Chronic anovulatory hyperandrogenism is a common heterogeneous disorder of unknown etiology characterized by hirsutism, oligo/amenorrhea, anovulation, infertility, acne, hyperandrogenism, increased LH/FSH ratio, and insulin resistance. Because insulin resistance is often accompanied by known risk factors for coronary artery disease, it has been speculated that chronic anovulatory hyperandrogenism indicates a greater propensity for coronary artery disease. Recently, it has been suggested that premature pubic hair is a harbinger of chronic anovulatory hyperandrogenism. If this proves to be true, it may he possible to identify and intervene earlier in the subset of patients at risk for chronic anovulatory hyperandrogenism and its associated complications. Preliminary data supports genotype analysis of steroidogenic enzymes especially 21- hydroxylase (CYP21). The hypotheses of this proposal are: 1) pre- mature pubic hair precedes chronic anovulatory hyperandrogenism in some patients; 2) the abnormal gonadal and/or adrenal steroid production limits FSH secretion to below the threshold concentrations needed for ovulation and 3) there are useful genetic and/or hormonal markers associated with an increased risk for chronic anovulatory hyperandrogenism. Genotype analysis of candidate genes in conjunction with sequential evaluation of patients with premature/excessive virilization, serial determinations of gonadotropin excretion and repeated assessments of insulin sensitivity will be used to test these hypotheses. Correlation of clinical features with results of hormonal and genetic evaluations may help unravel the sequence of events leading to chronic anovulatory hyperandrogenism.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29HD034808-02
Application #
2674039
Study Section
Reproductive Endocrinology Study Section (REN)
Project Start
1997-07-05
Project End
2002-06-30
Budget Start
1998-07-01
Budget End
1999-06-30
Support Year
2
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Children's Hosp Pittsburgh/Upmc Health Sys
Department
Type
DUNS #
044304145
City
Pittsburgh
State
PA
Country
United States
Zip Code
15224
Witchel, Selma Feldman; White, Carlie; Libman, Ingrid (2009) Association of the -243 A-->G polymorphism of the glutamate decarboxylase 2 gene with obesity in girls with premature pubarche. Fertil Steril 91:1869-76
Roldan, Maria Belen; White, Carlie; Witchel, Selma Feldman (2007) Association of the GAA1013-->GAG polymorphism of the insulin-like growth factor-1 receptor (IGF1R) gene with premature pubarche. Fertil Steril 88:410-7
Witchel, Selma Feldman (2006) Puberty and polycystic ovary syndrome. Mol Cell Endocrinol 254-255:146-53
Witchel, Selma F; Kahsar-Miller, Melissa; Aston, Christopher E et al. (2005) Prevalence of CYP21 mutations and IRS1 variant among women with polycystic ovary syndrome and adrenal androgen excess. Fertil Steril 83:371-5
Barker-Gibb, Mandi; Plant, Tony M; White, Carlie et al. (2004) Genotype analysis of the neuropeptide Y (NPY) Y1 and NPY Y5 receptor genes in gonadotropin-releasing hormone-dependent precocious gonadarche. Fertil Steril 82:491-4
Roldan Martin, Maria Belen; White, Carlie; Kammerer, Candice et al. (2004) Mutational analysis of the melanocortin-4 receptor (MC4R) gene in children with premature pubarche and adolescent girls with hyperandrogenism. Fertil Steril 82:1460-2
Witchel, Selma F; Trivedi, Ram N; Kammerer, Candace (2003) Frequency of the T228A polymorphism in the SORBS1 gene in children with premature pubarche and in adolescent girls with hyperandrogenism. Fertil Steril 80:128-32
Tomboc, Marlah; Witchel, Selma Feldman (2003) Frequencies of the D85 and Y85 variants of UGT2B15 in children and adolescent girls with hyperandrogenism. J Pediatr Endocrinol Metab 16:719-26
Sanders, Ellen B; Aston, Christopher E; Ferrell, Robert E et al. (2002) Inter- and intrafamilial variability in premature pubarche and polycystic ovary syndrome. Fertil Steril 78:473-8
Ibanez, Lourdes; Marcos, Maria Victoria; Potau, Neus et al. (2002) Increased frequency of the G972R variant of the insulin receptor substrate-1 (irs-1) gene among girls with a history of precocious pubarche. Fertil Steril 78:1288-93

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