2011 January 11 Tuesday
Testosterone Enzyme Inhibitor Side Effects

Drugs that prevent the conversion of testosterone into dihydrotestosterone (DHT) can prevent hair loss and benign prostate hyperplasia but at the cost of adverse effects in a subset of users.

(Boston) – Researchers from Boston University School of Medicine (BUSM), in collaboration with colleagues at Lahey Clinic and from Denmark and Germany, have found that 5a-reductase inhibitors (5a-RIs), while improving urinary symptoms in patients with benign prostatic hyperplasia (BPH) and possible hair loss prevention, produces significant adverse effects in some individuals including loss of libido, erectile dysfunction (ED), ejaculatory dysfunction and potential depression. These findings, which currently appear on-line in Journal of Sexual Medicine, suggest that extreme caution should be exercised prior to prescribing 5a-RIs therapy to patients for hair growth or for BPH symptoms.

5a-RIs, finasteride (Propecia™) and dutasteride, have been approved for treatment of lower urinary tract symptoms, due to BPH, with marked clinical efficacy. Finasteride is also approved for treatment of hair loss (androgenetic alopecia). Although the adverse side effects of these agents are thought to be minimal, the magnitude of adverse effects on sexual function, gynecomastia, depression, and quality of life remains ill-defined.

Whether long term use of dutasteride or finasteride cuts the risk of prostate cancer is not clear (at least not to me). Do these drugs reduce the incidence of all cause mortality? Hard to tell. I suspect a number of drugs could reduce all cause mortality if only it was possible to predict which potential users would derive more benefit than harm from their use.

According to the researchers, the adverse side effects of 5a-RIs on sexual function, gynecomastia and the impact on the overall health have received minimal attention. However, in some patients, these side effects are persistent with regard to sexual function and with an emotional toll including decreased quality of life.

The researchers see a need for research to identify the causes of persistent side effects in a subgroup of finasteride and dutasteride users. My reaction: This is an example of why we should be free to order our own genetic tests. If millions of people spent their own money to get a million of their genetic variants identified, then uploaded their genetic data to a genetic research server (with appropriate privacy safeguards) and then filled in reports on the web site every time they had an adverse drug or other treatment reaction medical researchers would gain a treasure trove of genetic and health data. With that database the researchers would be able to identify large numbers of genetic variants that increase or decrease risk of undesirable drug side effects.

Personal genetic testing holds the potential to produce the quantity of data needed to enable far more rapid identification of genetic variants that cause adverse drug reactions. With falling prices and increasing coverage by genetic tests what we need is a massive web-based project to collect the data from volunteers of their genetic and health data. We would all benefit from the results.

By Randall Parker    2011 January 11 11:03 PM   Entry Permalink | Comments (0)
2010 December 14 Tuesday
Lenalidomide To Restore Aging Immune Systems?

Lenalidomide, a derivative of thalidomide, was developed to treat multiple myeloma. But in low doses lenalidomide appears to reverse many immune systems which occur in some (though not all) people as they age.

UCSF researchers have identified an existing medication that restores key elements of the immune system that, when out of balance, lead to a steady decline in immunity and health as people age.

The team found that extremely low doses of the drug lenalidomide can stimulate the body’s immune-cell protein factories, which decrease production during aging, and rebalance the levels of several key cytokines – immune proteins that either attack viruses and bacteria or cause inflammation that leads to an overall decline in health.

Blood tests could tell you in your 50s if your immune system is aging in a way that lenalidomide might help.

In 2009, Goetzl had studied a group of 50 elderly adults through the National Institute on Aging, examining their levels of key cytokines – Interleukin (IL)-2, IFN-gamma and IL-17 – and discovered that truly healthy 70-80 year old women had the same levels of those as did healthy 20 year olds.

However, some elderly men and frail women who showed increased levels of inflammatory diseases and weakened defenses against infections tended to have lower levels of the first two cytokines, which are protective, and higher levels of inflammatory cytokines. That imbalance, the researchers found, began in late middle age.

Lenalidomide has plenty of potential side effects. So do not take it lightly. But since this purpose for its use involves lower doses perhaps the odds of side effects are lower than for other purposes?

In this study, the team tested the drug in healthy seniors, each of whom were matched in race, gender and national origin to a healthy young adult participant. They found that extremely low levels of lenalidomide – 0.1 μM – optimally stimulated IL-2 production in the young people (21-40 years) roughly sevenfold, but stimulated IL-2 production in patients over age 65 by 120-fold, restoring them to youthful levels for up to five days. At that dosage, the drug also increased IFN-gamma up to six fold in the elderly patients, without suppressing IL-17 generation.

The UCSF researchers are going to continue to explore its use for aging immune systems. They are also exploring other drugs for this purpose.

By Randall Parker    2010 December 14 12:04 AM   Entry Permalink | Comments (5)
2010 August 12 Thursday
Fast Food With Cholesterol-Lowering Drugs?

Would you like some fries and statins with the double cheeseburger and Coke?

Fast food outlets could provide statin drugs free of charge so that customers can neutralise the heart disease dangers of fatty food, researchers at Imperial College London suggest in a new study published this week.

Statins reduce the amount of unhealthy "LDL" cholesterol in the blood. A wealth of trial data has proven them to be highly effective at lowering a person's heart attack risk.

In a paper published in the Sunday 15 August issue of the American Journal of Cardiology, Dr Darrel Francis and colleagues calculate that the reduction in cardiovascular risk offered by a statin is enough to offset the increase in heart attack risk from eating a cheeseburger and a milkshake.

I'm thinking a Paleo Diet makes more sense than statins. But for people who insist upon eating junk food some statins in the french fries might make sense.

By Randall Parker    2010 August 12 10:03 PM   Entry Permalink | Comments (6)
2010 April 07 Wednesday
Dutasteride Cuts Prostate Cancer Risk?

Do drugs that block the conversion of testosterone into dihydrotestosterone reduce the risk of prostate cancer?

Results from a large, randomized clinical trial indicate that men at an increased risk for prostate cancer reduced their risk with regular use of the drug dutasteride (Avodart). The results came from the REDUCE trial, which is the second largest clinical trial to demonstrate a decreased risk of prostate cancer in men taking an agent from the class of drugs known as 5-α reductase inhibitors (5-αRIs). Previously, the Prostate Cancer Prevention Trial (PCPT) showed that the drug finasteride had a risk reduction similar to what has now been seen in REDUCE.

These drugs also slow or stop male pattern baldness as well as controlling benign prostate hyperplasia. So one could take them for one of the certain benefits with the hopes of getting an additional anti-cancer benefit.

The study included 4 years of follow-up. So it doesn't tell a guy who is, say, 40 whether it is worth taking dutasteride for decades in order to cut long term risk. Does dutasteride reduce the conversion of prostate cancer cells into cancerous cells? Or does it just slow the growth rate of cells that are already abnormal and cancerous?

The international trial involved more than 6,700 men between ages 50 and 75 who, at enrollment, had a prostate-specific antigen (PSA) test score between 2.5 and 10 and a negative biopsy in the prior 6 months. Participants, the large majority of who were white, also received biopsies 2 and 4 years after enrollment. After 4 years of follow up, there was a nearly 23 percent reduction in the relative risk of prostate cancer in men who took dutasteride compared with those who took a placebo (659 cancers versus 858 cancers).

