Insulin Resistance and Testosterone in Women
Condition: Insulin Resistance; Postmenopause
MeSH terms: Insulin Resistance
Study type: Interventional
Phase: Phase 2

Summary: 
      The purpose of this research study is to determine if a relationship between insulin
      resistance (IR) and testosterone (T) exists in women who have already gone through menopause.
    

Detailed description: 
      This study tests the central hypothesis that insulin resistance (IR) increases androgen (male
      sex hormone) production in postmenopausal women. Participation will include five visits, each
      lasting on average 2.5 hours, over a period of 13-20 weeks.

      At the screening visit, the participant's medical history, current use of medications and
      dietary supplements, and social habits will be recorded. This information will be reviewed on
      each subsequent visit; participants are asked to maintain their current diet and physical
      activity level throughout the study.

      A brief physical exam will be performed, and blood will be drawn.

      At the 2nd (baseline) visit, patients will undergo a euglycemic-hyperinsulinemic clamp (a
      procedure to measure insulin sensitivity by continuous intravenous infusion of insulin, and
      variable infusion of glucose). Blood samples will be drawn throughout the procedure. At
      completion, the insulin infusion will be stopped, participants will be fed, and the glucose
      infusion continued for at least 15 minutes to ensure stability of the blood glucose
      concentration. After the procedure, participants will be randomized to receive either
      metformin plus leuprolide placebo, leuprolide plus metformin placebo, or metformin placebo
      plus leuprolide placebo. The leuprolide or leuprolide placebo will be administered as an
      injection by a nurse. The metformin or metformin placebo will be dispensed to the participant
      in the form of pills, with instructions for titrating the dose. Participants will be
      contacted by telephone once weekly during the titration period to assess drug tolerability
      and adverse events (AEs). Participants will be maintained at their maximum tolerated dose for
      the duration of the study intervention period.

      Participants will return every 4 weeks for follow-up. Blood will be drawn, the nurse will
      administer the leuprolide or leuprolide placebo injection, and metformin or metformin placebo
      will be dispensed. At the final visit (week 12), participants will undergo a brief physical
      exam, and will then undergo a final euglycemic-hyperinsulinemic clamp.
    

Intervention name(s): metformin; leuprolide injection; placebo pill; placebo injection
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): Initiated on 500 mg daily and titrated up to 1000 mg twice a day during the first four weeks, remaining at that dose until 12 weeks; 3.75 mg injection every 4 weeks (e.g. at baseline, 4, and 8 weeks); matching pill twice a day for 12 weeks; matching injection every 4 weeks (e.g. baseline, 4, and 8 weeks)
Other intervention name(s): Glucophage; Lupron
Intervention MeSH terms: Metformin; Leuprolide
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment