BRIEF REPORTS
Combined Esterified Estrogen and
Methyltestosterone Treatment for Dry
Eye Syndrome in Postmenopausal
Women
Garrett Scott, MD, Samuel C. Yiu, MD, PhD,
Daniel Wasilewski, MD, Jonathan Song, MD, and
Ronald E. Smith, MD
PURPOSE: To determine whether systemic replacement
with combined esterified estrogen (EE) and methyltestos-
terone (MT) (EE MT) would reduce symptoms and
promote clinical improvement in postmenopausal women
with dry eye syndrome (DES).
DESIGN: Retrospective, noncomparative, interventional
case series.
METHODS: Investigators reviewed the charts of 11 post-
menopausal women treated within the last 3 years with
EE MT.
RESULTS: The mean patient age was 65.2 years (standard
deviation [SD] 11.4, range 48 84 years). The mean
treatment duration was 12.2 months (SD 6.2 months,
range 4 24 months). Ten (91%) of 11 patients reported
improvement in dry eye symptoms while receiving treat-
ment. For these 10, relief occurred after an average of 4.1
months of treatment (SD 3.2, range, 19 months).
CONCLUSIONS: Treatment with EE MT may be effica-
cious for DES of various etiologies. A randomized placebo-
controlled trial is planned to further evaluate these
encouraging findings. (Am J Ophthalmol 2005;139:
1109 1110. 2005 by Elsevier Inc. All rights reserved.)
D RY EYE SYNDROME (DES) IS A WORLDWIDE PROBLEM,
with higher prevalence in women than in men. This
may be attributable to an increased susceptibility to auto-
Accepted for publication Nov 15, 2004.
From the Ocular Surface Center, Doheny Eye Institute, Los Angeles,
California (G.S., S.C.Y., D.W., J.S., R.E.S.); and the Department of
Ophthalmology, Keck School of Medicine of the University of Southern
California, Los Angeles, California (S.C.Y., J.S., R.E.S.).
Presented in part at the American Academy of Ophthalmology
Annual Meeting, Anaheim, California, November, 2003.
Supported by an unrestricted grant from Research to Prevent Blind-
ness, New York, New York, NEI grant EYO3040, and by a Baxter
Foundation Junior Faculty Award to Dr. Yiu.
Inquiries to Samuel C. Yiu, MD, PHD, 1450 San Pablo Street
DEI5704, Los Angeles, CA 90033; fax: (323) 442-6515; e-mail: syiu@
dohenyeyeinstitute.org
0002-9394/05/$30.00 2005 BY ELSEVIER INC. ALL
immune disease, most notably Sjgrens syndrome (SS)
and to hormonal influences in the pathogenesis of DES.
Studies have found that testosterone levels correlate pos-
itively with tear function in postmenopausal women and
negatively in younger patients,1 suggesting that postmeno-
pausal women with DES may benefit from testosterone
replacement. Through a retrospective, noncomparative
chart review of patients seen by the Cornea Service of the
Doheny Eye Institute, 11 postmenopausal patients were
identified who received a combination of esterified estro-
gen (EE) and methyltestosterone (MT) (Estratest, Solvay
Pharmaceuticals, Inc., Baudette, Minnesota, USA) for
treatment of DES (2001 to 2003). Patients were already
receiving hormone replacement therapy as recommended
by their gynecologists. Estratest was recommended as an
alternative medication since some patients found the
testosterone component could also relieve DES; we sug-
gested it as a patient-option only. With a favorable
outcome reported, we initiated a review of individuals who
pursued the option and how many responded. The Insti-
tutional Review Board of the Keck School of Medicine of
the University of Southern California approved the study
protocol. Written informed consent was waived. The mean
age of the postmenopausal women treated was 65.2 years
(SD 11.4, range 48 84 years). Average duration of EE
MT treatment was 12.2 months (SD 6.2, range 4 24
months). Ten (91%) of 11 patients noticed a decrease in
their dry eye symptoms, either a significant or a mild/
moderate change (Table). Alleviation of symptoms oc-
curred after an average of 4.1 months of therapy (SD
3.2, range 19 months). Additionally, patients showed
improvement in ophthalmologic examination and
Schirmer test (Table).
In the future, DES therapy should be aimed at the
underlying cause of disease, that is, impaired secretion
and inflammation of the ocular surface. Investigators
have proposed that topical or systemically administered
testosterone may be efficacious for the treatment of SS
and primary lacrimal deficiency, because of its anti-
inflammatory properties.2 Our results are consistent with
a case study in the literature of a DES patient who
responded to topical androgen, reporting subjective
improvement in dryness, itching, and foreign body
sensation.3 There are no reports of using systemic
testosterone replacement specifically for DES, but one
study reported three patients with SS associated with
RIGHTS RESERVED. 1109
 TABLE. Dry Eye Syndrome Sign and Symptom Change With Combined Esterified Estrogen and Methyltestosterone Treatment