I'm mildly tempted to start taking dutasteride or finasteride and keep taking it for decades. Maybe it'll cut the risk of prostate cancer. But read the debate on finasteride and dutasteride versus prostate cancer if you are thinking about taking one of them.

I really wish there were more drugs worth taking for long term risk reduction. For example, daily statin drug usage might also deliver a long term benefit even for some with low cholesterol. Again, I read such reports but am reluctant to take drugs and so I hold back. As the link about statins shows, they have their own risks including elevated risk of type II insulin-resistant diabetes. Here is a a New York Times article on statin risks for healthy people.

I wish genetic tests for drug side effect prediction were already mature and widely available. I'd like to know my own specific risks for muscle or memory side effects from statins or other side effects from dutasteride. The trade-offs from long term drug use for risk reduction will become clearer for individuals once genetic markers for drug side effects become known for the major drugs.

By Randall Parker    2010 April 07 10:18 PM   Entry Permalink | Comments (5)
2010 January 26 Tuesday
Growth Hormone Lack Not Life Shortening

Low growth hormone among dwarves in a state in Brazil does not shorten their life expectancies.

People profoundly deficient in human growth hormone (HGH) due to a genetic mutation appear to live just as long as people who make normal amounts of the hormone, a new study shows. The findings suggest that HGH may not be the "fountain of youth" that some researchers have suggested.

"Without HGH, these people still live long, healthy lives, and our results don't seem to support the notion that lack of HGH slows or accelerates the aging process," says Roberto Salvatori, M.D., associate professor in the Department of Endocrinology at the Johns Hopkins University School of Medicine.

The researchers, working with an unusual population of dwarves residing in Itabaianinha county, a rural area in the northeastern Brazilian state of Sergipe, and led by Salvatori, sought to sort out conflicting results of previous studies on the effects of HGH on human aging.

Some studies have suggested that mice whose bodies don't efficiently produce or process the mouse equivalent to HGH have an extended lifespan. Other research has shown that people with low levels of HGH due to surgical or radiation damage to the pituitary gland that makes HGH have increased risk of cardiovascular disease, a factor that can shorten life span. These patients also have decreased levels of other important hormones that the pituitary produces, possibly confounding results.

Some people take HGH to reverse some of the effects of aging. Does HGH taken in this manner lengthen or shorten life spans?

By Randall Parker    2010 January 26 11:51 PM   Entry Permalink | Comments (0)
2009 November 14 Saturday
Drugs Better Than Diet For Cancer Prevention?

Gina Kolata, writing in the New York Times talks to a lot of top medical researchers and reports on cancer-preventing drugs that go unused and the many disappointing diet and vitamin interventions for cancer prevention.

Many Americans do not think twice about taking medicines to prevent heart disease and stroke. But cancer is different. Much of what Americans do in the name of warding off cancer has not been shown to matter, and some things are actually harmful. Yet the few medicines proved to deter cancer are widely ignored.

The article does an excellent job of reviewing assorted great hopes for reduced cancer risk via diet and vitamins and how many of these approaches failed in large scale intervention trials. Biogerontologist Aubrey de Grey probably doesn't find this surprising since he argues that if micronutrients could deliver large benefits we'd probably carry mutations to up their concentrations in our bodies. There is a counter evolutionary argument though: an antioxidant in higher concentrations might make us less fit in the short term and therefore would have been selected against.

I'm willing to use drugs to cut cancer risks. The drugs finasteride and dutasteride (both used to stop hair loss and treat swollen prostates) would eliminate over a quarter of all prostate cancer cases per year if taken long term to protect against prostate cancer.

A large and rigorous study found that a generic drug, finasteride, costing about $2 a day, could prevent as many as 50,000 cases each year. Another study found that finasteride’s close cousin, dutasteride, about $3.50 a day, has the same effect.

Did she say $2 per day? I used a drug price comparison web site and found Costco selling finasteride for $1.19 per 5 mg tablet in quantity 100. A 10 year supply would set you back about $4400. Having helped someone die from prostate cancer that seems like a very low price to pay to avoid a horrible end. Heck, you can do even cheaper abroad and this is a generic drug. You won't be ripping off intellectual property by buying abroad.

I'm already tempted to ask a doctor to prescribe finasteride or dutasteride. Preserve hair, avoid prostatic hyperplasia (where the prostate slows urine flow), and avoid prostate cancer. I mean, why not? The side effects are said to wear off after a year. Any readers taking it? One concern: what other effects come from lowering dihydrotestosterone? Does regular testosterone also rise as a result?

Tamoxifen cuts the risk of breast cancer in half. An osteoporosis drug, Evista, does the same thing with fewer risks.

Then, in 1999, he had a chance to do another breast cancer prevention trial, this time of an osteoporosis drug, raloxifene, or Evista, which did not have the cancer drug taint. It was to be compared with tamoxifen.

The $110 million study, involving 19,000 women, ended in 2006. The two drugs were found to be equally effective in preventing breast cancer, but with raloxifene there was no excess uterine cancer and the clotting risk was 30 percent less.

By Randall Parker    2009 November 14 02:44 PM   Entry Permalink | Comments (26)
2009 October 29 Thursday
Simvastatin Stops Parkinson's Disease In Mice

Might a widely available cholesterol-lowering drug slow or stop the progression of Parkinson's?

(CHICAGO) –Simvastatin, a commonly used, cholesterol-lowering drug, may prevent Parkinson's disease from progressing further. Neurological researchers at Rush University Medical Center conducted a study examining the use of the FDA-approved medication in mice with Parkinson's disease and found that the drug successfully reverses the biochemical, cellular and anatomical changes caused by the disease.

If this happens in humans surely some doctors would have noticed by now? Since Simvastatin is sold by Merck as Zocor and since at least some older patients with Parkinson's also have high cholesterol I wonder how difficult it would be to measure Parkinson's progression in patients already taking Zocor. Ditto for the other statin drugs such as lovastatin (Mevacor), rosuvastatin (Crestor), atorvastatin (Lipitor), and other statins.

"Statins are one of the most widely used cholesterol-lowering drugs throughout the world," said study author Kalipada Pahan, PhD, professor of neurological sciences at Rush University Medical Center. "This may be a safer approach to halt the disease progression in Parkinson's patients."

Pahan and colleagues from Rush, along with researchers at the University of Nebraska Medical Center in Omaha published these findings in the October 28 issue of the Journal of Neurosciences.

The authors have shown that the activity of one protein called p21Ras is increased very early in the midbrain of mice with Parkinson's pathology. Simvastatin enters into the brain and blocks the activity of the p21Ras protein and other associated toxic molecules, and goes on to protect the neurons, normalize neurotransmitter levels, and improves the motor functions in the mice with Parkinson's.

25 million people world-wide use statins including 13 million in the United States (yes, the US uses more statins than the rest of the world combined). So if statins are providing a benefit against Parkinson's does this show up in Parkinson's incidence data?

