Impact of Testosterone Replacement Therapy on Myocardial Infarction, Stroke, and Death in Men With Low Testosterone Concentrations in an Integrated Health Care System

Anderson, Jeffrey L.; May, Heidi T; Lappé, Donald; Bair, Tami L; Le, Viet T; Carlquist, John F.; Muhlestein, Joseph B.

doi:10.1016/j.amjcard.2015.11.063

Cited by 123 publications

(87 citation statements)

References 15 publications

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“…Two recent studies in men who received T therapy found reduced CV events in those whose follow-up T level normalized compared with men whose T concentration remained low. 60,61 There is no credible evidence at this time that T therapy increases CV risk and substantial evidence that it does not. Indeed, there is a strong signal that T therapy may offer CV benefits to men.…”

Section: Resolution 7 the Evidence Does Not Support Increased Risks mentioning

confidence: 97%

Fundamental Concepts Regarding Testosterone Deficiency and Treatment

Morgentaler

Zitzmann²,

Traish

et al. 2016

Mayo Clinic Proceedings

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To address widespread concerns regarding the medical condition of testosterone (T) deficiency (TD) (male hypogonadism) and its treatment with T therapy, an international expert consensus conference was convened in Prague, Czech Republic, on October 1, 2015. Experts included a broad range of medical specialties including urology, endocrinology, diabetology, internal medicine, and basic science research. A representative from the European Medicines Agency participated in a nonvoting capacity. Nine resolutions were debated, with unanimous approval: (1) TD is a well-established, clinically significant medical condition that negatively affects male sexuality, reproduction, general health, and quality of life; (2) symptoms and signs of TD occur as a result of low levels of T and may benefit from treatment regardless of whether there is an identified underlying etiology; (3) TD is a global public health concern; (4) T therapy for men with TD is effective, rational, and evidence based; (5) there is no T concentration threshold that reliably distinguishes those who will respond to treatment from those who will not; (6) there is no scientific basis for any age-specific recommendations against the use of T therapy in men; (7) the evidence does not support increased risks of cardiovascular events with T therapy; (8) the evidence does not support increased risk of prostate cancer with T therapy; and (9) the evidence supports a major research initiative to explore possible benefits of T therapy for cardiometabolic disease, including diabetes. These resolutions may be considered points of agreement by a broad range of experts based on the best available scientific evidence.

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Section: Resolution 7 the Evidence Does Not Support Increased Risks mentioning

confidence: 97%

Fundamental Concepts Regarding Testosterone Deficiency and Treatment

Morgentaler

Zitzmann²,

Traish

et al. 2016

Mayo Clinic Proceedings

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“…В то же время результаты более 100 исследований го-ворят о снижении сердечно-сосудистого риска по мере увеличения эндогенных концентраций тестостерона, О б з о р ы л и т е р а т у р ы о снижении выраженности известных факторов сер-дечно-сосудистого риска при проведении терапии тестостероном и о снижении смертности у мужчин с ДТ, которым проводилась терапия тестостероном, по сравнению с мужчинами без лечения. В двух не-давно проведенных исследованиях у мужчин, полу-чавших терапию тестостероном, отмечено снижение частоты сердечно-сосудистых осложнений при после-дующей нормализации концентраций тестостерона, по сравнению с мужчинами, у которых концентрации тестостерона оставались низкими [60,61]. На данный момент отсутствуют достоверные доказательные дан-ные, которые позволяли бы говорить об увеличении сердечно-сосудистого риска при проведении терапии тестостероном, в то время как, напротив, большой объем доказательных данных говорит об отсутствии подобного увеличения риска.…”

Section: заявление 3 дт представляет угрозу общественному здоровью вunclassified

“…Результаты двух наблюдатель-ных исследований, проведенных у пациентов с дефи-цитом тестостерона, одно из которых проводилось в лечебных учреждениях, оказывающих медицин-скую помощь ветеранам Вооруженных сил США [50], а другое в популяции пациентов с сахарным диабетом в Великобритании [49], говорят о снижении смертно-сти приблизительно в 2 раза у пациентов, получавших терапию тестостероном, по сравнению с пациентами, ее не получавшими. Еще в двух недавно проведенных исследованиях отмечено снижение сердечно-сосуди-стого риска у мужчин, чьи уровни тестостерона сы-воротки нормализовались на терапии тестостероном, по сравнению с мужчинами, уровни тестостерона у которых неизменно оставались низкими [60,61]. Патологические последствия разрастания жировой ткани, коррелирующего с низкими концентрациями тестостерона, наряду с тем фактом, что на терапии тестостероном наблюдается уменьшение массы жи-ровой ткани, представляет собой убедительный био-логический механизм возможных благоприятных сердечно-сосудистых эффектов и снижения риска сердечно-сосудистых осложнений при проведении терапии тестостероном [16].…”

Section: ответы экспертовunclassified

The consensus recommendations of a group of international experts on the fundamental concepts related to the issues of testosterone deficiency and its treatment.

