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
