Sunday, April 5, 2015


Drop_impact3Safety of Bioidentical Hormones

Are Women's Bio-identical hormones Safe? by Jeffrey Dach MD Bio-identical hormones exist naturally in the human body, so it is axiomatic that these are safe. However, we are interested in a slightly different question. What is the safety of bio-identical hormones as routinely used in medical practice? Let's try to answer this question. Left Image: Water with Droplets Courtesy of Wikimedia

The Safety of Water compared to Bio-Identical Hormones

Water is safe, beneficial and healthy. Yet, even so, drinking excess amounts of water causes death from Fatal Water Intoxication.(1) Similarly, just like water, bio-identical hormones are safe and beneficial when used at proper dosages. Like excessive water, excessive hormone dosage may result in their own adverse side effects. Excess estrogen, for example, causes fluid retention, breast sensitivity and enlargement, and disturbed mood.

Humans Have Bio-Identical Hormones - Ask Darwin

Another answer to the safety question is that bio-identical hormones are found in the human body naturally. Any harmful substance in the human body would impair survival, and over millions of years of evolution would be eliminated by natural selection. This is the basic concept of Darwinian evolution which is accepted by mainstream medical science.

A 50 Million Year Medical Experiment

Consider the following medical experiment, performed over the last 50 million years with the help of our friend, Darwinian evolution.(2) Bio-Identical Hormones have been present in the human body for 50 million years, and we humans are still here on the planet. I would consider that a successful medical experiment, wouldn't you?

Either Excess or Deficiency of Anything Can be Harmful

One of our routine labs tests called the Chem Panel measures electrolytes and glucose levels in the blood. The body automatically maintains these within narrow ranges to maintain health. If levels deviate above or below these normal ranges, this causes a serious health disturbance. For example elevated potassium levels causes cardiac arrest. Magnesium deficiency causes muscle spasm and arrhythmia. Excessive amounts of Vitamins A and D are toxic. Hormones levels enjoy a considerably wide range of acceptable limits. Even so, a deficiency or an excess of women's bio-identical hormones can produce adverse symptoms. This is called estrogen deficiency/excess, and progesterone deficiency/excess, and they each have typical signs and symptoms easily recognized.(3)

Common Signs of Estrogen Deficiency (4)

Mental fogginess Forgetfulness Depression Minor anxiety Mood change Difficulty falling asleep Hot flashes Night sweats Temperature swings Day-long fatigue Reduced stamina Decreased sense of sexuality Lessened self-image and attention to appearance Dry eyes, skin, and vagina Loss of skin radiance Feel balanced 2nd part of cycle Sagging breasts and loss of fullness Pain with sexual activity Weight gain Increased back and joint pain Episodes of rapid heartbeat Headaches and migraines Gastrointestinal discomfort Constipation

Common Signs of Excess Estrogen (takes longer to notice)

Breast tenderness or pain Increased breast size Water retention, fingers, legs Impatient, snappy behavior, but with clear mind Pelvic cramps Nausea

Common Signs of Progesterone Deficiency

No period at all (no ovulation) The period comes infrequently (every few months) Heavy and frequent periods (large clots, due to buildup in the uterus) Spotting a few days before the period. (Progesterone level is dropping) PMS Cystic breasts Painful breasts Breasts with lumps Most cases of endometriosis, adenomyosis, and fibroids. Anxiety, irritability, nervousness and water retention Above list courtesy of Uzzi Reiss MD (4)

No Reported Adverse Events from Bio-Identical Hormones

Over-the-counter pain pills (NSAIDs) such as aspirin, naproxen and ibuprofen are considered fairly safe. After all, you don't need a prescription to buy them, yet they cause an estimated 16,500 deaths in the US annually, mostly from gastric bleeding.(5) Compare this to no reported adverse events from bio-identical hormones last year, according to an FDA Press Conference on Bioidentical Hormones Jan 2008. (6)

Do Bio-Identical Hormones Cause Breast Cancer?(7) The answer is NO.

Eiffel_towerLeft Image: Eiffel Tower Paris France Courtesy of Wikimedia Commons

According to the French Cohort study, there is no increase in breast cancer in women using bio-identical hormones.(8) However, having said that, avoiding excess environmental estrogens as well as excessive estrogen levels from any source, is the key to preventing breast cancer.(9) My previous article covers our program for breast cancer prevention which includes iodine supplementation, Indole-3-carbinol and fiber. To read about this, see: Breast Cancer Prevention and Iodine Supplementation by Jeffrey Dach MD.(10)

What Causes Cancer ?  Environmental Chemicals

If bioidentical hormones do not cause cancer , What Does? The answer is known for many years. Carcinogenic chemicals in the environment , water and food supply cause cancer. Here is a partial list of carcinogens in our food supply- Bisphenol A (BPA) Phthalates, Pesticides, Styrene , Vinyl Chloride, etc. The list of environmental carcinogens is almost endless.

Do Bio-Identical Hormones Cause Heart Disease ?

Again, the answer is NO. A study of CAT calcium scores by JoAnn E. Manson in the June 2007 JAMA actually showed less heart disease in the women taking unopposed estrogen (they had hysterectomies and were not given the synthetic progestins).(11) These same results had already been published 2 years previously in a calcium score study by Budoff in J Womens Health 2005. (12)

A Closer Look at the Women's Health Initiative WHI Study

Understanding the Women's Health Inititative (WHI) study is not difficult, and is very important to answer the question of hormone safety. The WHI study was the large NIH sponsored medical study which compared synthetic hormones to placebo in two large groups of women. The WHI study consisted of two arms. The first arm used the synthetic hormones Premarin and Provera, and the second arm used Premarin alone.(13)(14)

What is Premarin and Provera?

Premarin and Provera are not bio-identical hormones. Premarin is a hormone obtained from pregnant horses, which contains Equilin, a horse hormone not found in humans.(15) Provera is a synthetic hormone which is not found anywhere in the natural world (see provera diagram below).(16) The Premarin and Provera combination is called PremPro, a synthetic hormone pill commonly prescribed by mainstream medicine. Prempro was the hormone preparation used in the first arm of the WHI study.(13)

WHI study First Arm:

The WHI study (first arm published in JAMA 2002) was terminated early because the combination of premarin and provera (Prempro) caused increased breast cancer and heart disease.(13) Immediately after this study was published, there was a massive switch by women to bio-identical hormones which resulted in a 4 billion dollar loss for Wyeth, the maker of Prempro. Wyeth is still trying to recoup that money by manipulating the FDA. They want the FDA to ban their competition, the bio-identical hormones or their components.(36-38)

WHI Study (Second Arm):

All the women in the second arm of the WHI study had prior hysterectomies (uterus absent), so they did not need the synthetic progestin, provera commonly given to prevent endometrial cancer. Rather, they were only given Premarin (the horse hormone, also called CEE, for Conjugated Equine Estrogen). Unlike the first arm of the study, these women had no increase in breast cancer risk.(18) (see chart below)
WHI_2_CC Left Chart: This chart shows data from the second arm of the WHI in JAMA 2004.(14)

