Brown Adipose Tissue Activity in Pre- and Postmenopausal Women
Condition: Menopause; Obesity
Study type: Interventional

Summary: 
      The physiological relevance of brown adipose tissue (BAT) in humans is largely unknown. The
      investigators have shown that suppressing ovarian function in premenopausal women reduces
      resting energy expenditure (REE), and this is prevented by adding back estradiol (E2). The
      investigators preliminary data suggest that this may be due, in part, to reduced brown
      adipose tissue (BAT) activity. The overarching hypothesis is that BAT activity in humans is
      modulated by E2. To determine if natural declines in endogenous E2 contribute to changes in
      BAT activity, we will compare BAT activity in pre-and post-menopausal women. The
      investigators will also explore whether suppression of ovarian hormones in pre-menopausal
      women impairs BAT activity. BAT activity will be quantified using dynamic positron emission
      topography/computed tomography (PET/CT) imaging combined with 11C-acetate tracers. We will
      assess the thermogenic response of BAT by measuring cold-induced changes in REE, shivering,
      and skin and core temperature.
    

Detailed description: 
      Participants will be asked to perform studies to measure resting metabolic rate and activity
      of brown adipose tissue or brown fat. Brown fat is different from regular "white fat" in that
      it produces heat and burns calories. The investigators will measure how active brown fat is
      at normal room temperature and after participants have been exposed to cold.

      The study will last 5-6 hours. It will consist of measurements made in warm temperatures and
      then after a period of cold exposure. For the cold exposure part of the study, participants
      will be asked to wear a cooling suit for 3 hrs. Skin temperature is normally about 90º
      Fahrenheit. The cooling suit will adjust the water temperature until your skin temperature is
      about 82º Fahrenheit. The suit will cover the entire body except for the face, hands, and
      feet. Participants may feel cold while wearing the suit and you may shiver some, but based on
      past studies, any shivering should be minor.

      Before and after the cooling suit is turned on, body scans will be performed using a
      procedure called positron emission tomography (PET). These scans do not use radiation. Before
      the PET scans, the investigators will infuse radioactive tracer into an arm. These tracers
      have a low dose of radiation and will show us where the brown fat is and how active it is.
      One PET scan will be performed at room temperature, and the second scan will be performed
      after the cooling suit has been worn for 3 hours. Two additional scans using computed
      tomography (CT) will be performed at end of the study. CT scans are like an x-ray, and use
      radiation. The radiation dose in the CT scan is much higher than the tracers. When the CT
      scans are combined with the PET scans, we can separate brown fat from white fat.

      15 pre-menopausal women will be asked to volunteer for a follow up study. For 5 months,
      pre-menopausal women in this study will receive monthly injections that contain a study drug
      (leuprolide) that reduces estrogen to postmenopausal levels. This drug is approved by the FDA
      to reduce estrogen for the treatment of uterine fibroids and endometriosis, but is not
      approved for use in healthy women. In this study, the drug is being used to decrease hormones
      to determine if this reduces brown fat activity. 6 months after the first injection, these
      women will be asked to repeat the PET/CT studies.
    

Intervention name(s): Leuprolide acetate
Intervention type(s): Drug
Intervention description(s): A subset of premenopausal women will receive GnRHAG (leuprolide acetate) 3.75 mg/mo by intramuscular injection every 4 weeks for 24 weeks (6 doses).
Other intervention name(s): Lupron
Intervention MeSH terms: Leuprolide
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Basic Science