Menopause Live - IMS Updates

Date of release: 08 February, 2016

The benefits and harms of alcohol consumption in women: cardiovascular aspects

Alcohol consumption has been associated with both benefits and harms, but most studies investigated men rather than women, or analyzed data from mixed cohorts composed of males and females, with necessary adjustments for age and sex. Also, most studies focused on one alcohol-related outcome or on a single group of related diseases rather than seeing the entire spectrum of human health. Despite a wealth of information on the outcomes of drinking alcohol, there is still inconsistency on some bottom-line guiding messages related to consumption patterns (quantity, frequency, and stratified combinations), and types of alcohol consumed. Ethnicity, socio-economical features, age and gender may be factors that influence disease protection or risk.

A recent study addressed the outcomes of drinking alcohol in a large cohort which included people from 12 countries in five continents with different socio-economical characteristics [1]. The PURE study included 114,970 adults, of whom 12,904 (11%) were from high-income countries, 24,408 (21%) were from upper-middle-income countries, 48,845 (43%) were from lower-middle-income countries, and 28,813 (25%) were from low-income countries. Mean age was 50 (41–58) years; median follow-up was 4.3 years (IQR 3.0–6.0). In the high- and upper-middle income countries, around 50% of the cohorts were women, but there were only 4% of women in the low-income countries. Overall, 74,685 (65%) participants were never drinkers, 4255 (4%) were former drinkers, and 36,030 (31%) were current drinkers. Of current drinkers, 26,025 (72%) had low intake, 6114 (17%) had moderate intake, and 2931 (8%) had high intake. Associations with mortality (n = 2723), cardiovascular disease (n = 2742), myocardial infarction (n = 979), stroke (n = 817), alcohol-related cancer (n = 764), injury (n = 824), admission to hospital (n = 8786), and for a composite of these outcomes (n = 11 963) were calculated. Data was adjusted for age and sex. Current drinking was associated with reduced myocardial infarction risk (HR 0.76; 95% CI 0.63–0.93), but with increased alcohol-related cancers (HR 1.51; 95% CI 1.22–1.89) and injury (HR 1.29; 95% CI 1.04–1.61). High intake was associated with increased mortality (HR 1.31; 95% CI 1.04–1.66). Compared with never drinkers, significantly reduced hazards for the composite outcome for current drinkers in high-income countries and upper-middle-income countries (HR 0.84; 95% CI 0.77–0.92), but not in lower-middle-income countries and low-income countries, for which there were no reductions in this outcome (HR 1.07; 95% CI 0.95–1.2).


Perhaps the best-known clinical bright side of alcohol consumption is cardiovascular protection, whereas the dark side is, of course, cirrhosis of the liver. The question was always how much one should drink to achieve benefits yet to avoid harms, and numerous publications have addressed this issue. The usual recommendation for healthy lifestyle encourages women to drink alcohol 'in moderation' in order to reduce the risk of cardiovascular disease. The American Heart Association guideline for the prevention of cardiovascular disease in women mentions in its Appendix that the desired quantity should be ≤ 1 serving/day, namely up to 4 oz wine, 12 oz beer, 1.5 oz of 80-proof spirits, or 1 oz of 100-proof spirits [2].

Twenty years ago, the 12-year follow-up data from the Nurses' Health Study showed that the relative risks of death in drinkers as compared with non-drinkers were 0.83 (0.74–0.93) for women who consumed 1.5–4.9 g of alcohol per day (one to three drinks per week), 0.88 (0.80–0.98) for those who consumed 5.0–29.9 g per day, and 1.19 (1.02–1.38) for those who consumed 30 g or more per day, after adjustment for other predictors of mortality [3]. Light-to-moderate drinking (1.5–29.9 g per day) was associated with a 27–43% lower risk of death from cardiovascular disease. The benefit associated with light-to-moderate drinking was most apparent among women with risk factors for coronary heart disease and those 50 years of age or older. A more recent publication on the same cohort addressed the younger women enrolled (27–44 years old at baseline) followed for 20 years [4]. The idea was to examine whether primordial prevention, defined as prevention of the development of clinical risk factors through maintenance or adoption of a healthy lifestyle, will sustain women in a low cardiovascular risk profile and reduce their future incidence of coronary heart disease. While optimal keeping of all lifestyle factors led to 92% lower risk compared to those women who did not follow any of the healthy lifestyle recommendations, the contribution of 'light drinking' (up to 14.9 g/day of alcohol intake) was in the order of 40% reduction in risk. The Women's Health Initiative Observational Study demonstrated similar results [5]. The cohort included 93,676 postmenopausal women 50–79 years of age at enrollment, followed for a median period of 10 years. Moderate alcohol use (consumption of greater than none but less than 1 drink per day) was associated with reduced incidence of cardiovascular disease [HR 0.83; 95% CI 0.72–0.95) as compared to all other non-smoking participants. This benefit was not seen in women who had more than 1 drink/day (HR 0.94; 95% CI 0.75–1.18). Another large study, the Women's Health Study, highlighted a linear association between alcohol consumption and cardiovascular disease risk [6]. Women above age 45 years (mean 55 ± 7 years, n = 26,399, mean follow-up of 12.2 years) were evaluated for different levels of alcohol intake. There were 1039 cardiovascular events and 785 deaths (153 cardiovascular deaths) during that period. Alcohol intake of 5–14.9 g/day was associated with 26%, 35%, and 51% lower risk of cardiovascular disease, total death, and cardiovascular death, respectively. Contrarily, lower (0.1–4.9 g/day), or higher (15–29.9 g/day, > 30 g/day) intakes gave non-significant benefits as confidence intervals included 1.

