Monday, September 19, 2016

Premature or early onset menopause is associated with increased risk of CVD and all-cause mortality.

Clinical pearls:

  • Women who had premature menopause are at high risk for CHD, CVD and all-cause mortality.
  • With every 1 in 3 women dying due to CVD, identifying those who are high risks for it is important from public health perspective.
  • Women with premature menopause can be benefited by pharmacological and life style interventions to prevent the increased all-cause mortality and CVD risk they are put at due to accelerated reproductive aging.

Majority of women around the world undergo menopause between 45 to 55 years of age with the average age being 51 years.[1] According to recent estimates about 5% of women attain natural menopause between the age of 41-45 years and additional 1% of have the last period before the age of 40.  Another 5% have premature menopause due to surgical removal of the ovaries, radiation and chemotherapy for malignancies or smoking.  The age at final menstrual period is of great public health significance and is considered as an important marker for predicting future cardiovascular, bone and overall health of the women. [2]

Women who attain menopause before 45 years of age have shorter total duration of estrogen exposure as compared to women who have menopause in 50s.

Multiple observational and cross sectional studies in the past have tried to assess the effect of loss of ovarian function and increased risk of cardiovascular diseases (CVD) and all-cause mortality in women undergoing premature menopause.

A recent meta-analysis published in JAMA cardiology by Muka et al [3] tried to systemically review and meta-analyze the relationship between age and duration of menopause and increased risk of cardiovascular diseases.

The analysis included 32 studies consisting of 310,329 non-overlapping women in their analysis.

The investigators compared the outcomes between women who entered menopause before 45 years of age to those women who were 45 or older at the onset. It was seen that women in the early menopause group had 1.5 times the risk of overall coronary heart disease, 1.11 times the risk of fatal coronary heart disease,1.23 times the risk for overall stroke, 0.99 for stroke mortality, 1.19 times the risk for CVD mortality, and 1.12 for all-cause mortality as compared to women who had menopause after the age of 45 years.

Women who had menopause between age of 50-54 have decreased risk (.87 times) of suffering from fatal CHD as compared to women who had menopause before 50 years of age. The risk for stroke was comparable in both the groups.

With every 1 in 3 women dying due to CVD, identifying those who are high risks for it might be important from public health perspective. Menopause might be a crucial period in women’s life to evaluate her future risk for CVD and introduce interventions to reduce the risk.

In an invited commentary about the article by Dr JoAnn E Manson (Harvard Medical School, Boston, MA) and D. Teresa K Woodruff (Northwestern University), the authors stress upon the complicated relationship between menopause and CVD. They discuss the findings of the Framingham Heart Study which states that increase in systolic, diastolic blood pressure, cholesterol and other vascular risk factors around pre and peri menopausal years led to an accelerated menopause at a younger age. The data from the study provides an important clue about cardiovascular health being responsible for menopausal timing, but it does not exclude a bidirectional relationship. [4]

An earlier Meta-analysis of observational study showed that bilateral surgical oophorectomy was associated with more than double the risk of CVD (risk ratio=2.62). Women who are put on HRT after the surgery nullify their increased risk for CVD as compared to women with intact ovaries.

A detailed analysis of Women’s Health Initiative study also stressed the beneficial effects of HRT in relation to cardiovascular health when initiated between the ages of 50 to 59 years as compared to older women. [5]

The ELITE: Early Versus Late Intervention Trial With Estradiol also affirms the timing hypothesis in relation to timing of estradiol administration, when a beneficial cardiovascular effect is only seen in women with early, but not later menopause. [6]

To conclude, the findings of the review indicates that women who had premature menopause are at high risk for CHD, CVD and all-cause mortality.

Complex relationship exists between cardiovascular health and accelerated reproductive aging and further research is needed to clarify the issue, but currently women with premature menopause can be benefited by pharmacological and life style interventions to prevent the increased all-cause mortality and CVD risk they are put at due to accelerated reproductive aging.





[1] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3285482/
[2] http://www.cdc.gov/reproductivehealth/infertility/
[3] http://cardiology.jamanetwork.com/article.aspx?articleid=2551981
[4] http://amaprod.silverchaircdn.com/data/Journals/CARDIOLOGY/0/hic160023.pdf.gif
[5] https://www.nhlbi.nih.gov/whi/
[6] https://clinicaltrials.gov/ct2/show/NCT00114517

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