Treatment VA (Change in No Clinical

Pt No. Age Duration Subjective Improvement Schirmer Test Snellen Lines) Exam

1 60 9 months slight improvement Not documented OD 2 1 OS

symptom free
2 48 21 months eyes improved OD 813 mm OS 714 mm OU
3 55 9 months doing better feeling better OD 03 mm OS 05 mm OU
4 51 24 months no improvement Not documented OU1 1
5 69 12 months symptoms better No change OU
6 63 16 months improved Not documented OU 1 1
7 80 15 months doing better OD 25 mm OS 31 mm OD OS 2
3
8 74 8 months doing better Not documented OU 1 4 0
9 66 8 months doing much better OD 410 mm OS 38 mm OU 0
10 67 4 month doing better Not documented OD 1 6 OS

11 84 8 month slight improvement Not documented OD OS 2
1

VA: 1 Snellen lines gain; 2 Snellen lines loss; no change in VA clinical exam; improvement (resolution or significantly
decreased severity of clinical signs indicative of dry eye disease, such as superficial punctuate keratopathy, punctuate epithelial erosions, and
tear breakup time, was regarded as ocular exam improvements; 0 no change.

Klinefelters syndrome whose SS resolved after oral
testosterone replacement.4
Although there is a scarcity of clinical investigation study-
ing testosterone treatment for DES, laboratory studies support
the plausibility of this therapy. Multiple mechanisms maybe
responsible for the amelioration of DES symptoms in those
treated with combined EE MT. Likely mechanisms include
(1) anti-inflammatory action within the lacrimal gland; (2)
ocular surface protection by increased IgA levels; and (3)
stimulation of meibomian gland secretions, affecting both the
quality and quantity of the lipid phase.5 Through one or a
combination of these three mechanisms, androgens could
improve the quality and quantity of the tear film. Prospective
controlled trials are necessary to determine the value of EE
MT therapy for DES.
REFERENCES
1. Mathers WD, Stovall D, Lane JA, Zimmerman MB, Johnson
S. Menopause and tear function: the influence of prolactin
and sex hormones on human tear production. Cornea 1998;
17:353358.
2. Mircheff AK, Warren DW, Wood RL. Hormonal support of
lacrimal function, primary lacrimal deficiency, autoimmunity,
and peripheral tolerance in the lacrimal gland. Ocul Immunol
Inflamm 1996;4:145172.
3. Worda C, Nepp J, Huber JC, Sator MO. Treatment of
keratoconjunctivitis sicca with topical androgen. Maturitas
2001;37:209 212.
4. Bizzarro A, Valentini G, Di Martino G, DaPonte A, De Bellis A,
Iacono G. Influence of testosterone therapy on clinical and immu-
nological features of autoimmune diseases associated with
Klinefelters syndrome. J Clin Endocrinol Metab 1987;64:3236.
5. Sullivan DA, Wickham LA, Rocha EM, Kelleher RS, da
Silveira LA, Toda I. Influence of gender, sex steroid hor-
mones, and the hypothalamic-pituitary axis on the structure
and function of the lacrimal gland. Adv Exp Med Biol
1998;438:11 42.
Selective Laser Trabeculoplasty (SLT)
Complicated by Intraocular Pressure
Elevation in Eyes With Heavily
Pigmented Trabecular Meshworks
Paul J. Harasymowycz, MD,
Demosthenes G. Papamatheakis, MD,
Mark Latina, MD, Mark De Leon, MD,
Mark R. Lesk, MD, MSc, and
Karim F. Damji, MD
PURPOSE: To report and assess the complication of in-
traocular pressure (IOP) elevations after selective laser
Accepted for publication Nov 16, 2004.
From the Ophthalmology Department, University of Montreal,
Montreal, Canada (P.J.H., D.G.P., M.R.L.); Department of Ophthalmol-
ogy, Tufts University, Medford, Massachusetts (M.L.); Massachusetts Eye
and Ear Infirmary, Boston, Massachusetts (M.d.L.); and University of
Ottawa Eye Institute, Ottawa, Canada (K.F.D.).
Dr. Latina is a patent holder of SLT and has a financial interest with
Lumenis.
Inquiries to Paul Harasymowycz, MD, Department of Ophthalmology,
Maisonneuve-Rosemont Hospital, 5689 Boulevard Rosemont, Montreal,
Quebec, Canada, H1T 2H1; fax: (514) 252-3905; e-mail: pavloh@
hotmail.com

1110 AMERICAN JOURNAL OF OPHTHALMOLOGY JUNE 2005