Life Extension Magazine December 2008
Preventing Macular Degeneration: A New Theory
Pioneering Eye Surgeon Sees Hope for Treating Macular Degeneration with Natural Hormones
By Debora Yost
Plant caroteinoids such as lutein and zeaxanthin were long ago shown to help prevent macular degeneration. But is there more that can be done to protect against this epidemic of blindness?
George W. Rozakis, MD is a Cornell-trained biomedical engineer specializing in laser eye surgery and lens implants. A pioneer in the field of LASIK surgery,1 Dr. Rozakis is now vigorously involved in anti-aging medical research.
Dr. Rozakis is focusing on a potential breakthrough in treating macular degeneration, a condition that gradually destroys central vision. Also called age-related macular degeneration, it is the leading cause of blindness in people aged 65 and older.
Dr. Rozakis believes that restoring the correct balance of natural hormones that decline with age can retard and possibly even reverse the progression of macular degeneration. To investigate this hypothesis, he is setting up a long-term study and is currently seeking subjects to participate in the trial.
Hormones and Your Vision
The hormonal link with macular degeneration began to evolve when Dr. Rozakis met another medical pioneer, Sergey A. Dzugan, MD, PhD, during a conference in Chicago four years ago. Dr. Dzugan is a cardiovascular surgeon and internationally known expert in anti-aging and hormonal medicine.
“Dr. Dzugan has done numerous studies2-4 and written numerous articles on the association between low hormone levels and multiple disease states, including the problem of atherosclerosis and cholesterol elevation,” says Dr. Rozakis. “As an ophthalmologist I was impressed by the evidence that restoring and optimizing levels of key hormones improve brain function, largely because the retina is part of the brain. For example, there is very impressive literature that testosterone slows down the progression of Alzheimer’s disease.5 Pregnenolone is extremely important for the brain and nervous system, as are progesterone and estrogens. Women whose progesterone levels drop develop negative personality changes.6 In animal models, pregnenolone and DHEA have been shown to profoundly stimulate the healing of neurologic injury.7-9 Women who enter into menopause at a young age develop macular degeneration, presumably because of the absence of estrogens.10,11 Blocking estrogens with the anti-cancer drug tamoxifen is harmful to the retina.12 This leads us to wonder if optimal hormonal health also positively impacts ocular health.”
“When an article appeared in the American Journal of Ophthalmology indicating that DHEA, or dehydroepiandrosterone, is exceptionally low in macular degeneration patients,13 I was shocked and excited,” says Dr. Rozakis. This finding provided a major clue that hormonal imbalance was part of the problem of macular degeneration.
“DHEA is like the Grand Central Station of hormone chemistry,” says Dr. Rozakis. “When DHEA levels drop, it strongly implies that levels of other hormones such as pregnenolone, estrogens, and testosterone are out of balance or suboptimal.” All of these hormones make the body thrive—they give us virility, fertility, and help us act and react quicker. Since the retina contains hormone receptors, hormones must be part of the biophysiology of vision itself.
Low DHEA levels in macular degeneration could also explain its association with heart disease, as it is known that macular degeneration is an independent risk factor for stroke and coronary artery disease. In a study conducted by Australian scientists,14 macular degeneration predicted a five-fold higher risk of cardiovascular mortality and a 10-fold higher risk of stroke mortality. After controlling for traditional cardiovascular risk factors, age-related macular degeneration predicted a doubling of cardiovascular mortality. Since hormone deficiency has been linked with both heart disease and eye disorders,13,15 it is a prime suspect that links the heart to the eye.
Further examination of the literature reveals a major review article from Italy that explains the importance of hormones to the retina.16 In this article, it is shown that the retina is able to attempt to make its own hormones, just like the brain. “The article also indicates that many of the hormones we use in anti-aging programs have a role in the retina, such as pregnenolone, DHEA, testosterone, estrogens, and progesterone. Few ophthalmologists and optometrists are aware of this relationship. This was the smoking gun that led to our hypothesis,” Dr. Rozakis notes.
Macular Degeneration and Cholesterol
A good theory needs to connect all the dots. Dr. Rozakis explains that one challenge in shaping his theory was explaining the presence of “drusen” or spots that appear in the retina in patients with macular degeneration. Many consider these spots to be “degradation products.”
