Delayed puberty and secondary amenorrhea due to hypothalamic mechanisms in young women are common events which are thought to be reversible and without permanent health effects. However, it is a well documented clinical observation that young women deprived of estrogen are at increased risk for the development of osteoporosis. No systematic study has been performed to date on young women who have repeated episodes of prolonged hypoestrogenism at a young age to document the occurrence and development of permanent long term problems such as osteopenia. In addition, the apposition of bone during adolescence is thought to have a critical bearing on the development of osteoporosis in later life. Yet, little scientific data exists on the effects of prolonged periods of hypoestrogenism during this critical period. Recent data shows that prolonged hypoestrogenism may be related to skeletal problems seen in young adults. The present research proposal is aimed at examining whether prolonged hypoestrogenism in young women affects bone density in the same manner that is documented in postmenopausal women. The pathogenesis of hypoestrogenism and skeletal complications which occur in a unique high risk group of young adults and adolescent girls will be examined in a detailed longitudinal fashion. This group shows a high incidence of stress fractures (46%) and adolescent scoliosis (23%) as well as prolonged intervals of hypoestrogenism manifested by delayed menarche or secondary amenorrhea. Intensive serial studies of 80 cohort members and 80 controls will be performed. These studies will be analyzed to elucidate the potential interrelationships of prolonged hypoestrogenism and abnormal nutritional patterns to the pathogenesis of osteopenia and scoliosis. Further understanding of the role of hypoestrogenism in the development of stress fractures and scoliosis would radically alter attitudes towards the importance of normal sexual maturation and estrogen replacement and may lead to the formulation of more effective treatment strategies for scoliosis.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
1R01HD022171-01
Application #
3321559
Study Section
Reproductive Endocrinology Study Section (REN)
Project Start
1986-08-01
Project End
1990-07-31
Budget Start
1986-08-01
Budget End
1987-07-31
Support Year
1
Fiscal Year
1986
Total Cost
Indirect Cost
Name
St. Luke's Roosevelt Hosp Center (New York)
Department
Type
DUNS #
City
New York
State
NY
Country
United States
Zip Code
10025
Schneider, Lisa F; Monaco, Sara E; Warren, Michelle P (2008) Elevated ghrelin level in women of normal weight with amenorrhea is related to disordered eating. Fertil Steril 90:121-8
Schneider, Lisa F; Warren, Michelle P (2006) Functional hypothalamic amenorrhea is associated with elevated ghrelin and disordered eating. Fertil Steril 86:1744-9
Warren, Michelle P; Brooks-Gunn, Jeanne; Fox, Richard P et al. (2003) Persistent osteopenia in ballet dancers with amenorrhea and delayed menarche despite hormone therapy: a longitudinal study. Fertil Steril 80:398-404
Warren, Michelle P; Brooks-Gunn, Jeanne; Fox, Richard P et al. (2002) Osteopenia in exercise-associated amenorrhea using ballet dancers as a model: a longitudinal study. J Clin Endocrinol Metab 87:3162-8
Kaufman, Becky A; Warren, Michelle P; Dominguez, Jennifer E et al. (2002) Bone density and amenorrhea in ballet dancers are related to a decreased resting metabolic rate and lower leptin levels. J Clin Endocrinol Metab 87:2777-83
Graber, J A; Brooks-Gunn, J; Warren, M P (1999) The vulnerable transition: puberty and the development of eating pathology and negative mood. Womens Health Issues 9:107-14
Warren, M P; Holderness, C C; Lesobre, V et al. (1994) Hypothalamic amenorrhea and hidden nutritional insults. J Soc Gynecol Investig 1:84-8
Holderness, C C; Brooks-Gunn, J; Warren, M P (1994) Eating disorders and substance use: a dancing vs a nondancing population. Med Sci Sports Exerc 26:297-302
Jonnavithula, S; Warren, M P; Fox, R P et al. (1993) Bone density is compromised in amenorrheic women despite return of menses: a 2-year study. Obstet Gynecol 81:669-74
Linday, L A; Greenblatt, D J; Warren, M P et al. (1991) Changes in salivary antipyrine pharmacokinetics during adolescence, correlated with age, hormonal levels and Tanner stage. Dev Pharmacol Ther 16:194-202

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