Hormone Replacement Therapy, Reproductive Factors, and Cataract The Blue Mountains Eye Study

Cumming, Robert; Mitchell, Paul

doi:10.1093/oxfordjournals.aje.a009097

Cited by 122 publications

(86 citation statements)

References 16 publications

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“…The incidence of age-related cataracts is higher in women (1), and their onset coincides with estrogen deficiency that occurs after menopause. Until recently, the eye had not been considered to be an estrogen target tissue; however, recent studies have begun to correlate estrogen status with risk of cataracts (2)(3)(4). In addition, the estrogen receptor (ER) has been detected in ocular tissues (5, 6,).…”

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“…In this study, a later onset of menopause was associated with a decreased risk of cortical cataracts; younger age at menarche (onset of menstruation) was associated with a protective effect regarding nuclear sclerosis; and hormone replacement therapy was associated with a lower prevalence of nuclear cataracts. In the Blue Mountains eye study, current use of hormone replacement therapy in women Ͼ65 years of age was associated with a lower prevalence of cortical cataracts (2). In addition, an increased prevalence of cortical, nuclear, and posterior subcapsular cataracts with later ages at menarche was detected (2), suggesting that a shorter lifetime exposure to estrogen may influence all types of agerelated cataracts.…”

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An estrogen receptor repressor induces cataract formation in transgenic mice

Davis

Chan

Schoen

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

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Despite the high prevalence of age-related cataracts, there are currently no known therapies to delay or prevent their occurrence. Studies in humans and rodent models suggest that estrogen may provide protection against age-related cataracts. The discovery of ocular estrogen receptors (ERs) indicates that estrogen protection may result from direct interactions with its receptors in the eye, instead an indirect consequence from effects on another tissue. Studies in our transgenic mouse model validate the concept that estrogen is beneficial for the eye. These mice express ER⌬3, a dominant-negative form of ER␣ that inhibits ER␣ function. In the ER⌬3 transgenic mice, cortical cataracts spontaneously form in ER⌬3 females after puberty and progress with age. The cataracts initiate in the equatorial region of the lens where the epithelial cells differentiate into elongating fiber cells. Cataract formation can be prevented if the females are ovariectomized before, but not after, sexual maturity. Both male and female ER⌬3 mice develop cataracts after neonatal treatment with the potent estrogen diethylstilbestrol (DES). The incidence of spontaneous and DESinduced cataracts in ER⌬3 mice is 100%, yet these cataracts are absent from the wild-type mice. These data suggest that repression of estrogen action induces cortical cataract formation because estrogen is required to activate the ER⌬3 repressor. Evidence of DES-induced cataracts in the ER⌬3 males as well as the females suggests that estrogen is important in lens physiology in both sexes. The ER⌬3 mice provide a powerful model for assessing the role of estrogen in maintaining the transparency of the lens. Currently there is no known therapy that can delay or prevent age-related cataracts that plague the ever-growing numbers of aging men and women. The incidence of age-related cataracts is higher in women (1), and their onset coincides with estrogen deficiency that occurs after menopause. Until recently, the eye had not been considered to be an estrogen target tissue; however, recent studies have begun to correlate estrogen status with risk of cataracts (2-4). In addition, the estrogen receptor (ER) has been detected in ocular tissues (5, 6,).Estrogens acting through the ER modulate transcription of estrogen-responsive genes (7). The ER is a ligand-dependent transcription factor belonging to the nuclear receptor superfamily (8). Currently, two subtypes of the ER are known to exist, ER␣ and ER␤. The classic ER, which has been associated for decades with female reproductive responses, is now designated as ER␣. The recently discovered second gene codes for ER␤ (9). Expression of the ER␣ protein has been detected in the rat and bovine (5) and human (6) retina and in the rat lens ʈ ; ER␤ mRNA has been detected in the rat lens (10). The presence of these receptors indicates that the eye can respond directly to estrogens or antiestrogens, such as tamoxifen.Studies in women suggest that estrogens may protect against the development of senile cataracts. The three types of agerelat...

