Does Menopause Cause
Arteries to Become Unhealthy?

The SHAPE study (Sex Hormones and Atherosclerosis Prevention in Perimenopausal Women) is looking to answer the above question.

As women go through menopause, their female hormones, estradiol and progesterone, decrease to very low levels. Also, with aging (and possibly with decreases in female hormones) the arteries located around the heart get stiffer. This increase in arterial stiffness can lead to health problems, such as high blood pressure and heart disease. In this study, we want to find out if it is specifically the loss of estrogen, rather than the aging process, that causes women’s arteries to stiffen..

The SHAPE study is examining women across the lifespan – premenopausal, perimenopausal, and postmenopausal. We will use a medication to decrease estrogen and progesterone levels in all women for 8 days, and some women will be given estrogen to bring the levels back up to normal. Women will have a series of screening tests to see if they qualify for the study, including a blood test, a bone density and body scan, and a treadmill exercise test. Women who qualify and choose to participate will have ultrasound tests to measure the stiffness of their arteries on 3 occasions. The first ultrasound test is a baseline assessment of arterial health. The second and third tests are re-assessments of arterial health after estrogen levels have been decreased (after 4 days) and then increased (after 4 more days) with medications.

The main inclusion criterial are:

• Premenopausal women 21-35 yrs, perimenopausal women 40-55 yrs, & postmenopausal women 45-70 yrs of age
• Non-smoker
• Normal blood pressure
• Not currently taking birth control or hormone therapy
• Not exercising vigorously more than 2 days per week

Kerrie Moreau, PhD is the Principal Investigator for this study. For further information, please contact the study coordinator, Nicole Hirsch, at 303-372-2921 or . This study is funded by the National Institutes of Health. It has been approved by the Colorado Multiple Institutional Review Board (protocol # 06-0537).

A Losing Battle?
Weight Loss-related Bone Loss

Although primary results from AFTER (Altering Fat Through Estrogen and Raloxifene) and SOS (Study of Stress) are still being analyzed, we are pleased to report some bone mineral density findings from these studies. As published in the Journal of Clinical Endocrinology and Metabolism in January 2005, we determined whether hormone therapy (Premarin) and/or raloxifene (Evista), an estrogen-like drug, helps prevent bone loss during modest weight loss. Both hormone therapy and raloxifene have previously been shown to have benefits on bone density and to reduce the risk of osteoporotic fracture.

Sixty-eight postmenopausal women participated in a 6-month exercise program to reduce weight; average weight loss was about 9 lbs. Another 26 women did not take part in the exercise program and remained weight stable over the 6 months. Women in both groups were randomly assigned to take hormone therapy, raloxifene, or placebo. Neither the investigators nor the participants knew what pill they were taking. Bone density testing (DXA scans) was done at the beginning of the study and at 6 months.

As expected in the weight stable groups (solid bars, figure below), bone density decreased with placebo (white), increased slightly with raloxifene (gray), and increased the most with hormone therapy (black). The weight loss groups all had larger decreases, or smaller increases in bone density, compared to the weight stable women in the same drug treatment group (striped bars compared with solid bars of the same color).

The main finding of this paper was that modest weight loss as a result of exercise training caused a reduction in bone density, particularly in women not on raloxifene or hormone therapy. Because weight loss was induced through exercise, which may protect bone through effects of weight-bearing and maintenance of muscle, studies are needed to determine whether dieting to lose weight causes an even greater loss of bone. An analysis is currently underway to determine whether weight loss-related bone loss is reversed with weight regain. Future studies will need to address whether the decrease in bone density during weight loss puts women at an increased risk of osteoporotic fracture. Stay tuned...

• The SHAPE study is examining how short-term changes in estrogen affect cardiovascular health. Eligible participants are premenopausal women 21-35, perimenopausal women 40-55, and postmenopausal women 45-70 years, who are non-smokers, have normal blood pressure, and who are not taking birth control or hormone therapy. (COMIRB # 06-0537)
• The HRT & Exercise study is investigating the cardiovascular effects of different types of hormone replacement therapy alone and in combination with exercise.  Eligible participants are sedentary postmenopausal women, 45-65 years, who are not currently taking HRT. (COMIRB #05-0606)

• The Kinetics study is examining the ability of leg muscles to use oxygen during exercise in healthy men and men with peripheral arterial disease. Eligible participants are non-smoking men, 50-70 years of age. (COMIRB #05-0718)
• The Mr. ACET study is examining how the use of acetaminophen and ibuprofen in older, exercising men, affects muscle and bone health. Eligible participants are men, 60 years and older, who are not currently in a weight lifting program, have no history of peptic ulcers or stomach bleeding, and do not typically use acetaminophen, ibuprofen, or similar drugs more than 3 days per month. (COMIRB # 06-0343)
• The New-to-ADT study is examining changes in muscle that occur in men on androgen deprivation therapy (ADT). Eligible participants are men, 45-85 years who have prostate cancer that has not spread to other organs, who plan to begin ADT. (COMIRB #05-0196)
• The TEAM study is examining the effects of testosterone supplementation and exercise in men who have low-normal testosterone levels. Eligible participants are men, 60 years and older, non-smokers, in good general health, and not currently doing high-intensity weight lifting exercise. (COMIRB # 02-1056)

• The PROXI study is determining if weight lifting helps to prevent the loss of muscle and bone mass that occurs in men with prostate cancer on androgen deprivation therapy (ADT). Eligible participants are men, 45-85 years, with prostate cancer, who are taking ADT or plan to start ADT. (COMIRB #02-0958)

• The DRIFT study is comparing the effect of two different diet methods - a normal, low calorie diet or intermittent fasting (not eating or drinking anything with calories every other day) - on weight loss and other health measures. Eligible participants are premenopausal women and men, 20-45 years, who are obese based on a body mass index (BMI) >35 (to determine your BMI go to www.nhlbisupport.com/bmi). (COMIRB # 06-0383)
• The Metabolic Syndrome and Cognition (MS-Cog) study is investigating how a drug (Pioglitazone) used to treat diabetes will affect memory and thinking ability of people at risk for diabetes and cognitive impairments. Eligible participants are 55 years and older who have risk factors for heart disease and diabetes such as high body fat, high cholesterol, high blood pressure, and high blood sugar. (COMIRB #06-0388)
• The Parkinson’s Disease study is examining how different forms of exercise help improve daily function and the ability to “stay active” in people with Parkinson’s disease. Eligible participants are people with Parkinson's who are able to function independently. (COMIRB #02-0750)