Recently, Goldis Malek, PhD, and others17-19 found that cholesterol was present in those spots. This led some people to think that cholesterol-lowering agents, such as statins, might help macular degeneration—but they do not. In fact, there is concern that statins actually increase the risk of dry macular degeneration advancing to the neovascular form of the disease, whereby tiny blood vessels in the eye begin to bleed.20
Dr. Rozakis notes, “To Dr. Dzugan and me, the presence of cholesterol in the macula was the key piece of data that integrated everything. The presence of cholesterol in the macula suggests that the retina is trying to make hormones—but that it can’t. So, the body’s accumulation of cholesterol and drusen worsen.” He continues, “The macula can’t get the hormones it needs from the blood because there aren’t much there. As a result, if the macula is having trouble converting cholesterol into hormones, drusen form, and this results in the drusen we see in macular degeneration. Why the macula stops making hormones is unknown, but it is associated with aging. We can speculate that it happens because the enzymes which do the conversion decrease or are down-regulated with aging.”
“This same ‘story’ of cholesterol and hormones plays itself out in the body as a whole,” says Dr. Rozakis. “We do know that the adrenal gland, which produces DHEA, loses the ability to manufacture hormones as we age. As Dr. Dzugan published, this hormonal decline stimulates the liver to produce more cholesterol in an attempt to create more hormones.3 This is why restoring hormones to their normal levels causes the liver to produce less cholesterol. That same paradigm may be happening in the macula. This is the basis of our hypothesis. The goal therefore must be to provide the retina the hormones it needs through supplementation.”
Reviewing the Evidence
There is already evidence to support the notion that DHEA protects the eyes against oxidative damage21 and that the hormone pregnenolone improves electrical activity in the retina, as measured by the electroretinogram (ERG).22,23 There is also evidence to support the use of melatonin in the treatment of macular degeneration.24,25
The theory that optimizing hormones may help promote macular health is based on these scientific facts:
Dr. Rozakis speculates that the solution for treating macular degeneration is to measure and restore age-depleted hormones to optimal levels so that the macula can absorb the hormones it needs from the blood. “Hopefully restoring hormones to their normal levels in the bloodstream will cause the macula to stop absorbing cholesterol and, as a result, drusen formation will hopefully decline,” says Dr. Rozakis. “We certainly need a better understanding of the pathophysiology of this blinding disease.”27
A Higher Level of Natural Treatment
Dr. Rozakis sees hormone restoration as a strategy to improve on existing studies showing that certain nutrients can reduce the progression of age-related macular degeneration. The long-term Age-Related Eye Disease Study (AREDS), conducted by the National Eye Institute, found that supplementing the anti-oxidants beta-carotene, vitamin C, vitamin E, and the mineral zinc reduced the risk of developing advanced states of macular degeneration in more than 4,700 high-risk patients aged 55 to 80 who were enrolled in the study.28
The specific amounts of nutrients used by the study researchers were:
The copper, administered as cupric oxide, was included in the formula to prevent copper-deficiency anemia, which is associated with high zinc intake.
As a result of the AREDS trial, many ophthalmologists are recommending supplements containing the study’s recommended dosages for patients with or at a high risk for age-related macular degeneration.
Dr. Rozakis is currently developing his own study to test his theory concerning the relationship between low levels of DHEA and macular degeneration. “Our study is going to focus on overall hormonal balance and will include the supplements used in the AREDS study as well,” says Dr. Rozakis. “Our goal is to do everything we can to stop macular degeneration. The fact that hormones are much more powerful than vitamins holds hope that the results will be significant.”
If you have any questions on the scientific content of this article, please contact a Life Extension Health Advisor at 1-800-226-2370.
Article review by Richard P. Kratz, MD, DSci Life Extension Scientific Advisory Board Member
Tragically, the leading cause of age-related visual loss is macular degeneration which remains largely untreatable. By the age of 65, nearly one-third of adults or 20-25 million Americans will have experienced some decrease in their ability to read, drive, or see fine details. At present, the cause of age-related macular degeneration is unknown. The disorder is characterized by the development of small yellow spots in the retina called drusen. Theories to explain the occurrence of drusen include accumulation of cellular waste products, age-related reduction of blood flow, inflammation, nutrient deficiency, cigarette smoking, and high fat intake. New strategies for the prevention and management of macular degeneration are sorely needed.
