New Dry Eye Treatment Options: Testosterone Cream and Testosterone Drops

New Dry Eye Treatment Options: 3% Testosterone Cream and Testosterone Drops 0.03% (currently available at Leiter’s pharmacy)

We know hormonal changes affect dry eye symptoms. While there are no randomized, double blinded controlled studies proving testosterone creams or drops helps, there are many observational studies noting a significant relief in dry eye symptoms in patients who use Testosterone cream or drops.

Below are all the studies to date on “testosterone” and “dry eye”.

The reason why testosterone would work in dry eye patients is related to a relative decrease in testosterone experienced as we get older, especially in women. This is especially true in patients with autoimmune diseases. A couple of summaries below shed more light on the complex pathway that can contribute to dry eyes. The most compelling report is a letter describing a series of patients who improved after the use of a Testosterone (=Androgen) patch. It was published in a reputible journal but was not a randomized, double blinded study.

Sandra Lora Cremers

Results: 51

1.
Ebeigbe JA, Ebeigbe PN.
Afr J Med Med Sci. 2014 Sep;43(3):205-11.
PMID:

 

26223137
2.
Gokce G, Hurmeric V, Mumcuoglu T, Ozge G, Basaran Y, Unal HU, Bolu E, Mutlu FM.
Postgrad Med. 2015 May;127(4):376-80. doi: 10.1080/00325481.2015.1033376. Epub 2015 Mar 27.
PMID:

 

25812631
3.
Konttinen YT, Stegajev V, Al-Samadi A, Porola P, Hietanen J, Ainola M.
J Steroid Biochem Mol Biol. 2015 Jan;145:237-44. doi: 10.1016/j.jsbmb.2014.08.014. Epub 2014 Aug 23. Review.
PMID:

 

25158020

Conclusion

Sjögren’s syndrome is an autoimmune disease primarily targeting exocrine glands. It is suggested that low systemic estrogen levels together with failure to maintain high enough local protective androgen levels in the exocrine glands lead to abnormal acinar cell changes and death. Indeed, in postmenopausal women, the mean ± SD S-DHEA is 2.03 ± 1.33 ng/ml, but the range, the 5th and 95th centiles, is very wide, being 0.55 ng/ml and 4.35 ng/ml, which makes a 7.9-fold difference. This predisposes some women to DHEA deficiency with its potential and not yet completely known symptoms and signs[31]. The local intracrine failure in SS seems to have a 2-fold basis: diminished endocrine production of DHEA and A by the reticular zone of the adrenal gland, combined with a peripheral failure of the local intracrine enzymatic steroidogenic machinery to produce enough DHT to support acinar remodeling and to prevent abnormal acinar changes. This endo-intracrine failure could lead to production and exposure of antigenic material and danger signals, which break self-tolerance and lead to autoimmunity in form of focal adenitis. Endo-intracrine events certainly also regulate subsequent immune responses, but because SS seems to be similar in men and women, the impact of the endo-intracrine events on exocrine glands seems to be the primary event. This failure of central and peripheral exocrine-targeted DHEA handling could be the initial noxious stimulus, factor X, initiating the development of SS against a predisposing genetic and hormonal background. This hypothesis of the 2-stage disease development offers a platform for future research, early diagnosis and potential new intracrine treatments. The last mentioned prediction is favored by the multiplicity (diversity) of steroidogenic enzyme isoforms, which suggests tissue, cell and perhaps disease specific regulation of the intracrine steroid metabolism, often also enabling both forward and backward reactions.
4.
Truong S, Cole N, Stapleton F, Golebiowski B.
Clin Exp Optom. 2014 Jul;97(4):324-36. doi: 10.1111/cxo.12147. Epub 2014 Apr 1. Review.
PMID:

 

24689906
5.
Gagliano C, Caruso S, Napolitano G, Malaguarnera G, Cicinelli MV, Amato R, Reibaldi M, Incarbone G, Bucolo C, Drago F, Avitabile T.
Br J Ophthalmol. 2014 Mar;98(3):371-6. doi: 10.1136/bjophthalmol-2012-302705. Epub 2014 Jan 3.
PMID:

 

24390165
Br J Ophthalmol. 2014 Mar;98(3):371-6. doi: 10.1136/bjophthalmol-2012-302705. Epub 2014 Jan 3.

Low levels of 17-β-oestradiol, oestrone and testosterone correlate with severe evaporative dysfunctional tear syndrome in postmenopausal women: a case-control study.

Abstract

AIMS:

To evaluate the role of 17-β-oestradiol, oestrone and total testosterone (TT) deficiency in the pathogenesis of severe evaporative dry eye syndrome (DES), investigating the relationship between tear osmolarity, tear film break-up time (TF-BUT), Schirmer test and serum sex hormones in postmenopausal women.