I would be reluctant to take statins just to cut my risk of Parkinson's. Though for someone with a lot of genetic risk factors for Parkinson's running the other risks from statin side effects (e.g. a skeletal myopathy that damages muscles) might be worth it. My guess is that as genetic risk factors for statin side effects become known it should be possible to accurately predict your individual costs and benefits from statin usage.

Update: In the comments Dave Gore points to a 2007 study that found the protective effect is specific to simvastatin. Thanks Dave.

The researchers examined data from the Decision Support System database of the United States Veterans Affairs Medical System, a database of medical centers throughout the United States which contains diagnostic, pharmaceutical and demographic information on approximately 4.5 millions people.

Using three different models for analysis, the researchers examined the effects of three different statins (atorvastatin, lovastatin and simvastatin) and found that simvastatin showed a strong reduction in the incidence of Alzheimer’s disease in each of the models. The data also showed the same statin was associated with a reduced incidence of Parkinson’s disease.

The researchers speculate that the selective benefit observed with simvastatin might be due to the combination of high potency and the ability to enter the brain.

“The strength of reduction of incidence of dementia with simvastatin is striking,” said lead author Benjamin Wolozin, MD, PhD, a professor of pharmacology at BUSM.

Sounds promising. A good genetic test that would predict side effects might allow many people to take simvastatin for protection.

By Randall Parker    2009 October 29 10:42 PM   Entry Permalink | Comments (6)
2009 October 11 Sunday
On The Paucity Of Disease Prevention Measures

Heather Mac Donald thinks the rhetoric promoting the potential for disease prevention by doctors is overblown.

We need to induce doctors to practice preventive, not just reactive, care! is a favored nostrum in the current health care debate. I’ve yet to hear an example of what this means. Prevention lies overwhelmingly within the realm of individual behavior, but our modern reflex of transferring agency from favored victim groups—in this case, millions of artery-clogged, waddling Americans—onto less-favored entities guarantees that we see the problems of Fat America as the failure of doctors to practice the right kind of medicine. Perhaps more doctors could counsel their patients to exercise and avoid over-eating, but my guess is that if they stay silent on these topics, it is from hard-won experience regarding the futility of such suggestions.

This all sounds very true to me. I wish it were otherwise. But the sum total of what can be prevented by doctors is far too short. This is very unfortunate. But there it is.

Sure, there are things you can do with a doctor's help: Go get a bunch of vaccinations. Now what? Weight loss to prevent future disease development? Unless you are up for bariatric surgery medicine has little to offer. You can take statins or blood pressure lowering medicines to prevent assorted cardiovascular diseases. Or a blood sugar lowering medicine if you've got high blood sugar and insulin resistance. Anything else major come to mind? One thought: should guys take dutasteride or finasteride to reduce prostate cancer risk or benign prostate hyperplasia risk?

I want a long list of actionable items for preventing future diseases. My motto: First, don't die.

There are a few things one can do for early cancer detection such as mammograms, PAP smears, PSA tests, and colonoscopy. Note these are not disease prevention measures. These are early detection measures. I'd like to see a good set of lists of things to do at various ages for disease prevention and disease detection. Sort of like a car maintenance schedule.

I've got a practical question for all my readers: What disease prevention measures can doctors do that do not get the attention they deserve?

For example, should fully grown adults go and get vaccinations? I'm thinking seriously about getting influenza vaccination this year. But are there other vaccinations we ought to think seriously about getting as adults?

By Randall Parker    2009 October 11 02:10 PM   Entry Permalink | Comments (7)
2009 August 17 Monday
Will Aging Decelerator Drugs Work?

Nicholas Wade of the New York Times has a pretty good article surveying efforts to translate research on resveratrol and other anti-aging compounds into drugs that slow the rate of aging. But resveratrol's mechanism of action is to mimic the effeects of life extending calorie restriction. One problem arises: calorie restriction might only work under special conditions that do not apply to humans.

Two experts on aging, Jan Vijg of the Albert Einstein College of Medicine and Judith Campisi of the Lawrence Berkeley National Laboratory, argued recently in Nature that the whole phenomenon of caloric restriction may be a misleading result unwittingly produced in laboratory mice. The mice are selected for quick breeding and fed on rich diets. A low-calorie diet could be much closer to the diet that mice are adapted to in the wild, and therefore it could extend life simply because it is much healthier for them.

“Life extension in model organisms may be an artifact to some extent,” they wrote. To the extent caloric restriction works at all, it may have a bigger impact in short-lived organisms that do not have to worry about cancer than in humans. Thus the hope of mimicking caloric restriction with drugs “may be an illusion,” they write.

Of course, humans in industrial societies eat rich diets rather than the sorts of diets we ate in our wilder ancestral past. Our ancestors were also hungry most of the time. So perhaps resveratrol still might help to slow down our aging by adapting our metabolism to our modern industrialized diets..

Biogerontologist Aubrey de Grey has long argued that he does not expect calorie restriction to extend life as much in humans percentage wise as in mice. This makes sense to me. First off, humans have many mutations for life extension that mice do not have. Some of the effects that calorie restriction can have on mouse metabolism to make them live longer are probably changes that our human metabolisms gained as permanent features as a result of mutations that enabled us to live far longer than mice. Second, calorie restriction's effects might be designed to enable an organism to survive until a better season of food supply. That suggests calorie restrictions benefits might be more tied to the length of seasons than to percentage of total life.

Some of the scientists in the article express skepticism at the arguments by evolutionary biologists that it'll be hard to extend life with simple drugs. The evolutionary biologists argue that if simple metabolic changes could extend life without substantial downsides then mutations to cause these changes would already have happened and spread. If the evolutionary biologists turn out to be wrong about these experimental drugs I can think of a reason: the drugs that extend life will exact some cost that matters far less for humans living in an industrial society. For example, they might make people less energetic or mentally more sluggish or perhaps increase the need for sleep. Or the drugs might increase risks of death in event of trauma of an accident. If mutations haven't already given us the same life-extending benefits that some drugs can provide then there's a decent chance there's a cost to those benefits.

What we need even more than drugs that slow aging: treatments that rejuvenate and reverse aging.

By Randall Parker    2009 August 17 11:48 PM   Entry Permalink | Comments (7)
2009 July 22 Wednesday
ACE Inhibitor Blood Pressure Drugs Cut Risk Of Dementia

Not all blood pressure drugs are equal in protection provided against brain function decline with age. The angiotensin-converting enzyme (ACE) inhibitors are better for the brain than other blood pressure reducing drugs. But not all ACE inhibitors are equal either. The centrally acting ACE inhibitors provide the benefit.

WINSTON-SALEM, N.C. – A particular class of medication used to treat high blood pressure could protect older adults against memory decline and other impairments in cognitive function, according to a newly published study from Wake Forest University School of Medicine.

Research suggests that some of the drugs classified as angiotensin-converting enzyme (ACE) inhibitors, specifically those types of ACE inhibitors that affect the brain by crossing the blood-brain barrier, may reduce inflammation that could contribute to the development of Alzheimer's disease, a major cause of dementia.

The study appears in the current issue of Archives of Internal Medicine.