The blue bars represents adverse events in the placebo group. The red bars represents adverse events in women (ages 50-59) on premarin only, with no Provera (progestin). Note that the Red bars are all Lower than the Blue bars. The Red bar (Premarin-only) group shows LESS heart disease, LESS breast cancer and LESS Mortality when compared to placebo (blue bar). Chart Courtesy of Susan Ott MD Bone Physiology.(19)
Premarin causes endometrial cancer, so the mainstream medical system always gives Provera (progestins) to prevent endometrial cancer, unless of course, the uterus is absent from prior hysterectomy.(20)

The WHI Culprit was the Synthetic Progestin (an altered form of Progesterone)

Back to the first arm of the WHI which used Prempro, it is clear from the data that the culprit which caused breast cancer and heart disease was Provera, a synthetic monster hormone. This is nothing new. For years, Provera has been known to cause heart disease and breast cancer.(21)(22)(39)

Provera Proven to Cause Breast Cancer

In fact, medical studies prove that Provera causes breast cancer. In these studies, Primates were treated with either Progesterone or Provera showing that the Provera causes breast cancer, while the Progesterone provides protection from breast cancer.(22)

Frankenstein_3Monster Hormones are Chemically Altered

Chemically altered hormones were used in the WHI study, and are routinely handed out by the medical system. These altered hormones are monsters that should never have been approved for marketing to the American people. They should be banned. Image Left: Another Monster: Boris Karloff from Frankenstein 1931.Courtesy of Wikimedia.

The Media Says Hormones Cause Cancer and Heart Disease

If bio-identical hormones are so safe, then why do the newspapers say that women's hormones cause breast cancer and heart disease?(23) The answer is that the media and the medical profession routinely confuse synthetic chemically altered monster hormones with the bio-identical hormones. The drug companies intentionally create this confusion because they want to hide the fact that synthetic hormones are monsters that should be banned. Chemically altered hormones were made because of a quirk in our legal system which grants patent protection for chemically altered versions of a natural substance. The natural hormones were chemically altered so that they could be patented to protect profits from competition. Naturally occurring bio-identical hormones by law cannot be patented. Examples of monster synthetic hormones are provera, all progestins, and birth control pills which are never found in nature. These are the monster hormones.

A Listing of a Few Monster Hormones:

Chemically Altered forms of progesterone: Dienogest, Desogestrel, Drospirenone, Dydrogesterone, Ethisterone, Etonogestrel, Ethynodiol diacetate, Gestodene, Gestonorone, Levonorgestrel, Lynestrenol, Medroxyprogesterone, Megestrol, Norelgestromin, Norethisterone, Norethynodrel, Norgestimate, Norgestrel, Norgestrienone, Tibolone Chemically altered forms of estrogen: Dienestrol, Diethylstilbestrol, Ethinylestradiol, Fosfestrol, Mestranol Chemically alered hormones in BCP's Birth Control Pills: levonorgestrel and ethinyl estradiol [oral contraceptive] (ALESSE 28, AVIANE, NORDETTE, SEASONALE, TRIPHASIL, TRIVORA-28); norethindrone and ethinyl estradiol (COMBI PATCH, LOESTRIN FE 1/20, NEOCON 1/35, ORTHO-NOVUM 7/7/7, OVCON 35); norgestimate and ethinyl estradiol (ORTHO-CYCLEN, ORTHOTRI-CYCLEN, TRINESSA); norgestrel and ethinyl estradiol (LO/OVRAL 28, LOW-OGESTREL), desogestrel and ethinyl estradiol (DESOGEN, MIRCETTE, ORTHO-CEPT), drospirenone and ethinyl estradiol (YASMIN) Chemically altered forms of testosterone: Androstanolone, Fluoxymesterone, Mesterolone, Methyltestosterone



progesterone_biodientical hormone
Take a good look at human bio-identical Progesterone ( upper left image), and the chemically altered version (below left image) Provera also called medroxyprogesterone. The added side-chain is labeled in RED on the right side of the Provera molecule.

How to make a Monster Hormone, Add a Side-Chain (in Red below) Below Images: Courtesy of wikimedia commons.

 Human Progesterone Provera - the Monster Hormone

medroxy_progesterone3aThis side-chain (in red) has been added in order to make a totally new structure that can be patented, and is the only difference with progesterone (upper left). In the process of adding this side-chain, a Monster was created. In the opinion of John R Lee MD, "to prescribe a chemically altered version of progesterone called Provera is medical malpractice", and yet this practice is common in mainstream medicine.

 

An Illustration which Explains the Problem with Synthetic Chemically Altered Drugs

Supposing a biochemist working for a drug company has an idea to alter the chemical structure of vitamin C so a patent can be obtained. The biochemist adds a chlorine molecule to the vitamin C carbon ring, and gives is a new name "super-Vitamin C", which is really a chlorinated version of vitamin C. Next they do a one year medical study with 5,000 people taking the chlorinated vitamin C tablet every day, and another 5000 people taking a placebo. After the year is up, they count a .5 per cent incidence of heart disease events in the Super Vitamin C group and a 1.0 percent in the placebo group. FDA approval is easily obtained based on reduction in heart disease events by 50 per cent (.5 per cent is 50% of 1.0 %). The drug company is at liberty to spend million dollars on television advertising designed to rake in millions more for the new heart prevention miracle drug. This absurd scenario is now the norm for our medical system. Why would anyone want to spend money for a monster version of vitamin C when the real thing is available for pennies? Why use a monster hormone when human hormones are available? Compared to their monster counterparts, Bio-Identical Hormones are more effective, have fewer adverse side effects, and are less costly.

High Hormone Levels of Early Pregnancy Confer Protection from Breast Cancer.

Pregnancy_36_weeks

During the 16th century in Italy, breast cancer was quite rare. An Italian doctor, Bernardino Ramazzini, noted in 1713 the relatively high incidence of breast cancer in nuns and wondered whether this was related to celibate lifestyle.(24) Recent studies confirm that early pregnancy and multiple pregnancies confer protection from breast cancer, while no pregnancies (as in the nuns) leads to increased risk of breast cancer.(25) This protection is thought to be confered by high levels of progesterone. This was confirmed in a 2007 study by Rajkumar who showed that hormone treatment protected genetically engineered mice from developing breast cancer. (26) Left image Pregnancy, courtesy of wikimedia commons.

Progesterone, the Great Protector

Progesterone is so safe, it is available over the counter without a prescription. In addition, a deficiency of progesterone is associated with an increase in breast cancer risk.(27) Progesterone is known to be protective and prevents breast cancer.(28)

Why Don't Birth Control Pills use Natural Progesterone?

Birth Control Pills, BCP's, are very effective at preventing pregnancy by suppressing ovulation. However, BCP's contain synthetic hormones which have adverse side effects.(29)(30)(31) To avoid these monster hormones, the non-hormonal Copper T- IUD (intra-uterine device) is available.  See my article on this topic HERE..

