Menopausal Hormone Therapy and Health Outcomes During the Intervention and Extended Poststopping Phases of the Women’s Health Initiative Randomized Trials

Manson, Jo Ann E.; Chlebowski, Rowan T.; Stefanick, Marcia L.; Aragaki, Aaron K.; Rossouw, Jacques E.; Prentice, Ross L.; Anderson, Garnet L.; Howard, Barbara V.; Thomson, Cynthia A.; LaCroix, Andrea Z.; Wactawski‐Wende, Jean; Jackson, Rebecca D.; Limacher, Marian C.; Margolis, Karen L.; Wassertheil‐Smoller, Sylvia; Beresford, Shirley A.A.; Cauley, Jane A.; Eaton, Charles B.; Gass, Margery; Hsia, Judith; Johnson, Karen C.; Kooperberg, Charles; Kuller, Lewis H.; Lewis, Cora E.; Liu, Simin; Martin, Lisa W.; Ockene, Judith K.; OʼSullivan, Mary J.; Powell, Lynda H.; Simon, Michael S.; Horn, Linda Van; Vitolins, Mara Z.; Wallace, Robert B.

doi:10.1001/jama.2013.278040

Cited by 1,217 publications

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“…Previous reports showed that among women aged 50 to 59 years at baseline in the overall WHI E‐Alone trial, randomization to E‐Alone versus placebo was associated with lower risk of MI, CHD, and mortality during the trial and in long‐term follow‐up 3. Among women aged 50 to 59 years at baseline in the WHI E‐Alone Trial, the WHI‐CACS showed that randomization to E‐Alone versus placebo resulted in lower odds of CAC measured ≈8.7 years after baseline, independent of CVD risk factors also associated with subsequent CAC 5.…”

Section: Discussionmentioning

confidence: 96%

Coronary Artery Calcification (CAC) and Post‐Trial Cardiovascular Events and Mortality Within the Women's Health Initiative (WHI) Estrogen‐Alone Trial

Poornima

Mackey

Allison

et al. 2017

JAHA

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BackgroundAmong women aged 50 to 59 years at baseline in the Women's Health Initiative (WHI) Estrogen‐Alone (E‐Alone) trial, randomization to conjugated equine estrogen‐alone versus placebo was associated with lower risk of myocardial infarction and mortality, and, in an ancillary study, the WHI‐CACS (WHI Coronary Artery Calcification Study) with lower CAC, measured by cardiac computed tomography ≈8.7 years after baseline randomization. We hypothesized that higher CAC would be related to post‐trial coronary heart disease (CHD), cardiovascular disease (CVD), and total mortality, independent of baseline randomization or risk factors.Methods and ResultsWHI‐CACS participants (n=1020) were followed ≈8 years from computed tomography scan in 2005 (mean age=64.4) through 2013 for incident CHD (myocardial infarction and fatal CHD, n=17), CVD (n=69), and total mortality (n=55). Incident CHD and CVD analyses excluded women with CVD before scan (n=89). Women with CAC=0 (n=54%) had very low age‐adjusted rates/1000 person‐years of CHD (0.91), CVD (5.56), and mortality (3.45). In comparison, rates were ≈2‐fold higher for women with any CAC (>0). Associations were not modified by baseline randomization to conjugated equine estrogen–alone versus placebo. Adjusted for baseline randomization and risk factors, the hazard ratio (95% confidence interval) for CAC >100 (19%) was 4.06 (2.11, 7.80) for CVD and 2.70 (1.26, 5.79) for mortality.ConclusionsAmong a subset of postmenopausal women aged 50 to 59 years at baseline in the WHI E‐Alone Trial, CAC at mean age of 64 years was strongly related to incident CHD, CVD, and to total mortality over ≈8 years, independent of baseline randomization to conjugated equine estrogen–alone versus placebo or CVD risk factors.Clinical Trial RegistrationURL: https://www.clinicaltrials.gov. Unique identifier: NCT00000611.

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Section: Discussionmentioning

confidence: 96%

Coronary Artery Calcification (CAC) and Post‐Trial Cardiovascular Events and Mortality Within the Women's Health Initiative (WHI) Estrogen‐Alone Trial

Poornima

Mackey

Allison

et al. 2017

JAHA

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“…Data to support these conclusions come from multiple sources as reviewed extensively as well as from the a 13-year follow-up of the WHI study (Manson et al 2013). For this reason, the term HRT, which implies that all women should accept this therapy, has been replaced by the term MHT.…”

