CVD risks linked to menopause

HRT potentially decreases the risk of CHD events, mainly observed in women who initiate therapy in the first decade after menopause

Although cardiovascular disease (CVD) mortality increases with age, coronary artery disease (CAD) mortality becomes steeper after menopause indicating it is an independent risk factor for CAD compared to stroke, lung cancer, breast cancer, colon cancer, and endometrial cancer.

Dr. Amos Pines, the co-founder of the Israel Menopausal Society and an associate professor at the Sackler Faculty of Medicine, Tel-Aviv University, discussed the increase in cardiovascular risk observed in women after menopause.

According to The Framingham Study, the incidence of CVD in relation to menopausal status shows a two to six times higher rate of CVD in post-menopausal women. (Ann Intern Med. 1976;85:447-52)

The Cancer Prevention Study II in the USA demonstrated the relationship of the age of menopause and CAD. After 20 years of follow-up, women who entered menopause at age <44 had a 10 percent increased risk of dying unlike women who had menopause at age >50.

In the Netherlands, age adjusted mortality was reduced by 2 percent with each increasing year of age at menopause. This can lead to a difference of several years in longevity or life span.

Of the 2,607 deaths, 963 of the Dutch participants were caused by CVD and 812 were due to cancer. (Ossewaarde ME, et al. Epidemiology 2005; 16:556) It was apparent that the risk was lowest among the women entering menopause >55 years old.

In addition, most studies highlighted women who entered menopause at an earlier age <40 years old seemed to have had a higher chance of having CAD at any post-menopausal age than women who get menopausal >46 years old.

Menopause and the body

Dr. Pines also stressed that decline in bone density is expected from early menopause and onwards. He noted that all older women had lower bone density than younger women, and the lower the bone mineral density the higher the fracture risks.

However, another factor that should be taken into consideration would be fat distribution. Female body shapes are classified as the apple/abdominal obesity type and the pear/hip obesity type. The former is associated with increased CV risk compared to the latter type.

Menopause is often accompanied by change of fat distribution which correlates with an increased risk of CHD.

A lean body is associated with at least a 40-percent decrease in risk of dying. “Fasting glucose increases by 1-2mg/dL per decade and post prandial glucose increases by up to 15 mg/dL per decade. This is the result of insulin resistance (after) the age of menopause,” Dr. Pines added.

Hypertension, obesity, and insulin resistance are all components of the classical metabolic syndrome—a constellation of closely related metabolic risk factors for CVD.

At least 30 percent of women >60 years old have metabolic syndrome which is associated with an increased risk of CAD.

Clinical hypertension in the USA is diagnosed in more than half of women age 55 or older, and more than 80 percent of women age 75. “Any increase of blood pressure even from optimal to normal or from normal to high-normal is associated with an increased risk of cardiovascular events,” said Dr. Pines. He also noted that BMI increases at least until age 50 to 60 years old.

“The globally accepted way to reduce the risk cardiovascular disease is to implement healthy lifestyle behaviors which can be summarized as follows: Eat healthy, manage your weight, exercise regularly, and stop smoking,” Dr. Pines reiterated.

The World Health Organization also added that significant effects are most likely evident when lifestyle recommendations are implemented.

Major risk factors for CVD are cholesterol levels >240, systolic BP >160 or diastolic BP >100, diabetes, and smoking.

Hormone replacement therapy

Hormone replacement therapy (HRT) can have significant results in metabolic, functional, and morphological aspect of the body.

In the National Health and Nutrition Examination Survey (NHANES) III Study, women with diabetes currently taking HRT had better glycemic control as compared to those who were not on HRT. (Diabetes Care 2002; 25:1675-1680)

A total of 28 randomized controlled trials with 33,426 participants and 5,516 fracture cases revealed an evidence that HRT is associated with a reduced risk of total, vertebral, and hip fractures, with a possible attenuation of this protection effect after it is stopped or when it is begun after 60 years. (Menopause 2015; Oct 27)

HRT potentially decreases the risk of CHD events, but this is mainly observed in women who initiate therapy in the first decade after menopause, and use certain hormonal combinations.

Dr. Pines highlighted the importance of women’s decision on choosing or declining HRT, and reluctance in finding help for treating menopausal symptoms, which has hindered the clinical care of midlife women, adding a large unnecessary burden of misery.

As part of the Israel Menopause Society’s (IMS) governing principles, Menopausal Hormone Therapy (MHT) remains the most effective therapy for vasomotor and urogenital atrophy. MHT must fit according to symptoms and the need for prevention, as well as personal and family history, results of relevant investigations, the woman’s preferences and expectations. (IMS updated recommendations Climacteric 2016; 19:109-150)

MHT is an option for one’s better quality of life and health priorities as wells as personal risk factors such as age, time since menopause, and the risk of venous thromboembolism, stroke, ischemic heart disease, and breast cancer.

Moreover, dose and duration should be consistent with treatment goals such as symptom relief and should be individualized. (Global Consensus, November 2012 Climacteric 2013; 16:203-4)

Early initiation of treatment

According to Global Consensus, there is strong evidence that standard-dose estrogen-alone MHT decreases CAD and all-cause mortality in women <60 years old and within a decade of menopause.

Similarly, Dr. Pines said that there is strong and consistent findings that estrogen therapy may be cardioprotective if started around the time of menopause (often referred to as the ‘window of opportunity’ or ‘timing hypothesis’) and may be harmful if started 10 years after menopause.

Global Consensus advises that MHT is most effective among women before age 60 years old or within 10 years after menopause in treatment for the prevention of fracture. The IMS guidelines recommend MHT for decreasing vertebral and hip fracture incidences even in women who are not at high risk of fracture.

IMS reiterate that it is the only therapy proven to be effective in reducing fracture in patients with osteopenia. The benefits of MHT are most likely to outweigh any risk and can be considered as first-line therapy among 50 to 60 year olds or within a decade after menopause. Ma. Vanessa L. Estinozo

June 2016 Health and Lifestyle

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