More on Breast Cancer and Hormone Levels

If high estrogen levels were the primary cause of breast cancer, we would expect to find more breast cancer mortality in women with higher hormone levels at age 30, and less breast cancer in women with low hormone levels at age 60 (post-menopausal). However, what we find is the exact opposite. According to the CDC, mortality from breast cancer is 7 times higher in the older women aged 60 (0.7 per cent), compared to younger women aged 30 (0.1 per cent). Mortality from breast cancer is 700 % higher in post-menopausal women with low hormone levels.(link) Conclusion In conclusion, bio-identical hormones used at appropriate dosages are safe, effective, and beneficial for health. On the other hand, any chemical alteration of a human hormone creates a monster hormone, which is not bioidentical. These monster hormones should never have been approved for marketing and sale to the American people. These monster hormones are unsafe, causing cancer and heart disease, and should be banned immediately.

Articles With Related Interest

The Safety of Bio-Identical Hormones
The Importance of BioIdentical Hormones
Bioidentical Hormones Prevent Arthritis
Bioidentical Hormone Estrogen Prevents Heart Disease
Morning Rounds With Steven Economou MD
Don’t Monkey With My Hormones
Waking Up from the Synthetic Hormone Nightmare
HRT Does Not Cause Breast Cancer

Resources for the Safety of BioIdentical Hormones

(1) The Case for Bioidentical Hormones Steven F Hotze MD. 2008.(33)
(2) The Safety of Bioidentical Hormones — the Data vs. the Hype by Jacob Teitelbaum, MD From the Townsend Letter June 2007.(34)
3) The Truth About Hormone Therapy Wall Street Journal  By ERIKA SCHWARTZ , KENT HOLTORF , and DAVID BROWNSTEIN March 16, 2009
4) The_Bioidentical_Hormone_Debate_Ken_Holtorf_MD-3
5) Hormones__in_wellness_and_disease_prevention_common_practices_current_state_evidence_Erika_Schwartz_Kent_Holtorf
6) Hermite_Could_Transdermal_estradiol_Progesterone_be_Safer_HRT
Recommended Books by John R Lee MD (35)
What Your Doctor May Not Tell You About Menopause (TM): The Breakthrough Book on Natural Hormone Balance WHAT YOUR DOCTOR MAY NOT TELL YOU ABOUT MENOPAUSE: The Breakthrough Book on Natural Progesterone (Warner Books, 1996)(35)
WHAT YOUR DOCTOR MAY NOT TELL YOU ABOUT PREMENOPAUSE: Balance Your Hormones and Your Life from Thirty to Fifty (Warner Books, 1999)(35)
WHAT YOUR DOCTOR MAY NOT TELL YOU ABOUT BREAST CANCER: How Hormone Balance Can Help Save Your Life, by John Lee, David Zava and Virginia Hopkins (Warner Books, 2005)(35)
References
(1) http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1770067 Fatal water intoxication. D J Farrell1 and L Bower. J Clin Pathol. 2003 October; 56(10): 803–804.
(2) http://en.wikipedia.org/wiki/Charles_Darwin Charles Darwin, theory of natural selection.
(3) http://www.johnleemd.com/store/premenstrual_syndrome.html Excerpted From: WHAT YOUR DOCTOR MAY NOT TELL YOU ABOUT BREAST CANCER: Balance Your Hormones and Your Life from Thirty to Fifty. PHYSIOLOGICAL EFFECTS OF ESTROGEN AND PROGESTERONE. How Hormone Balance Can Help Save Your Life. by John R. Lee, M.D., David Zava, Ph.D. and Virginia Hopkins. Warner Books 2002
(4) http://www.uzzireissmd.com/book_naturalhormone.html Natural Hormone Balance for Women: Look Younger, Feel Stronger, and Live Life with Exuberance. by Uzzi Reiss MD
(5) http://www.drtheo.com/news/NSAIDs.pdf Medical Progress. p 1888. June 17, 1999 The New England Journal of Medicine GASTROINTESTINAL TOXICITY OF NONSTEROIDAL ANTIINFLAMMATORY DRUGS M. MICHAEL WOLFE , M.D., DAVID R. LICHTENSTEIN, M.D.,AND GURKIRPAL SINGH, M.D.
(6) FDA Press COnference on Bioidentical Hormones Jan 2008 Transcript of FDA Press Conference on FDA Actions on Bio-Identical Hormones FTS HHS FDA Susan Cruzan January 9, 2008
(7) http://www.womentowomen.com/breasthealth/estrogenbreastcancer.aspx Causes of Brea6t Cancer- the Estrogen Controversy, Dixie Mills MD
(8) http://www.ncbi.nlm.nih.gov/pubmed/12626212 Climacteric. 2002 Dec;5(4):332-40. Combined hormone replacement therapy and risk of breast cancer in a French cohort study of 3175 women.de Lignières B et al. French Cohort Study.
(9) http://www.johnleemd.com/store/cancer_progest.html Breast Cancer Book Intro. WHAT YOUR DOCTOR MAY NOT TELL YOU ABOUT BREAST CANCER. How Hormone Balance Can Help Save Your Life By John R. Lee, M.D., David Zava Ph.D., and Virginia Hopkins INTRODUCTION
(10) http://jeffreydach.com/2007/05/05/jeffreydachdrdachiodine.aspx Breast Cancer Prevention and Iodine Supplementation by Jeffrey Dach MD
(11) http://content.nejm.org/cgi/content/short/356/25/2591 Estrogen Therapy and Coronary-Artery Calcification. NEJM Volume 356:2591-2602 June 21, 2007 Number 25. JoAnn E. Manson, M.D., et al.
(12) http://www.ncbi.nlm.nih.gov/pubmed/15989413 J Womens Health (Larchmt). 2005 Jun;14(5):410-7. Effects of hormone replacement on progression of coronary calcium as measured by electron beam tomography.Budoff MJ, et al.
(13) http://jama.ama-assn.org/cgi/content/abstract/288/3/321 Risks and Benefits of Estrogen Plus Progestin in Healthy Postmenopausal Women Principal Results From the Women's Health Initiative Randomized Controlled Trial Writing Group for the Women's Health Initiative Investigators JAMA. 2002;288:321-333. First Arm.
(14) http://jama.ama-assn.org/cgi/content/full/291/14/1701 Effects of Conjugated Equine Estrogen in Postmenopausal Women With Hysterectomy The Women's Health Initiative Randomized Controlled Trial. JAMA. 2004;291:1701-1712. Second Arm. This is the Second Arm of the Study. Premarin Only.
(15) http://en.wikipedia.org/wiki/Premarin Premarin From Wikipedia, the free encyclopedia (16) http://en.wikipedia.org/wiki/Medroxyprogesterone Provera, Medroxyprogesterone, From Wikipedia, the free encyclopedia
(17) http://homecoalition.org/TakeAction Take Action. Write a letter to your elected officials using our online advocacy tool. Act now to defend your right to bio-identical hormones! Please contact your congressional representative, senators, and the White House immediately. HOMECoalition.org.
(18) http://jama.ama-assn.org/cgi/content/full/295/14/1647 Effects of Conjugated Equine Estrogens on Breast Cancer and Mammography Screening in Postmenopausal Women With Hysterectomy. Marcia L. Stefanick, PhD et al. for the WHI Investigators. JAMA. 2006;295:1647-1657. Conclusions Treatment with CEE alone for 7.1 years does not increase breast cancer incidence in postmenopausal women with prior hysterectomy. (19)