Morgentaler

Абрахам²,

Zitzmann³

et al. 2016

Obes. metabol.

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Conference on the development of the international expert consensus to address frequently asked questions related to a medical condition of testosterone deficiency (TD, male hypogonadism) and testosterone therapy was held in Prague (Czech Republic) on October 1, 2015. The included experts were representatives from a variety of medical specialties, including urology, endocrinology, diabetology, internal medicine, as well as representatives of basic medical sciences. An international team of experts came to the following conclusions: TD - an important medical condition that affects the health and well-being of men; TD symptoms is a consequence of low testosterone levels, regardless of whether background etiology installed; TD consequences are global; care must be taken in an attempt to use any uniform threshold levels of testosterone for a decision on the appointment of testosterone therapy; a person does not have any reason to refrain from appointing testosterone therapy only on the basis of age; the existing evidence does not suggest increasing the prostate cancer or cardiovascular disease risk during testosterone therapy; there is evidence conserning the feasibility of a major research initiative to explore possible cardioprotective beneficial effects of testosterone therapy in men with metabolic disorders, including diabetes.

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“…19 Two recent studies in men who received TRT found reduced CV events in those whose follow-up T level normalized compared to men whose T concentration remained low. 20,21 Another large observational study noted that T therapy was associated with reduced risk of myocardial infarction in men in the highest risk category. 22 A recently published meta-analysis of 75 placebo-controlled studies, the largest to date, found no evidence of increased CV risk with T therapy and clear evidence of improved metabolic profiles.…”

Section: Impact Of Testosterone Replacement Therapy Overall Mortalitymentioning

confidence: 99%

Testosterone and the Heart

Goodale

Sadhu

Petak

et al. 2017

Methodist DeBakey Cardiovascular Journal

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Testosterone (T) is the principal male sex hormone, secreted primarily by the testes and transported in the blood by the carrier protein, sex-hormone binding globulin (SHBG). Only 1% to 2% of testosterone circulates in blood as unbound "free" testosterone, but this fraction exhibits the most potent biological activity. Dihydrotestosterone (DHT), the most biologically active androgen, is synthesized from testosterone by 5a-reductase and exerts its effects via a family of androgen receptors. Some biological effects of testosterone may result from its aromatization to estradiol and subsequent interaction with the estrogen receptor. In addition to developing primary and secondary sex characteristics, androgens have diverse anabolic functions such as increasing muscle mass and bone density.1 Testosterone has also demonstrated a number of important effects on the cardiovascular system. In men, T levels begin to decrease after age 40, and this decrease has been associated with an increase in all-cause mortality and cardiovascular risk.2,3 However, whether low T causes negative cardiovascular events or is simply associated with them has yet to be determined. 4 This review highlights the evidence underlying the major interrelationships between androgens and the cardiovascular system. Testosterone Actions on Cardiovascular CellsTestosterone and the more potent DHT bind to cytoplasmic androgen receptors (AR) that are chaperoned by heat shock proteins. Once bound, the DHT-AR complex migrates to the nucleus, dimerizes with another DHT-AR complex, associates with coactivator proteins, and transactivates a family of genes with androgen response elements that alter myocardial and vascular cell behavior.1 Evidence also supports a direct rapid membrane effect of T on G-protein-coupled receptors, with an increase in inositol trisphosphate and diacylglycerol and subsequent alterations in cytoplasmic calcium and potassium channel activity. 5 Cardiovascular Risk in Testosterone Deficiency DefinitionTestosterone deficiency (TD) is a well-established major medical condition that negatively impacts male sexuality, general health, and quality of life. Symptoms include decreased libido, erectile dysfunction, decreased energy, depressed mood, irritability, and decreased sense of well-being. In the correct clinical setting, the diagnosis of TD is usually confirmed by low serum concentrations of total T (e.g., < 200 ng/mL) drawn in the early morning. However, there is no specific value that reliably distinguishes men who experience signs and symptoms of TD from those who do not nor those who will likely respond to treatment. Interpretation of total T concentrations is confounded by variation between individuals, variation in serum SHBG, and variation in androgen sensitivity. 6 Furthermore, considerable controversy has arisen regarding the accuracy of currently available commercial testosterone assays, especially those showing T levels at the lower end of the "normal" range. 4 Free testosterone level may be a more reliable indicator of androg...

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Impact of Testosterone Replacement Therapy on Myocardial Infarction, Stroke, and Death in Men With Low Testosterone Concentrations in an Integrated Health Care System

Cited by 123 publications

References 15 publications

Fundamental Concepts Regarding Testosterone Deficiency and Treatment

Fundamental Concepts Regarding Testosterone Deficiency and Treatment

The consensus recommendations of a group of international experts on the fundamental concepts related to the issues of testosterone deficiency and its treatment.

Testosterone and the Heart

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