The past decade has seen an explosion of interest in managing wellness by restoring hormones. Unfortunately, progress in this arena has been complicated by the use of non-bioidentical, pharmaceutical hormones such as Premarin® (horse urine estrogen). The scientific literature contains many studies examining the use of single hormones, which further confuses the issues at hand. Studies that focus on the balance of all hormones are greatly needed. For example, a study to determine the value of estrogen therapy alone in managing a particular disorder is insufficient, as an estrogen deficiency must be looked at in the context of progesterone levels and other adjacent hormones in the biological hormonal cascades.
Today, innovative clinicians are increasingly using bioidentical hormones in their practice. These are true hormones that are identical to those naturally produced by the body, which often become depleted due to the aging process. Examples of these bioidentical hormones include pregnenolone, dehydroepiandro-sterone (DHEA), estriol, estradiol, estrone, progesterone, testosterone, dihydrotestosterone, and cortisol.
George W. Rozakis, MD, has been a student of hormonal medicine for a number of years, thanks to his association with Sergey A. Dzugan, MD, PhD, one of the leading experts in hormonal medicine. Dr. Rozakis has proposed a new theory for one of the leading causes of blindness, which he titles “The Hormonal Theory of Macular Degeneration.” The prime mover for this idea is the embryologic association between the retina and the brain. Since hormones are known to benefit the brain, Dr. Rozakis theorizes whether hormones also benefit the macula. When recent scientific literature showed that blood DHEA levels are low in patients with macular degeneration, that the macula can make its own hormones, and that cholesterol is present in the pathological lesions known as drusen, the stage was set for Dr. Rozakis’ theory.
Dr. Rozakis postulates that cholesterol-containing drusen are the retina’s failed last-ditch attempt to make needed hormones, including DHEA, from cholesterol. Such a failed attempt leads to the findings we see in the retina, namely the small yellow spots called drusen.
If Dr. Rozakis is correct, restoring normal hormone levels should help to prevent macular degeneration and might even improve early-stage macular degeneration. This is a novel idea, which he intends to test in clinical trials. His theory is in keeping with the modern trend of measuring hormone levels and then administering hormone replacement to re-establish hormonal balance and restore health.
Careful clinical trials will be required to evaluate Dr. Rozakis’ hormonal theory of macular degeneration.
1. Available at: http://patft.uspto.gov/netacgi/nph-Parser? u=%2Fnetahtml%2Fsrchnum.htm&Sect1=PTO1&Sect2=HITOFF&p=1&r=1&l=50&f=G&d=PALL&s1=5843070.
2. Dzugan SA, Smith RA. Broad spectrum restoration in natural steroid hormones as possible treatment for hypercholesterolemia. Bull Urg Rec Med. 2002;3:278-84.
3. Dzugan SA, Arnold SR. Hypercholesterolemia treatment: a new hypothesis or just an accident? Med Hypotheses. 2002 Dec;59(6):751-6.
4. Dzugan SA, Smith RA. Kuznetsov AS. A new statin free method of hypercholesterolemia. The Health of Donbass. 2004;4:19-25.
5. Driscoll I, Resnick SM. Testosterone and cognition in normal aging and Alzheimer’s disease: an update. Curr Alzheimer Res. 2007 Feb;4(1):33-45.
6. Andreen L, Sundstrom-Poromaa I, Bixo M, Nyberg S, Backstrom T. Allopregnanolone concentration and mood--a bimodal association in postmenopausal women treated with oral progesterone. Psychopharmacology (Berl). 2006 Aug;187(2):209-21.
7. Li H, Klein G, Sun P, Buchan AM. Dehydroepiandrosterone (DHEA) reduces neuronal injury in a rat model of global cerebral ischemia. Brain Res. 2001 Jan 12;888(2):263-6.
8. Bucolo C, Drago F. Effects of neurosteroids on ischemia-reperfusion injury in the rat retina: role of sigma1 recognition sites. Eur J Pharmacol. 2004 Sep 13;498(1-3):111-4.