http://courses.washington.edu/bonephys/opestrogen.html#WHI Osteoporosis and Bone Physiology, Susan Ott, MD, Associate Professor, Department of Medicine, University of Washington. A Review of the results from the Women's Health Initiative.
(20) http://www.ncbi.nlm.nih.gov/pubmed/3358913 The dose-effect relationship between 'unopposed' oestrogens and endometrial mitotic rate: its central role in explaining and predicting endometrial cancer risk.Key TJ, Pike MC. Br J Cancer. 1988 Feb;57(2):205-12.
(21) http://atvb.ahajournals.org/cgi/content/full/24/7/1171 Should Progestins Be Blamed for the Failure of Hormone Replacement Therapy to Reduce Cardiovascular Events in Randomized Controlled Trials? Kwang Kon Koh; Ichiro Sakuma. Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:1171.
(22) http://www.ncbi.nlm.nih.gov/pubmed/16841178 Effects of estradiol with micronized progesterone or medroxyprogesterone acetate on risk markers for breast cancer in postmenopausal monkeys.Wood CE et al. Breast Cancer Res Treat. 2007 Jan;101(2):125-34.
(23) http://www.time.com/time/magazine/article/0,9171,1002897,00.html The Truth About Hormones Monday, Jul. 22, 2002 Time Magazine. By CHRISTINE GORMAN AND ALICE PARK
(24) http://www.ama-assn.org/amednews/2006/04/17/hlsa0417.htm AMA Medical NEws. Collecting clues: Cancer registries might have an answer. By Kathleen Phalen Tomaselli, AMNews correspondent. April 17, 2006.
(25) http://breast-cancer-research.com/content/7/3/131 The protective role of pregnancy in breast cancer. Jose Russo et al.Breast Cancer Research 2005, 7:131-142doi:10.1186/bcr1029
(26) http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=17257424 Hormone-induced protection of mammary tumorigenesis in genetically engineered mouse models Lakshmanaswamy Rajkumar et al.Breast Cancer Res. 2007; 9(1): R12.
(27) http://aje.oxfordjournals.org/cgi/content/abstract/114/2/209 BREAST CANCER INCIDENCE IN WOMEN WITH A HISTORY OF PROGESTERONE DEFICIENCY LINDA D. COWAN et al. American Journal of Epidemiology Vol. 114, No. 2: 209-217
(28) http://www.annclinlabsci.org/cgi/content/abstract/28/6/360 Progesterone inhibits growth and induces apoptosis in breast cancer cells: inverse effects on Bcl-2 and p53. B Formby and TS Wiley. Annals of Clinical and Laboratory Science, Vol 28, Issue 6, 360-369
(29) http://en.wikipedia.org/wiki/Birth_control_pill Combined oral contraceptive pill. From Wikipedia, the free encyclopedia. (Redirected from Birth control pill)
(30) http://www.worstpills.org/results.cfm?disease_id=26 Oral Contraceptives on Worst Pills.org. The pill can cause many adverse effects. Some of them are merely a nuisance, while others can be life-threatening. The pill can cause headaches, bloating, nausea, irregular bleeding and spotting, breast tenderness, weight gain, or vision changes. Other more serious adverse effects that can occur from a few months to a few years after starting oral contraceptives include high blood pressure, gallbladder disease, liver tumors, depression, and metabolic disorders, such as diabetes. Temporary infertility has been associated with the period of time right after pill use is stopped. But the two most dangerous risks associated with taking birth control pills are blood clots and cancer.
(31) http://www.jeffreywarber.com/hc%20pages/pillsideeffects.html Birth COntrol Pill Adverse Side Effects by Jeffrey Warber MD
(32) http://www.quickoverview.com/reproductive/birth-control-pill.html History and Development of an effective combined oral contraceptive. People Involved.
(33) http://www.jpands.org/vol13no2/hotze.pdf Point/Counterpoint: The Case for Bioidentical Hormones Steven F. Hotze, M.D.Donald P. Ellsworth, M.D.Journal of American Physicians and Surgeons Volume 13 Number 2 Summer 2008
(34) http://www.townsendletter.com/June2007/painfree0607.htm The Safety of Bioidentical Hormones — the Data vs. the Hype by Jacob Teitelbaum, MD
(35) http://www.johnleemd.com/store/main_books.html Books by John R Lee MD Wyeth and the FDA (36) http//:naturalnews.com/022595.html FDA's Assault of Bioidentical Hormones Demonstrates Pro-Pharma Loyalties, Disregard for Consumer Choice Tuesday, February 05, 2008 by: Mike Adams
(37) February 16, 2008. Women, Doctors Wage Crucial Battle With FDA To Save Bioidentical Hormones From Wyeth's Wrath. A major coalition of informed women and their doctors have launched an all out war on the Federal Drug Administration's (FDA) cynical and corrupt decision to ban compounded hormones containing Estriol.
(38) FDA Declares War on BioIdentical Hormones by Jeffrey Dach MD Provera and Heart Disease
(39) http://atvb.ahajournals.org/cgi/content/full/17/1/217 Medroxyprogesterone Acetate Antagonizes Inhibitory Effects of Conjugated Equine Estrogens on Coronary Artery Atherosclerosis. Michael R. Adams; Thomas C. Register; Deborah L. Golden; Janice D. Wagner; J. Koudy Williams .Arteriosclerosis, Thrombosis, and Vascular Biology. 1997;17:217-221. Bio-Identical Hormone Inititiative
(40)  Bioidentical vs. Synthetic HRT, A review of the literature
(41) Bio-Identical Hormone Inititiative, Erika Schwartz MD, David Brownstein MD, Kent Holtorf MD Additional References
http://www.endfatigue.com/health_articles_f-n/Menapause-safety_effectiveness_bioidentical_hormones.html
The Safety and Effectiveness of Bio-Identical Hormones: Natural (Bio-Identical) vs. Synthetic HRT Kent Holtorf, M.D. Dr. Holtorf is the Medical Director of the Holtorf Medical Group, Inc, Center for Hormone Imbalance and Fatiguing Conditions in Los Angeles, specializing in CFS, FM, hypothyroidism, chronic illness and the treatment of complex endocrine dysfunction. He is board certified and is a Board Examiner for the American Academy of Anti-Aging Medicine. He is also chief of the Medical Advisory Board for the Fibromyalgia and Fatigue Centers, Inc.
http://www.thorne.com/media/hormones11-3.pdf
A Comprehensive Review of the Safety and Efficacy of Bioidentical Hormones for the Management of Menopause and Related Health Risks Deborah Moskowitz, ND. Altern Med Rev 2006;11(3):208-223)
http://www.drcranton.com/hrt/hrt_references.htm
Hormone Replacement References. Most references below are linked to the National Library of Medicine (MEDLINE)
http://www.medscape.com/viewarticle/408096_print
Special Article: Addressing Postmenopausal Estrogen Deficiency: A Position Paper of the American Council on Science and Health January 26, 2001 Sander Shapiro, MD Medscape General Medicine 3(1), 2001.

