CONTEXT: Adult women with polycystic ovary syndrome (PCOS) have decreased GnRH pulse generator sensitivity to progesterone (P)-mediated slowing. This defect is androgen mediated because it is reversed with androgen receptor blockade. Adolescent hyperandrogenism often precedes PCOS. OBJECTIVE: The aim of the study was to evaluate GnRH pulse generator sensitivity to P-mediated slowing in normal and hyperandrogenic girls. DESIGN: We conducted a controlled interventional study. SETTING: The study was conducted in a general clinical research center. PARTICIPANTS: A total of 26 normal control (NC) and 26 hyperandrogenic (HA) girls were studied. INTERVENTION: Frequent blood sampling was performed for 11 h to assess LH pulse frequency before and after 7 d of oral estradiol and P. MAIN OUTCOME MEASURE: We measured the slope of the percentage reduction in LH pulse frequency as a function of d 7 P (slope). RESULTS: Overall, Tanner 3-5 HA subjects were less sensitive to P-mediated slowing than Tanner 3-5 NC (slope, 4.7 +/- 3.4 vs. 10.3 +/- 7.7; P = 0.006). However, there was variability in the responses of HA subjects; 15 had P sensitivities within the range seen in NC, whereas nine were relatively P insensitive. The two groups had similar testosterone levels. Fasting insulin levels were higher in P-insensitive HA girls (39.6 +/- 30.6 vs. 22.2 +/- 13.9 microIU/ml; P = 0.02), and there was an inverse relationship between fasting insulin and P sensitivity in HA girls (P = 0.02). Tanner 1-2 NC had lower testosterone levels and were more P sensitive than Tanner 3-5 NC (slope, 19.3 +/- 5.8; P = 0.04). CONCLUSIONS: Hyperandrogenism is variably associated with reduced GnRH pulse generator sensitivity to P-mediated slowing during adolescence. In addition to androgen levels, insulin resistance may modulate P sensitivity.
CONTEXT: Adult women with polycystic ovary syndrome (PCOS) have decreased GnRH pulse generator sensitivity to progesterone (P)-mediated slowing. This defect is androgen mediated because it is reversed with androgen receptor blockade. Adolescent hyperandrogenism often precedes PCOS. OBJECTIVE: The aim of the study was to evaluate GnRH pulse generator sensitivity to P-mediated slowing in normal and hyperandrogenic girls. DESIGN: We conducted a controlled interventional study. SETTING: The study was conducted in a general clinical research center. PARTICIPANTS: A total of 26 normal control (NC) and 26 hyperandrogenic (HA) girls were studied. INTERVENTION: Frequent blood sampling was performed for 11 h to assess LH pulse frequency before and after 7 d of oral estradiol and P. MAIN OUTCOME MEASURE: We measured the slope of the percentage reduction in LH pulse frequency as a function of d 7 P (slope). RESULTS: Overall, Tanner 3-5 HA subjects were less sensitive to P-mediated slowing than Tanner 3-5 NC (slope, 4.7 +/- 3.4 vs. 10.3 +/- 7.7; P = 0.006). However, there was variability in the responses of HA subjects; 15 had P sensitivities within the range seen in NC, whereas nine were relatively P insensitive. The two groups had similar testosterone levels. Fasting insulin levels were higher in P-insensitive HA girls (39.6 +/- 30.6 vs. 22.2 +/- 13.9 microIU/ml; P = 0.02), and there was an inverse relationship between fasting insulin and P sensitivity in HA girls (P = 0.02). Tanner 1-2 NC had lower testosterone levels and were more P sensitive than Tanner 3-5 NC (slope, 19.3 +/- 5.8; P = 0.04). CONCLUSIONS: Hyperandrogenism is variably associated with reduced GnRH pulse generator sensitivity to P-mediated slowing during adolescence. In addition to androgen levels, insulin resistance may modulate P sensitivity.
Authors: Christopher R McCartney; Melissa B Gingrich; Yun Hu; William S Evans; John C Marshall Journal: J Clin Endocrinol Metab Date: 2002-05 Impact factor: 5.958
Authors: C A Eagleson; M B Gingrich; C L Pastor; T K Arora; C M Burt; W S Evans; J C Marshall Journal: J Clin Endocrinol Metab Date: 2000-11 Impact factor: 5.958
Authors: E Diamanti-Kandarakis; C R Kouli; A T Bergiele; F A Filandra; T C Tsianateli; G G Spina; E D Zapanti; M I Bartzis Journal: J Clin Endocrinol Metab Date: 1999-11 Impact factor: 5.958
Authors: Stephanie B Seminara; Sophie Messager; Emmanouella E Chatzidaki; Rosemary R Thresher; James S Acierno; Jenna K Shagoury; Yousef Bo-Abbas; Wendy Kuohung; Kristine M Schwinof; Alan G Hendrick; Dirk Zahn; John Dixon; Ursula B Kaiser; Susan A Slaugenhaupt; James F Gusella; Stephen O'Rahilly; Mark B L Carlton; William F Crowley; Samuel A J R Aparicio; William H Colledge Journal: N Engl J Med Date: 2003-10-23 Impact factor: 91.245
Authors: Christine A Eagleson; Amy B Bellows; Kathy Hu; Melissa B Gingrich; John C Marshall Journal: J Clin Endocrinol Metab Date: 2003-11 Impact factor: 5.958
Authors: Karen L Knudsen; Susan K Blank; Christine Burt Solorzano; James T Patrie; R Jeffrey Chang; Sonia Caprio; John C Marshall; Christopher R McCartney Journal: Obesity (Silver Spring) Date: 2010-03-25 Impact factor: 5.002
Authors: Su Hee Kim; Jessica A Lundgren; Ruchi Bhabhra; Jessicah S Collins; James T Patrie; Christine M Burt Solorzano; John C Marshall; Christopher R McCartney Journal: J Clin Endocrinol Metab Date: 2018-03-01 Impact factor: 5.958
Authors: David H Abbott; Lindsey E Nicol; Jon E Levine; Ning Xu; Mark O Goodarzi; Daniel A Dumesic Journal: Mol Cell Endocrinol Date: 2013-01-29 Impact factor: 4.102