In conclusion, although the exact definitions of light or moderate alcohol intake vary in different studies, it seems well validated that small amounts of alcohol have potential protective cardiac effects. However, in regard to stroke, some studies show favorable consequences, while other studies are less promising in this respect. Women consuming < 2 drinks/day in the Nurses’ Health Study (to note that it included a primarily white cohort) had a 12–18% lower risk of ischemic stroke compared with non-drinkers [7]. In contrast, new data from the Atherosclerosis Risk in Communities study showed that self-reported light-to-moderate alcohol consumption at midlife was not associated with reduced stroke risk compared with abstention over 20 years of follow-up [8]. Furthermore, heavier consumption increased the risk for both ischemic and hemorrhagic stroke, as did moderate intake for intracerebral bleeding. The downside of alcohol consumption should be balanced with the benefits. In the Nurses' Health Study, heavier drinking was associated with an increased risk of death from several causes, particularly breast cancer (up to 67%) and cirrhosis (255%) [3]. The link between breast cancer and alcohol deserves more attention because of the continuously increasing incidence of both drinking and breast cancer in recent decades.


Amos Pines

Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel


  1. Smyth A, Teo KK, Rangarajan S, et al. Alcohol consumption and cardiovascular disease, cancer, injury, admission to hospital, and mortality: a prospective cohort study. Lancet 2015 Sep 17. Epub ahead of print

  2. Mosca L, Benjamin EJ, Berra K, et al. Effectiveness-based guidelines for the prevention of cardiovascular disease in women--2011 update: a guideline from the American Heart Association. J Am Coll Cardiol 2011;57:1404-23

  3. Fuchs CS, Stampfer MJ, Colditz GA, et al. Alcohol consumption and mortality among women. N Engl J Med1995;332:1245-50

  4. Chomistek AK, Chiuve SE, Eliassen AH, et al. Healthy lifestyle in the primordial prevention of cardiovascular disease among young women. J Am Coll Cardiol 2015;65:43-51

  5. Paynter NP, LaMonte MJ, Manson JE, et al. Comparison of lifestyle-based and traditional cardiovascular disease prediction in a multiethnic cohort of nonsmoking women. Circulation 2014;130:1466-73

  6. Djoussé L, Lee IM, Buring JE, Gaziano JM. Alcohol consumption and risk of cardiovascular disease and death in women: potential mediating mechanisms. Circulation 2009;120:237-44

  7. Jimenez M, Chiuve SE, Glynn RJ, et al. Alcohol consumption and risk of stroke in women. Stroke 2012;43:939–45

  8. Jones SB, Loehr L, Avery CL, et al. Midlife alcohol consumption and the risk of stroke in the Atherosclerosis Risk in Communities Study. Stroke 2015;46:3124-30

El siguiente comentario es una traducción de una contribución original en Inglés enviada a los miembros el Noviembre 18, 2013. La traducción ha sido gentilmente efectuada por el

Dr Peter Chedraui

Riesgo de cáncer de mama y niveles de estrógeno pre-tratamiento

La base de datos del WHI probablemente proporcionará un número infinito de publicaciones. Esta vez el foco de análisis fue explorar si los niveles de hormonas sexuales pre-tratamiento modifican el efecto del estrógeno + progestina (E + P) sobre el cáncer de mama [1]. Este fue un estudio anidado de casos y controles dentro del ensayo clínico aleatorizado WHI de E + P. El estudio incluyó a 16,608 mujeres postmenopáusicas de entre 50–79 años con útero intacto y sin antecedentes de cáncer de mama. Por una media de 5.6 años de seguimiento, se identificaron 348 casos de cáncer de mama incidental y aparearon a 348 controles. Se les midió tanto a casos y controles niveles de hormonas sexuales al inicio del estudio (estrógenos, testosterona, progesterona y hormona sexual globulina vinculante [SHBG]) y al año (estrógenos y SHBG) utilizando ensayos sensibles. Se observaron elevaciones estadísticamente significativas en el riesgo de cáncer de mama en aquellas con mayores niveles de estradiol total pretratamiento (p la tendencia = 0.04), estradiol biodisponible (p la tendencia = 0.03), estrona (p la tendencia = 0.007), y sulfato de estrona (p la tendencia = 0.007). La E + P aumentó todos los estrógenos medidos y SHGB al año 1 (todas p < 0.001). El efecto de E + P sobre el riesgo de cáncer de mama fue más fuerte en las mujeres cuyos niveles de estradiol total, estradiol biodisponible y estrona pretratamiento se encontraban en los cuartiles más bajos. Por ejemplo, el odds ratio para E + P en relación con el placebo fue 2.47 (intervalo de confianza (IC) del 95% 1.28–4.79) en el cuartil más bajo de estradiol total, en comparación con 0.96 (IC 95% 0.44–2.09) en el cuartil más alto de estradiol; p la interacción = 0.04). La principal conclusión fue que las mujeres con niveles más bajos de estrógenos endógenos pretratamiento estaban en mayor riesgo de cáncer de mama durante el tratamiento con E + P en comparación con aquellas con los niveles más altos.


