Clinical Review

Diabetes and menopause: a special population and growing

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More studies are needed to definitively answer whether or not HRT can play a primary or secondary role in the prevention of CVD. In the meantime, physicians may consider its use in patients with diabetes, but should not start HRT in women who have had a myocardial event in the past 6 to 12 months.

Low-dose aspirin. The American Diabetes Association (ADA) recommends 81 to 325 mg of aspirin a day for the prevention of adverse cardiovascular events associated with diabetes. In the past, there has been concern that low-dose aspirin increases the risk of retinal hemorrhage and interferes with the actions of oral hyperglycemic medications. Neither is true.

Studies on the prevention of diabetic retinopathy with aspirin have shown neither risk nor benefit with regard to retinal bleeding.11 Further, only high-dose aspirin—more than 1,000 mg per day—increases the risk of hypoglycemia. Additionally, studies have shown that taking low-dose aspirin decreases the chance of myocardial events by 30%.12 Therefore, menopausal women with or without diabetes may benefit from taking low-dose aspirin.

ACE inhibitors. The role of this agent is evolving. The Heart Outcomes Prevention Study (HOPE) examined whether the addition of an ACE inhibitor in 9,000 patients with vascular disease or diabetes could lower the risk of CVD. It showed that 10 mg of this agent administered over a 5-year period reduced the risk of myocardial infarction, stroke, or cardiovascular death.13 While women and their doctors may not wish to add yet another medication to a list that may include ther apy for hyperglycemia, hypertension, dyslipidemia, and osteoporosis, ACE inhibitors are worth considering given their beneficial effects on the microvascular complications of diabetes including nephropathy, retinopathy, and neuropathy.

Thiazolidinediones. In addition to reducing insulin resistance, TZDs may have a direct effect on CVD risk factors. Studies have shown that TZDs reduce vascular intimamedia thickness and promote vascular relaxation. Further, the use of this medication has been known to improve lipid profiles, decrease triglycerides, and reduce the progression of atherogenesis.14 On the other hand, studies also have shown that TZD users may experience fluid retention, edema, and weight gain. In addition, physicians should observe patients for signs and symptoms of heart failure and discontinue if any deterioration in cardiac status occurs. Monitoring of liver function also is advised.


Health issues at menopause: additional effects of diabetes and cardiovascular disease

Cardiovascular protectionGreater benefit
Urogenital maintenanceGreater benefit
CosmeticSlightly more benefit
Osteoporosis preventionIndividual benefits
Symptom reliefSimilar benefit
Prevention or delay of Alzheimers’s diseasePossible greater benefit
Breast cancer concernSimilar
Hassle and expense of pillSimilar or slightly greater
Worsening of hypertriglyceridemiaGreater


There are many opportunities to decrease the risk of CVD in menopausal women with diabetes who have no family history of CVD and a range of modifiable risk factors. On the other hand, options are limited for women with a strong family history of premature CVD with low-risk blood pressure and lipid profiles who cannot take HRT and who bleed with prophylactic anticoagulants. Women who fall under this category should still be advised to follow a low-fat, nutritious diet and exercise regularly.

Clearly, each woman will have varying risk factor profiles and priorities. Therefore, it is important that she be routinely screened during her menopausal years, and, if possible, when she is perimenopausal.

Cardiovascular interventions in menopause
HRT makes you fatIf anything, HRT is associated with a small decrease in weight, blood pressure, and insulin resistance and with a healthier gynecoid (“pear”) fat distribution
HRT causes high blood pressure
HRT worsens insulin resistance
HRT increases the risk of cardiovascular eventsHRT halves the cardiovascular event rate
Alternative therapies (e.g., plant phytoestrogens, evening primrose oil) are effective and safe substitutes for HRTThere is no evidence of the benefit of alternative therapies in the menopause; in fact, placebo therapy reduces symptoms in 30% to 50% of postmenopausal women. Further, the formulations of most preparations are not regulated, and the unopposed estrogen activity of phytoestrogens may increase the risk of endometrial cancer
Weight gain fearedThe benefits of cardiovascular risk reduction greatly exceed the risks associated with weight gain, which is common but not inevitable
Increased risk of retinal hemorrhageNo increased risk found in clinical trials
Interference with oral hyperglycemic agents (sulfonylureas)No adverse interactions found in clinical trials

While there are no definitive studies that compare cardiovascular risk factor intervention in women with diabetes to those without, at the very least, patients should be advised to quit smoking, follow a low-fat diet with exercise, and take HRT and low-dose aspirin. This strategy will go a long way toward reducing the impact of serious heart conditions in menopausal women with diabetes.

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