http://www.womeninbalance.org/research/ research available women in balance. Fatal Water Intoxication http://www.msnbc.msn.com/id/16614865/ Woman dies after water-drinking contest Natural and Synthetic Substances in Medicine
http://www.fimdefelice.org/archives/arc.promise.htmlThe Promise and Problems of Natural Substances in Medicine Stephen L. DeFelice, M.D.
http://www.iupac.org/publications/pac/2002/pdf/7410x1957.pdf Natural and synthetic substances related to human health. The dubious honor of being the most powerful toxic substance goes to a protein produced by the bacterium, Clostridium botulinum. This protein is responsible for fatal food poisoning—botulism—being produced when the bacterium grows in the absence of oxygen in canned or preserved food. 2002 IUPAC, Pure and Applied Chemistry 74, 1957–1985 Synthetic Hormones and Breast Cancer
http://www.nwhn.org/healthinfo/detail.cfm?info_id=9&topic=Fact%20Sheets Menopause Hormone Therapy and Breast Cancer. National Women's Health Network
http://www.bmj.com/cgi/content/full/310/6979/598/b BMJ 1995;310:598 (4 March) Letters Risk factors for breast cancer Hormone Levels, Age and Breast Cancer
http://www.cdc.gov/cancer/breast/statistics/age.htm Risk of Breast Cancer by Age, CDC .Percent of U.S. Women Who Die from Breast Cancer Over 10-, 20-, and 30-Year Intervals. According to Their Current Age, 2002–2004. Age 30 is 0.1% age 60 is 0.7% .
Jeffrey Dach MD 7450 Griffin Road Davie, Fl 33314 954-983-1443
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Testosterone for Dry Eye Syndrome JEffrey Dach MDTestosterone for  Dry Eye Syndrome

by Jeffrey Dach MD

Mrs. B was 58 years old with typical menopausal symptoms of night sweats and hot flashes, and came to see me because of dry itchy, red eyes.  The lids sometimes swell because of the irritation.  Over the years, Mrs B had been to numerous eye doctors who gave her various drops to lubricate the eye, antibiotic drops and steroid drops.  She has been given instructions for cleaning and irrigating the eyes.  The eye drops seem to help somewhat but the irritation always returns whenever she stops them.  Lately, the condition is getting worse and nothing seems to help.

Above left image: courtesy of wikimedia commons, red arrow points to meibomian glands in edge of eye lid which secrete oil which lubricates the eye.

Low Testosterone Level

A routine hormone panel showed that Mrs B had low hormone levels, and her testosterone level was especially low. I explained to Mrs B that her dry eye syndrome was caused by low testosterone levels, and testosterone would help.

Cured With Testosterone, Surely You Must Be Joking, Doctor

Six week later, after starting her testosterone as sublingual drops, Mrs B reported her eyes were much better.  She also started a complete bioidentical hormone program. Mrs B's ophthalmologist, Dr H, was an old friend of mine and we would occasionally attend the same social functions.   At one of these social functions, Dr H approached to say that a patient (no name) reported that I had cured her dry eyes with testosterone, and surely you must be joking, Doctor.  His gesture and facial expression with his eyes rolling back were quite distinctive.


Testosterone for Dry Eyes in the Opthalmology Medical Literature

Apparently, Dr H is unaware of the supportive evidence in his own specialty medical journals.  We will look at a few of these supportive articles that recommend testosterone for evaporative dry eye syndrome.  About 5 million Americans have Dry Eye Syndrome caused by dysfunction of the lubricating glands, which are called the lacrimal and meibomian glands.  The small glands at the upper outer eye are the lacrimal glands, and the meibomian glands are located in the eye lid at the upper and lower edges (see diagram below).

Tears in the Lacrinmal System Testosterone Dry EyesLeft Image :Tear system: a. tear gland / lacrimal gland, b. superior lacrimal punctum, c. superior lacrimal canal, d. tear sac / lacrimal sac, e. inferior lacrimal punctum, f. inferior lacrimal canal,  g. nasolacrimal canal.

Dr David A Sullivan and Dry Eye Research

Much of the research on testosterone and dry eyes has been done by David A Sullivan at Schepens Eye Research Institute at Harvard Medical School.(4)

Dr Sullivan Research in Mouse Model Of Sjogren's

Dr. Sullivan's early work in the 1990's involved Sjogrens syndrome, and the discovery that women with Sjögren'ssyndrome are androgen-deficient causing meibomian gland dysfunction, tear film instability, and the evaporative dry eye characteristic Sjogren's, which is an autoimmune disorder. (1)  Sullivan published a study in 1991 which showed that testosterone inhibited the progression of autoimmune disease in the lacrimal glands mice with Sjogren's. His mouse model of Sjogren's showed that the testosterone suppressed the magnitude of lymphocyte infiltration in the lacrimal gland 22- to 46-fold.(6)

Lacrimal and Meibomian Glands Regulated by Testosterone

In a 1999 report, Sullivan suggested that androgens (testosterone) regulate both lacrimal and meibomian gland function, and suggest that eye drops containing testosterone may be safe and effective treatment for dry eyes in Sjögren's syndrome.(1)

Chalazion of the Meibomian Gland, Testosterone for Dry EyesLeft Image: Chalazion, obstructed, infected meibomian gland upper eye lid.  This image is useful to give you an idea of where the glands are locared in the lid.  There are 20 - 30 small Meibomian glands located along the edge of the upper and lower lid that secrete oil which lubricates the surface of the eye.  When one becomes obstructed, it swells up and is called a Chalazion. Treatment is to relieve the obstruction and allow drainage. Courtesy of wikimedia commons. 

Men on Testosterone Blockers Get Dry Eyes

In 2000,  Dr Sullivan reported that men taking testosterone blockers have dry eye syndrome.  Men on testosterone blocker drug treatment for prostate cancer were found to had poor quality of tear fluid.  This was demonstrated by analyzing the meibomian gland secretions.  Their dry eye symptoms included light sensitivity, painful and blurry eyes.  Sullivan said,"the use of anti-androgen pharmaceuticals was associated with significant changes in the relative amounts of lipids in meibomian gland secretions. Our findings indicate that chronic androgen deficiency is associated with meibomian gland dysfunction and dry eye." (2)

In 2001, Drs Worda and Nepp from Vienna Austria reported that topically administered androgen can restore the lipid phase of the tear film, and was useful in treatment of keratoconjunctivitis sicca, medical terms for Dry Eyes. (3)

Complete Insensitivity to Androgen and Dry Eyes

Next, Dr Sullivan turned his attention to a genetic disorder called Complete Insensitivity to Androgen (CIAS).  In this genetic disorder, the androgen receptor is nonfunctional, and subsequently, there is insensitivity to testosterone.  Without a functioning receptor, the normal activity of testosterone is completely blocked.

