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Controlled Clinical Trial
. 2009 Jul;94(7):2360-6.
doi: 10.1210/jc.2008-2606. Epub 2009 Apr 7.

Modulation of gonadotropin-releasing hormone pulse generator sensitivity to progesterone inhibition in hyperandrogenic adolescent girls--implications for regulation of pubertal maturation

Susan K Blank  1 , Christopher R McCartney, Sandhya Chhabra, Kristin D Helm, Christine A Eagleson, R Jeffrey Chang, John C Marshall
Affiliations
Controlled Clinical Trial

Modulation of gonadotropin-releasing hormone pulse generator sensitivity to progesterone inhibition in hyperandrogenic adolescent girls--implications for regulation of pubertal maturation

Susan K Blank et al. J Clin Endocrinol Metab. 2009 Jul.

Abstract

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.

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Figures

Figure 1
Figure 1
The percentage change in LH pulse frequency per 11 h after 7 d of oral E2 and P in NC (A) and HA (B) adolescent girls. The data are plotted as a function of mean plasma P on d 7. The white circles represent the Tanner 3-5 girls. The shaded circles represent the Tanner 1-2 girls. The shaded areas represent the range of responses to 7 d of oral E2 and P in NC adult women (A) and adult women with PCOS (B). The outlined area in panel B represents the range of responses in NC adolescent girls.
Figure 2
Figure 2
The relationship of fasting insulin concentration and the slope of the percentage reduction in LH pulse frequency as a function of d 7 P in HA girls. One outlier (fasting insulin 119 μIU/ml, slope 2.8) was excluded from the graph.
Figure 3
Figure 3
The percentage change in LH pulse frequency per 11 h after 7 d of oral E2 and P in Tanner 1-2 NC (A), Tanner 3-5 NC (B), and HA adolescent girls (C). The data are plotted as a function of mean plasma P on d 7. The Tanner 1-2 subjects are labeled with the Tanner stages of the individual subjects. The shaded areas represent the range of responses to 7 d of oral E2 and P in NC adult women.
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Comment in

References

    1. Asunción M, Calvo RM, San Millán JL, Sancho J, Avila S, Escobar-Morreale HF 2000 A prospective study of the prevalence of the polycystic ovary syndrome in unselected Caucasian women from Spain. J Clin Endocrinol Metab 85:2434–2438 - PubMed
    1. Azziz R, Woods KS, Reyna R, Key TJ, Knochenhauer ES, Yildiz BO 2004 The prevalence and features of the polycystic ovary syndrome in an unselected population. J Clin Endocrinol Metab 89:2745–2749 - PubMed
    1. Diamanti-Kandarakis E, Kouli CR, Bergiele AT, Filandra FA, Tsianateli TC, Spina GG, Zapanti ED, Bartzis MI 1999 A survey of the polycystic ovary syndrome in the Greek island of Lesbos: hormonal and metabolic profile. J Clin Endocrinol Metab 84:4006–4011 - PubMed
    1. Zawadski J, Dunaif A 1992 Diagnostic criteria for polycystic ovary syndrome: towards a rational approach. In: Dunaif A, Givens J, Haseltine F, Merriam G, eds. Polycystic ovary syndrome. Oxford, UK: Blackwell Scientific; 377–384
    1. Azziz R, Carmina E, Dewailly D, Diamanti-Kandarakis E, Escobar-Morreale HF, Futterweit W, Janssen OE, Legro RS, Norman RJ, Taylor AE, Witchel SF 2006 Position statement: criteria for defining polycystic ovary syndrome as a predominantly hyperandrogenic syndrome: an Androgen Excess Society guideline. J Clin Endocrinol Metab 91:4237–4245 - PubMed

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