"High blood pressure is an important risk factor for Alzheimer's disease and vascular dementia," said Kaycee Sink, M.D., M.A.S., lead author of the study, geriatrician and an assistant professor of internal medicine – gerontology. "Our study found that all blood pressure medications may not be equal when it comes to reducing the risk of dementia in patients with hypertension."

Inflammation as an agent of accelerated aging is a recurring theme in a lot of research on aging mechanisms. Dietary and drug factors that reduce inflammation tend to slow aging and lower disease risks.

ACE inhibitors that can cross the blood-brain barrier get into the brain and dampen inflammation.

The study found an association between taking centrally-active ACE inhibitors and lower rates of mental decline as measured by the Modified Mini-Mental State Exam, a test that evaluates memory, language, abstract reasoning and other cognitive functions. The research showed that participants who were exposed to ACE inhibitors that cross the blood-brain barrier saw an average 65 percent less cognitive decline per year of exposure compared to participants taking other blood pressure medications.

What I would like to know: For people who do not have high blood pressure (knock on wood) which drugs or dietary elements will best lower brain inflammation? Anyone have insights on this?

Non-centrally active ACE inhibitors definitely do not help.

Researchers also found that non-centrally active ACE inhibitors were associated with an increased risk of dementia and the people taking them were more likely to develop difficulty performing daily activities. Specifically, participants who, for three years, took ACE inhibitors that do not cross the blood-brain barrier were at a 73 percent greater risk of developing dementia than were the individuals taking other anti-hypertensive drugs.

Okay, those of you with high blood pressure are wondering: which ACE inhibitors are centrally acting? Here's your list:

Centrally-acting ACE inhibitors include captropril (Capoten®), fosinopril (Monopril®), lisinopril (Prinivil® or Zestri®), perindopril (Aceon®), ramipril (Altace®) and trandolapril (Mavik®).

Anyone going to get their high blood pressure drug changed as a result of this news?

By Randall Parker    2009 July 22 03:51 PM   Entry Permalink | Comments (4)
2009 June 15 Monday
Testosterone Cuts Incidence Of Metabolic Syndrome

Should older men take testosterone as a replacement therapy for declining natural testosterone levels?

In middle-aged and older men with low testosterone levels, long-term testosterone replacement therapy greatly improves their fatty liver disease and their risk factors for cardiovascular disease and diabetes, a new study found. The results were presented at The Endocrine Society’s 91st Annual Meeting in Washington, D.C.

Testosterone deficiency, which becomes more common with age, is linked not only to decreased libido but also to a number of medical problems. These include the metabolic syndrome—a cluster of metabolic risk factors that increase the chances of developing heart disease, stroke and type 2 diabetes. Nonalcoholic fatty liver disease, also called a fatty liver, commonly co-occurs with the metabolic syndrome and may aggravate the metabolic problems. To receive a diagnosis of the metabolic syndrome, patients must have three of the following five risk factors: abdominal obesity (a large waist line), low HDL (“good”) cholesterol, high triglycerides (fats in the blood), high blood pressure and high blood sugar.

“Physicians often are reluctant to prescribe testosterone for conditions not related to sexual function,” said the study’s co-author, Farid Saad, PhD, of Berlin-headquartered Bayer Schering Pharma. “However, our study shows that testosterone has a much wider therapeutic role than just for improving sexual desire and erectile function.”

The study included 122 testosterone-deficient men, ages 36 to 69 years (mean age: 59.5). Results showed that restoring testosterone to normal levels led to major and progressive improvements in many features of the metabolic syndrome over the 2 years of treatment. Specifically, the men’s weight, waist line and body mass index (a measure of body fat) continued to decline over the full study period. The other metabolic risk factors also significantly improved during the first year of testosterone treatment. Of the 47 men who met the criteria for a diagnosis of the metabolic syndrome at the beginning of the study, 36 (77 percent) no longer had the diagnosis after 2 years of treatment, the authors reported.

Furthermore, liver function significantly improved during the first 12 to 18 months of therapy and stabilized for the remainder of the study period. Treatment also greatly decreased blood levels of C-reactive protein, a measure of inflammation that is linked to increased risk of cardiovascular disease.

“We conclude that testosterone therapy in men with testosterone deficiency can largely improve or even remedy the metabolic syndrome, which will most likely decrease their risk of diabetes and cardiovascular disease,” Saad said.

The various symptoms of metabolic syndrome (including bad blood lipids profile, reduced insulin sensitivity, more belly fat, and higher levels of C-reactive protein) set you up for all sorts of problems such as sleep apnea (where people wake up constantly while sleeping due to inability to breathe well while sleeping) and heart disease. A treatment that reduces the symptoms of metabolic syndrome might increase longevity. Though testosterone treatment might put men at higher risk of other diseases. So is there a net benefit from testosterone therapy in older men? The answer is not clear and might depend on whether one has metabolic syndrome. Those who have metabolic syndrome will probably derive a bigger benefit from testosterone therapy.

What I wonder: Is testosterone therapy safer if taken with a 5-alpha-reductase inhibitor drug such as dutasteride or finasteride? These 5-alpha-reductase inhibitors block the conversion of testosterone into dihydrotestosterone (DHT) and are used to stop hair loss and to treat benign prostate hyperplasia (enlarged prostate). A boost of testosterone combined with a lowering of dihydrotestosterone might deliver more benefits with fewer harmful side effects. For example, risk of prostate cancer might be lowered. I'm not sure on that point. If anyone has insights on this please pipe up in the comments.

By Randall Parker    2009 June 15 11:30 PM   Entry Permalink | Comments (15)
2009 March 01 Sunday
Statins Cut Needed Cholesterol Synthesis In Brain?

Statins might cause problems for some people by reducing brain synthesis of cholesterol.

AMES, Iowa -- Research by an Iowa State University scientist suggests that cholesterol-reducing drugs known as statins may lessen brain function.

Yeon-Kyun Shin, a biophysics professor in the department of biochemistry, biophysics and molecular biology, says the results of his study show that drugs that inhibit the liver from making cholesterol may also keep the brain from making cholesterol, which is vital to efficient brain function.

"If you deprive cholesterol from the brain, then you directly affect the machinery that triggers the release of neurotransmitters," said Shin. "Neurotransmitters affect the data-processing and memory functions. In other words -- how smart you are and how well you remember things."

Statins are quite the mixed bag. On the one hand, statins appear to reduce the risk of dementia. Makes sense since statins probably reduce the risk of clogged arteries in the brain. They also appear to have anti-inflammatory effects independent of their cholesterol-lowering effects. But a long history of anecdotal reports of memory problems taking statins suggests that at least for some people statins cause memory problems.

If you are really lucky you already have low cholesterol. If you are moderately lucky (and have the needed discipline) you can lower your cholesterol with diet and exercise. Otherwise, you need to consider taking a statin. But try other measures before taking that step. Statins are not without risk.

By Randall Parker    2009 March 01 10:59 PM   Entry Permalink | Comments (8)
2009 February 14 Saturday
Drug Boosts Muscle Mass In Older Adults

A drug under development boosts lean muscle mass in older adults. This is pretty gutsy for a drug company to do active development on what is basically a rejuvenation drug - albeit a very limited scope rejuvenation drug.

