Chapter 15.

Testosterone for Dry Eye Syndrome

Bernice 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, Bernice 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.  A routine hormone panel showed low hormone levels, and the testosterone level was especially low.  Bernice listened closely as I explained that her dry eye syndrome was caused by low testosterone levels, and testosterone administered to the eyes would help.  Eye drops are available.

Cured With Testosterone, Surely You Must Be Joking, Doctor

A few weeks after starting a bioidentical hormone program including testosterone eye drops, Bernice reported her eyes were much better.   Her ophthalmologist was an old friend of mine, and at a social function he informed me that one of his patients with Dry Eye Syndrome was treated by me 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 Ophthalmology Medical Literature

Apparently, Bernice’s ophthalmologist was unaware of the medical evidence published in the ophthalmology 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, the lacrimal and meibomian glands.  The small glands at the upper outer eye are the lacrimal glands, while the meibomian glands are located in the edges of the upper and lower lids.

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's early work in the 1990's involved Sjogrens syndrome, and the discovery that women with Sjögren's syndrome are androgen-deficient causing meibomian gland dysfunction, tear film instability, and the evaporative dry eye characteristic of Sjögren'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 Sjögren's. His mouse model of Sjögren'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)

Men on Testosterone Blockers Get Dry Eyes

In 2000, Dr. Sullivan reported that men taking testosterone blocking drugs have dry eye syndrome.  Men on testosterone blocking drug treatment for prostate cancer were found to have poor quality tear fluid.  This was demonstrated by analyzing the meibomian gland secretions.  The dry eye symptoms included light sensitivity, painful and blurry eyes.  Dr. 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”, the medical term for Dry Eye Syndrome. (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 fluid in tears from 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. This study was published in a 2002 report in Arch Ophthalmology (5).

Trans-Dermal Testosterone 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 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 Oils Also Useful for Dry Eye

Conclusion: The evidence is overwhelming that testosterone deficiency plays a role in dry eye syndrome, and testosterone supplementation is curative.

For references and links, see my web site: www.bioidenticalhormones101.com

Articles with Related Interest:

References for Chapter 15. Testosterone for Dry Eyes

(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. 

(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

(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.
 
(4) http://www.schepens.harvard.edu/sullivan/research_story.html Sullivan research summary at Schepens Harvard Medical School

(5) http://www.aissg.org/PDFs/BD-Sullivan-CAIS-Meibomian-2002.pdf  also see:
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,

(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

(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

(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). 

(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

(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

(12) 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.

(13) 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.