9. Guth L, Zhang Z, Roberts E. Key role for pregnenolone in combination therapy that promotes recovery after spinal cord injury. Proc Natl Acad Sci USA. 1994 Dec 6;91(25):12308-12.
10. Boekhoorn SS, Vingerling JR, Uitterlinden AG, et al. Estrogen receptor alpha gene polymorphisms associated with incident aging macula disorder. Invest Ophthalmol Vis Sci. 2007 Mar;48(3):1012-7.
11. Smith W, Mitchell P, Wang JJ. Gender, oestrogen, hormone replacement and age-related macular degeneration: results from the Blue Mountains Eye Study. Aust N Z J Ophthalmol. 1997 May;25 Suppl 1:S13-5.
12. Vinding T, Nielsen NV. Retinopathy caused by treatment with tamoxifen in low dosage. Acta Ophthalmol (Copenh). 1983 Feb;61(1):45-50.
13. Tamer C, Oksuz H, Sogut S. Serum dehydroepiandrosterone sulphate level in age-related macular degeneration. Am J Ophthalmol. 2007 Feb;143(2):212-6.
14. Tan JS, Wang JJ, Liew G, Rochtchina E, Mitchell P. Age-related macular degeneration and mortality from cardiovascular disease or stroke. Br J Ophthalmol. 2008 Apr;92(4):509-12.
15. Thijs L, Fagard R, Forette F, Nawrot T, Staessen JA. Are low dehydroepiandrosterone sulphate levels predictive for cardiovascular diseases? A review of prospective and retrospective studies. Acta Cardiol. 2003 Oct;58(5):403-10.
16. Guarneri P, Cascio C, Russo D, et al. Neurosteroids in the retina: neurodegenerative and neuroprotective agents in retinal degeneration. Ann NY Acad Sci. 2003 Dec;1007:117-28.
17. Malek G, Li CM, Guidry C, Medeiros NE, Curcio CA. Apolipoprotein B in cholesterol-containing drusen and basal deposits of human eyes with age-related maculopathy. Am J Pathol. 2003 Feb;162(2):413-25.
18. Li CM, Clark ME, Rudolf M, Curcio CA. Distribution and composition of esterified and unesterified cholesterol in extra-macular drusen. Exp Eye Res. 2007 Aug;85(2):192-201.
19. Curcio CA, Presley JB, Millican CL, Medeiros NE. Basal deposits and drusen in eyes with age-related maculopathy: evidence for solid lipid particles. Exp Eye Res. 2005 Jun;80(6):761-5.
20. Available at: http://www.medscape.com/viewarticle/573810?src=rss. Accessed September 16, 2008.
21. Bucolo C, Drago F, Lin LR, Reddy VN. Neuroactive steroids protect retinal pigment epithelium against oxidative stress. Neuroreport. 2005 Aug 1;16(11):1203-7.
22. Jaliffa CO, Howard S, Hoijman E, et al. Effect of neurosteroids on the retinal gabaergic system and electroretinographic activity in the golden hamster. J Neurochem. 2005 Sep;94(6):1666-75.
23. Binns AM, Margrain TH. Evaluating retinal function in age-related maculopathy with the ERG photostress test. Invest Ophthalmol Vis Sci. 2007 Jun;48(6):2806-13.
24. Lundmark PO, Pandi-Perumal SR, Srinivasan V, Cardinali DP. Role of melatonin in the eye and ocular dysfunctions. Vis Neurosci. 2006 Nov;23(6):853-62.
25. Yi C, Pan X, Yan H, Guo M, Pierpaoli W. Effects of melatonin in age-related macular degeneration. Ann NY Acad Sci. 2005 Dec;1057:384-92.
26. Guarneri P, Guarneri R, Cascio C, Pavasant P, Piccoli F, Papadopoulos V. Neurosteroidogenesis in rat retinas. J Neurochem. 1994 Jul;63(1):86-96.
27. Zarbin MA. Current concepts in the pathogenesis of age-related macular degeneration. Arch Ophthalmol. 2004 Apr;122(4):598-614.
28. Schutt F, Pauleikhoff D, Holz FG. Vitamins and trace elements in age-related macular degeneration. Current recommendations, based on the results of the AREDS study. Ophthalmologe. 2002 Apr;99(4):301-3.