Postmenopausal Hormone Therapy and Atherosclerosis — Time Is of the Essence

Keaney, John F.; Solomon, Caren G.

doi:10.1056/nejme1602846

Cited by 29 publications

(14 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The conclusions of the older observational studies from the 1980s and 1990s have been partially discredited. 1 More recent randomized control trials (RCTs) such as the Heart and Estrogen/Progestin Replacement Study (HERS), 2 Women's Health Initiative (WHI), 3 Kronos Early Estrogen Prevention Study (KEEPS), 4 and Early versus Late Intervention Trial of Estradiol (ELITE), 5 newer observational studies, for example, Study of Women Across the Nation (SWAN), 6 and animal studies (cynomolgus monkeys by Clarkson et al 7 - 10 including JR Kaplan, CA Shively, Thomas Register, KP Klein, MS Anthony, TS Mikkola et al) have changed the paradigm of estrogen administration for the hypo-estrogenemic woman. In this personal perspective, we attempt to clarify the data and present a unifying concept which we call eu-estrogenemia (Eu-E) 11 —the true and good concentration of estrogen at which more than 3,600 ubiquitous estrogen receptors (ERs) 12 function optimally and continuously.…”

mentioning

confidence: 99%

A theory of eu-estrogenemia: a unifying concept

Turner

Kerber

2017

Menopause

View full text Add to dashboard Cite

Objective:The aim of the study was to propose a unifying theory for the role of estrogen in postmenopausal women through examples in basic science, randomized controlled trials, observational studies, and clinical practice.Methods:Review and evaluation of the literature relating to estrogen.Discussion:The role of hormone therapy and ubiquitous estrogen receptors after reproductive senescence gains insight from basic science models. Observational studies and individualized patient care in clinical practice may show outcomes that are not reproduced in randomized clinical trials. The understanding gained from the timing hypothesis for atherosclerosis, the critical window theory in neurosciences, randomized controlled trials, and numerous genomic and nongenomic actions of estrogen discovered in basic science provides new explanations to clinical challenges that practitioners face. Consequences of a hypo-estrogenemic duration in women's lives are poorly understood. The Study of Women Across the Nation suggests its magnitude is greater than was previously acknowledged. We propose that the healthy user bias was the result of surgical treatment (hysterectomy with oophorectomy) for many gynecological maladies followed by pharmacological and physiological doses of estrogen to optimize patient quality of life. The past decade of research has begun to demonstrate the role of estrogen in homeostasis.Conclusions:The theory of eu-estrogenemia provides a robust framework to unify the timing hypothesis, critical window theory, randomized controlled trials, the basic science of estrogen receptors, and clinical observations of patients over the past five decades.

show abstract

mentioning

confidence: 99%

A theory of eu-estrogenemia: a unifying concept

Turner

Kerber

2017

Menopause

View full text Add to dashboard Cite

show abstract

“…For several agents, preclinical models have accurately predicted efficacy in humans [2], with both negative [124–128] and positive outcomes [29,31,129]. Nevertheless, new animal models must be developed with long enough latency periods to enable preventive intervention and to explore optimal timing of administration [130,131]. Engineered mouse strains should effectively model the genetic diversity of human cancer to enable ‘precision’ cancer prevention [132].…”

Section: Discussionmentioning

confidence: 99%

Cancer Prevention: Lessons Learned and Future Directions

Dunn

Kramer

2016

Trends in Cancer

View full text Add to dashboard Cite

In this review, we address selected areas that are central to the state-of-the-art of cancer prevention science. The emphasis on prevention as a viable and critical approach to decreasing cancer mortality has gained traction in recent years, evidenced by its inclusion in the US Vice President's Cancer Initiative (also termed ‘Moonshot’). Cancer prevention occurs by arresting, slowing down, or reversing the carcinogenic process before invasion into surrounding tissue or by avoiding or blocking causative exposure. An important challenge is to identify individuals who will benefit most from preventive interventions with the least possible harm. Preventive interventions range from avoiding known carcinogens (e.g., tobacco or asbestos) to intervening with anticarcinogenic strategies (behavioral modifications , such as diet and exercise; medications; nutritional agents; and vaccination against causative agents). Here, we focus on active intervention with measures involving pharmaceutical and immunological agents.

show abstract

“… 13 At present, HT is not recommended for the purpose of preventing adverse cardiovascular events. 35 …”

Section: Cardiovascular Diseasementioning

confidence: 99%

Menopausal Hormone Therapy, Age, and Chronic Diseases: Perspectives on Statistical Trends

Bolton

2016

Chem. Res. Toxicol.

View full text Add to dashboard Cite

The release of the Women’s Health Initiative (WHI) study in 2002 was a shock to the medical community. Hormone therapy (HT) had generally been considered to be highly beneficial for postmenopausal women since it was the gold standard for relief of menopausal symptoms (hot flashes, night sweats, vaginal atrophy) and it was thought to protect women from osteoporosis, heart disease, and cognitive decline and to generally improve quality of life. However, WHI showed a statistically significant increase in a number of disease states, including breast cancer, cardiovascular disease, and stroke. One problem with the WHI study was that the average age of women in the study was 63, which is considerably older than the age at which most women enter menopause (about 51). The timing hypothesis attempts to rationalize the effect of age on response to HT and risk of various diseases. The data suggests that younger women (50–60) may be protected from heart disease with only a slight increase in breast cancer risk. In contrast, older women (>65) are more susceptible to breast cancer and heart disease and should avoid HT. This Perspective on Statistical Trends evaluates the current data on HT and risk for chronic diseases as a function of age.

show abstract

Postmenopausal Hormone Therapy and Atherosclerosis — Time Is of the Essence

Cited by 29 publications

References 12 publications

A theory of eu-estrogenemia: a unifying concept

A theory of eu-estrogenemia: a unifying concept

Cancer Prevention: Lessons Learned and Future Directions

Menopausal Hormone Therapy, Age, and Chronic Diseases: Perspectives on Statistical Trends

Contact Info

Product

Resources

About