An investigational drug that stimulates the body to produce more growth hormone improves lean muscle mass and physical function in older adults, potentially helping to combat frailty, according to researchers at Duke University Medical Center, VA Puget Sound Health Care System, the University of Washington School of Medicine, and 10 other study centers.

The Phase II study is the first to show improvements in physical performance among at-risk seniors taking capromorelin, an oral compound developed by Pfizer, which can help the body release more growth hormone. Older adults have greatly reduced production of growth hormone, which regulates metabolism and aids in the building of muscle mass even after adolescent growth has been completed.

But can it improve function without causing side effects that decrease life expectancy? Ideally the drug will increase functioning and increase life expectancy. But that's hard to do. Our bodies wear out as we age. Attempts to stimulate them to function better can backfire. Look at the problems with replacement hormones for post menopausal women. Hormone replacement isn't guaranteed to yield a net benefit.

Cures for cancer will eventually allow hormone replacement to deliver a net benefit in more cases. Hormone therapies that boost cancer risk but deliver benefits in other areas will probably become net benefits once cancer cures are available.

By Randall Parker    2009 February 14 10:15 PM   Entry Permalink | Comments (2)
2009 February 11 Wednesday
Statins Cut Death Risk In High Cholesterol Group

Statins cut death risk.

Varda Shalev, M.D., and colleagues at Maccabi Healthcare Services and Sackler Faculty of Medicine, Tel Aviv, Israel, analyzed data from 229,918 adults (average age 57.6) enrolled in a health maintenance organization who began taking statins between 1998 and 2006. This included 136,052 individuals without heart disease (primary prevention group), who were followed for an average of four years, and 93,866 already diagnosed with heart disease (secondary prevention group), with an average five years of follow-up. Researchers checked pharmacy records to calculate the proportion of days that each individual took statins.

During the study, 4,259 patients in the primary prevention group and 8,906 in the secondary prevention group died. In both groups, continuity of taking statins—defined as taking statins for at least 90 percent of the follow-up period—conferred at least a 45 percent reduction in the risk of death compared with patients who took statins less than 10 percent of the time. The risk reduction was stronger among patients with high levels of LDL cholesterol at the beginning of the study and among patients whose initial treatment was with high-efficacy statins.

"In conclusion, this study showed that the continuation of statin treatment provided an ongoing reduction in all-cause mortality [death] for up to 9.5 years among patients with and without a history of coronary heart disease," they continue. "The observed benefits from statins were greater than expected from randomized clinical trials, emphasizing the importance of promoting statin therapy and increasing its continuation over time for both primary and secondary prevention."

If you have high cholesterol do something to lower it. Take statins if you can't be bothered to radically change your diet. Or take statins and radically change your diet. Or at least change your diet. On the other hand, if you have a death wish I don't have any arguments to offer for why to take statins. But maybe if you changed your diet for the better you might feel better and less inclined to die.

Eat the Mediterranean Diet enhanced with the Ape or Portfolio Diet. The Portfolio Diet rivals statins in cholesterol lowering ability. But popping a pill requires less effort.

Update: Keep in mind that for a minority of statin users the side effects are severe and even damaging (e.g. myopathy - muscle damage). Try diet first. If you are willing to change your diet you can cut your cholesterol and also cut your risks of many diseases besides cardiovascular diseases. For example, the Mediterranean Diet will cut your risks of cancer. Also, as I point out in the comments, genetic tests that will identify those who will suffer side effects are probably on the way. The research on genetic variants responsible for statin side effects looks promising.

By Randall Parker    2009 February 11 11:20 PM   Entry Permalink | Comments (15)
2009 January 06 Tuesday
Clioquinol Slows Brain Aging?

Clioquinol might help against a few neurodegenerative diseases by slowing aging.

Recent animal studies have shown that clioquinol – an 80-year old drug once used to treat diarrhea and other gastrointestinal disorders – can reverse the progression of Alzheimer's, Parkinson's and Huntington's diseases. Scientists, however, had a variety of theories to attempt to explain how a single compound could have such similar effects on three unrelated neurodegenerative disorders.

Researchers at McGill University have discovered a dramatic possible new answer: According to Dr. Siegfried Hekimi and colleagues at McGill's Department of Biology, clioquinol acts directly on a protein called CLK-1, often informally called "clock-1," and might slow down the aging process. The advance online edition of their study was published in Oct. 2008 in the Journal of Biological Chemistry.

"Clioquinol is a very powerful inhibitor of clock-1," explained Hekimi, McGill's Strathcona Chair of Zoology and Robert Archibald & Catherine Louise Campbell Chair in Developmental Biology. "Because clock-1 affects longevity in invertebrates and mice, and because we're talking about three age-dependent neurodegenerative diseases, we hypothesize that clioquinol affects them by slowing down the rate of aging."

Does clioquinol get inhibited by calorie restriction?

I do not recommend you start taking this drug. Clioquinol varies between species of animals and even between dog breeds. It might cause neurotoxicity by chelating metals. But at lower doses that same chelation might be beneficial for some. It might be the cause of subacute myelo-optico-neuropathy (SMON) in 10,000 people in Japan. A recent Cochrane review of the use of clioquinol against Alzheimer's Disease does not find that studies to date show a clear benefit.

Let the researchers mess with this one. If you want to slow your brain aging there are lots of lower risk ways to do that with more certain benefits. Start with more fruits, vegetables, and fish. Then spice it up with turmeric for the curcumin.

By Randall Parker    2009 January 06 11:05 PM   Entry Permalink | Comments (4)
2008 November 09 Sunday
Crestor Cuts Mortality Risks From High hs-CRP Levels

For people with normal cholesterol but high scores in a test for the inflammation marker high-sensitivity C-reactive protein (hs-CRP) the statin drug rosuvastatin (Crestor) very substantially cuts cardiovascular disease risks and mortality risks. So getting an hs-CRP test is a good idea.

Montreal, November 9th 2008 - A team of international researchers – including scientists from the McGill University Health Centre (MUHC) and McGill University – have discovered that having high levels of particular protein puts patients at increased risk of developing cardiovascular disease. The results of the study were so conclusive that the clinical trial had to be stopped before its scheduled completion date.

Researchers associated with the international JUPITER Project have demonstrated that high levels of high-sensitivity C-reactive protein (hs-CRP) leads to increased risk of cardiovascular disease. This risk decreases by up to 44% if the patients are treated with statin medications.

Dr. Jacques Genest, of the Research Institute of the MUHC and McGill's Faculty of Medicine led the Canadian component of the JUPITER clinical study, which was initiated by Dr. Paul Ridker of the Harvard University Faculty of Medicine.

"The risk of cardiovascular disease due to increased hs-CRP levels has been greatly underestimated until now," according to Dr Genest. "Our results show that this is an extremely important indicator that doctors will have to consider in the future."

"We hope that this study will prompt a review of current clinical practices, especially in terms of screening and prevention in adults," he added. "However, we still need to do more research to establish specific standards."

A 21% decrease in mortality in just a couple of years treatment is impressive.

The JUPITER study included 17,802 patients from 27 different countries. All had normal levels of cholesterol (LDL-c) and high levels of hs-CRP, and according to current standards, were not considered "at risk" for cardiovascular events, and were therefore not receiving any treatment. During the study, participants received a daily dose of the statin drug rosuvastin, and its consequences were striking: a 44% decrease in the risk of cardiovascular disease and a 21% decrease in mortality.

