Obesity is more prevalent in women than in men, a fact that may be related to fluctuations in reproductive hormones across a woman's lifespan. Menopause is associated with increased body weight and abdominal adiposity independent of aging. Diet and activity factors are implicated in the weight gain at menopause; however, the role of these factors is not well-understood. Our original study tested the hypotheses that 1) menopause-associated increases in visceral fat are hormone-related, 2) increased body fat at menopause is due to decreased energy expenditure and increased energy intake, and 3) African-American and Caucasian women have differential body fat changes at menopause. We began testing these hypotheses in a biethnic cohort of 161 middle-aged, premenopausal women recruited in 1998-99. To date, we have completed 3- year follow-up on 132 women and 4-year follow-up on approximately 80 women (the remainder are in progress). As only 34 women went through menopause by the 3-year follow-up, the first objective of this renewal is to continue to follow our initial cohort for an additional 3 years, by which time most subjects should be postmenopausal with a mean age of 54 years. This is necessary to address our major hypotheses related to the impact of menopause per se on body composition and energy balance. The second objective of the current proposal is to test the hypothesis that decreased leptin pulsatile secretion and subsequent changes in sympathetic nervous system (SNS) activity are a mechanism by which menopause may increase body weight. Specifically, we hypothesize that, 1) in relation to their altered LH secretion, postmenopausal women will have lower 24-hr leptin pulsatile secretion, 2) African-American women will have higher 24-hr leptin pulsatile secretion than Caucasians, 3) Decreased 24-hr serum leptin secretion will be associated with decreased leptin secretion and leptin mRNA in adipose tissue, 4) Subjects with lower 24-hr leptin secretion will exhibit lower SNS activity. To accomplish this objective, we will recruit new cohorts of premenopausal and postmenopausal women for 24-hr hormone pulsatility studies. Overall, continuing to follow the longitudinal cohort for up to 7 years provides a unique and valuable opportunity to examine the natural history of body composition changes during the menopause transition, while the new studies will provide novel mechanistic information about the role of hormonal changes at menopause on obesity.