Section: Oestrogen Therapy and Menopausementioning

confidence: 99%

Celebrating 75 years of oestradiol

Simpson

Santen

2015

Journal of Molecular Endocrinology

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Oestrogens exert important effects on the reproductive as well as many other organ systems in both men and women. The history of the discovery of oestrogens, the mechanisms of their synthesis, and their therapeutic applications are very important components of the fabric of endocrinology. These aspects provide the rationale for highlighting several key components of this story. Two investigators, Edward Doisy and Alfred Butenandt, purified and crystalized oestrone nearly simultaneously in 1929, and Doisy later discovered oestriol and oestradiol. Butenandt won the Nobel Prize for this work and Doisy's had to await his purification of vitamin K. Early investigators quickly recognized that oestrogens must be synthesized from androgens and later investigators called this process aromatization. The aromatase enzyme was then characterized, its mechanism determined, and its structure identified after successful crystallization. With the development of knock-out methodology, the precise effects of oestrogen in males and females were defined and clinical syndromes of deficiency and excess described. Their discovery ultimately led to the development of oral contraceptives, treatment of menopausal symptoms, therapies for breast cancer, and induction of fertility, among others. The history of the use of oestrogens for postmenopausal women to relieve symptoms has been characterized by cyclic periods of enthusiasm and concern. The individuals involved in these studies, the innovative thinking required, and the detailed understanding made possible by evolving biologic and molecular techniques provide many lessons for current endocrinologists. Discovery of oestrogenThe concept that substances secreted by one organ could then be transported internally to another via the blood stream is the underpinning of the field of endocrinology. The 'father of physiology', Claude Bernard, articulated the concept of internal secretion by describing how the liver produces glucose, which then travels to and is utilized by other tissues in the body. This concept underlies studies on the ovaries, which became a focus of investigation later in the century. In 1896, Emil Knauer, a 29-year-old Austrian, excised the ovaries of adult rabbits and then re-implanted pieces into different locations in the same animals (Watkins 2007 Doisy then enlisted a nurse in the obstetrics clinic to supply each pregnant patient with a 1 gal jug and ask for her urine. This provided the needed material but was fraught with difficulties. Suspected to be a bootlegger because of the large jugs of yellow material in his car, one of Doisy's drivers was nearly arrested until he suggested using the sniff test with the response 'My god, it is urine'. Doisy, then being recruited to St Louis University, continued his efforts to purify the active substance. Each extract was tested with a bioassay and its effect on uterine stimulation. Urine, the material of choice for study, was initially extracted with a very large countercurrent apparatus (Fig. 1). Costing the exorbitan...

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“…Esta hipóte-sis parece confirmarse en un análisis del Nurses' Health Study, el cual encontró que las mujeres que iniciaron la THM combinada en los primeros 10 años tenían un RR de enfermedad coronaria de 0,72 (IC 95% 0,56 a 0,92), mientras que las que la iniciaron posteriormente tenían un RR de 0,90, (IC 95% 0,62 A 1,29) (27) . Igualmente, el mismo WHI mostró que las mujeres que usaban THM en los primeros 10 años de posmenopausia no tenían aumento del riesgo coronario, mientras que las que iniciaban su uso 20 años después de la menopausia sí tenían un mayor riesgo en 52% (IC 95% 7,0 a 117%) (28) . Aquí se ha planteado el concepto de ventana de oportunidad de la THM; en mujeres menopáusicas recientes, con sistema cardiovascular más sano, la THM sería cardioprotectora, fenómeno más evidente aun en mujeres con insuficiencia ovárica primaria, a diferencia de las mujeres mayores de 60 años, con arterias dañadas y con placas de ateroesclerosis inestables, en quienes sería perjudicial.…”

Section: Enfermedad Cardiovascularunclassified

Terapia hormonal de la menopausia, ¿por qué prescribirla?

Maldonado

2018

Rev peru ginecol obstet.

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Financiamiento: Autofinanciado Conflicto de interés:La autora declara no tener algún conflicto de interés RESUMENDurante el climaterio, la mayoría de las mujeres presenta muchos síntomas que afectan su calidad de vida. Estos síntomas han sido vinculados con trastornos de la neuroquímica provocados por la carencia de estrógenos. El sistema nervioso central-SNC también está involucrado en los cambios de la composición corporal y en el aumento de tejido adiposo que se produce durante el climaterio. El adipocito del obeso produce adipocitoquinas que llevan a un estado inflamatorio crónico con incremento del riesgo de diabetes, hipertensión e hipercoagulabilidad, aumentando el riesgo cardiovascular. El déficit de estrógenos también modula señales celulares (RANKL, NPY) que favorecen la reabsorción ósea y el riesgo de osteoporosis. La obesidad asociada al climaterio incrementa además el riesgo de cáncer de mama, endometrio, colon y vesícula al aumentar la leptina e interleucina 6. Estas adipocitoquinas modulan una serie señales celulares (STAT3, AP-1, MAPK, ERKs) que a su vez aumentan la aromatasa, la síntesis de estrógenos y la activación de receptores alfa en las células malignas, estimulando la proliferación celular. También, algunos estudios experimentales sugieren una acción anti-Alzheimer de los esteroides ováricos. Palabras clave. Terapia hormonal, Menopausia, Calidad de vida, Enfermedades crónicas. ABSTRACTDuring the climacteric, most women have many symptoms that affect their quality of life. These symptoms have been linked to neurochemical disorders caused by the lack of estrogen. The CNS is also involved in changes in body composition and in the gain in adipose tissue that occurs during the climacteric. Obese adipocytes produce adipocytokines that lead to a chronic inflammatory status with a higher risk for diabetes, hypertension and hypercoagulability; all these increase the cardiovascular risk. Estrogen deficiency also modulates cellular signals (RANKL, NPY) that favor bone resorption and osteoporosis risk. Obesity associated with menopause also increases the risk of breast, endometrial, colon and bladder cancer by raising the levels of leptin and interleukin 6. These adipocytokines modulate a series of cellular signals (STAT3, AP-1, MAPK, ERKs) series which in turn increase aromatase, the synthesis of estrogens and the activation of alpha receptors in malignant cells, stimulating cell proliferation. Also, some experimental studies suggest an anti-Alzheimer action of ovarian steroids.

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Menopausal Hormone Therapy and Health Outcomes During the Intervention and Extended Poststopping Phases of the Women’s Health Initiative Randomized Trials

Cited by 1,217 publications

References 55 publications

Coronary Artery Calcification (CAC) and Post‐Trial Cardiovascular Events and Mortality Within the Women's Health Initiative (WHI) Estrogen‐Alone Trial

Coronary Artery Calcification (CAC) and Post‐Trial Cardiovascular Events and Mortality Within the Women's Health Initiative (WHI) Estrogen‐Alone Trial

Celebrating 75 years of oestradiol

Terapia hormonal de la menopausia, ¿por qué prescribirla?

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