Estradiol levels in men with congenital hypogonadotropic hypogonadism and the effects of different modalities of hormonal treatment Séverine Trabado,

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Estradiol levels in men with congenital hypogonadotropic hypogonadism and the effects of different modalities of hormonal treatment Séverine Trabado, D.Pharm., Ph.D., Luigi Maione, M.D., Sylvie Salenave, M.D., Stéphanie Baron, D.Pharm., Françoise Galland, M.D., Ph.D., Hélène Bry-Gauillard, M.D., Anne Guiochon-Mantel, M.D., Ph.D., Philippe Chanson, M.D., Nelly Pitteloud, M.D., Antonio Agostino Sinisi, M.D., Sylvie Brailly-Tabard, M.D., Ph.D., Jacques Young, M.D., Ph.D. Fertility and Sterility Volume 95, Issue 7, Pages 2324-2329.e3 (June 2011) DOI: 10.1016/j.fertnstert.2011.03.091 Copyright © 2011 American Society for Reproductive Medicine Terms and Conditions

Figure 1 Total (A), bioavailable (B), and free (C) E2 levels in healthy young men (controls) and untreated young patients with CHH and Klinefelter syndrome. P<.001 for all groups. Conversion to SI units: To convert total, bioavailable and free E2 concentration from pg/mL to picomoles per liter, multiply by 3.671. Fertility and Sterility 2011 95, 2324-2329.e3DOI: (10.1016/j.fertnstert.2011.03.091) Copyright © 2011 American Society for Reproductive Medicine Terms and Conditions

Figure 2 (A) Correlation between circulating total testosterone and circulating total E2 levels in untreated patients with CHH; P=.003. (B) Correlation between serum LH and circulating total E2 levels in the combined population of controls and untreated patients with CHH; P<.001. Fertility and Sterility 2011 95, 2324-2329.e3DOI: (10.1016/j.fertnstert.2011.03.091) Copyright © 2011 American Society for Reproductive Medicine Terms and Conditions

Figure 3 Total E2 (A), bioavailable E2 (B), and free E2 (C) in patients with CHH receiving either testosterone enanthate (TE) or FSH–hCG combination therapy, by comparison with untreated patients with CHH and healthy men (controls); P<.001 for all groups. To convert total, bioavailable, and free E2 concentration from picograms per milliliter to picomoles per liter, multiply by 3.671. Fertility and Sterility 2011 95, 2324-2329.e3DOI: (10.1016/j.fertnstert.2011.03.091) Copyright © 2011 American Society for Reproductive Medicine Terms and Conditions

Figure 4 Effect of testosterone enanthate (TE) (A) and FSH-hCG combined therapy (B) on circulating total E2 levels in patients with CHH; P<.0001. (C) Effect of percutaneous dihydrotestosterone (DHT) administration followed by TE therapy on circulating total E2 levels in patients with CHH; P<.001. Mean (±SD, nanograms per milliliter) serum total T (TT) before and under therapy is indicated (TT normal range in healthy men: 2.8–8.9 ng/mL). To convert total E2 concentration from picograms per milliliter to picomoles per liter, multiply by 3.671. Fertility and Sterility 2011 95, 2324-2329.e3DOI: (10.1016/j.fertnstert.2011.03.091) Copyright © 2011 American Society for Reproductive Medicine Terms and Conditions

Supplemental Figure 1 In patients with CHH, correlation between bioavailable E2 (BE2) measured by differential precipitation of globulin-bound E2 with 50% ammonium sulfate, after equilibration of the serum sample with [3H]-E2 and calculated bioavailable E2 based on the equations of Södergard et al. (15). Fertility and Sterility 2011 95, 2324-2329.e3DOI: (10.1016/j.fertnstert.2011.03.091) Copyright © 2011 American Society for Reproductive Medicine Terms and Conditions

Supplemental Figure 2 Serum total E2 to serum total T (TE2/TT) ratio in healthy men (controls) and in T enanthate-treated (TE) or FSH+hCG-treated patients with CHH; P<.001. Fertility and Sterility 2011 95, 2324-2329.e3DOI: (10.1016/j.fertnstert.2011.03.091) Copyright © 2011 American Society for Reproductive Medicine Terms and Conditions