Una vez más, los investigadores del WHI rascan el suelo de su base de datos y producen, resultados detallados adicionales, que proveen más luz sobre la controversial asociación TH y el riesgo de cáncer de mama. Sus análisis confirman reportes anteriores de que mayores niveles basales de estradiol total, estradiol biodisponible, estrona y sulfato de estrona se asocian con un mayor riesgo de cáncer de mama en mujeres postmenopáusicas. Además, encontraron que existe una asociación entre los niveles sanguíneos de hormonas sexuales femeninas pretratamiento y el riesgo subsecuente de cáncer de mama posterior, mientras se toma hormonas. Las usuarias de hormonas en el cuarto cuartil, que tienen un nivel de estradiol pretratamiento de 15 pg/ml o superior, no tuvieron un mayor riesgo de cáncer de mama en comparación con el grupo placebo. Las mujeres con niveles de estradiol pretratamiento entre 15 y 8 pg/ml (cuartiles 2, 3) tuvo un aumento no significativo en el riesgo de cáncer de mama, y sólo aquellos con estradiol basal de 8 pg/ml o menos (cuartil 1) demostraron un aumento significativo en el riesgo de cáncer de mama (OR 2.47; IC 95% 1.28–4.79).

La pregunta que surge de estos datos es el razonamiento para tal asociación. La forma más fácil de explicar yace en el conocido factor de riesgo para el cáncer de mama – obesidad. Un reciente reporte del WHI, que combina estudios clínicos y observacionales, demostró una vez más una asociación significativa entre el cáncer de mama y el peso, en correlación con los resultados de muchos estudios anteriores [2]. La fuerza de aquellos hallazgos del WHI se encuentra en sus números: el estudio incluyó 147,202 mujeres de entre 50–79, que fueron seguidas durante una media de 8 años. Por otro lado, la asociación entre los parámetros antropométricos, principalmente el índice de masa corporal (IMC), y estradiol endógeno, también ha sido bien documentada [3]. Las mujeres obesas tienen mayores niveles de estradiol endógeno y menores niveles de SHBG, lo que se atribuye a la mayor conversión de andrógenos a estrógenos en el tejido graso. Además, hay evidencia para mostrar una correlación negativa entre el IMC y el efecto de los estrógenos sobre el riesgo de cáncer de mama [4]. La famosa colaboración de re-análisis de 1997 encontró que el riesgo relativo de cáncer de mama asociado con la TH disminuyó progresivamente con el aumento de índice de masa corporal, siendo un IMC de 25 kg/m2 el punto de inflexión que marcó la zona de exclusión de riesgo [5]. Así que todo lo que se necesita ahora es añadir 1 + 1 para obtener 2, principalmente, que la mujer postmenopáusica con niveles mayores de estradiol pretratamiento, son propensas a ser obesas y tienen un mayor riesgo basal de cáncer de mama, y como tales no están expuestas a un mayor aumento en el riesgo de cáncer de mama, mientras usa TH. Esta bonita y sencilla explicación sería plausible, pero, de hecho, los datos actuals del WHI sobre hormonas sexuales pretratamiento se ajustaron para IMC y por lo tanto el razonamiento anterior podría no sostener y otros mecanismos deben buscarse. En cualquier caso, como escriben los investigadores del WHI, la determinación pretratamiento de los niveles de estradiol podría ser útil en la identificación de mujeres con riesgo de cáncer de mama particularmente elevado que están usando TH combinada.

Amos Pines

Department of Medicine T, Ichilov Hospital, Tel-Aviv, Israel


  1. Farhat GN, Parimi N, Chlebowski RT, et al. Sex hormone levels and risk of breast cancer with estrogen plus progestin. J Natl Cancer Inst 2013 Sep 16. Epub ahead of print.

  2. Hartz AJ, He T. Cohort study of risk factors for breast cancer in post menopausal women. Epidemiol Health 2013;35:e2013003.

  3. Baglietto L, English DR, Hopper JL, et al. Circulating steroid hormone concentrations in postmenopausal women in relation to body size and composition. Breast Cancer Res Treat 2009;115:1719.

  4. Kuhl H. Breast cancer risk in the WHI study: the problem of obesity. Maturitas 2005;51:83-97.

  5. Collaborative Group on Hormonal Factors in Breast Cancer. Breast cancer and hormone replacement therapy: collaborative reanalysis of data from 51 epidemiological studies with 52,705 women with breast cancer and 108,411 women without breast cancer. Lancet 1997;350:104759.

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