Hormone Replacement in Young Women With Premature Ovarian Failure
Condition: Healthy; Osteoporosis; Premature Ovarian Failure
MeSH terms: Osteoporosis; Premature Birth; Primary Ovarian Insufficiency; Menopause, Premature
Study type: Interventional
Phase: Phase 2

Summary: 
      The human ovary produces male sex hormones (androgen) and female sex hormones (estrogen).
      Currently, androgen is not included in hormone replacement therapy for women with premature
      ovarian failure. Present hormone replacement therapy (HRT) was designed to treat women who
      experience ovarian failure at menopause (around the age of 50). However, 1% of women will
      experience premature failure of the ovaries before the age of 40. There have been no studies
      conducted to determine proper hormone replacement therapies for these younger women. Some
      research suggests that the usual menopausal hormone replacement therapy is not adequate to
      protect young women with premature ovarian failure from developing osteoporosis. Women with
      premature ovarian failure have abnormally low levels of androgens circulating in their blood.
      This may contribute to the increase risk for osteoporosis.

      This study will compare two treatment plans for women with premature ovarian failure.
      Treatment plan one will be physiological estrogen hormone replacement. Treatment plan two
      will be physiological estrogen hormone replacement plus androgen. The study will attempt to
      determine which plan is more beneficial to women in relation to osteoporosis and heart
      disease.

      The hormones will be contained in patches and given by placing the patches against the
      patient's skin. The patches were designed to deliver the same amount of hormone as would be
      normally produced by the ovary in young women.

      The success of the treatment will be measured by periodically checking the density of
      patient's bone in the leg (femoral neck bone) . Researchers will take an initial (baseline)
      measurement of bone density before beginning treatment and then once a year, for 3 additional
      years, during treatment. The study will also consider bone density of the spine, bone
      turnover, heart disease risk factors, and psychological state.
    

Detailed description: 
      Present menopausal hormone replacement therapy regimens were designed for women who
      experience ovarian failure around age 50. At least 1% of women, however, experience premature
      ovarian failure before the age of 40, but there have been no studies establishing optimal
      hormone replacement therapy regimens for these younger women. Available evidence suggests
      that the usual menopausal hormone replacement therapy is not adequate to protect young women
      with premature ovarian failure from developing osteoporosis. Women with premature ovarian
      failure have abnormally low circulating androgen levels, which may contribute to their risk
      for osteoporosis. We plan to compare physiological estrogen replacement with physiological
      estrogen plus androgen replacement in young women with premature ovarian failure to determine
      which regimen is more beneficial for bone mineral density and other metabolic parameters
      related to the risk for cardiovascular disease. This study employs transdermal estradiol and
      testosterone "patches" designed to deliver the same amount for each sex steroid normally
      produced by the ovary in young women in a physiological manner. Women with premature ovarian
      failure will be randomized to receive either estradiol plus placebo patches or estradiol plus
      testosterone patches. Both groups will receive cyclic progestin treatment. A group of
      age-matched women with normal ovarian function will serve as contemporaneous controls for
      bone density and other study measures. The primary outcome parameter is femoral neck bone
      mineral density, to be assessed at baseline, and after 1, 2, and 3 years of treatment. Other
      outcome parameters include lumbar spine bone mineral density, markers of bone turnover,
      cardiovascular disease risk factors, and cognitive function.
    

Intervention name(s): TMTDS
Intervention type(s): Drug
Primary purpose: Treatment
Keywords: Bone; Cognition; Estrogen; Mood; Testosterone; Osteoporosis; Ovarian Failure; Hormone Replacement Therapy; POF; Premature Ovarian Failure