METHODS:

44 postmenopausal women were recruited for a case-control study: 22 women with severe evaporative DES (Group A) and 22 without DES (Group B). The tests performed included laboratory blood analysis: fasting plasma profile (17-β-oestradiol, oestrone and TT), glucose level and lipid profile. Detailed eye examinations, including corneal and conjunctival staining, tear osmolarity measurement, tear volume and TF-BUT, were performed. The Ocular Surface Disease Index Questionnaire was also administered.

RESULTS:

Values of Schirmer test and TF-BUT in Group A were significantly lower in comparison with Group B (p<0.001). Serum levels of 17-β-oestradiol, oestrone and TT were significantly lower in Group A compared with Group B (p<0.05). In women with severe evaporative DES, the levels of 17-β-oestradiol, oestrone and TT were inversely correlated with the tear film osmolarity (r=-0.7, -0.88, -0.81, respectively).

CONCLUSIONS:

In postmenopausal women with severe evaporative DES, sex hormone levels are lower than control and that tear osmolarity is negatively correlated with sex hormone levels.
6.
Nanavaty MA, Long M, Malhotra R.
Br J Ophthalmol. 2014 Apr;98(4):567-9. doi: 10.1136/bjophthalmol-2013-304637. Epub 2013 Dec 16. No abstract available.
PMID:

 

24344229
7.
Song X, Zhao P, Wang G, Zhao X.
Invest Ophthalmol Vis Sci. 2014 Feb 4;55(2):745-51. doi: 10.1167/iovs.12-10457.
PMID:

 

24334444
8.
Scuderi G, Contestabile MT, Gagliano C, Iacovello D, Scuderi L, Avitabile T.
Can J Ophthalmol. 2012 Dec;47(6):489-92. doi: 10.1016/j.jcjo.2012.08.019.
PMID:

 

23217501
9.
Konttinen YT, Fuellen G, Bing Y, Porola P, Stegaev V, Trokovic N, Falk SS, Liu Y, Szodoray P, Takakubo Y.
J Autoimmun. 2012 Aug;39(1-2):49-56. doi: 10.1016/j.jaut.2012.01.004. Epub 2012 Feb 1. Review.
PMID:

 

22300712
10.
Porola P, Straub RH, Virkki LM, Konttinen YT, Nordström DC.
Scand J Rheumatol. 2011;40(5):387-90. doi: 10.3109/03009742.2011.580000. Epub 2011 Aug 31.
PMID:

 

21877998
11.
Porola P, Laine M, Virtanen I, Pöllänen R, Przybyla BD, Konttinen YT.
J Rheumatol. 2010 Jun;37(6):1181-7. doi: 10.3899/jrheum.091354. Epub 2010 May 1.
PMID:

 

20436081
12.
Wang F, Peng QH, Yao XL, Wu QL, Li D.
Int J Ophthalmol. 2010;3(1):32-5. doi: 10.3980/j.issn.2222-3959.2010.01.08. Epub 2010 Mar 18.
PMID:

 

22553513

 

Free PMC Article

13.
Crow JM, Nelson JD, Remington SG.
Curr Eye Res. 2009 Dec;34(12):1042-9. doi: 10.3109/02713680903316290.
PMID:

 

19958123
14.
Sullivan DA, Jensen RV, Suzuki T, Richards SM.
Mol Vis. 2009 Aug 10;15:1553-72.
PMID:

 

19693291

 

Free PMC Article

15.
Forsblad-d’Elia H, Carlsten H, Labrie F, Konttinen YT, Ohlsson C.
J Clin Endocrinol Metab. 2009 Jun;94(6):2044-51. doi: 10.1210/jc.2009-0106. Epub 2009 Mar 24.
PMID:

 

19318446
16.
Porola P, Virkki L, Przybyla BD, Laine M, Patterson TA, Pihakari A, Konttinen YT.
J Rheumatol. 2008 Nov;35(11):2229-35. Epub 2008 Oct 1.
PMID:

 

18843777
17.
Duarte MC, Pinto NT, Moreira H, Moreira AT, Wasilewski D.
Arq Bras Oftalmol. 2007 May-Jun;70(3):465-9. Portuguese.
PMID:

 

17768554

 

Free Article

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Bai H, Yu P, Yu M.
Zhen Ci Yan Jiu. 2007;32(3):203-6. Chinese.
PMID:

 

17691581
19.
Hartkamp A, Geenen R, Godaert GL, Bootsma H, Kruize AA, Bijlsma JW, Derksen RH.
Ann Rheum Dis. 2008 Jan;67(1):91-7. Epub 2007 Jun 1.
PMID:

 

17545193
20.
Erdem U, Ozdegirmenci O, Sobaci E, Sobaci G, Göktolga U, Dagli S.
Maturitas. 2007 Mar 20;56(3):257-62. Epub 2006 Oct 9.
PMID:

