Clinical toxicology of estrogens

Westerholm, B

doi:10.1016/0163-7258(80)90087-x

Cited by 10 publications

(4 citation statements)

References 112 publications

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“…Although the photosensitizing properties of estrogens have been recognized for decades, 6 , 8 few epidemiologic studies have examined the relationship between exogenous estrogen use, female reproductive factors, and risk of BCC. 13 – 15 Studies examining the use of OCs and MHT have found an increased risk of BCC 14 , 15 or no association.…”

Section: Introductionmentioning

confidence: 99%

Female Estrogen-Related Factors and Incidence of Basal Cell Carcinoma in a Nationwide US Cohort

Cahoon

Kitahara

Ntowe

et al. 2015

JCO

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PurposeUV radiation exposure is the primary risk factor for basal cell carcinoma (BCC), the most common human malignancy. Although the photosensitizing properties of estrogens have been recognized for decades, few studies have examined the relationship between reproductive factors or exogenous estrogen use and BCC.MethodsUsing data from the US Radiologic Technologists Study, a large, nationwide, prospective cohort, we assessed the relationship between reproductive factors, exogenous estrogen use, and first primary BCC while accounting for sun exposure, personal sun sensitivity, and lifestyle factors for geographically dispersed women exposed to a wide range of ambient UV radiation.ResultsElevated risk of BCC was associated with late age at natural menopause (hazard ratio [HR] for ≥ 55 years v 50 to 54 years, 1.50; 95% CI, 1.04 to 2.17) and any use of menopausal hormone therapy (MHT; HR, 1.16; 95% CI, 1.03 to 1.30; P for trend for duration = .001). BCC risk was most increased among women reporting natural menopause who used MHT for 10 or more years versus women who never used MHT (HR, 1.97; 95% CI, 1.35 to 2.87). Risk of BCC was not associated with age at menarche, parity, age at first birth, infertility, use of diethylstilbestrol by participant's mother, age at hysterectomy, or use of oral contraceptives.ConclusionThese analyses confirm a previous finding of increased risk of BCC associated with MHT. Novel findings of increased BCC risk associated with MHT in women experiencing natural menopause and for late age at natural menopause warrant further investigation. Users of MHT may constitute an additional high-risk group in need of more frequent skin cancer screening.

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Section: Introductionmentioning

confidence: 99%

Female Estrogen-Related Factors and Incidence of Basal Cell Carcinoma in a Nationwide US Cohort

Cahoon

Kitahara

Ntowe

et al. 2015

JCO

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“…As alluded to above, animal safety data on estrogens, either in vitro or in vivo, have not proven to be quantitatively predictive of the effects of these products in women [Stern, 1982;Heywood and Wadsworth, 1980;Westerholm, 1980]. Consequently, one view would be that the most confident conclusions can be drawn from human experience.…”

Section: Additional Perspectives Regarding the Safety And Efficacy Ofmentioning

confidence: 91%

Review of the effects of 17α‐estradiol in humans: a less feminizing estrogen with neuroprotective potential

Moos

Dykens

Nohynek

et al. 2009

Drug Development Research

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ABSTRACT17a-Estradiol is a less feminizing isomer of the potent hormonal estrogen, 17b-estradiol. 17a-Estradiol is an orally active small molecule with conflicting reports of efficacy in preclinical models of degenerative diseases. A number of studies suggest neuroprotective potential in human neurodegenerative disorders, including Alzheimer's disease (AD) and Parkinson's disease. Several studies have established an antioxidant effect of 17a-estradiol in humans. The sodium salt of 17a-estradiol 3-sulfate is a minor component (2.5-9.5%) of several widely marketed estrogen hormone replacement products, such as Premarin s , that are approved by the U.S. Food and Drug Administration and have been prescribed and studied in women and men for more than 65 years. Most of the more than 100 published reports on the neurological effects of feminizing estrogens found positive responses in at least one measure relating to cognition or prevention and treatment of AD, notwithstanding the negative results in the Women's Health Initiative studies. Whether these limited, and often not statistically significant, findings are clinically meaningful remains unknown. In many in vitro and in vivo preclinical neuroprotection and related studies, 17a-estradiol and 17b-estradiol are active at similar concentrations and doses. However, 17a-estradiol is less pleiotropic than 17b-estradiol, and thus its potential toxicity might be lower. Given decades of mixed reports regarding the potential efficacy and safety of strongly feminizing hormones in neurodegenerative diseases, the weakly feminizing 17a-estradiol might be a suitable candidate for clinical testing of the neuroprotective potential of this chemical class because it avoids, or significantly reduces, the adverse effects of potent hormonal compounds. Drug Dev Res 70: 1-21, 2009. r

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“…For a brief primer on the production and actions of estrogens, see Gruber et al [2002]. For background on the pharmacology and toxicology of estrogens, see reviews by Hart [1990], Heywood and Wadsworth [1980], Stern [1982], Westerholm [1980], and Woolley [2007].…”

Section: Introductionmentioning

confidence: 98%

17α‐estradiol: a less‐feminizing estrogen

Moos

Dykens

Howell³

2008

Drug Development Research

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Alzheimer's disease (AD) is a major neurodegenerative disorder in the elderly and is the most common form of dementia. Approved AD drugs like donepezil and memantine provide some cognitive benefits to a subset of patients. However, the cost burden of AD will continue to increase in the absence of more effective drugs that treat its symptoms and ultimately slow its progression or delay or prevent its onset. A substantial number of studies report that 17b-estradiol (E2; estrogen), a potent endogenous feminizing hormone, is neuroprotective. Unfortunately, negative results from the Women's Health Initiative (WHI) and its ancillary Memory Study (WHIMS) have overshadowed the positive data collected over several decades. Importantly, there are a number of reasons why the WHIMS results should not be generalized to less-or nonfeminizing estrogens. For the sake of argument, consider ''non-hormonal'' or non-feminizing estrogens to be worthwhile drug development candidates for AD and other neurodegenerative conditions because they have the potential to retain the positive neuroprotective activities of E2 while reducing the potential complications associated with feminizing hormones. Because the literature comparing estrogenicity of various estrogens is complex and spans multiple decades, we summarize herein the available hormonal comparisons of a common less-feminizing estrogen, 17a-estradiol (17aE2), with E2. 17aE2 is less feminizing than E2 in every published study where reasonable comparisons can be made. One-half of these studies report a difference of two orders of magnitude or greater. In practice, compounds like 17aE2 may prove to be largely nonfeminizing at doses to be explored in human clinical trials. Moreover, other novel E2 analogues have been identified that are essentially devoid of feminizing actions. If the positive effects of feminizing estrogens on neurodegeneration prove useful in treating neurodegenerative diseases, less-feminizing and non-feminizing estrogen analogues may be even more effective, safer, and better tolerated. Drug Dev Res 69 : 177-184, 2008.

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Clinical toxicology of estrogens

Cited by 10 publications

References 112 publications

Female Estrogen-Related Factors and Incidence of Basal Cell Carcinoma in a Nationwide US Cohort

Female Estrogen-Related Factors and Incidence of Basal Cell Carcinoma in a Nationwide US Cohort

Review of the effects of 17α‐estradiol in humans: a less feminizing estrogen with neuroprotective potential

17α‐estradiol: a less‐feminizing estrogen

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