing androgens for greater prostate safety. In fact, the strong possibility exists that non-aromatizable androgens may indeed lower the risk for prostate cancer by lowering levels of serum estrogen. Perhaps the future will hold a day when men can go to the doctor for “Primobolan Supplementation Therapy,” or maybe a new cocktail of testosterone and an anti-estrogen.
References
[1] High Hormone Levels Linked to Prostate Risk. Reuters Newswire. May 9, 2004
[2] Antiestrogens and selective estrogen receptor modulators reduce prostate cancer risk. Steiner MA. Raghow S. World J Urol. 2003 May;21(1):31-6
[3] Induction of estrogen-related hyperplasic changes in the prostate of the Cynomologus Monkey by androstenedione and its antagonism by aromatase inhibitor. Prostate, 1987; 11:313-26
[4] Treatment of benign prostatic hyperplasia by androgen deprivation: effects on prostate size and urodynamic parameters. K Urol, 1989; 141:68-72
[5] Effects of testosterone supplementation in the aging male. Tenover JS. J Clin Endocrinol Metab, 1992; 75:1092-8
[6] Transdermal dihydrotestosterone treatment of “Andropause”. Lignieres B. Ann Med, 25: 235-41
Cancer of the reproductive system is frequent in both men and women. In females, it’s commonly breast or uterine cancer, while we males have to worry about the dreaded “Big C” in the form of prostate cancer. This disease occurs in men with such alarming frequency that one in five will be affected by it in their lifetime. The chance for developing it also increases significantly with age, making it most common in men over the age of 50. The risks for benign prostate hypertrophy (BPH) also go up as we get older, a disease characterized by the non-cancerous enlargement of the prostate gland. BPH is an early warning sign that prostate cancer may be looming and it occurs so often in men over the age of 60 that it’s almost considered normal. With these diseases affecting many millions of men in this country, scientists have long sought to understand the root causes, the first step to establishing effective treatments and preventative measures. Although their triggers have not yet been fully made clear, as is the case with women and breast cancer, sex hormones have long been understood to play a role in their etiology.
Sex steroids can be potent growth mediating hormones. This holds true not only for skeletal muscle, but also for reproductive tissues. These hormones are responsible for stimulating the development of our sex organs in early life, and are vital to maintaining their proper functioning throughout the rest of it. It seems reasonable that they would be linked to the growth of cancer when it strikes these bodily tissues. But what role exactly do these hormones play in the development of these diseases? Are androgens inherently dangerous to the human body? With androgen replacement therapy in older men strongly on the rise, it begs the obvious and important question: Are we taking unnecessary risks by artificially maintaining youthful levels of testosterone into late adulthood? According to a major press release on the Reuters Newswire, the answer to that question is a resounding yes.
Free Testosterone
The headline reads, “High Hormone Levels Linked to Prostate Risk.”[1] It goes on to briefly discuss a recently conducted study at Johns Hopkins University in Baltimore, Maryland, which focused on discerning the relationship between androgen levels, various markers of body composition and prostate cancer. The study involved a relatively large group of men, more than 750 in total. Although the exact details have not yet been made public, the news brief notes that the key risk factor uncovered for prostate cancer during this study was one’s level of free testosterone. According to Dr. Kellogg Parsons, the urologist who led the study, “The association between free testosterone and prostate cancer risk in older men was not affected by height, weight, percent of body fat or muscle mass.” He also warned, “Since testosterone replacement therapy increases the amount of free testosterone in the blood, older men considering or receiving testosterone replacement should be counseled as to the association until data from long-term clinical trials becomes available.”
Misplacing the Blame?