"These results definitely surpassed our predictions," said Dr. Genest. "We had to stop the study before its scheduled completion, as the benefit of the treatment for the selected patients was so great that we needed to present our findings to the medical community as soon as possible."

Since statins have a cholesterol-lowering effect, they are currently used to prevent cardiovascular disease in patients who are at-risk due to high LDL-c levels. But cardiovascular disease is also caused by vascular inflammation, which is marked by levels of hs-CRP. This study shows that statins indeed act on both cholesterol and inflammation, an effect that has long been suspected but not proven.

The study was stopped a few years early because it was so successful.

The researchers planned to follow the subjects for five years, but an independent panel monitoring the study stopped the trial in March after an average follow-up of less than two years, concluding that the benefit was so striking that it would be unethical to continue withholding the real drug from those taking the placebo. But no details were released at the time.

But these results do not prove all cause mortality will be lowered if statins are taken for decades by those with high hs-CRP. Still, these results are very suggestive.

Widespread screening might turn up 6 million Americans who could benefit from statin use due to high hs-CRP.

Dr. Ridker said an analysis by study statistician Robert Glynn of Brigham estimated that applying the Jupiter findings to medical practice for six million Americans for five years would prevent 250,000 major cardiovascular events. The study suggests 25 patients would need to be treated for five years to prevent one major event, a number Dr. Ridker says appears at least as cost effective as strategies screening for high LDL.

Reports of serious adverse events were evenly divided -- 1,352 on the drug and 1,377 on placebo -- as were reports of muscle weakness -- 1,421 on the drug and 1,375 on placebo. Muscle side effects cause some patients to go off statins. There were 270 cases of diabetes among Crestor patients, compared with 216 on placebo.

The higher rate of diabetes among statin users is troubling. Muscle problems and memory problems also show up as side effects. Statins are not risk free. My hope is that cheap widespread genetic testing will eventually allow much more precise targeting of statin use. Those with high genetic risks of side effects will be able to steer clear of statins while those at great risk can know to take the drugs.

Some of you might have read that C-Reactive Protein (CRP) isn't looking as useful for identifying those at risk for heart disease as originally thought. However, this latest study use a more telling CRP test called the highly sensitive C-reactive protein (hs-CRP) assay. This hs-CRP assay sounds like it really picks up on risks that cholesterol tests miss.

C-reactive protein (CRP) is one of the acute phase proteins that increase during systemic inflammation. It’s been suggested that testing CRP levels in the blood may be an additional way to assess cardiovascular disease risk. A more sensitive CRP test, called a highly sensitive C-reactive protein (hs-CRP) assay, is available to determine heart disease risk.

What I'd like to know: What diet and lifestyle factors will lower hs-CRP? My guess is all the usual suspects: vegetables, fruits, fish, exercise. Anybody up for some googling (or maybe Pub Med searching) on this question?

Update: Writing in a New England Journal of Medicine editorial Mark A. Hlatky, M.D. observes that long term safety is unproven.

On the other side of the balance, of concern are the significantly higher glycated hemoglobin levels and incidence of diabetes in the rosuvastatin group in JUPITER (3.0%, vs. 2.4% in the placebo group; P=0.01). There are also no data on the long-term safety of lowering LDL cholesterol to the level of 55 mg per deciliter (1.4 mmol per liter), as was attained with rosuvastatin in JUPITER, which is lower than in previously reported trials. Long-term safety is clearly important in considering committing low-risk subjects without clinical disease to 20 years or more of drug treatment. Finally, the cost of rosuvastatin (roughly $3.45 per day) is much higher than that of generic statins.

Update: Stephen Colbert weighs in on the Jupiter Crestor trial:

Well worth a watch.

By Randall Parker    2008 November 09 08:31 PM   Entry Permalink | Comments (15)
2007 November 27 Tuesday
Higher Testosterone Men Face Lower All Cause Mortality

If your high testosterone doesn't get you killed from recklessness it probably makes you live longer.

CAMBRIDGE, England, Nov. 26 -- In otherwise healthy men, low testosterone is associated with an increased risk of death from any cause as well as from cardiovascular causes and cancer, researchers here said.

For all-cause mortality, each increase of six nanomoles of testosterone per liter of serum was associated with about a 14% drop in the risk of death, Kay-Tee Khaw, M.B.B.Ch., of the University of Cambridge School of Clinical Medicine, and colleagues reported in the Dec. 4 issue of Circulation.

These results come from a study on over eleven thousand men enrolled in the European Prospective Investigation into Cancer in Norfolk England. If you have low testosterone you especially ought to try to reduce other risk factors.

Lead author Dr Kay-Tee Khaw (University of Cambridge School of Clinical Medicine, UK) commented to heartwire: "This is the largest study of testosterone levels ever conducted. We don't know whether the association shown between higher levels of testosterone and lower mortality is causal or just a marker of something else, but regardless of this, it appears that low testosterone levels do identify a group at increased risk of cardiovascular death who could benefit from more aggressive treatments in terms of cholesterol and blood-pressure lowering."

Curiously, the men with higher testosterone did not appear to have higher risk of prostate cancer.

This result is consistent with some other recent studies on this topic. See my posts Low Testosterone Men Die More Rapidly and Low Testosterone Men Die Sooner.

By Randall Parker    2007 November 27 10:57 PM   Entry Permalink | Comments (7)
2007 October 16 Tuesday
Low Testosterone Men Die More Rapidly

But levels above average do not help and so don't go hog wild with the testosterone.

Older men with low levels of testosterone may have an increased long-term risk of death compared to men with normal testosterone, according to a new study accepted for publication in the Journal of Clinical Endocrinology & Metabolism (JCEM).

"This is the first report linking low levels of testosterone with earlier death in relatively healthy older men,” said Gail Laughlin, Ph.D., assistant professor at the University of California San Diego. “These results do not suggest testosterone supplementation for all older men, because levels above average did not make a difference.”

This study involved 794 men, ages 50 to 91 years, who were living in a southern California community and who participated in the Rancho Bernardo Study in the 1980s. Men whose total testosterone levels at the beginning of the study were in the lowest quartile (<241 ng/dl) were 40 percent more likely to die over the next 18 hears than those with higher levels. This difference was not explained by age, illness, adiposity, or lifestyle.

“We want to emphasize that this is an observational study,” said Laughlin. “We cannot recommend that any man take testosterone based on these results. Only randomized clinical trials can determine whether testosterone supplements are safe and can promote longevity. In the meantime, lifestyle changes to prevent or decrease obesity may also extend longevity."

Approximately 30 percent of men 60 years and older are estimated to have low testosterone, which is often accompanied by symptoms such as low bone and muscle mass, increased fat mass, low energy, and impaired physical, sexual, and cognitive function.

Keep in mind that boosting testosterone might boost your risk of prostate cancer. We need much more detailed information about hormone supplement therapies. Probably they are a net benefit for some people and a net harm for others. We can't predict accurately enough who will gain and who will lose from assorted hormone replacements.

