This research award will support the development of Christine M. Burt Solorzano, M.D., of the University of Virginia (UVA), as she continues to train in patient-oriented research under the mentorship of John C. Marshall, M.D., Ph.D., an established investigator in reproductive neuroendocrinology and the polycystic ovary syndrome (PCOS). Dr. Solorzano is a pediatric endocrinologist with previous research experience focusing on aspects of obesity. Her immediate goal is to understand the origins of PCOS and identify new treatment strategies. Her long-term goal is to become a leader in pediatric PCOS research, assessing the efficacy of interventions to prevent PCOS. This training will allow Dr. Solorzano to acquire skills needed to become an independent clinical investigator. The application outlines a career development plan that includes comprehensive instruction in clinical trials methodology, biostatistics, epidemiology, research ethics, assay methodology, and study design, partly via a Masters of Clinical Research. Dr. Solorzano's research proposal is designed to determine the source and timing of androgen excess in overweight girls and to identify potential strategies to reduce androgen production in this population. Androgen excess during puberty is a forerunner to PCOS-a common chronic endocrine disorder associated with infertility, metabolic disorders, and hirsutism in women. Childhood obesity - an international problem -puts girls at risk for androgen excess, even in early puberty. Identifying sources of androgen excess during puberty is needed to elucidate targets for preventing PCOS. Women and older adolescents with PCOS have predominantly ovarian overproduction of androgens. However, it is unknown whether the adrenal gland, ovary, or both are responsible for androgen excess in overweight girls prior to developing the full PCOS syndrome. This is especially true during early puberty when ovarian function is thought to be minimal.
Aim 1 will use adrenal suppression/stimulation testing and ovarian stimulation testing to examine sources of androgen production in normal and overweight girls throughout puberty.
Aim 2 will use low-dose hydrocortisone and leuprolide therapy to test whether short-term suppression of adrenocorticotropin or gonadotropin production can reduce androgen levels in overweight girls with androgen excess.
Aim 3 will examine the potential efficacy of longer-term therapies (e.g., low-dose hydrocortisone, metformin, or spironolactone) to reduce obesity-related androgen excess in girls during all stages of puberty. The research will be performed in the Clinical Research Center at UVA and would extend diagnostic tools to examine adrenal and ovarian androgen production to young girls. It may identify targets for therapeutic strategies to treat or prevent androgen excess during puberty - a critical stage for the development of PCOS.

Public Health Relevance

Childhood obesity - an international problem - puts girls at risk for excess male hormone (androgen) production and polycystic ovary syndrome (PCOS). PCOS leads to infertility, metabolic problems, and male-pattern hair growth in women and adolescents. This project would identify sources of obesity-related androgen excess during puberty and examine the efficacy of potential therapies in reducing androgen levels in girls during all stages of puberty, with the goal of preventing PCOS.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Mentored Patient-Oriented Research Career Development Award (K23)
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Pediatrics Subcommittee (CHHD)
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Eisenberg, Esther
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University of Virginia
Schools of Medicine
United States
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Kim, Su Hee; Lundgren, Jessica A; Bhabhra, Ruchi et al. (2018) Progesterone-Mediated Inhibition of the GnRH Pulse Generator: Differential Sensitivity as a Function of Sleep Status. J Clin Endocrinol Metab 103:1112-1121
Lundgren, Jessica A; Kim, Su Hee; Burt Solorzano, Christine M et al. (2018) Progesterone Suppression of Luteinizing Hormone Pulse Frequency in Adolescent Girls With Hyperandrogenism: Effects of Metformin. J Clin Endocrinol Metab 103:263-270
Kim, Su Hee; Burt Solorzano, Christine M; McCartney, Christopher R (2018) Progesterone administration does not acutely alter LH pulse secretion in the mid-follicular phase in women. Physiol Rep 6:e13680
Burt Solorzano, Christine M; Knudsen, Karen L; Anderson, Amy D et al. (2018) Insulin Resistance, Hyperinsulinemia, and LH: Relative Roles in Peripubertal Obesity-Associated Hyperandrogenemia. J Clin Endocrinol Metab 103:2571-2582
Burt Solorzano, Christine M; Helm, Kristin D; Patrie, James T et al. (2017) Increased Adrenal Androgens in Overweight Peripubertal Girls. J Endocr Soc 1:538-552
Hou, Jingwen; Cook-Andersen, Heidi; Su, H Irene et al. (2016) 17-Hydroxyprogesterone responses to human chorionic gonadotropin are not associated with serum anti-Mullerian hormone levels among adolescent girls with polycystic ovary syndrome. J Pediatr Endocrinol Metab 29:835-40
Collins, Jessicah S; Beller, Jennifer P; Burt Solorzano, Christine et al. (2014) Blunted day-night changes in luteinizing hormone pulse frequency in girls with obesity: the potential role of hyperandrogenemia. J Clin Endocrinol Metab 99:2887-96
Anderson, Amy D; Solorzano, Christine M Burt; McCartney, Christopher R (2014) Childhood obesity and its impact on the development of adolescent PCOS. Semin Reprod Med 32:202-13