Dr Sullivan examined the tears (ie. Meibomian gland secretions), in women with CIAS and compared them to normal controls.  The patients with CIAS had alteration in the lipid fractions of tear fluid, ( ie meibomian gland secretions). This study was published in a 2002 report in Arch Ophthalmology (5).

Trans-Dermal Testostorone For Dry Eye Syndrome

In 2003, Dr Connor reported transdermal testosterone is safe and effective treatment for dry eye, with the post-menopausal females having the greatest relief of symptoms. (10)

Molecular Biology Mouse Studies of Gene Expression

In 2005, Dr Schirra et al studied the molecular biology of testosterone, and gene expression in the meibomian gland of mice. Dr Schirra reported that testosterone regulates the expression of more than 1500 genes in the mouse meibomian gland which serves to stimulate lipid and fatty acid metabolism in the lubricating eye fluid.(11)

The Evidence is Overwhelming
The sum total of the above evidence is overwhelming that testosterone plays a key role in production of oil, the lipid component for lubricating the eyes, and that testosterone deficiency is a treatable cause of dry eye syndrome.  The treatment is testosterone, a bioidentical hormone.

Omega 3 Fish Oil for Dry Eye Syndrome

Since the lubrication of the eye is an oily film, one might think that nutritional oil consumption to be of benefit in the disorder.  That is what Dr Rahul Bhargava found in a 2013 study in the Journal of Opthalmology.  Be careful to avoid the ethyl ester form of fish oil
An opthalmologist colleague reports good results with the following Omega 3 Fish Oil from PRNOmegaHealth

We also use the CO2 Super Critical Extract Omega Oil directly from Purecaps factory.
Medline List of studies showing use of Omega 3 Fish Oil Benefits Dry Eye Syndrome.
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Jeffrey Dach MD
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Davie, FL 33314
Phone: 954-792-4663
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Links and References

