Risk of venous thromboembolism events in postmenopausal women using oral versus non-oral hormone therapy: A systematic review and meta-analysis

Rovinski, Denise; Ramos, Ramon Bossardi; Fighera, Tayane Muniz; Casanova, Gislaine Krolow; Spritzer, Poli Mara

doi:10.1016/j.thromres.2018.06.014

Cited by 73 publications

(39 citation statements)

References 53 publications

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“…Nonetheless, while endogenous estradiol is only correlated with this nature of events when associated with increased free testosterone and decreased se hormone binding globulin (SHBG) [ 268 ], the correlation of exogenous estrogens and thromboembolism is largely justified by the route of administration, orally administered estrogens lead to increased hepatic production of pro-coagulants induced by its first liver first-passage effect, that does not occur in non-oral regimens. Indeed, large observational studies and a meta-analysis have shown no increased risk of thromboembolism among women taking non-oral estrogen replacement therapies [ 269 – 271 ].…”

Section: Main Textmentioning

confidence: 99%

Repurposing existing drugs for COVID-19: an endocrinology perspective

Cadegiani

2020

BMC Endocr Disord

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Background Coronavirus Disease 2019 (COVID-19) is a multi-systemic infection caused by the novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), that has become a pandemic. Although its prevailing symptoms include anosmia, ageusia, dry couch, fever, shortness of brief, arthralgia, myalgia, and fatigue, regional and methodological assessments vary, leading to heterogeneous clinical descriptions of COVID-19. Aging, uncontrolled diabetes, hypertension, obesity, and exposure to androgens have been correlated with worse prognosis in COVID-19. Abnormalities in the renin-angiotensin-aldosterone system (RAAS), angiotensin-converting enzyme-2 (ACE2) and the androgen-driven transmembrane serine protease 2 (TMPRSS2) have been elicited as key modulators of SARS-CoV-2. Main text While safe and effective therapies for COVID-19 lack, the current moment of pandemic urges for therapeutic options. Existing drugs should be preferred over novel ones for clinical testing due to four inherent characteristics: 1. Well-established long-term safety profile, known risks and contraindications; 2. More accurate predictions of clinical effects; 3. Familiarity of clinical management; and 4. Affordable costs for public health systems. In the context of the key modulators of SARS-CoV-2 infectivity, endocrine targets have become central as candidates for COVID-19. The only endocrine or endocrine-related drug class with already existing emerging evidence for COVID-19 is the glucocorticoids, particularly for the use of dexamethasone for severely affected patients. Other drugs that are more likely to present clinical effects despite the lack of specific evidence for COVID-19 include anti-androgens (spironolactone, eplerenone, finasteride and dutasteride), statins, N-acetyl cysteine (NAC), ACE inhibitors (ACEi), angiotensin receptor blockers (ARB), and direct TMPRSS-2 inhibitors (nafamostat and camostat). Several other candidates show less consistent plausibility. In common, except for dexamethasone, all candidates have no evidence for COVID-19, and clinical trials are needed. Conclusion While dexamethasone may reduce mortality in severely ill patients with COVID-19, in the absence of evidence of any specific drug for mild-to-moderate COVID-19, researchers should consider testing existing drugs due to their favorable safety, familiarity, and cost profile. However, except for dexamethasone in severe COVID-19, drug treatments for COVID-19 patients must be restricted to clinical research studies until efficacy has been extensively proven, with favorable outcomes in terms of reduction in hospitalization, mechanical ventilation, and death.

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Section: Main Textmentioning

confidence: 99%

Repurposing existing drugs for COVID-19: an endocrinology perspective

Cadegiani

2020

BMC Endocr Disord

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“…In general, oral bioavailability of estrogens is poor due to limited absorption and metabolism in the gastrointestinal tract and liver; however, transdermal absorption of estradiol varies widely between individuals. A recent meta-analysis reported that oral, but not transdermal, administration of estradiol is associated with an increased risk of thromboembolism (135). In addition, oral (58,75), but not transdermal (58), estradiol increases angiotensinogen production by the liver.…”

Section: Variations In Mhtmentioning

confidence: 99%

A heartfelt message, estrogen replacement therapy: use it or lose it

Speth

D'Ambra

et al. 2018

American Journal of Physiology-Heart and Circulatory Physiology

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The issue of cardiovascular and cognitive health in women is complex. During the premenopausal phase of life women have healthy blood pressure (BP) levels that are lower than age-matched men and they have less cardiovascular disease. However, in the post-menopausal stage of life women's BP increases and they are increasingly susceptible to cardiovascular disease, cognitive impairments and dementia, exceeding the incidence in men. The major difference between pre- and post-menopausal women is the loss of estrogen. Thus, it seemed logical that post-menopausal estrogen replacement therapy, with or without a progestin, generally referred to as menopausal hormone treatment (MHT), would prevent these adverse sequelae. However, despite initially promising results, a major randomized clinical trial refuted the benefits of MHT leading to it falling from favor. However, reappraisal of this study in the framework of a "Critical Window", or "Timing Hypothesis" has changed our perspective on the benefit to risk ratio of MHT and this review discusses the historical, current and future approaches to MHT.

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“…Oral estrogens (CEE and estradiol) multiply the risk of VTE in the general population by a factor of 1.7 compared with placebo [175] [LE1]. The risk appears to be greater with CEE than with estradiol [LE2] and to be modulated by the type of progestin [176] [LE2].…”

Section: Venous Thromboembolic Riskmentioning

confidence: 99%