So, case closed, right? Androgens cause prostate cancer. Or is it that simple? It may not be, and it may not even be the androgens that are of primary blame here. We will not know what other hormones were examined during the study until it’s officially published, but I, for one, would really like to know what was happening to estrogen. Several other studies seem to strongly contradict the notion that testosterone is the primary culprit. Their determinations support the idea that estrogens and androgens are both important to the progress of prostate cancer and BPH, and estrogen suppression may be a more effective preventative or treatment option. For instance, one study published in early 2003 discusses various instances in which anti-estrogenic drugs have been shown to be very effective treatment options for prostate hyperplasia.[2] It goes on to report that toremifene, an estrogen receptor antagonist that could only be described as “Super Nolvadex,” is entering phase III human clinical trials in the U.S. for the treatment of prostate cancer. Such therapy would only serve to increase testosterone levels, due to the antagonism of estrogen’s action. Despite this, disease progression can be effectively retarded with a pure anti-estrogenic drug like this. Another study makes note of the prostate tissue growth-promoting effects of testosterone in monkeys, but also reports that these effects are reversed when an aromatase inhibitor is concurrently taken.[3] Again, this provides strong support for primarily targeting estrogen, not testosterone. Yet another study notes that testosterone suppression needs to be profound in order to significantly affect prostate size. Here, levels needed to be suppressed to .3 nanomoles per liter, a figure 50 times below normal serum levels, just to get an 18 percent reduction in prostate size.[4]
DHT: The Better Alternative
If we want to believe it’s the estrogen conversion from testosterone that is of key importance, we need to not only look at what happens when we supplement this hormone, but also what happens with a steroid that cannot convert to estrogen. Two studies illustrate the variance in affect between testosterone and its non-aromatizable relative dihydrotestosterone, when it comes to the prostate. The first study involved 13 men, ages 57-70.[5] They were given a standard replacement dose of testosterone enanthate, 100 milligrams per week, for three months. During the course of this study, the men noticed a significant increase in PSA (prostate specific antigen, a marker for prostate growth stimulation and cancer risk). This increase remained for three months after stopping treatment, suggesting clearly that testosterone administration may create side effects at the prostate level in older men. The second looked at 37 men ages 55-70 who supplemented transdermal DHT for anywhere from six months to five years.[6] Twenty-seven subjects noted very significant and lasting elevations in serum DHT, which coincided with a drop in serum testosterone (to a point well below normal), and a drop in estrogen of approximately 50 percent. Ultrasound and PSA evaluations showed a significant decrease, not increase, in prostate size. The remaining 10 subjects did not respond as well to transdermal hormone therapy, and as a result did not note the same strong elevations in DHT. They also noticed only a slight reduction in testosterone levels and no changes in serum estrogen. This group reported a 14 percent increase in prostate size.
In Closing
Prostate cancer and benign prostatic hypertrophy have long been understood to be partially dependent on sex steroid hormones. The exact relationship that these hormones play in triggering these diseases remains to be fully discovered. Studies using dihydrotestosterone seem to make an excellent reference for the role androgens specifically play in diseases like BPH and prostate cancer, as this hormone is understood to be the most potent androgen in the human body. Were androgen action the sole specific trigger, one would expect DHT to present even greater risks for prostate enlargement than testosterone. That does not seem to be the case and actually, the opposite seems to be holding true. With the data provided, it would be extremely premature to abandon the notion that androgen replacement therapy is a high-risk undertaking. Instead, it suggests that estrogen is of most importance. This understanding might lead to new ways of supplementing androgens for greater prostate safety. In fact, the strong possibility exists that non-aromatizable androgens may indeed lower the risk for prostate cancer by lowering levels of serum estrogen. Perhaps the future will hold a day when men can go to the doctor for “Primobolan Supplementation Therapy,” or maybe a new cocktail of testosterone and an anti-estrogen.
References
[1] High Hormone Levels Linked to Prostate Risk. Reuters Newswire. May 9, 2004
[2] Antiestrogens and selective estrogen receptor modulators reduce prostate cancer risk. Steiner MA. Raghow S. World J Urol. 2003 May;21(1):31-6
[3] Induction of estrogen-related hyperplasic changes in the prostate of the Cynomologus Monkey by androstenedione and its antagonism by aromatase inhibitor. Prostate, 1987; 11:313-26
[4] Treatment of benign prostatic hyperplasia by androgen deprivation: effects on prostate size and urodynamic parameters. K Urol, 1989; 141:68-72
[5] Effects of testosterone supplementation in the aging male. Tenover JS. J Clin Endocrinol Metab, 1992; 75:1092-8
[6] Transdermal dihydrotestosterone treatment of “Andropause”. Lignieres B. Ann Med, 25: 235-41