(1) http://www.ncbi.nlm.nih.gov/pubmed/10415627
Androgens and dry eye in Sjögren's syndrome.
Ann N Y Acad Sci. 1999 Jun 22;876:312-24. Sullivan DA et al.
Our results demonstrate that androgens regulate both lacrimal and meibomian gland function, and suggest that topical androgen administration may serve as a safe and effective therapy for the treatment of dry eye in Sjögren's syndrome.
(2)http://jcem.endojournals.org/cgi/content/abstract/85/12/4874
The Journal of Clinical Endocrinology & Metabolism Vol. 85, No. 12 4874-4882,2000
Effect of Androgen Deficiency on the Human Meibomian Gland and Ocular Surface.  Kathleen L. Krenzer, M. Reza Dana, M. David Ullman, Jennifer M. Cermak, Dorothy B. Tolls, James E. Evans and David A. Sullivan
Schepens Eye Research Institute (K.L.K., M.R.D., J.M.C., D.A.S.), Brigham and Women’s Hospital (M.R.D., J.M.C.), Department of Ophthalmology, Harvard Medical School
The purpose of this study was to determine whether the chronic use of antiandrogen medications leads to meibomian gland dysfunction, altered lipid profiles in meibomian gland secretions, decreased tear film stability, and evaporative dry eye.
Subjects taking antiandrogen therapy for prostatic indications, as well as age-related controls, were asked to complete a questionnaire that assessed dry eye symptoms and then were given a complete anterior segment examination. Moreover, meibomian gland secretions were obtained from each eye and analyzed by high-performance liquid chromatography/mass spectrometry for the relative content of cholesterol, cholesterol esters, wax esters, diglycerides, triglycerides, and specific molecular species in the diglyceride fraction.
Our results demonstrate that patients taking antiandrogen treatment, compared with age-related controls, had a:
1) significant increase in the frequency of appearance of tear film debris, an abnormal tear film meniscus, irregular posterior lid margins, conjunctival tarsal injection, and orifice metaplasia of the meibomian glands;
2) significant increase in the degree of ocular surface vital dye staining; 3) significant decrease in the tear film breakup time and quality of meibomian gland secretions; and
4) significant increase in the frequency of light sensitivity, painful eyes, and blurred vision.
In addition, the use of antiandrogen pharmaceuticals was associated with significant changes in the relative amounts of lipids in meibomian gland secretions. Our findings indicate that chronic androgen deficiency is associated with meibomian gland dysfunction and dry eye.
(3) http://www.ncbi.nlm.nih.gov/pubmed/11173183
Maturitas. 2001 Jan 31;37(3):209-12.
Treatment of keratoconjunctivitis sicca with topical androgen.
by Worda C, Nepp J, Huber JC, Sator MO. Department of Obstetrics and Gynecology, Division of Gynecological Endocrinology and Reproductive Medicine, Vienna University Hospital, Währinger Gürtel 18-20, 1090, Vienna, Austria.
OBJECTIVE: Androgens have been reported to influence lipid production of sebaceous glands and even many ocular tissues. The effect of topical androgen therapy on a 54-year-old patient with keratoconjunctivitis sicca (KCS) and decreased lipid phase of the tear film is reported.
METHODS: For assessment of the lipid phase of the tear film, break up time (BUT) and lipid layer thickness (LLT) were monitored during 6 months before treatment as well as 3 months while using a daily topical androgen therapy.
RESULTS: During the topical androgen therapy the pathological lipid phase of the tear film was completely restored indicated by the normalisation of the values of BUT and LLT.
CONCLUSION: These findings are consistent with animal experiments indicating that topical administered androgen can restore the decreased lipid phase of the tear film. This may open up new therapeutic strategies for KCS.
(4) http://www.schepens.harvard.edu/profiledevid/david-sullivan-phd/profile.html
Sullivan research summary at Schepens Harvard Medical School
we have shown that dry eye syndromes occur predominantly in women and that estrogen replacement therapy increases the prevalence of dry eye signs and symptoms in postmenopausal women. This latter finding is extraordinary, given that many millions of women worldwide are prescribed estrogen to alleviate menopausal symptoms and are therefore at heightened risk of developing dry eye. The precise mechanism(s) underlying the sex-related difference in, and the estrogen effect on, dry eye prevalence is unclear. However, we hypothesize that: [a] androgen deficiency and estrogen use are key factors in the predominance of dry eye syndromes in women; and [b] sex, androgen and estrogen effects are mediated through the regulation of gene expression in the cornea and the lacrimal and meibomian glands.
(5) http://www.aissg.org/PDFs/BD-Sullivan-CAIS-Meibomian-2002.pdf
http://www.ncbi.nlm.nih.gov/pubmed/12470144
Arch Ophthalmol. 2002 Dec;120(12):1689-99.
Complete androgen insensitivity syndrome: effect on human meibomian gland secretions. by Sullivan BD, Evans JE, Cermak JM, Krenzer KL, Dana MR, Sullivan DA. Schepens Eye Research Institute,
OBJECTIVE: To determine whether androgen receptors affect the fatty acid profiles of neutral and polar lipids in human meibomian gland secretions.
METHODS: Meibomian gland secretion samples were obtained from both eyes of
(1) women with complete androgen insensitivity syndrome, a condition characterized by dysfunctional androgen receptors, and (2) age-matched female and male controls.
Samples were processed for high-performance liquid chromatography, mass spectrometry, or both and for analysis of the mass spectra of neutral and polar lipid fatty acid fragment ions by 3 different methods.
RESULTS: Androgen receptor dysfunction is associated with significant alterations in the appearance of numerous molecular species in the neutral and polar lipid fractions of meibomian gland secretions. The ability to detect these differences, and to assess their nature and extent, was facilitated by the use of several analytic approaches. Sex-related differences exist in the expression of a variety of neutral and, especially, polar fatty acid products in meibomian gland secretions.
CONCLUSIONS: Androgens exert a significant effect on neutral and polar lipids in human meibomian gland secretions, and these hormonal effects may be mediated through androgen receptors.
Sjogren's syndrome
(6) http://www.iovs.org/cgi/reprint/32/11/3002.pdf
http://www.iovs.org/cgi/content/abstract/32/11/3002
Investigative Ophthalmology & Visual Science, Vol 32, 3002-3006.1991
Testosterone-induced suppression of autoimmune disease in lacrimal tissue of a mouse model (NZB/NZW F1) of Sjogren's syndrome AC Vendramini, C Soo and DA Sullivan Department of Ophthalmology, Harvard Medical School, Boston, MA 02114.
The current investigation was designed to examine whether androgen administration might suppress autoimmune disease in lacrimal glands of a mouse model (NZB/NZW F1) of Sjogren's syndrome. Autoimmune, female mice were treated with vehicle or varying concentrations of testosterone for 0, 17, 34, or 51 days, and tears, lacrimal glands, as well as submandibular tissue, were collected from killed mice after androgen exposure. Glands were histologically processed and evaluated with a computer-assisted image analysis system.
Results showed that testosterone administration induced a significant, time-dependent decrease in the extent of lymphocytic accumulation in the lacrimal gland. After 34-51 days of androgen therapy, the magnitude of lymphocyte infiltration had been suppressed 22- to 46-fold, compared with that in placebo-treated tissue. This hormone effect was associated with significant reductions in the number of focal infiltrates, the area of individual foci, and the total quantity of lymphocyte infiltration per lacrimal section. Testosterone exposure also stimulated an increase in lacrimal gland weight and a rise in tear volumes, relative to those measured in the same mice before treatment. In addition, androgens significantly diminished the extent of lymphocyte accumulation in submandibular tissue.
In summary, our results demonstrate that androgen administration may inhibit the progression of autoimmune disease in lacrimal and submandibular glands of NZB/NZW F1 mice. 
(7)http://www3.interscience.wiley.com/journal/120778210/abstract
http://www.ncbi.nlm.nih.gov/pubmed/12114274
Sullivan DA et al. Ann N Y Acad Sci. 2002 Jun;966:211-22.
Androgen Deficiency, Meibomian Gland Dysfunction, and Evaporative Dry Eye
Abstract: Objective. We have recently discovered that women with primary and secondary Sjögren's syndrome are androgen-deficient. We hypothesize that this hormone insufficiencycontributes to the meibomian gland dysfunction, tear film instability, and evaporative dry eye that are characteristic of this autoimmune disorder. If our hypothesis is correct, we predict: (1) that androgens regulate meibomian gland function, control the quality and/or quantity of lipids produced by this tissue, and promote the formation of the tear film's lipid layer; and (2) thatandrogen deficiency, due to an attenuation in androgen synthesis (e.g., during Sjögren's syndrome, menopause, aging, complete androgen-insensitivity syndrome [CAIS] and anti-androgen use), will lead to meibomian gland dysfunction andevaporative dry eye.
Methods. Experimental procedures included clinical studies, animal models, and histological, biochemical, molecular biological, and biomedical engineering techniques.
Results. (1) androgens regulate the meibomian gland. This tissue contains androgen receptor mRNA, androgen receptor protein within acinar epithelial cell nuclei, and Types 1 and 2 5a-reductase mRNAs. Moreover, androgens appear to modulate lipid production and gene expression in mouse and/or rabbit meibomian glands; and