By Randall Parker    2007 October 16 06:00 PM   Entry Permalink | Comments (1)
2007 June 05 Tuesday
Low Testosterone Men Die Sooner

Men with lower testosterone in their 50s and beyond do not live as long.

Low levels of testosterone may increase the long-term risk of death in men over 50 years old, according to researchers with the Department of Family and Preventive Medicine at the University of California, San Diego School of Medicine.

“The new study is only the second report linking deficiency of this sex hormone with increased death from all causes, over time, and the first to do so in relatively healthy men who are living in the community,” said Gail Laughlin, Ph.D., assistant professor and study author.

This result surprises me. I would have expected the testosterone to reduce life expectancies by upping the incidence of prostate cancer and by basically turning up the body's metabolism to a level that would cause the body to wear out more rapidly.

The men in this study have been tracked for the last 18 years.

“We have followed these men for an average of 18 years and our study strongly suggests that the association between testosterone levels and death is not simply due to some acute illness,” said Laughlin.

In the study, Laughlin and co-workers looked at death, no matter the cause, in nearly 800 men, ages 50 to 91 years, who were living in Rancho Bernardo, California. The participants have been members of the Rancho Bernardo Heart and Chronic Disease Study since the 1970s. At the beginning of the 1980s, almost one-third of these men had suboptimal blood testosterone levels for men their age.

The group with low testosterone levels had a 33 percent greater risk of death during the next 18 years than the men with higher testosterone. This difference was not explained by smoking, drinking, physical activity level or pre-existing diseases (such as diabetes or heart disease).

In this study, "low testosterone" levels were set at the lower limit of the normal range for young adult men. Testosterone declines slowly with aging in men and levels vary widely, with many older men still having testosterone levels in the range of young men. Twenty-nine percent of Rancho Bernardo men had low testosterone.

So them maybe testosterone patches would increase life expectancy in men who have lower levels of testosterone?

The men with lower testosterone had more fat on their wastes and more inflammation in their bodies.

Men with low testosterone were more likely to have elevated markers of inflammation, called inflammatory cytokines, which contribute to many diseases. Another characteristic that distinguished the men with low testosterone was a larger waist girth along with a cluster of cardiovascular and diabetes risk factors related to this type of fat accumulation.

This begs the question: If these low testosterone men took testosterone would their inflammation markers go down and their fat decrease? If so, would they then live longer? I would at least expect the reduction in body fat.

By Randall Parker    2007 June 05 10:14 PM   Entry Permalink | Comments (13)
2007 January 16 Tuesday
Growth Hormone Bad Anti-Aging Bet

Older folks who are taking growth hormone aren't doing themselves any favors.

PHILADELPHIA, Jan. 16, 2007 -- A review of published data on use of human growth hormone (GH) by healthy elderly people found that the synthetic hormone was associated with small changes in body composition but not in body weight or other clinically important outcomes.

Further, people who took GH had increased rates of unhealthy side effects such as soft tissue swelling, joint pain, carpal tunnel syndrome, and, in men, abnormal breast development. They were also somewhat more likely to develop diabetes.

The review, "The Safety and Efficacy of Growth Hormone in the Healthy Elderly," was published in the Jan. 16, 2007, issue of Annals of Internal Medicine and is available on the Web at www.annals.org on that day.

"Growth hormone has been widely promoted as an anti-aging therapy," said Hau Liu, MD, a research fellow in endocrinology and health policy at Stanford University and an author of the review.

"But the scant clinical experience of GH in the healthy elderly suggests that although GH may minimally alter body composition, it does not improve other clinically relevant outcomes such as bone density, cholesterol levels, stamina, and longevity in this population.

"And it's associated with high rates of adverse events.

"So, on the basis of available evidence, we cannot recommend growth hormone use for anti-aging in the healthy elderly."

Growth hormone always struck me as a bad idea for rejuvenation. It is about growth and we can't go on growing in size. If higher hormone levels could extend life then selective pressures would likely have caused humans to make more hormones in their old age. But lower hormone levels probably reduce the risk that aged cells will get too stimulated and go cancerous.

We need gene therapies, cell therapies and replacement organs to reverse the accumulated damage that comes with age. Hormones aren't going to do it.

By Randall Parker    2007 January 16 09:32 PM   Entry Permalink | Comments (5)
2005 August 24 Wednesday
Testosterone Replacement Therapy May Up Prostate Cancer Risk

While the evidence is by no means conclusive a small study of prostate cancer patients suggests that testosterone therapy increases the risk of prostate cancer.

Researchers in the United States say that prostate cancer developed in 20 men within months to a few years after they began testosterone supplementation, to correct a deficiency of the hormone.

Dr. Franklin D. Gaylis from the University of California at San Diego Medical Center, says that there are several anecdotal case reports, small studies, and observational studies such as theirs, that raise concern but do not as yet, provide conclusive evidence.

A major method of treatment for prostate cancer is the use of drugs that knock out the body's production of testosterone. This typically adds a few years to the lives of prostate cancer sufferers until the prostate cancer mutates into a form that is called "hormone refractory" or "androgen independent". At that point the cancer cells no longer need testosterone in order to grow.

That such a large fraction of the men developed prostate cancer in the first year of testosterone use suggests testosterone contributed to the development of prostate cancer.

To describe the characteristics of prostate cancer in men taking testosterone, researchers reviewed 20 cases of prostate cancer that developed among men taking testosterone. A majority of these cancers developed during the first two years on testosterone, and roughly one-third developed in the first year. Prostate cancer was detected by abnormalities in both prostate-specific antigen (PSA) levels and findings on digital-rectal exam (DRE) in 40% of men, by abnormal DRE alone in 35% of men, and by elevated PSA alone in 25% of men.

A lot of old guys have very low testosterone levels.

Testosterone therapy products have been approved by the U.S. Food and Drug Administration for treating a limited number of conditions, particularly hypogonadism associated with low testosterone levels. Hypogonadism occurs in men of various ages, and most clinical studies of the therapy so far have been in younger men. Recent studies have shown that a significant percentage of otherwise healthy older men have testosterone levels consistent with hypogonadism. Data also suggests that low testosterone in elderly men is associated with a loss of lean body mass and muscle strength and increased central body fat. There may also be decreased bone density and mental dysfunction associated with low testosterone levels. For these reasons an increasing number of elderly men are being treated with exogenous testosterone. However, the risks of administering testosterone to elderly men have yet to be defined.

I am skeptical of the notion that hormone replacement therapies can provide net benefit for most aged people. Testosterone is not that hard to synthesize. Therefore its decline may not be due to damage to pathways that make it. The aging body does not lose the ability to synthesize the complex cholesterol molecule from which testosterone gets made Cholesterol is a 4 ringed polycyclic aromatic hydrocarbon with some chains hanging off it. Relatively minor modifications and pruning of those chains (which my aging brain can no longer remember) produce testosterone, estrogen, and the other sex hormones and corticosteroids. Therefore the decline in testosterone in aged men might be a product of evolutionary selective pressures to lower the risk of prostate cancer and possibly to lower the risks of other types of cancers as well.