 

17030104
21.
Tamer C, Oksuz H, Sogut S.
Ophthalmic Res. 2006;38(5):280-6. Epub 2006 Sep 15.
PMID:

 

16974129
22.
Khurana RN, LaBree LD, Scott G, Smith RE, Yiu SC.
Am J Ophthalmol. 2006 Sep;142(3):494-5.
PMID:

 

16935599
23.
Schirra F, Suzuki T, Richards SM, Jensen RV, Liu M, Lombardi MJ, Rowley P, Treister NS, Sullivan DA.
Invest Ophthalmol Vis Sci. 2005 Oct;46(10):3666-75.
PMID:

 

16186348
24.
Rosário PW, Cardoso LD, Barroso AL, Padrão EL, Rezende LL, Purisch S.
Arq Bras Endocrinol Metabol. 2005 Apr;49(2):241-5. Epub 2005 Sep 12. Portuguese.
PMID:

 

16184252

 

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Scott G, Yiu SC, Wasilewski D, Song J, Smith RE.
Am J Ophthalmol. 2005 Jun;139(6):1109-10.
PMID:

 

15953447
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27.
Sullivan DA, Bélanger A, Cermak JM, Bérubé R, Papas AS, Sullivan RM, Yamagami H, Dana MR, Labrie F.
J Rheumatol. 2003 Nov;30(11):2413-9.
PMID:

 

14677186
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Brennan MT, Sankar V, Leakan RA, Grisius MM, Collins MT, Fox PC, Baum BJ, Pillemer SR.
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Zhang H, Zhou Z, Chen Z, Wu Y, Zhang Q.
Yan Ke Xue Bao. 1998 Mar;14(1):1-8.
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Sullivan DA, Sullivan BD, Evans JE, Schirra F, Yamagami H, Liu M, Richards SM, Suzuki T, Schaumberg DA, Sullivan RM, Dana MR.
Ann N Y Acad Sci. 2002 Jun;966:211-22. Review.
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Horwath-Winter J, Flögel I, Ramschak-Schwarzer S, Hofer A, Kroisel PM.
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ARG101 is a testosterone cream or gel formulation used to treat DES in
menopausal women. Waning androgen levels in women before, during, and
after menopause has been identified as a primary cause of DES in this
population. ARG101 is unique in that it is applied to the upper and
lower eyelids for transdermal delivery of testosterone directly to the
affected glands. Delivering the active pharmaceutical ingredient
transdermally allows better access to the glands and enables convenient
twice-daily dosing. ARG101 restores aqueous and lipid production thereby
restoring the natural process of tear production.

Clinical practice at the Southern College of Optometry (SCO) has
documented ARG101 efficacy and safety. Patients using ARG101 achieved a
51% increase in aqueous secretion (p=0.01) and a 68% increase in tear
breakup time, a measure of meibomian gland function, versus baseline
measurements. There was also a 51% (p=0.01) decrease in symptoms as
measured by the Ocular Severity Disease Index (OSDI), a validated
measure of DES symptoms. There have been no adverse events and,
importantly, no increase in intraocular pressure in patients using the
testosterone cream for three years. Results of the use of testosterone
in patients at SCO have been presented at the Annual Meeting of the
American Association of Optometrists in each year 2002-2006.

ARG102 is a progesterone cream or gel formulation used to treat DES in
men and younger women. The cross-reactivity between progesterone and
corticosteroid receptors in the ocular region is believed to activate
corticosteroid anti-inflammatory activity in the glands and on the
ocular surface, restoring normal aqueous and lipid production. ARG102 is
also applied to the upper and lower eyelids for transdermal delivery of
progesterone directly to the affected glands.

Patient data from clinical practice at SCO has shown that patients using
ARG102 had a 34% increase in tear breakup time (p=0.01) and a 20%
decrease in symptom severity (p=0.05) after only three weeks of use
versus baseline measurements. There were no reported adverse events or
increases in intraocular pressure. These results were presented at the
2006 Annual Meeting of the American Association of Optometrists.

ARG103 is a combination of testosterone and progesterone in a cream or
gel formulation used to treat previously untreated post-menopausal
women. Anecdotal results from SCO have shown promise in treating these
women who because of lack of treatment options may have more severe
glandular dysfunction.

These treatments share several characteristics which make them unique among current DES therapies and those in development:

■A patient-friendly application with a cream or gel formulation to the
outer upper and lower eyelids versus conventional drop application.
■Transdermal delivery of anti-inflammatory hormones directly to the affected glands.
■Restores the natural process of tear production versus tear replacement of conventional therapies.
■Convenient twice-daily dosing versus the frequent applications required by tear replacement therapies.
■No stinging or burning of the skin to which it is applied or of the ocular surface.

Reference:

http://www.argentisrx.com/content/show.asp?mne=pipeline

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