(2) androgen deficiency may lead to meibomian gland dysfunction, altered lipid profiles in meibomian gland secretions, tear film instability, and evaporative dry eye. Thus, we have found that anti-androgen therapy in men is associated with meibomian gland disease, a decreased tear film breakup time, and functional dry eye.
Furthermore, we have discovered that androgen receptor dysfunction in women with CAIS is associated with meibomian gland changes and a significant increase in the signs and symptoms of dry eye. Of interest, we have also found that androgen deficiency is associated with significant and striking alterations in the neutral and polar lipid patterns of human meibomian gland secretions.
Conclusions. Our findings show that the meibomian gland is an androgen target organ and that androgen deficiency may promote meibomian gland dysfunction and evaporative dry eye. Overall, these results support our hypothesis that androgen deficiency may be an important etiologic factor in the pathogenesis of evaporative dry eye in women with Sjögren's syndrome.
(8) http://www.aissg.org/INDEX.HTM
Androgen Insensitivity Syndrome or AIS
(old name Testicular Feminization Syndrome or Testicular Feminisation Syndrome).
(9)http://en.wikipedia.org/wiki/Androgen_insensitivity_syndrome
The incidence of complete AIS is about in 1 in 20,000.   Androgen Insensitivity Syndrome is a phenotypic female with a chromosomal genotype of 46,XY.The Androgen Insensitivity Syndrome has been linked to mutations in AR, the gene for the human Androgen Receptor, located at Xq11-12 (i.e. on the X chromosome).
The principal androgens are testosterone and dihydrotestosterone (DHT).The androgen receptor (AR) is a large protein of at least 910 amino acids. Each molecule consists of a portion which binds the androgen, a zinc finger portion that binds to DNA in steroid sensitive areas of nuclear chromatin, and an area that controls transcription.
(10) http://abstracts.iovs.org/cgi/content/abstract/44/5/2450
Invest Ophthalmol Vis Sci 2003;44: E-Abstract 2450.
Treatment of Dry Eye with a Transdermal 3% Testosterone Cream
by C.G. Connor Optometry, Southern College of Optometry, Memphis, TN, United States
Sullivan and colleagues have shown androgens play a key role in regulating the function of both the lacrimal and meibomian glands. Previous work from our laboratory has shown that androgenic supplemented artificial tears were effective in relieving the symptoms of dry eye. The poor solubility of androgens resulted in considerable irritation and poor patient compliance. The present study employs transdermal delivery of testosterone to treat dry eye.
Methods:Twenty eight subjects 3 males and 25 females with a mean age of 52.5 yrs that ranged from 25 to 76 yrs. with a subjective complaint of dry eye were enrolled in the study. The subjects were divided into two groups.
One group received the transdermal cream alone, while the second group used the transdermal cream supplemented with 3% testosterone. The subjects applied the cream 2 times daily for two weeks. The groups were reversed after two weeks of cream use. Baseline TBUT(tear breakup time) and Schirmer test were done prior to the study and after the use of each the two transdermal creams(control and testosterone).
Results:Baseline TBUT was 3.83 +/- 2.07 sec, testosterone was 4.13 +/- 1.83 sec, and cream alone was 4.53 +/- 2.2 sec. Schirmer results are 8.53 mm+/- 5.27 in 5 min baseline , 11.5 mm +/- 5.8 testosterone, and 7.8mm +/- 4.4 cream alone. ANOVA with post hoc student Newman-Keuls reveals that the Schirmer test results with 3% testosterone is different from baseline and cream alone at p=.05 level.
Over half the subjects reported significant improvement in dry eye symptoms with the testosterone cream.
Conclusion:Transdermal delivery of testosterone appears to be a safe and effective treatment for dry eye. The transdermal cream allows use of increased testosterone concentration and dramatically improves patient comfort.  Post-menopausal females perceived the greatest relief of symptoms from the treatment, while males had the least benefit.
(11) http://www.iovs.org/cgi/content/full/46/10/3666
Investigative Ophthalmology and Visual Science. 2005;46:3666-3675.)
Androgen Control of Gene Expression in the Mouse Meibomian Gland by Frank Schirra,1,2 Tomo Suzuki,1,2 Stephen M. Richards,1 Roderick V. Jensen,3 Meng Liu,1,2 Michael J. Lombardi,3 Patricia Rowley,3 Nathaniel S. Treister,1,4 and David A. Sullivan1,2
From the Schepens Eye Research Institute, and the 2Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts
PURPOSE. In prior work, it has been found that the meibomian gland is an androgen target organ, that androgens modulate lipid production within this tissue, and that androgen deficiency is associated with glandular dysfunction and evaporative dry eye. This study’s purpose was to test the hypothesis that the androgen control of the meibomian gland involves the regulation of gene expression.
METHODS. Meibomian glands were obtained from orchiectomized mice that were treated with placebo or testosterone for 14 days. Tissues were processed for the analysis of differentially expressed mRNAs by using gene bioarrays, gene chips, and real-time PCR procedures. Bioarray data were analyzed with GeneSifter software (VizX Labs LLC, Seattle, WA).
RESULTS. The results show that testosterone influenced the expression of more than 1590 genes in the mouse meibomian gland. This hormone action involved a significant upregulation of 1080 genes (e.g., neuromedin , and a significant downregulation of 518 genes (e.g., small proline-rich protein 2A). Some of the most significant androgen effects were directed toward stimulation of genes associated with lipid metabolism, sterol biosynthesis, fatty acid metabolism, protein transport, oxidoreductase activity, and peroxisomes.
CONCLUSIONS. These findings demonstrate that testosterone regulates the expression of numerous genes in the mouse meibomian gland and that many of these genes are involved in lipid metabolic pathways.
http://archopht.ama-assn.org/cgi/content/full/122/2/151
Dry Eye Signs and Symptoms in Women With Premature Ovarian Failure
Janine A. Smith, MD; Susan Vitale, PhD, MHS; George F. Reed, PhD; Shirley A. Grieshaber, RN, CRNO; Linda A. Goodman, COT; Vien H. Vanderhoof, RN, CRNP; Karim A. Calis, PharmD, MPH; Lawrence M. Nelson, MBA, MD Arch Ophthalmol. 2004;122:151-156.
Objective  To examine whether women with premature ovarian failure (POF) have abnormal findings in ocular surface or tear parameters and whether they report symptoms of ocular discomfort compared with age-matched controls.
Methods  Sixty-five patients with POF and 36 age-matched healthy controls were examined for signs and symptoms of dry eye. The Ocular Surface Disease Index questionnaire and the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ 25) were administered to the participants. Assessments of ocular surface damage (Oxford and van Bijsterveld scores of vital dye staining) and tear status (Schirmer tests 1 [without anesthesia] and 2 [with anesthesia] and tear breakup time) were performed.
Results  Women with POF scored significantly worse than controls on all ocular surface damage parameters: Oxford score (3.2 vs 1.7; P = .001), conjunctival lissamine green (2.1 vs 1.3; P = .02), corneal fluorescein staining (1.2 vs 0.4; P = .005), and van Bijsterveld score (2.1 vs 1.3; P = .02). Further, the proportion of patients with POF meeting the dry eye diagnostic criterion of a van Bijsterveld score greater than or equal to 4 was significantly greater among women with POF than among controls (20% vs 3%; P = .02). The POF group also tended to have worse scores than controls on self-reported symptoms, as measured by the overall Ocular Surface Disease Index (12.5 vs 2.1; P<.001) and the overall NEI-VFQ (94 vs 98; P = .001) after adjustment for age and race. Schirmer test scores and tear breakup time did not differ.
Conclusions  Women with POF were more likely to exhibit ocular surface damage and symptoms of dry eye than age-matched controls. They were not, however, more likely to have reduced tear production. To our knowledge, this association between ocular surface disease and POF has not been previously reported. These data provide further evidence of the multifaceted role of sex hormones in the health and disease of the ocular surface.
http://www.tearfilm.org/dewsreport/pdfs/TOS-0502-DEWS-noAds.pdf
Based on data from the largest studies of dry eye to date, the Women’s Health Study (WHS), and the Physicians’ Health Study (PHS), and other studies,3-14 it has been estimated that about 3.23 million women and 1.68 million men, for a total of 4.91 million Americans 50 years and older have dry eye.
http://commons.wikimedia.org/wiki/File:Tear_system.svg
lacrimal gland Tear system:
a. tear gland / lacrimal gland,
b. superior lacrimal punctum,
c. superior lacrimal canal,
d. tear sac / lacrimal sac,
e. inferior lacrimal punctum,
f. inferior lacrimal canal,
g. nasolacrimal canal
http://en.wikipedia.org/wiki/Meibomian_gland
The Meibomian glands are the 25-30 oil-producing glands located in both the upper and lower eyelids that release oil slowly into the tear film.  This oil helps to stop the water in the tears from evaporating, so helping to prevent dry eyes.
Dysfunctional meibomian glands often cause dry eyes, one of the more common eye conditions. They may also cause blepharitis, as the dry eyeball rubs off small pieces of skin from the eyelid, which may get infected. Inflammation of the meibomian glands (also known as meibomitis, meibomian gland dysfunction, or posterior blepharitis [1]) causes the glands to be obstructed by thick secretions, the resulting swelling is termed a chalazion. Besides leading to dry eyes, the obstructions can be degraded by bacterial lipases, resulting in the formation of free fatty acids, which irritate the eyes and sometimes cause punctate keratitis.
Jeffrey Dach MD
7450 Griffin Road Suite 190
Davie, Florida 33314
954-792-4663
http://www.jeffreydachmd.com
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