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confidence: 99%

mentioning

confidence: 99%

An estrogen receptor repressor induces cataract formation in transgenic mice

Davis

Chan

Schoen

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

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“…However, higher DHEAS levels were associated with lower odds of cataract (OR 0.81; 95% CI 0.66, 0.99); this association remained significant after adjustment for other cataract risk factors. Other studies of post-menopausal women have shown that women who reported ever using HT, current use of HT, or use of HT for a longer period of time had a reduced risk of cataracts [30,[32][33][34][35][36][37]. In contrast, it should be noted that studies by Eisner et al [38] have shown no changes in the optic cups of users of anastrozole, an aromatase inhibitor that blocks estrogen production, compared to a control group, suggesting no association between estrogen and visual changes.…”

Section: Discussionmentioning

confidence: 99%

Endogenous hormones, participant characteristics, and symptoms among midlife women

et al. 2008

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Objectives-The primary aim of this study was to examine the associations between endogenous hormone levels and symptoms other than hot flashes in a sample of midlife women.Methods-Data from a community-based sample of 603 women aged 45 to 54 years who had never used hormone therapy were analyzed. Each participant completed a questionnaire to obtain data on demographic and lifestyle characteristics as well as symptoms, including headache, insomnia, vision problems, vaginal discharge and dryness, irritability, and incontinence. In addition, each participant provided a blood sample that was used to measure estrogen, androgen, and sex hormone binding globulin (SHBG) concentrations by enzyme-linked immunosorbent assay.Results-Prevalence rates of symptoms ranged from 51.4% (irritability) to 18.6% (vision problems). In adjusted analyses, the free estradiol index (FEI) was significantly and positively associated with the reporting of insomnia (odds ratio (OR) 1.28; 95% confidence interval (CI) 1.01, 1.61). Further, higher SHBG levels were significantly associated with lower odds of reporting vision problems (OR 0.44; 95% CI 0.23, 0.81).Conclusions-This study provides evidence that hormones are associated with insomnia and visual problems during midlife. However, some of these results conflict with previous findings. Given the overall paucity of literature on these issues, more investigation is warranted.

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“…For example, the protective effect of oestrogen-only HRT against any cataract found in this study agrees with results from the Nutrition and Vision Project in the United States. 15 In addition, both Blue Mountains Eye Studies 16,17 found that oestrogenprogestogen HRT had a protective effect against cortical and nuclear cataract. The only previous study in the UK, 13 a prospective cohort study based on a population of 250 participants, did not find any association with HRT.…”

Section: Discussionmentioning

confidence: 99%

“…Despite evidence from animal studies, previous epidemiological studies of the association between HRT and cataract have produced inconclusive results. [10][11][12][13][14][15][16][17] We therefore conducted a case-control study to examine whether the use of HRT was associated with a reduction in cataract diagnoses, using data from the United Kingdom General Practice Research Database.…”

Section: Introductionmentioning

confidence: 99%

Hormone replacement therapy and cataract: a population-based case–control study

Aina

Smeeth

Hubbard

et al. 2005

Eye

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Purpose Laboratory studies have suggested that hormone replacement therapy (HRT) may protect against the development of cataract, but epidemiological studies in humans have thus far been inconclusive. The aim of this study was to assess the association between hormone replacement therapy and cataract. Methods Population-based case-control study using data from the General Practice Research Database in the UK. Participants were 10 000 women aged 45 years and over with diagnosed cataract and 10 000 controls matched on age, general practice, and calendar period. Results The crude odds ratio for the association between cataract and ever-use of oestrogen-only hormone replacement therapy was 1.13 (95% CI 0.99-1.29). This reduced to 0.81 (95% CI 0.71-0.94) after adjustment for consultation rate. Similarly, the crude odds ratio for the association between cataract and ever-use of a formulation containing oestrogen and progestogen was 1.18 (95% CI 1.01-1.39), reducing to 0.86 (95% CI 0.72-1.02) after adjustment for consultation rate. Conclusions Oestrogen-only and oestrogenprogestogen hormone replacement therapies are associated with a small reduced risk of cataract. This data adds to the growing body of evidence on the effects of HRT on health. All potential benefits and risks of this therapy should be taken into account when considering its use.

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Hormone Replacement Therapy, Reproductive Factors, and Cataract The Blue Mountains Eye Study

Cited by 122 publications

References 16 publications

An estrogen receptor repressor induces cataract formation in transgenic mice

An estrogen receptor repressor induces cataract formation in transgenic mice

Endogenous hormones, participant characteristics, and symptoms among midlife women

Hormone replacement therapy and cataract: a population-based case–control study

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