If we had effective and safe cures for prostate cancer and other cancers that feed off of sex hormones then some of the hormone replacement therapies might provide a net benefit. Also, as genetic screening for cancer risks becomes more advanced then it might turn out that some aging people with the right genetic variations can derive a net benefit from replacement hormone therapies.

This reminds me of the research on thyroid hormone levels and breast cancer. Women with underactive thyroids have less risk of getting breast cancer.

Researchers at The University of Texas M. D. Anderson Cancer Center have found that women with a common thyroid gland disorder appear to have a reduced chance of developing invasive breast cancer, according to a study published in the March 15 issue of Cancer, out online Feb. 14.

In a retrospective case-control study of 2,226 females, researchers found that women with primary hypothyroidism (under-active thyroid) had a 61 percent lower risk of developing invasive breast cancer. Additionally, women newly diagnosed with breast cancer were 57 percent less likely to have the under-active thyroid gland condition compared to a control group of healthy women.

Also, women with underactive thyroids who did get breast cancer got less aggressive forms of breast cancer on average.

"Women with a history of hypothyroidism had many more stage I and II breast cancers and very few stage III diseases," lead researcher Massimo Cristofanilli, MD, tells WebMD. "Overall, their disease was less aggressive." He is with The University of Texas M.D. Anderson Cancer Center.

When our aged cells get run at youthful speed the cells are more likely to spin out of control and go cancerous. We need to repair or replace our old cells so that we can turn up the accelerators on our bodies and function once again at youthful levels. We also need great, fast, safe, and effective cures for cancer and treatments that tell pre-cancerous cells to commit cellular suicide. Cancer is a major obstacle in the way of rejuvenation.

By Randall Parker    2005 August 24 04:04 PM   Entry Permalink | Comments (13)
2002 December 22 Sunday
Are Replacement Hormones A Fountain Of Youth?

Gina Kolata has an article in the New York Times about the growing popularity of the use of hormones to try to roll back some of the effects of aging. Testosterone and human growth hormone (HGH) are used for men and women. Plus, estrogen and progesterone are used by women. Some use DHEA, thyroid or other hormones as well. This has intensified the debate about whether these hormones provide a net benefit.

Until recently, most scientists considered anti-aging treatments to be little more than snake oil, provided by hucksters. Now, few doubt that growth hormone and testosterone can reshape aging bodies, potentially making them more youthful.

But whether they counteract aging is unknown. And their long-term risks are ill defined. So medical experts ask whether it is right to regard aging as a disease, as fierce as a malignant cancer, to be fought with any and all means, tested or not.

First of all, yes, aging really should be fought by any means that really works. There is nothing beneficial to the individual about physical aging. An older body does not function as well as it did when it was younger. The mind doesn't function as well either. Learning is more difficult, the ability to do complex problem solving is diminished, old memories are harder to recall, and assorted brain disorders such as depression, Alzheimer's Disease, Parkinson's, and dementia are more common, . Various cells can no longer do their jobs at all and in some cases even whole organs can no longer carry out their functions. The body has a reduced ability to handle environmental changes, infections, stresses and trauma. The aged body makes life harder and less pleasureable for the person whose body has aged and for those whose jobs it is to help the aging and for those who care about and give care to aging family members and friends. The body is at greater risk of all manners of illness and death. What reason is there to be complacent in the face of all that if we can possibly do anything about it?

People who are taking testosterone and HGH are doing so because they feel immediate benefits such as better muscle tone, less fat, more stamina, perceived greater ability to concentrate, and other benefits that can be directly experienced in the short term. However, these benefits do not provide any clue as to whether replacement hormones will shorten or lengthen life expectancy. There's reason for skepticism from an evolutionary perspective: it would not have been that hard for evolution to select for an aging body to retain its ability to make hormones at the same level as the body made them in its youth. The fact that it doesn't may be because it was harmful to do so. Some hormones are known to boost the risk of some types of cancers. Also, a metabolism sped up by hormones may be akin to an engine that is operated at higher RPMs. Parts of it may wear out faster if they are being stimulated by higher hormone levels.

Another reason to be skeptical of hormone therapies is that they do cause side-effects in the short term. Most worryingly some people develop insulin resistance while on hormone therapy. The resistance usually goes away once the therapy is stopped and not all people who take hormones to feel rejuvenated suffer this side effect. Still, it is possible that a period of time spent on hormone therapy will increase the chance of developing insulin resistance (aka type II diabetes) later on.

Another reason to be skeptical of the benefits of hormones as an anti-aging therapy is that scientists have tried large numbers of experiments on animals to try to find ways to increase life expectancy. Many combinations of hormones have been tried. The only consistently successful method to increase average and max life expectancy in wild type (ie not special in-bred lab strains) found to date is calorie restriction. Hormones do not increase animal life expectancy and more often than not actually decrease it.

Is the lack of known data on the long term effects of hormone therapies an argument against taking them? The answer depends on your own personal values. Some people (I know one such person) are taking hormones chiefly for the short term benefits. They know they are taking a risk. They want a more vigorous life and a greater feeling of healthiness in their 40s, 50s, and 60s even if there is a chance of decreased life expectancy as a result. For someone such as myself who thinks that people should be able to do with their bodies as they please as long as they do not create costs for others (and someone who dies sooner is probably decreasing their net burden in terms of total government benefits that they receive in retirement) its hard to argue why this choice should not be allowed. As Blondie put it: "Die young, stay pretty, live fast because it won't last."

Having said all this, it is still possible that some combination of hormones could increase life expectancy. The problem is that there are probably many more combinations that are harmful than are beneficial and we just don't have any idea what combination might be beneficial. To know that ideal hormone regimen might well require knowledge of an individual's genetic variations and the condition of the various organs in the individual's body. It is possible that the only way to improve longer term health with hormones would involve the implantation of a genetically engineered or silicon-based hormone dispenser organ that could deliver hormones with a greater precision than what is possible thru the use of pills or shots. Such an implant could take into account the constantly changing internal condition of the body to adjust the levels of hormones to a more optimized level. This sort of capability still lies somewhere in the future. But it seems plausible that some day it will be possible to develop a better endocrine regulatory system than the one that we are all born with naturally.

The problem today is that we lack the knowledge to know whether or how we could tweak the endocrine system of humans to extend life. Even if we knew how to design and build an incredibly sophisticated device for monitoring metabolism in real time to adjust hormone levels of aging people we still wouldn't know what to tell the device to do. Hormone levels change as we age. Why? Here are some possibilities for why hormone levels change as we age:

  • The change in hormone levels of aging bodies could be the result of natural selection aimed at maximizing life expectancy of an aging body.
  • But the changes might instead be a result of a decay in the ability of the aging endocrine systen to optimally regulate hormone levels.
  • The changes might be because natural selection just did not select strongly enough for an optimal regulation of hormones in an aging body (as an analogy think of a computer program that hasn't been well enough tested, debugged and optimized under some operating condition).

We do not know which one or combination of these possibilities is correct. Even if we did we wouldn't then immediately know what to do about it. People who are taking replacement hormones are therefore engaging in a massive experiment in hopes that anything that provides an immediate benefit will provide a longer term benefit as well.

By Randall Parker    2002 December 22 03:46 PM   Entry Permalink | Comments (3)
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