Fat Mediated Modulation of Reproductive and Endocrine Function in Young Athletes
Condition: Exercise-related Amenorrhea
MeSH terms: Amenorrhea
Intervention: Transdermal 17Beta-estradiol, progesterone; Ethinyl Estradiol + Desogestrel; Sham Comparator
Intervention description: 100 mcg/day 17Beta-estradiol; transdermal twice weekly application for 12 months (with cyclic micronized progesterone pills (Prometrium): 200 mg taken orally daily Day 1 to Day 12 each month) + Elemental calcium 1200 mg and Vit D 400 IU taken orally daily; Oral ethinyl estradiol (0.03 mg) + desogestrel (0.15 mg) + Elemental calcium 1200 mg and Vit D 400 IU taken once daily; Elemental calcium 1200 mg and Vit D 400 IU taken orally daily
Intervention MeSH terms: Estradiol 17 beta-cypionate; Estradiol 3-benzoate; Ethinyl Estradiol; Desogestrel; Estradiol; Polyestradiol phosphate; Progesterone
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 121.0
Sex: Female
Minimum age: 14 Years
Maximum age: 21 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Amenorrhea; Adolescent; Endurance; Athletes; Females; Osteopenia; Osteoporosis; Estrogen

Summary:

      One aim of this study is to determine changes in body composition and hormones that
      differentiate athletes who stop getting their periods versus those who continue to get their
      periods and non-athletes. The second aim of this study is to determine whether transdermal or
      oral estrogen (versus no estrogen) is effective in increasing bone density and improving bone
      microarchitecture in adolescent athletes who are not getting their periods and are thus
      estrogen deficient. The investigators hypothesize that transdermal estrogen will be more
      effective than oral estrogen or no estrogen in improving bone health in amenorrheic
      adolescent athletes.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Females 14-21 years old Note: Our pilot data are reassuring in that young women 18-25
             years old with hypothalamic amenorrhea are not adversely affected with estrogen use.
             In fact, in our prospective study, beneficial effects were observed both in young
             women 18-25 years old using oral estrogen, and in 14-18 year old adolescent girls
             using transdermal estrogen. We therefore feel that including girls in the 14-21 year
             age range will not be hazardous to their bone health. In fact, given the lack of data
             in this age group, it is important to study younger women and teenagers rather than
             extrapolate data from studies in adults to this younger population. Hormone dynamics
             differ in teenagers compared with adults, and bone mass accrual is even more dependent
             on estrogen and IGF-1 in younger than older women who have already achieved peak bone
             mass.

          -  Bone age (BA) >15 years Note: 99% of adult height is achieved at a BA of 15 years,
             thus estrogen replacement will not result in stunting of height potential after this
             age. Although we could have chosen to include girls with a BA >14 in this study, we
             are limiting this to girls with a BA of >15 years. This is because 2% of growth
             potential persists at a BA of 14 years, versus only 1% at a BA of 15 years (~0.6" of
             potential height (130)). Thus, to avoid potential stunting of growth potential with
             estrogen replacement, we have chosen to include girls with BA of > 15 years.

          -  BMI between 10th-90th percentiles for age.

          -  Amenorrhea (for AA): absence of menses for > three months (74) within a period of
             oligomenorrhea (cycle length > six weeks) for >six months, or absence of menarche at
             >16 years.

          -  Eumenorrhea (EA and controls): > nine menses (cycle length 21-35 days) in preceding
             year.

          -  Non-athlete healthy controls will be eligible if weight bearing exercise activity is
             less than two hours a week and if they are not participating in organized team sports.

          -  Endurance athletes Note: severity of low BMD and menstrual dysfunction differ by kind
             of exercise and activity. For example, runners have a higher prevalence of menstrual
             irregularity than swimmers and cyclists (131). By limiting enrollment to endurance
             athletes, we will eliminate variability from the type of activity. Endurance training
             is defined as > 4 h of aerobic weight-bearing training of the legs or specific
             endurance training weekly, or > 20 miles of running weekly for a period of > 6 months
             in the last year.

        Exclusion Criteria:

          -  Other conditions that may affect bone metabolism